                         SEQUENCE LISTING

<110>  The Trustees of the University of Pennsylvania
 
<120>  LDL Variants and Their Use in Compositions for Reducing 
       Circulating Cholesterol Levels

<130>  14-7025PCT

<150>  62/022627
<151>  2014-07-09

<150>  61/984620
<151>  2014-04-25

<160>  40    

<170>  PatentIn version 3.5

<210>  1
<211>  839
<212>  PRT
<213>  Homo sapiens

<400>  1

Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe Gln Cys Gln Asp Gly 
1               5                   10                  15      


Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly Ser Ala Glu Cys Gln 
            20                  25                  30          


Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu Ser Val Thr Cys Lys 
        35                  40                  45              


Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn Arg Cys Ile Pro Gln 
    50                  55                  60                  


Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp Asn Gly Ser Asp Glu 
65                  70                  75                  80  


Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp Glu Phe Arg Cys His 
                85                  90                  95      


Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys Asp Ser Asp Arg Asp 
            100                 105                 110         


Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro Val Leu Thr Cys Gly 
        115                 120                 125             


Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys Ile Pro Gln Leu Trp 
    130                 135                 140                 


Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly Ser Asp Glu Trp Pro 
145                 150                 155                 160 


Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly Asp Ser Ser Pro Cys 
                165                 170                 175     


Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu Cys Ile His Ser Ser 
            180                 185                 190         


Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp Lys Ser Asp Glu Glu 
        195                 200                 205             


Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu Phe Gln Cys Ser Asp 
    210                 215                 220                 


Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp Arg Glu Tyr Asp Cys 
225                 230                 235                 240 


Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn Val Thr Leu Cys Glu 
                245                 250                 255     


Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu Cys Ile Thr Leu Asp 
            260                 265                 270         


Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp Trp Ser Asp Glu Pro 
        275                 280                 285             


Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp Asn Asn Gly Gly Cys 
    290                 295                 300                 


Ser His Val Cys Asn Asp Leu Lys Ile Gly Tyr Glu Cys Leu Cys Pro 
305                 310                 315                 320 


Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys Glu Asp Ile Asp Glu 
                325                 330                 335     


Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys Val Asn Leu Glu Gly 
            340                 345                 350         


Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln Leu Asp Pro His Thr 
        355                 360                 365             


Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr Leu Phe Phe Thr Asn 
    370                 375                 380                 


Arg His Glu Val Arg Lys Met Thr Leu Asp Arg Ser Glu Tyr Thr Ser 
385                 390                 395                 400 


Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu Asp Thr Glu Val Ala 
                405                 410                 415     


Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln Arg Met Ile Cys Ser 
            420                 425                 430         


Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser Tyr Asp Thr Val Ile 
        435                 440                 445             


Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala Val Asp Trp Ile His 
    450                 455                 460                 


Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly Thr Val Ser Val Ala 
465                 470                 475                 480 


Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe Arg Glu Asn Gly Ser 
                485                 490                 495     


Lys Pro Arg Ala Ile Val Val Asp Pro Val His Gly Phe Met Tyr Trp 
            500                 505                 510         


Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys Gly Gly Leu Asn Gly 
        515                 520                 525             


Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile Gln Trp Pro Asn Gly 
    530                 535                 540                 


Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr Trp Val Asp Ser Lys 
545                 550                 555                 560 


Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly Gly Asn Arg Lys Thr 
                565                 570                 575     


Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro Phe Ser Leu Ala Val 
            580                 585                 590         


Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile Asn Glu Ala Ile Phe 
        595                 600                 605             


Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn Leu Leu Ala Glu Asn 
    610                 615                 620                 


Leu Leu Ser Pro Glu Asp Met Val Leu Phe His Asn Leu Thr Gln Pro 
625                 630                 635                 640 


Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu Ser Asn Gly Gly Cys 
                645                 650                 655     


Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn Pro His Ser Pro Lys 
            660                 665                 670         


Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu Ala Arg Asp Met Arg 
        675                 680                 685             


Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala Thr Gln Glu Thr Ser 
    690                 695                 700                 


Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val Arg Thr Gln His Thr 
705                 710                 715                 720 


Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu Pro Gly Ala Thr Pro 
                725                 730                 735     


Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser His Gln Ala Leu Gly 
            740                 745                 750         


Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro Ser Ser Val Arg Ala 
        755                 760                 765             


Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val Phe Leu Cys Leu Gly 
    770                 775                 780                 


Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys Asn Ile Asn Ser Ile 
785                 790                 795                 800 


Asn Phe Asp Asn Pro Val Tyr Gln Lys Thr Thr Glu Asp Glu Val His 
                805                 810                 815     


Ile Cys His Asn Gln Asp Gly Tyr Ser Tyr Pro Ser Arg Gln Met Val 
            820                 825                 830         


Ser Leu Glu Asp Asp Val Ala 
        835                 


<210>  2
<211>  21
<212>  PRT
<213>  Homo sapiens

<400>  2

Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu 
1               5                   10                  15      


Ala Ala Ala Gly Thr 
            20      


<210>  3
<211>  682
<212>  PRT
<213>  Homo sapien Hu LDLR isoform 2

<400>  3

Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu 
1               5                   10                  15      


Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe 
            20                  25                  30          


Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly 
        35                  40                  45              


Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu 
    50                  55                  60                  


Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn 
65                  70                  75                  80  


Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp 
                85                  90                  95      


Asn Gly Ser Asp Glu Gln Gly Cys Pro Val Ala Thr Cys Arg Pro Asp 
            100                 105                 110         


Glu Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys 
        115                 120                 125             


Asp Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val 
    130                 135                 140                 


Asn Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly 
145                 150                 155                 160 


Glu Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg 
                165                 170                 175     


Asp Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu 
            180                 185                 190         


Asp Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Leu Lys Ile Gly 
        195                 200                 205             


Tyr Glu Cys Leu Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg 
    210                 215                 220                 


Cys Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu 
225                 230                 235                 240 


Cys Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe 
                245                 250                 255     


Gln Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala 
            260                 265                 270         


Tyr Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp 
        275                 280                 285             


Arg Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala 
    290                 295                 300                 


Leu Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser 
305                 310                 315                 320 


Gln Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser 
                325                 330                 335     


Ser Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu 
            340                 345                 350         


Ala Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu 
        355                 360                 365             


Gly Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu 
    370                 375                 380                 


Phe Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val 
385                 390                 395                 400 


His Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys 
                405                 410                 415     


Lys Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn 
            420                 425                 430         


Ile Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu 
        435                 440                 445             


Tyr Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn 
    450                 455                 460                 


Gly Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His 
465                 470                 475                 480 


Pro Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile 
                485                 490                 495     


Ile Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val 
            500                 505                 510         


Asn Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe 
        515                 520                 525             


His Asn Leu Thr Gln Pro Arg Glu Ala Glu Ala Ala Val Ala Thr Gln 
    530                 535                 540                 


Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val Arg Thr 
545                 550                 555                 560 


Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu Pro Gly 
                565                 570                 575     


Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser His Gln 
            580                 585                 590         


Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro Ser Ser 
        595                 600                 605             


Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val Phe Leu 
    610                 615                 620                 


Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys Asn Ile 
625                 630                 635                 640 


Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Lys Thr Thr Glu Asp 
                645                 650                 655     


Glu Val His Ile Cys His Asn Gln Asp Gly Tyr Ser Tyr Pro Ser Arg 
            660                 665                 670         


Gln Met Val Ser Leu Glu Asp Asp Val Ala 
        675                 680         


<210>  4
<211>  693
<212>  PRT
<213>  Homo sapien

<400>  4

Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu 
1               5                   10                  15      


Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe 
            20                  25                  30          


Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly 
        35                  40                  45              


Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu 
    50                  55                  60                  


Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn 
65                  70                  75                  80  


Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp 
                85                  90                  95      


Asn Gly Ser Asp Glu Gln Gly Cys Pro Leu Thr Leu Cys Glu Gly Pro 
            100                 105                 110         


Asn Lys Phe Lys Cys His Ser Gly Glu Cys Ile Thr Leu Asp Lys Val 
        115                 120                 125             


Cys Asn Met Ala Arg Asp Cys Arg Asp Trp Ser Asp Glu Pro Ile Lys 
    130                 135                 140                 


Glu Cys Gly Thr Asn Glu Cys Leu Asp Asn Asn Gly Gly Cys Ser His 
145                 150                 155                 160 


Val Cys Asn Asp Leu Lys Ile Gly Tyr Glu Cys Leu Cys Pro Asp Gly 
                165                 170                 175     


Phe Gln Leu Val Ala Gln Arg Arg Cys Glu Asp Ile Asp Glu Cys Gln 
            180                 185                 190         


Asp Pro Asp Thr Cys Ser Gln Leu Cys Val Asn Leu Glu Gly Gly Tyr 
        195                 200                 205             


Lys Cys Gln Cys Glu Glu Gly Phe Gln Leu Asp Pro His Thr Lys Ala 
    210                 215                 220                 


Cys Lys Ala Val Gly Ser Ile Ala Tyr Leu Phe Phe Thr Asn Arg His 
225                 230                 235                 240 


Glu Val Arg Lys Met Thr Leu Asp Arg Ser Glu Tyr Thr Ser Leu Ile 
                245                 250                 255     


Pro Asn Leu Arg Asn Val Val Ala Leu Asp Thr Glu Val Ala Ser Asn 
            260                 265                 270         


Arg Ile Tyr Trp Ser Asp Leu Ser Gln Arg Met Ile Cys Ser Thr Gln 
        275                 280                 285             


Leu Asp Arg Ala His Gly Val Ser Ser Tyr Asp Thr Val Ile Ser Arg 
    290                 295                 300                 


Asp Ile Gln Ala Pro Asp Gly Leu Ala Val Asp Trp Ile His Ser Asn 
305                 310                 315                 320 


Ile Tyr Trp Thr Asp Ser Val Leu Gly Thr Val Ser Val Ala Asp Thr 
                325                 330                 335     


Lys Gly Val Lys Arg Lys Thr Leu Phe Arg Glu Asn Gly Ser Lys Pro 
            340                 345                 350         


Arg Ala Ile Val Val Asp Pro Val His Gly Phe Met Tyr Trp Thr Asp 
        355                 360                 365             


Trp Gly Thr Pro Ala Lys Ile Lys Lys Gly Gly Leu Asn Gly Val Asp 
    370                 375                 380                 


Ile Tyr Ser Leu Val Thr Glu Asn Ile Gln Trp Pro Asn Gly Ile Thr 
385                 390                 395                 400 


Leu Asp Leu Leu Ser Gly Arg Leu Tyr Trp Val Asp Ser Lys Leu His 
                405                 410                 415     


Ser Ile Ser Ser Ile Asp Val Asn Gly Gly Asn Arg Lys Thr Ile Leu 
            420                 425                 430         


Glu Asp Glu Lys Arg Leu Ala His Pro Phe Ser Leu Ala Val Phe Glu 
        435                 440                 445             


Asp Lys Val Phe Trp Thr Asp Ile Ile Asn Glu Ala Ile Phe Ser Ala 
    450                 455                 460                 


Asn Arg Leu Thr Gly Ser Asp Val Asn Leu Leu Ala Glu Asn Leu Leu 
465                 470                 475                 480 


Ser Pro Glu Asp Met Val Leu Phe His Asn Leu Thr Gln Pro Arg Gly 
                485                 490                 495     


Val Asn Trp Cys Glu Arg Thr Thr Leu Ser Asn Gly Gly Cys Gln Tyr 
            500                 505                 510         


Leu Cys Leu Pro Ala Pro Gln Ile Asn Pro His Ser Pro Lys Phe Thr 
        515                 520                 525             


Cys Ala Cys Pro Asp Gly Met Leu Leu Ala Arg Asp Met Arg Ser Cys 
    530                 535                 540                 


Leu Thr Glu Ala Glu Ala Ala Val Ala Thr Gln Glu Thr Ser Thr Val 
545                 550                 555                 560 


Arg Leu Lys Val Ser Ser Thr Ala Val Arg Thr Gln His Thr Thr Thr 
                565                 570                 575     


Arg Pro Val Pro Asp Thr Ser Arg Leu Pro Gly Ala Thr Pro Gly Leu 
            580                 585                 590         


Thr Thr Val Glu Ile Val Thr Met Ser His Gln Ala Leu Gly Asp Val 
        595                 600                 605             


Ala Gly Arg Gly Asn Glu Lys Lys Pro Ser Ser Val Arg Ala Leu Ser 
    610                 615                 620                 


Ile Val Leu Pro Ile Val Leu Leu Val Phe Leu Cys Leu Gly Val Phe 
625                 630                 635                 640 


Leu Leu Trp Lys Asn Trp Arg Leu Lys Asn Ile Asn Ser Ile Asn Phe 
                645                 650                 655     


Asp Asn Pro Val Tyr Gln Lys Thr Thr Glu Asp Glu Val His Ile Cys 
            660                 665                 670         


His Asn Gln Asp Gly Tyr Ser Tyr Pro Ser Arg Gln Met Val Ser Leu 
        675                 680                 685             


Glu Asp Asp Val Ala 
    690             


<210>  5
<211>  819
<212>  PRT
<213>  Homo sapiens LDLR Isoform 4

<400>  5

Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu 
1               5                   10                  15      


Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe 
            20                  25                  30          


Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly 
        35                  40                  45              


Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Ser 
    50                  55                  60                  


Pro Lys Thr Cys Ser Gln Asp Glu Phe Arg Cys His Asp Gly Lys Cys 
65                  70                  75                  80  


Ile Ser Arg Gln Phe Val Cys Asp Ser Asp Arg Asp Cys Leu Asp Gly 
                85                  90                  95      


Ser Asp Glu Ala Ser Cys Pro Val Leu Thr Cys Gly Pro Ala Ser Phe 
            100                 105                 110         


Gln Cys Asn Ser Ser Thr Cys Ile Pro Gln Leu Trp Ala Cys Asp Asn 
        115                 120                 125             


Asp Pro Asp Cys Glu Asp Gly Ser Asp Glu Trp Pro Gln Arg Cys Arg 
    130                 135                 140                 


Gly Leu Tyr Val Phe Gln Gly Asp Ser Ser Pro Cys Ser Ala Phe Glu 
145                 150                 155                 160 


Phe His Cys Leu Ser Gly Glu Cys Ile His Ser Ser Trp Arg Cys Asp 
                165                 170                 175     


Gly Gly Pro Asp Cys Lys Asp Lys Ser Asp Glu Glu Asn Cys Ala Val 
            180                 185                 190         


Ala Thr Cys Arg Pro Asp Glu Phe Gln Cys Ser Asp Gly Asn Cys Ile 
        195                 200                 205             


His Gly Ser Arg Gln Cys Asp Arg Glu Tyr Asp Cys Lys Asp Met Ser 
    210                 215                 220                 


Asp Glu Val Gly Cys Val Asn Val Thr Leu Cys Glu Gly Pro Asn Lys 
225                 230                 235                 240 


Phe Lys Cys His Ser Gly Glu Cys Ile Thr Leu Asp Lys Val Cys Asn 
                245                 250                 255     


Met Ala Arg Asp Cys Arg Asp Trp Ser Asp Glu Pro Ile Lys Glu Cys 
            260                 265                 270         


Gly Thr Asn Glu Cys Leu Asp Asn Asn Gly Gly Cys Ser His Val Cys 
        275                 280                 285             


Asn Asp Leu Lys Ile Gly Tyr Glu Cys Leu Cys Pro Asp Gly Phe Gln 
    290                 295                 300                 


Leu Val Ala Gln Arg Arg Cys Glu Asp Ile Asp Glu Cys Gln Asp Pro 
305                 310                 315                 320 


Asp Thr Cys Ser Gln Leu Cys Val Asn Leu Glu Gly Gly Tyr Lys Cys 
                325                 330                 335     


Gln Cys Glu Glu Gly Phe Gln Leu Asp Pro His Thr Lys Ala Cys Lys 
            340                 345                 350         


Ala Val Gly Ser Ile Ala Tyr Leu Phe Phe Thr Asn Arg His Glu Val 
        355                 360                 365             


Arg Lys Met Thr Leu Asp Arg Ser Glu Tyr Thr Ser Leu Ile Pro Asn 
    370                 375                 380                 


Leu Arg Asn Val Val Ala Leu Asp Thr Glu Val Ala Ser Asn Arg Ile 
385                 390                 395                 400 


Tyr Trp Ser Asp Leu Ser Gln Arg Met Ile Cys Ser Thr Gln Leu Asp 
                405                 410                 415     


Arg Ala His Gly Val Ser Ser Tyr Asp Thr Val Ile Ser Arg Asp Ile 
            420                 425                 430         


Gln Ala Pro Asp Gly Leu Ala Val Asp Trp Ile His Ser Asn Ile Tyr 
        435                 440                 445             


Trp Thr Asp Ser Val Leu Gly Thr Val Ser Val Ala Asp Thr Lys Gly 
    450                 455                 460                 


Val Lys Arg Lys Thr Leu Phe Arg Glu Asn Gly Ser Lys Pro Arg Ala 
465                 470                 475                 480 


Ile Val Val Asp Pro Val His Gly Phe Met Tyr Trp Thr Asp Trp Gly 
                485                 490                 495     


Thr Pro Ala Lys Ile Lys Lys Gly Gly Leu Asn Gly Val Asp Ile Tyr 
            500                 505                 510         


Ser Leu Val Thr Glu Asn Ile Gln Trp Pro Asn Gly Ile Thr Leu Asp 
        515                 520                 525             


Leu Leu Ser Gly Arg Leu Tyr Trp Val Asp Ser Lys Leu His Ser Ile 
    530                 535                 540                 


Ser Ser Ile Asp Val Asn Gly Gly Asn Arg Lys Thr Ile Leu Glu Asp 
545                 550                 555                 560 


Glu Lys Arg Leu Ala His Pro Phe Ser Leu Ala Val Phe Glu Asp Lys 
                565                 570                 575     


Val Phe Trp Thr Asp Ile Ile Asn Glu Ala Ile Phe Ser Ala Asn Arg 
            580                 585                 590         


Leu Thr Gly Ser Asp Val Asn Leu Leu Ala Glu Asn Leu Leu Ser Pro 
        595                 600                 605             


Glu Asp Met Val Leu Phe His Asn Leu Thr Gln Pro Arg Gly Val Asn 
    610                 615                 620                 


Trp Cys Glu Arg Thr Thr Leu Ser Asn Gly Gly Cys Gln Tyr Leu Cys 
625                 630                 635                 640 


Leu Pro Ala Pro Gln Ile Asn Pro His Ser Pro Lys Phe Thr Cys Ala 
                645                 650                 655     


Cys Pro Asp Gly Met Leu Leu Ala Arg Asp Met Arg Ser Cys Leu Thr 
            660                 665                 670         


Glu Ala Glu Ala Ala Val Ala Thr Gln Glu Thr Ser Thr Val Arg Leu 
        675                 680                 685             


Lys Val Ser Ser Thr Ala Val Arg Thr Gln His Thr Thr Thr Arg Pro 
    690                 695                 700                 


Val Pro Asp Thr Ser Arg Leu Pro Gly Ala Thr Pro Gly Leu Thr Thr 
705                 710                 715                 720 


Val Glu Ile Val Thr Met Ser His Gln Ala Leu Gly Asp Val Ala Gly 
                725                 730                 735     


Arg Gly Asn Glu Lys Lys Pro Ser Ser Val Arg Ala Leu Ser Ile Val 
            740                 745                 750         


Leu Pro Ile Val Leu Leu Val Phe Leu Cys Leu Gly Val Phe Leu Leu 
        755                 760                 765             


Trp Lys Asn Trp Arg Leu Lys Asn Ile Asn Ser Ile Asn Phe Asp Asn 
    770                 775                 780                 


Pro Val Tyr Gln Lys Thr Thr Glu Asp Glu Val His Ile Cys His Asn 
785                 790                 795                 800 


Gln Asp Gly Tyr Ser Tyr Pro Ser Arg Gln Met Val Ser Leu Glu Asp 
                805                 810                 815     


Asp Val Ala 
            


<210>  6
<211>  858
<212>  PRT
<213>  Homo sapiens LDLR isoform 5

<400>  6

Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu 
1               5                   10                  15      


Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe 
            20                  25                  30          


Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly 
        35                  40                  45              


Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu 
    50                  55                  60                  


Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn 
65                  70                  75                  80  


Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp 
                85                  90                  95      


Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp 
            100                 105                 110         


Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys 
        115                 120                 125             


Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro 
    130                 135                 140                 


Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys 
145                 150                 155                 160 


Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly 
                165                 170                 175     


Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly 
            180                 185                 190         


Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu 
        195                 200                 205             


Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp 
    210                 215                 220                 


Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu 
225                 230                 235                 240 


Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp 
                245                 250                 255     


Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn 
            260                 265                 270         


Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu 
        275                 280                 285             


Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp 
    290                 295                 300                 


Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp 
305                 310                 315                 320 


Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Leu Lys Ile Gly Tyr 
                325                 330                 335     


Glu Cys Leu Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys 
            340                 345                 350         


Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys 
        355                 360                 365             


Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln 
    370                 375                 380                 


Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr 
385                 390                 395                 400 


Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg 
                405                 410                 415     


Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu 
            420                 425                 430         


Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln 
        435                 440                 445             


Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser 
    450                 455                 460                 


Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala 
465                 470                 475                 480 


Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly 
                485                 490                 495     


Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe 
            500                 505                 510         


Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His 
        515                 520                 525             


Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys 
    530                 535                 540                 


Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile 
545                 550                 555                 560 


Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr 
                565                 570                 575     


Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly 
            580                 585                 590         


Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro 
        595                 600                 605             


Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile 
    610                 615                 620                 


Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn 
625                 630                 635                 640 


Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His 
                645                 650                 655     


Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu 
            660                 665                 670         


Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn 
        675                 680                 685             


Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu 
    690                 695                 700                 


Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala 
705                 710                 715                 720 


Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val 
                725                 730                 735     


Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu 
            740                 745                 750         


Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser 
        755                 760                 765             


His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro 
    770                 775                 780                 


Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val 
785                 790                 795                 800 


Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys 
                805                 810                 815     


Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Lys Thr Thr 
            820                 825                 830         


Glu Asp Glu Val His Ile Cys His Asn Gln Asp Gly Tyr Ser Tyr Pro 
        835                 840                 845             


Ser Met Val Ser Leu Glu Asp Asp Val Ala 
    850                 855             


<210>  7
<211>  739
<212>  PRT
<213>  Homo sapiens LDLR isoform 6

<400>  7

Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu 
1               5                   10                  15      


Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe 
            20                  25                  30          


Gln Cys Asn Ser Ser Thr Cys Ile Pro Gln Leu Trp Ala Cys Asp Asn 
        35                  40                  45              


Asp Pro Asp Cys Glu Asp Gly Ser Asp Glu Trp Pro Gln Arg Cys Arg 
    50                  55                  60                  


Gly Leu Tyr Val Phe Gln Gly Asp Ser Ser Pro Cys Ser Ala Phe Glu 
65                  70                  75                  80  


Phe His Cys Leu Ser Gly Glu Cys Ile His Ser Ser Trp Arg Cys Asp 
                85                  90                  95      


Gly Gly Pro Asp Cys Lys Asp Lys Ser Asp Glu Glu Asn Cys Ala Val 
            100                 105                 110         


Ala Thr Cys Arg Pro Asp Glu Phe Gln Cys Ser Asp Gly Asn Cys Ile 
        115                 120                 125             


His Gly Ser Arg Gln Cys Asp Arg Glu Tyr Asp Cys Lys Asp Met Ser 
    130                 135                 140                 


Asp Glu Val Gly Cys Val Asn Val Thr Leu Cys Glu Gly Pro Asn Lys 
145                 150                 155                 160 


Phe Lys Cys His Ser Gly Glu Cys Ile Thr Leu Asp Lys Val Cys Asn 
                165                 170                 175     


Met Ala Arg Asp Cys Arg Asp Trp Ser Asp Glu Pro Ile Lys Glu Cys 
            180                 185                 190         


Gly Thr Asn Glu Cys Leu Asp Asn Asn Gly Gly Cys Ser His Val Cys 
        195                 200                 205             


Asn Asp Leu Lys Ile Gly Tyr Glu Cys Leu Cys Pro Asp Gly Phe Gln 
    210                 215                 220                 


Leu Val Ala Gln Arg Arg Cys Glu Asp Ile Asp Glu Cys Gln Asp Pro 
225                 230                 235                 240 


Asp Thr Cys Ser Gln Leu Cys Val Asn Leu Glu Gly Gly Tyr Lys Cys 
                245                 250                 255     


Gln Cys Glu Glu Gly Phe Gln Leu Asp Pro His Thr Lys Ala Cys Lys 
            260                 265                 270         


Ala Val Gly Ser Ile Ala Tyr Leu Phe Phe Thr Asn Arg His Glu Val 
        275                 280                 285             


Arg Lys Met Thr Leu Asp Arg Ser Glu Tyr Thr Ser Leu Ile Pro Asn 
    290                 295                 300                 


Leu Arg Asn Val Val Ala Leu Asp Thr Glu Val Ala Ser Asn Arg Ile 
305                 310                 315                 320 


Tyr Trp Ser Asp Leu Ser Gln Arg Met Ile Cys Ser Thr Gln Leu Asp 
                325                 330                 335     


Arg Ala His Gly Val Ser Ser Tyr Asp Thr Val Ile Ser Arg Asp Ile 
            340                 345                 350         


Gln Ala Pro Asp Gly Leu Ala Val Asp Trp Ile His Ser Asn Ile Tyr 
        355                 360                 365             


Trp Thr Asp Ser Val Leu Gly Thr Val Ser Val Ala Asp Thr Lys Gly 
    370                 375                 380                 


Val Lys Arg Lys Thr Leu Phe Arg Glu Asn Gly Ser Lys Pro Arg Ala 
385                 390                 395                 400 


Ile Val Val Asp Pro Val His Gly Phe Met Tyr Trp Thr Asp Trp Gly 
                405                 410                 415     


Thr Pro Ala Lys Ile Lys Lys Gly Gly Leu Asn Gly Val Asp Ile Tyr 
            420                 425                 430         


Ser Leu Val Thr Glu Asn Ile Gln Trp Pro Asn Gly Ile Thr Leu Asp 
        435                 440                 445             


Leu Leu Ser Gly Arg Leu Tyr Trp Val Asp Ser Lys Leu His Ser Ile 
    450                 455                 460                 


Ser Ser Ile Asp Val Asn Gly Gly Asn Arg Lys Thr Ile Leu Glu Asp 
465                 470                 475                 480 


Glu Lys Arg Leu Ala His Pro Phe Ser Leu Ala Val Phe Glu Asp Lys 
                485                 490                 495     


Val Phe Trp Thr Asp Ile Ile Asn Glu Ala Ile Phe Ser Ala Asn Arg 
            500                 505                 510         


Leu Thr Gly Ser Asp Val Asn Leu Leu Ala Glu Asn Leu Leu Ser Pro 
        515                 520                 525             


Glu Asp Met Val Leu Phe His Asn Leu Thr Gln Pro Arg Gly Val Asn 
    530                 535                 540                 


Trp Cys Glu Arg Thr Thr Leu Ser Asn Gly Gly Cys Gln Tyr Leu Cys 
545                 550                 555                 560 


Leu Pro Ala Pro Gln Ile Asn Pro His Ser Pro Lys Phe Thr Cys Ala 
                565                 570                 575     


Cys Pro Asp Gly Met Leu Leu Ala Arg Asp Met Arg Ser Cys Leu Thr 
            580                 585                 590         


Glu Ala Glu Ala Ala Val Ala Thr Gln Glu Thr Ser Thr Val Arg Leu 
        595                 600                 605             


Lys Val Ser Ser Thr Ala Val Arg Thr Gln His Thr Thr Thr Arg Pro 
    610                 615                 620                 


Val Pro Asp Thr Ser Arg Leu Pro Gly Ala Thr Pro Gly Leu Thr Thr 
625                 630                 635                 640 


Val Glu Ile Val Thr Met Ser His Gln Ala Leu Gly Asp Val Ala Gly 
                645                 650                 655     


Arg Gly Asn Glu Lys Lys Pro Ser Ser Val Arg Ala Leu Ser Ile Val 
            660                 665                 670         


Leu Pro Ile Val Leu Leu Val Phe Leu Cys Leu Gly Val Phe Leu Leu 
        675                 680                 685             


Trp Lys Asn Trp Arg Leu Lys Asn Ile Asn Ser Ile Asn Phe Asp Asn 
    690                 695                 700                 


Pro Val Tyr Gln Lys Thr Thr Glu Asp Glu Val His Ile Cys His Asn 
705                 710                 715                 720 


Gln Asp Gly Tyr Ser Tyr Pro Ser Arg Gln Met Val Ser Leu Glu Asp 
                725                 730                 735     


Asp Val Ala 
            


<210>  8
<211>  7756
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Synthetic pAAV-CB-hLDLR


<220>
<221>  CDS
<222>  (6)..(2588)
<223>  hLDLR

<220>
<221>  misc_feature
<222>  (2188)..(2207)
<223>  Y828F seq primer

<220>
<221>  misc_feature
<222>  (2434)..(2471)
<223>  K6 R primer

<220>
<221>  misc_feature
<222>  (2436)..(2534)
<223>  IDOL mutations

<220>
<221>  misc_feature
<222>  (2436)..(2588)
<223>  cytoplasmic tail

<220>
<221>  misc_feature
<222>  (2451)..(2453)
<223>  K5 mutation

<220>
<221>  misc_feature
<222>  (2477)..(2510)
<223>  K20 R primter

<220>
<221>  misc_feature
<222>  (2493)..(2495)
<223>  K20 mutation

<220>
<221>  misc_feature
<222>  (2505)..(2537)
<223>  C29 A primer

<220>
<221>  misc_feature
<222>  (2505)..(2537)
<223>  C29 A primer

<220>
<221>  misc_feature
<222>  (2520)..(2522)
<223>  C29 mutation

<220>
<221>  polyA_signal
<222>  (2655)..(2781)
<223>  rabbit globulin polyA

<220>
<221>  repeat_region
<222>  (2870)..(2999)
<223>  3' ITR (complement)

<220>
<221>  rep_origin
<222>  (3176)..(3631)
<223>  complementary strand f1 ori

<220>
<221>  misc_feature
<222>  (3762)..(4619)
<223>  AP(R) marker

<220>
<221>  rep_origin
<222>  (4793)..(5381)
<223>  origin of replication

<220>
<221>  repeat_region
<222>  (5821)..(5950)
<223>  5' ITR

<220>
<221>  promoter
<222>  (6018)..(6399)
<223>  CMV IE promoter

<220>
<221>  promoter
<222>  (6402)..(6688)
<223>  CB promoter

<220>
<221>  TATA_signal
<222>  (6656)..(6659)

<220>
<221>  Intron
<222>  (6778)..(7750)
<223>  chicken beta actin intron

<400>  8
cgcgt atg ggg ccc tgg ggc tgg aaa ttg cgc tgg acc gtc gcc ttg ctc       50
      Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu         
      1               5                   10                  15          

ctc gcc gcg gcg ggg act gca gtg ggc gac aga tgt gaa aga aac gag         98
Leu Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu           
                20                  25                  30                

ttc cag tgc caa gac ggg aaa tgc atc tcc tac aag tgg gtc tgc gat        146
Phe Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp           
            35                  40                  45                    

ggc agc gct gag tgc cag gat ggc tct gat gag tcc cag gag acg tgc        194
Gly Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys           
        50                  55                  60                        

ttg tct gtc acc tgc aaa tcc ggg gac ttc agc tgt ggg ggc cgt gtc        242
Leu Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val           
    65                  70                  75                            

aac cgc tgc att cct cag ttc tgg agg tgc gat ggc caa gtg gac tgc        290
Asn Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys           
80                  85                  90                  95            

gac aac ggc tca gac gag caa ggc tgt ccc ccc aag acg tgc tcc cag        338
Asp Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln           
                100                 105                 110               

gac gag ttt cgc tgc cac gat ggg aag tgc atc tct cgg cag ttc gtc        386
Asp Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val           
            115                 120                 125                   

tgt gac tca gac cgg gac tgc ttg gac ggc tca gac gag gcc tcc tgc        434
Cys Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys           
        130                 135                 140                       

ccg gtg ctc acc tgt ggt ccc gcc agc ttc cag tgc aac agc tcc acc        482
Pro Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr           
    145                 150                 155                           

tgc atc ccc cag ctg tgg gcc tgc gac aac gac ccc gac tgc gaa gat        530
Cys Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp           
160                 165                 170                 175           

ggc tcg gat gag tgg ccg cag cgc tgt agg ggt ctt tac gtg ttc caa        578
Gly Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln           
                180                 185                 190               

ggg gac agt agc ccc tgc tcg gcc ttc gag ttc cac tgc cta agt ggc        626
Gly Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly           
            195                 200                 205                   

gag tgc atc cac tcc agc tgg cgc tgt gat ggt ggc ccc gac tgc aag        674
Glu Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys           
        210                 215                 220                       

gac aaa tct gac gag gaa aac tgc gct gtg gcc acc tgt cgc cct gac        722
Asp Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp           
    225                 230                 235                           

gaa ttc cag tgc tct gat gga aac tgc atc cat ggc agc cgg cag tgt        770
Glu Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys           
240                 245                 250                 255           

gac cgg gaa tat gac tgc aag gac atg agc gat gaa gtt ggc tgc gtt        818
Asp Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val           
                260                 265                 270               

aat gtg aca ctc tgc gag gga ccc aac aag ttc aag tgt cac agc ggc        866
Asn Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly           
            275                 280                 285                   

gaa tgc atc acc ctg gac aaa gtc tgc aac atg gct aga gac tgc cgg        914
Glu Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg           
        290                 295                 300                       

gac tgg tca gat gaa ccc atc aaa gag tgc ggg acc aac gaa tgc ttg        962
Asp Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu           
    305                 310                 315                           

gac aac aac ggc ggc tgt tcc cac gtc tgc aat gac ctt aag atc ggc       1010
Asp Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Leu Lys Ile Gly           
320                 325                 330                 335           

tac gag tgc ctg tgc ccc gac ggc ttc cag ctg gtg gcc cag cga aga       1058
Tyr Glu Cys Leu Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg           
                340                 345                 350               

tgc gaa gat atc gat gag tgt cag gat ccc gac acc tgc agc cag ctc       1106
Cys Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu           
            355                 360                 365                   

tgc gtg aac ctg gag ggt ggc tac aag tgc cag tgt gag gaa ggc ttc       1154
Cys Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe           
        370                 375                 380                       

cag ctg gac ccc cac acg aag gcc tgc aag gct gtg ggc tcc atc gcc       1202
Gln Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala           
    385                 390                 395                           

tac ctc ttc ttc acc aac cgg cac gag gtc agg aag atg acg ctg gac       1250
Tyr Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp           
400                 405                 410                 415           

cgg agc gag tac acc agc ctc atc ccc aac ctg agg aac gtg gtc gct       1298
Arg Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala           
                420                 425                 430               

ctg gac acg gag gtg gcc agc aat aga atc tac tgg tct gac ctg tcc       1346
Leu Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser           
            435                 440                 445                   

cag aga atg atc tgc agc acc cag ctt gac aga gcc cac ggc gtc tct       1394
Gln Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser           
        450                 455                 460                       

tcc tat gac acc gtc atc agc agg gac atc cag gcc ccc gac ggg ctg       1442
Ser Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu           
    465                 470                 475                           

gct gtg gac tgg atc cac agc aac atc tac tgg acc gac tct gtc ctg       1490
Ala Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu           
480                 485                 490                 495           

ggc act gtc tct gtt gcg gat acc aag ggc gtg aag agg aaa acg tta       1538
Gly Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu           
                500                 505                 510               

ttc agg gag aac ggc tcc aag cca agg gcc atc gtg gtg gat cct gtt       1586
Phe Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val           
            515                 520                 525                   

cat ggc ttc atg tac tgg act gac tgg gga act ccc gcc aag atc aag       1634
His Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys           
        530                 535                 540                       

aaa ggg ggc ctg aat ggt gtg gac atc tac tcg ctg gtg act gaa aac       1682
Lys Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn           
    545                 550                 555                           

att cag tgg ccc aat ggc atc acc cta gat ctc ctc agt ggc cgc ctc       1730
Ile Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu           
560                 565                 570                 575           

tac tgg gtt gac tcc aaa ctt cac tcc atc tca agc atc gat gtc aat       1778
Tyr Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn           
                580                 585                 590               

ggg ggc aac cgg aag acc atc ttg gag gat gaa aag agg ctg gcc cac       1826
Gly Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His           
            595                 600                 605                   

ccc ttc tcc ttg gcc gtc ttt gag gac aaa gta ttt tgg aca gat atc       1874
Pro Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile           
        610                 615                 620                       

atc aac gaa gcc att ttc agt gcc aac cgc ctc aca ggt tcc gat gtc       1922
Ile Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val           
    625                 630                 635                           

aac ttg ttg gct gaa aac cta ctg tcc cca gag gat atg gtc ctc ttc       1970
Asn Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe           
640                 645                 650                 655           

cac aac ctc acc cag cca aga gga gtg aac tgg tgt gag agg acc acc       2018
His Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr           
                660                 665                 670               

ctg agc aat ggc ggc tgc cag tat ctg tgc ctc cct gcc ccg cag atc       2066
Leu Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile           
            675                 680                 685                   

aac ccc cac tcg ccc aag ttt acc tgc gcc tgc ccg gac ggc atg ctg       2114
Asn Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu           
        690                 695                 700                       

ctg gcc agg gac atg agg agc tgc ctc aca gag gct gag gct gca gtg       2162
Leu Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val           
    705                 710                 715                           

gcc acc cag gag aca tcc acc gtc agg cta aag gtc agc tcc aca gcc       2210
Ala Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala           
720                 725                 730                 735           

gta agg aca cag cac aca acc acc cgg cct gtt ccc gac acc tcc cgg       2258
Val Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg           
                740                 745                 750               

ctg cct ggg gcc acc cct ggg ctc acc acg gtg gag ata gtg aca atg       2306
Leu Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met           
            755                 760                 765                   

tct cac caa gct ctg ggc gac gtt gct ggc aga gga aat gag aag aag       2354
Ser His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys           
        770                 775                 780                       

ccc agt agc gtg agg gct ctg tcc att gtc ctc ccc atc gtg ctc ctc       2402
Pro Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu           
    785                 790                 795                           

gtc ttc ctt tgc ctg ggg gtc ttc ctt cta tgg aag aac tgg cgg ctt       2450
Val Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu           
800                 805                 810                 815           

aag aac atc aac agc atc aac ttt gac aac ccc gtc tat cag aag acc       2498
Lys Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Lys Thr           
                820                 825                 830               

aca gag gat gag gtc cac att tgc cac aac cag gac ggc tac agc tac       2546
Thr Glu Asp Glu Val His Ile Cys His Asn Gln Asp Gly Tyr Ser Tyr           
            835                 840                 845                   

ccc tcg aga cag atg gtc agt ctg gag gat gac gtg gcg tga               2588
Pro Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala                       
        850                 855                 860                       

acgcgtggta cctctagagt cgacccgggc ggcctcgagg acggggtgaa ctacgcctga     2648

ggatccgatc tttttccctc tgccaaaaat tatggggaca tcatgaagcc ccttgagcat     2708

ctgacttctg gctaataaag gaaatttatt ttcattgcaa tagtgtgttg gaattttttg     2768

tgtctctcac tcggaagcaa ttcgttgatc tgaatttcga ccacccataa tacccattac     2828

cctggtagat aagtagcatg gcgggttaat cattaactac aaggaacccc tagtgatgga     2888

gttggccact ccctctctgc gcgctcgctc gctcactgag gccgggcgac caaaggtcgc     2948

ccgacgcccg ggctttgccc gggcggcctc agtgagcgag cgagcgcgca gccttaatta     3008

acctaattca ctggccgtcg ttttacaacg tcgtgactgg gaaaaccctg gcgttaccca     3068

acttaatcgc cttgcagcac atcccccttt cgccagctgg cgtaatagcg aagaggcccg     3128

caccgatcgc ccttcccaac agttgcgcag cctgaatggc gaatgggacg cgccctgtag     3188

cggcgcatta agcgcggcgg gtgtggtggt tacgcgcagc gtgaccgcta cacttgccag     3248

cgccctagcg cccgctcctt tcgctttctt cccttccttt ctcgccacgt tcgccggctt     3308

tccccgtcaa gctctaaatc gggggctccc tttagggttc cgatttagtg ctttacggca     3368

cctcgacccc aaaaaacttg attagggtga tggttcacgt agtgggccat cgccctgata     3428

gacggttttt cgccctttga cgttggagtc cacgttcttt aatagtggac tcttgttcca     3488

aactggaaca acactcaacc ctatctcggt ctattctttt gatttataag ggattttgcc     3548

gatttcggcc tattggttaa aaaatgagct gatttaacaa aaatttaacg cgaattttaa     3608

caaaatatta acgcttacaa tttaggtggc acttttcggg gaaatgtgcg cggaacccct     3668

atttgtttat ttttctaaat acattcaaat atgtatccgc tcatgagaca ataaccctga     3728

taaatgcttc aataatattg aaaaaggaag agtatgagta ttcaacattt ccgtgtcgcc     3788

cttattccct tttttgcggc attttgcctt cctgtttttg ctcacccaga aacgctggtg     3848

aaagtaaaag atgctgaaga tcagttgggt gcacgagtgg gttacatcga actggatctc     3908

aacagcggta agatccttga gagttttcgc cccgaagaac gttttccaat gatgagcact     3968

tttaaagttc tgctatgtgg cgcggtatta tcccgtattg acgccgggca agagcaactc     4028

ggtcgccgca tacactattc tcagaatgac ttggttgagt actcaccagt cacagaaaag     4088

catcttacgg atggcatgac agtaagagaa ttatgcagtg ctgccataac catgagtgat     4148

aacactgcgg ccaacttact tctgacaacg atcggaggac cgaaggagct aaccgctttt     4208

ttgcacaaca tgggggatca tgtaactcgc cttgatcgtt gggaaccgga gctgaatgaa     4268

gccataccaa acgacgagcg tgacaccacg atgcctgtag caatggcaac aacgttgcgc     4328

aaactattaa ctggcgaact acttactcta gcttcccggc aacaattaat agactggatg     4388

gaggcggata aagttgcagg accacttctg cgctcggccc ttccggctgg ctggtttatt     4448

gctgataaat ctggagccgg tgagcgtggg tctcgcggta tcattgcagc actggggcca     4508

gatggtaagc cctcccgtat cgtagttatc tacacgacgg ggagtcaggc aactatggat     4568

gaacgaaata gacagatcgc tgagataggt gcctcactga ttaagcattg gtaactgtca     4628

gaccaagttt actcatatat actttagatt gatttaaaac ttcattttta atttaaaagg     4688

atctaggtga agatcctttt tgataatctc atgaccaaaa tcccttaacg tgagttttcg     4748

ttccactgag cgtcagaccc cgtagaaaag atcaaaggat cttcttgaga tccttttttt     4808

ctgcgcgtaa tctgctgctt gcaaacaaaa aaaccaccgc taccagcggt ggtttgtttg     4868

ccggatcaag agctaccaac tctttttccg aaggtaactg gcttcagcag agcgcagata     4928

ccaaatactg ttcttctagt gtagccgtag ttaggccacc acttcaagaa ctctgtagca     4988

ccgcctacat acctcgctct gctaatcctg ttaccagtgg ctgctgccag tggcgataag     5048

tcgtgtctta ccgggttgga ctcaagacga tagttaccgg ataaggcgca gcggtcgggc     5108

tgaacggggg gttcgtgcac acagcccagc ttggagcgaa cgacctacac cgaactgaga     5168

tacctacagc gtgagctatg agaaagcgcc acgcttcccg aagggagaaa ggcggacagg     5228

tatccggtaa gcggcagggt cggaacagga gagcgcacga gggagcttcc agggggaaac     5288

gcctggtatc tttatagtcc tgtcgggttt cgccacctct gacttgagcg tcgatttttg     5348

tgatgctcgt caggggggcg gagcctatgg aaaaacgcca gcaacgcggc ctttttacgg     5408

ttcctggcct tttgctggcc ttttgctcac atgttctttc ctgcgttatc ccctgattct     5468

gtggataacc gtattaccgc ctttgagtga gctgataccg ctcgccgcag ccgaacgacc     5528

gagcgcagcg agtcagtgag cgaggaagcg gaagagcgcc caatacgcaa accgcctctc     5588

cccgcgcgtt ggccgattca ttaatgcagc tggcacgaca ggtttcccga ctggaaagcg     5648

ggcagtgagc gcaacgcaat taatgtgagt tagctcactc attaggcacc ccaggcttta     5708

cactttatgc ttccggctcg tatgttgtgt ggaattgtga gcggataaca atttcacaca     5768

ggaaacagct atgaccatga ttacgccaga tttaattaag gccttaatta ggctgcgcgc     5828

tcgctcgctc actgaggccg cccgggcaaa gcccgggcgt cgggcgacct ttggtcgccc     5888

ggcctcagtg agcgagcgag cgcgcagaga gggagtggcc aactccatca ctaggggttc     5948

cttgtagtta atgattaacc cgccatgcta cttatctacc agggtaatgg ggatcctcta     6008

gaactatagc tagtcgacat tgattattga ctagttatta atagtaatca attacggggt     6068

cattagttca tagcccatat atggagttcc gcgttacata acttacggta aatggcccgc     6128

ctggctgacc gcccaacgac ccccgcccat tgacgtcaat aatgacgtat gttcccatag     6188

taacgccaat agggactttc cattgacgtc aatgggtgga gtatttacgg taaactgccc     6248

acttggcagt acatcaagtg tatcatatgc caagtacgcc ccctattgac gtcaatgacg     6308

gtaaatggcc cgcctggcat tatgcccagt acatgacctt atgggacttt cctacttggc     6368

agtacatcta cgtattagtc atcgctatta ccatggtcga ggtgagcccc acgttctgct     6428

tcactctccc catctccccc ccctccccac ccccaatttt gtatttattt attttttaat     6488

tattttgtgc agcgatgggg gcgggggggg ggggggggcg cgcgccaggc ggggcggggc     6548

ggggcgaggg gcggggcggg gcgaggcgga gaggtgcggc ggcagccaat cagagcggcg     6608

cgctccgaaa gtttcctttt atggcgaggc ggcggcggcg gcggccctat aaaaagcgaa     6668

gcgcgcggcg ggcggggagt cgctgcgacg ctgccttcgc cccgtgcccc gctccgccgc     6728

cgcctcgcgc cgcccgcccc ggctctgact gaccgcgtta ctcccacagg tgagcgggcg     6788

ggacggccct tctcctccgg gctgtaatta gcgcttggtt taatgacggc ttgtttcttt     6848

tctgtggctg cgtgaaagcc ttgaggggct ccgggagggc cctttgtgcg gggggagcgg     6908

ctcggggggt gcgtgcgtgt gtgtgtgcgt ggggagcgcc gcgtgcggct ccgcgctgcc     6968

cggcggctgt gagcgctgcg ggcgcggcgc ggggctttgt gcgctccgca gtgtgcgcga     7028

ggggagcgcg gccgggggcg gtgccccgcg gtgcgggggg ggctgcgagg ggaacaaagg     7088

ctgcgtgcgg ggtgtgtgcg tgggggggtg agcagggggt gtgggcgcgt cggtcgggct     7148

gcaacccccc ctgcaccccc ctccccgagt tgctgagcac ggcccggctt cgggtgcggg     7208

gctccgtacg gggcgtggcg cggggctcgc cgtgccgggc ggggggtggc ggcaggtggg     7268

ggtgccgggc ggggcggggc cgcctcgggc cggggagggc tcgggggagg ggcgcggcgg     7328

cccccggagc gccggcggct gtcgaggcgc ggcgagccgc agccattgcc ttttatggta     7388

atcgtgcgag agggcgcagg gacttccttt gtcccaaatc tgtgcggagc cgaaatctgg     7448

gaggcgccgc cgcaccccct ctagcgggcg cggggcgaag cggtgcggcg ccggcaggaa     7508

ggaaatgggc ggggagggcc ttcgtgcgtc gccgcgccgc cgtccccttc tccctctcca     7568

gcctcggggc tgtccgcggg gggacggctg ccttcggggg ggacggggca gggcggggtt     7628

cggcttctgg cgtgtgaccg gcggctctag agcctctgct aaccatgttc atgccttctt     7688

ctttttccta cagctcctgg gcaacgtgct ggttattgtg ctgtctcatc attttggcaa     7748

agaattca                                                              7756


<210>  9
<211>  860
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Construct

<400>  9

Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu 
1               5                   10                  15      


Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe 
            20                  25                  30          


Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly 
        35                  40                  45              


Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu 
    50                  55                  60                  


Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn 
65                  70                  75                  80  


Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp 
                85                  90                  95      


Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp 
            100                 105                 110         


Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys 
        115                 120                 125             


Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro 
    130                 135                 140                 


Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys 
145                 150                 155                 160 


Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly 
                165                 170                 175     


Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly 
            180                 185                 190         


Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu 
        195                 200                 205             


Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp 
    210                 215                 220                 


Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu 
225                 230                 235                 240 


Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp 
                245                 250                 255     


Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn 
            260                 265                 270         


Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu 
        275                 280                 285             


Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp 
    290                 295                 300                 


Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp 
305                 310                 315                 320 


Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Leu Lys Ile Gly Tyr 
                325                 330                 335     


Glu Cys Leu Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys 
            340                 345                 350         


Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys 
        355                 360                 365             


Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln 
    370                 375                 380                 


Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr 
385                 390                 395                 400 


Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg 
                405                 410                 415     


Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu 
            420                 425                 430         


Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln 
        435                 440                 445             


Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser 
    450                 455                 460                 


Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala 
465                 470                 475                 480 


Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly 
                485                 490                 495     


Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe 
            500                 505                 510         


Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His 
        515                 520                 525             


Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys 
    530                 535                 540                 


Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile 
545                 550                 555                 560 


Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr 
                565                 570                 575     


Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly 
            580                 585                 590         


Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro 
        595                 600                 605             


Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile 
    610                 615                 620                 


Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn 
625                 630                 635                 640 


Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His 
                645                 650                 655     


Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu 
            660                 665                 670         


Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn 
        675                 680                 685             


Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu 
    690                 695                 700                 


Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala 
705                 710                 715                 720 


Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val 
                725                 730                 735     


Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu 
            740                 745                 750         


Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser 
        755                 760                 765             


His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro 
    770                 775                 780                 


Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val 
785                 790                 795                 800 


Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys 
                805                 810                 815     


Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Lys Thr Thr 
            820                 825                 830         


Glu Asp Glu Val His Ile Cys His Asn Gln Asp Gly Tyr Ser Tyr Pro 
        835                 840                 845             


Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala 
    850                 855                 860 


<210>  10
<211>  7756
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Synthetic CB7.hLDLR (K25R-C29A) - IDOL


<220>
<221>  polyA_signal
<222>  (66)..(192)
<223>  rabbit globulin polyA

<220>
<221>  repeat_region
<222>  (281)..(410)
<223>  3' ITR, located on complement

<220>
<221>  rep_origin
<222>  (587)..(1042)
<223>  f1/ori, located on complement

<220>
<221>  misc_feature
<222>  (1173)..(2030)
<223>  maker AP(R)

<220>
<221>  rep_origin
<222>  (2204)..(2792)
<223>  origin of replication

<220>
<221>  repeat_region
<222>  (3232)..(3361)
<223>  5' ITR

<220>
<221>  repeat_region
<222>  (3429)..(3810)
<223>  CMV IE promoter

<220>
<221>  promoter
<222>  (3813)..(4094)

<220>
<221>  TATA_signal
<222>  (4067)..(4070)

<220>
<221>  Intron
<222>  (4189)..(5161)

<220>
<221>  CDS
<222>  (5173)..(7755)
<223>  hLDLR

<220>
<221>  misc_feature
<222>  (6187)..(6189)
<223>  site of L318D mutation affecting PCSK9 binding

<220>
<221>  misc_feature
<222>  (7601)..(7638)
<223>  K6 \R\primer

<220>
<221>  misc_feature
<222>  (7603)..(7701)
<223>  IDOL mutations

<220>
<221>  misc_feature
<222>  (7618)..(7620)
<223>  K6-mutation

<220>
<221>  misc_feature
<222>  (7644)..(7677)
<223>  K20 R primer

<220>
<221>  misc_feature
<222>  (7660)..(7662)
<223>  K20 mutation

<220>
<221>  misc_structure
<222>  (7672)..(7704)
<223>  C29 primer

<220>
<221>  misc_feature
<222>  (7689)..(7689)
<223>  C29 mutation

<400>  10
cgcgtggtac ctctagagtc gacccgggcg gcctcgagga cggggtgaac tacgcctgag       60

gatccgatct ttttccctct gccaaaaatt atggggacat catgaagccc cttgagcatc      120

tgacttctgg ctaataaagg aaatttattt tcattgcaat agtgtgttgg aattttttgt      180

gtctctcact cggaagcaat tcgttgatct gaatttcgac cacccataat acccattacc      240

ctggtagata agtagcatgg cgggttaatc attaactaca aggaacccct agtgatggag      300

ttggccactc cctctctgcg cgctcgctcg ctcactgagg ccgggcgacc aaaggtcgcc      360

cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc gagcgcgcag ccttaattaa      420

cctaattcac tggccgtcgt tttacaacgt cgtgactggg aaaaccctgg cgttacccaa      480

cttaatcgcc ttgcagcaca tccccctttc gccagctggc gtaatagcga agaggcccgc      540

accgatcgcc cttcccaaca gttgcgcagc ctgaatggcg aatgggacgc gccctgtagc      600

ggcgcattaa gcgcggcggg tgtggtggtt acgcgcagcg tgaccgctac acttgccagc      660

gccctagcgc ccgctccttt cgctttcttc ccttcctttc tcgccacgtt cgccggcttt      720

ccccgtcaag ctctaaatcg ggggctccct ttagggttcc gatttagtgc tttacggcac      780

ctcgacccca aaaaacttga ttagggtgat ggttcacgta gtgggccatc gccctgatag      840

acggtttttc gccctttgac gttggagtcc acgttcttta atagtggact cttgttccaa      900

actggaacaa cactcaaccc tatctcggtc tattcttttg atttataagg gattttgccg      960

atttcggcct attggttaaa aaatgagctg atttaacaaa aatttaacgc gaattttaac     1020

aaaatattaa cgcttacaat ttaggtggca cttttcgggg aaatgtgcgc ggaaccccta     1080

tttgtttatt tttctaaata cattcaaata tgtatccgct catgagacaa taaccctgat     1140

aaatgcttca ataatattga aaaaggaaga gtatgagtat tcaacatttc cgtgtcgccc     1200

ttattccctt ttttgcggca ttttgccttc ctgtttttgc tcacccagaa acgctggtga     1260

aagtaaaaga tgctgaagat cagttgggtg cacgagtggg ttacatcgaa ctggatctca     1320

acagcggtaa gatccttgag agttttcgcc ccgaagaacg ttttccaatg atgagcactt     1380

ttaaagttct gctatgtggc gcggtattat cccgtattga cgccgggcaa gagcaactcg     1440

gtcgccgcat acactattct cagaatgact tggttgagta ctcaccagtc acagaaaagc     1500

atcttacgga tggcatgaca gtaagagaat tatgcagtgc tgccataacc atgagtgata     1560

acactgcggc caacttactt ctgacaacga tcggaggacc gaaggagcta accgcttttt     1620

tgcacaacat gggggatcat gtaactcgcc ttgatcgttg ggaaccggag ctgaatgaag     1680

ccataccaaa cgacgagcgt gacaccacga tgcctgtagc aatggcaaca acgttgcgca     1740

aactattaac tggcgaacta cttactctag cttcccggca acaattaata gactggatgg     1800

aggcggataa agttgcagga ccacttctgc gctcggccct tccggctggc tggtttattg     1860

ctgataaatc tggagccggt gagcgtgggt ctcgcggtat cattgcagca ctggggccag     1920

atggtaagcc ctcccgtatc gtagttatct acacgacggg gagtcaggca actatggatg     1980

aacgaaatag acagatcgct gagataggtg cctcactgat taagcattgg taactgtcag     2040

accaagttta ctcatatata ctttagattg atttaaaact tcatttttaa tttaaaagga     2100

tctaggtgaa gatccttttt gataatctca tgaccaaaat cccttaacgt gagttttcgt     2160

tccactgagc gtcagacccc gtagaaaaga tcaaaggatc ttcttgagat cctttttttc     2220

tgcgcgtaat ctgctgcttg caaacaaaaa aaccaccgct accagcggtg gtttgtttgc     2280

cggatcaaga gctaccaact ctttttccga aggtaactgg cttcagcaga gcgcagatac     2340

caaatactgt tcttctagtg tagccgtagt taggccacca cttcaagaac tctgtagcac     2400

cgcctacata cctcgctctg ctaatcctgt taccagtggc tgctgccagt ggcgataagt     2460

cgtgtcttac cgggttggac tcaagacgat agttaccgga taaggcgcag cggtcgggct     2520

gaacgggggg ttcgtgcaca cagcccagct tggagcgaac gacctacacc gaactgagat     2580

acctacagcg tgagctatga gaaagcgcca cgcttcccga agggagaaag gcggacaggt     2640

atccggtaag cggcagggtc ggaacaggag agcgcacgag ggagcttcca gggggaaacg     2700

cctggtatct ttatagtcct gtcgggtttc gccacctctg acttgagcgt cgatttttgt     2760

gatgctcgtc aggggggcgg agcctatgga aaaacgccag caacgcggcc tttttacggt     2820

tcctggcctt ttgctggcct tttgctcaca tgttctttcc tgcgttatcc cctgattctg     2880

tggataaccg tattaccgcc tttgagtgag ctgataccgc tcgccgcagc cgaacgaccg     2940

agcgcagcga gtcagtgagc gaggaagcgg aagagcgccc aatacgcaaa ccgcctctcc     3000

ccgcgcgttg gccgattcat taatgcagct ggcacgacag gtttcccgac tggaaagcgg     3060

gcagtgagcg caacgcaatt aatgtgagtt agctcactca ttaggcaccc caggctttac     3120

actttatgct tccggctcgt atgttgtgtg gaattgtgag cggataacaa tttcacacag     3180

gaaacagcta tgaccatgat tacgccagat ttaattaagg ccttaattag gctgcgcgct     3240

cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc gggcgacctt tggtcgcccg     3300

gcctcagtga gcgagcgagc gcgcagagag ggagtggcca actccatcac taggggttcc     3360

ttgtagttaa tgattaaccc gccatgctac ttatctacca gggtaatggg gatcctctag     3420

aactatagct agtcgacatt gattattgac tagttattaa tagtaatcaa ttacggggtc     3480

attagttcat agcccatata tggagttccg cgttacataa cttacggtaa atggcccgcc     3540

tggctgaccg cccaacgacc cccgcccatt gacgtcaata atgacgtatg ttcccatagt     3600

aacgccaata gggactttcc attgacgtca atgggtggag tatttacggt aaactgccca     3660

cttggcagta catcaagtgt atcatatgcc aagtacgccc cctattgacg tcaatgacgg     3720

taaatggccc gcctggcatt atgcccagta catgacctta tgggactttc ctacttggca     3780

gtacatctac gtattagtca tcgctattac catggtcgag gtgagcccca cgttctgctt     3840

cactctcccc atctcccccc cctccccacc cccaattttg tatttattta ttttttaatt     3900

attttgtgca gcgatggggg cggggggggg gggggggcgc gcgccaggcg gggcggggcg     3960

gggcgagggg cggggcgggg cgaggcggag aggtgcggcg gcagccaatc agagcggcgc     4020

gctccgaaag tttcctttta tggcgaggcg gcggcggcgg cggccctata aaaagcgaag     4080

cgcgcggcgg gcggggagtc gctgcgacgc tgccttcgcc ccgtgccccg ctccgccgcc     4140

gcctcgcgcc gcccgccccg gctctgactg accgcgttac tcccacaggt gagcgggcgg     4200

gacggccctt ctcctccggg ctgtaattag cgcttggttt aatgacggct tgtttctttt     4260

ctgtggctgc gtgaaagcct tgaggggctc cgggagggcc ctttgtgcgg ggggagcggc     4320

tcggggggtg cgtgcgtgtg tgtgtgcgtg gggagcgccg cgtgcggctc cgcgctgccc     4380

ggcggctgtg agcgctgcgg gcgcggcgcg gggctttgtg cgctccgcag tgtgcgcgag     4440

gggagcgcgg ccgggggcgg tgccccgcgg tgcggggggg gctgcgaggg gaacaaaggc     4500

tgcgtgcggg gtgtgtgcgt gggggggtga gcagggggtg tgggcgcgtc ggtcgggctg     4560

caaccccccc tgcacccccc tccccgagtt gctgagcacg gcccggcttc gggtgcgggg     4620

ctccgtacgg ggcgtggcgc ggggctcgcc gtgccgggcg gggggtggcg gcaggtgggg     4680

gtgccgggcg gggcggggcc gcctcgggcc ggggagggct cgggggaggg gcgcggcggc     4740

ccccggagcg ccggcggctg tcgaggcgcg gcgagccgca gccattgcct tttatggtaa     4800

tcgtgcgaga gggcgcaggg acttcctttg tcccaaatct gtgcggagcc gaaatctggg     4860

aggcgccgcc gcaccccctc tagcgggcgc ggggcgaagc ggtgcggcgc cggcaggaag     4920

gaaatgggcg gggagggcct tcgtgcgtcg ccgcgccgcc gtccccttct ccctctccag     4980

cctcggggct gtccgcgggg ggacggctgc cttcgggggg gacggggcag ggcggggttc     5040

ggcttctggc gtgtgaccgg cggctctaga gcctctgcta accatgttca tgccttcttc     5100

tttttcctac agctcctggg caacgtgctg gttattgtgc tgtctcatca ttttggcaaa     5160

gaattcacgc gt atg ggg ccc tgg ggc tgg aaa ttg cgc tgg acc gtc gcc     5211
              Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala         
              1               5                   10                      

ttg ctc ctc gcc gcg gcg ggg act gca gtg ggc gac aga tgt gaa aga       5259
Leu Leu Leu Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg           
    15                  20                  25                            

aac gag ttc cag tgc caa gac ggg aaa tgc atc tcc tac aag tgg gtc       5307
Asn Glu Phe Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val           
30                  35                  40                  45            

tgc gat ggc agc gct gag tgc cag gat ggc tct gat gag tcc cag gag       5355
Cys Asp Gly Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu           
                50                  55                  60                

acg tgc ttg tct gtc acc tgc aaa tcc ggg gac ttc agc tgt ggg ggc       5403
Thr Cys Leu Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly           
            65                  70                  75                    

cgt gtc aac cgc tgc att cct cag ttc tgg agg tgc gat ggc caa gtg       5451
Arg Val Asn Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val           
        80                  85                  90                        

gac tgc gac aac ggc tca gac gag caa ggc tgt ccc ccc aag acg tgc       5499
Asp Cys Asp Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys           
    95                  100                 105                           

tcc cag gac gag ttt cgc tgc cac gat ggg aag tgc atc tct cgg cag       5547
Ser Gln Asp Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln           
110                 115                 120                 125           

ttc gtc tgt gac tca gac cgg gac tgc ttg gac ggc tca gac gag gcc       5595
Phe Val Cys Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala           
                130                 135                 140               

tcc tgc ccg gtg ctc acc tgt ggt ccc gcc agc ttc cag tgc aac agc       5643
Ser Cys Pro Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser           
            145                 150                 155                   

tcc acc tgc atc ccc cag ctg tgg gcc tgc gac aac gac ccc gac tgc       5691
Ser Thr Cys Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys           
        160                 165                 170                       

gaa gat ggc tcg gat gag tgg ccg cag cgc tgt agg ggt ctt tac gtg       5739
Glu Asp Gly Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val           
    175                 180                 185                           

ttc caa ggg gac agt agc ccc tgc tcg gcc ttc gag ttc cac tgc cta       5787
Phe Gln Gly Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu           
190                 195                 200                 205           

agt ggc gag tgc atc cac tcc agc tgg cgc tgt gat ggt ggc ccc gac       5835
Ser Gly Glu Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp           
                210                 215                 220               

tgc aag gac aaa tct gac gag gaa aac tgc gct gtg gcc acc tgt cgc       5883
Cys Lys Asp Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg           
            225                 230                 235                   

cct gac gaa ttc cag tgc tct gat gga aac tgc atc cat ggc agc cgg       5931
Pro Asp Glu Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg           
        240                 245                 250                       

cag tgt gac cgg gaa tat gac tgc aag gac atg agc gat gaa gtt ggc       5979
Gln Cys Asp Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly           
    255                 260                 265                           

tgc gtt aat gtg aca ctc tgc gag gga ccc aac aag ttc aag tgt cac       6027
Cys Val Asn Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His           
270                 275                 280                 285           

agc ggc gaa tgc atc acc ctg gac aaa gtc tgc aac atg gct aga gac       6075
Ser Gly Glu Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp           
                290                 295                 300               

tgc cgg gac tgg tca gat gaa ccc atc aaa gag tgc ggg acc aac gaa       6123
Cys Arg Asp Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu           
            305                 310                 315                   

tgc ttg gac aac aac ggc ggc tgt tcc cac gtc tgc aat gac ctt aag       6171
Cys Leu Asp Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Leu Lys           
        320                 325                 330                       

atc ggc tac gag tgc ctg tgc ccc gac ggc ttc cag ctg gtg gcc cag       6219
Ile Gly Tyr Glu Cys Leu Cys Pro Asp Gly Phe Gln Leu Val Ala Gln           
    335                 340                 345                           

cga aga tgc gaa gat atc gat gag tgt cag gat ccc gac acc tgc agc       6267
Arg Arg Cys Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser           
350                 355                 360                 365           

cag ctc tgc gtg aac ctg gag ggt ggc tac aag tgc cag tgt gag gaa       6315
Gln Leu Cys Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu           
                370                 375                 380               

ggc ttc cag ctg gac ccc cac acg aag gcc tgc aag gct gtg ggc tcc       6363
Gly Phe Gln Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser           
            385                 390                 395                   

atc gcc tac ctc ttc ttc acc aac cgg cac gag gtc agg aag atg acg       6411
Ile Ala Tyr Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr           
        400                 405                 410                       

ctg gac cgg agc gag tac acc agc ctc atc ccc aac ctg agg aac gtg       6459
Leu Asp Arg Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val           
    415                 420                 425                           

gtc gct ctg gac acg gag gtg gcc agc aat aga atc tac tgg tct gac       6507
Val Ala Leu Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp           
430                 435                 440                 445           

ctg tcc cag aga atg atc tgc agc acc cag ctt gac aga gcc cac ggc       6555
Leu Ser Gln Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly           
                450                 455                 460               

gtc tct tcc tat gac acc gtc atc agc agg gac atc cag gcc ccc gac       6603
Val Ser Ser Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp           
            465                 470                 475                   

ggg ctg gct gtg gac tgg atc cac agc aac atc tac tgg acc gac tct       6651
Gly Leu Ala Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser           
        480                 485                 490                       

gtc ctg ggc act gtc tct gtt gcg gat acc aag ggc gtg aag agg aaa       6699
Val Leu Gly Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys           
    495                 500                 505                           

acg tta ttc agg gag aac ggc tcc aag cca agg gcc atc gtg gtg gat       6747
Thr Leu Phe Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp           
510                 515                 520                 525           

cct gtt cat ggc ttc atg tac tgg act gac tgg gga act ccc gcc aag       6795
Pro Val His Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys           
                530                 535                 540               

atc aag aaa ggg ggc ctg aat ggt gtg gac atc tac tcg ctg gtg act       6843
Ile Lys Lys Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr           
            545                 550                 555                   

gaa aac att cag tgg ccc aat ggc atc acc cta gat ctc ctc agt ggc       6891
Glu Asn Ile Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly           
        560                 565                 570                       

cgc ctc tac tgg gtt gac tcc aaa ctt cac tcc atc tca agc atc gat       6939
Arg Leu Tyr Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp           
    575                 580                 585                           

gtc aat ggg ggc aac cgg aag acc atc ttg gag gat gaa aag agg ctg       6987
Val Asn Gly Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu           
590                 595                 600                 605           

gcc cac ccc ttc tcc ttg gcc gtc ttt gag gac aaa gta ttt tgg aca       7035
Ala His Pro Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr           
                610                 615                 620               

gat atc atc aac gaa gcc att ttc agt gcc aac cgc ctc aca ggt tcc       7083
Asp Ile Ile Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser           
            625                 630                 635                   

gat gtc aac ttg ttg gct gaa aac cta ctg tcc cca gag gat atg gtc       7131
Asp Val Asn Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val           
        640                 645                 650                       

ctc ttc cac aac ctc acc cag cca aga gga gtg aac tgg tgt gag agg       7179
Leu Phe His Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg           
    655                 660                 665                           

acc acc ctg agc aat ggc ggc tgc cag tat ctg tgc ctc cct gcc ccg       7227
Thr Thr Leu Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro           
670                 675                 680                 685           

cag atc aac ccc cac tcg ccc aag ttt acc tgc gcc tgc ccg gac ggc       7275
Gln Ile Asn Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly           
                690                 695                 700               

atg ctg ctg gcc agg gac atg agg agc tgc ctc aca gag gct gag gct       7323
Met Leu Leu Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala           
            705                 710                 715                   

gca gtg gcc acc cag gag aca tcc acc gtc agg cta aag gtc agc tcc       7371
Ala Val Ala Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser           
        720                 725                 730                       

aca gcc gta agg aca cag cac aca acc acc cgg cct gtt ccc gac acc       7419
Thr Ala Val Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr           
    735                 740                 745                           

tcc cgg ctg cct ggg gcc acc cct ggg ctc acc acg gtg gag ata gtg       7467
Ser Arg Leu Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val           
750                 755                 760                 765           

aca atg tct cac caa gct ctg ggc gac gtt gct ggc aga gga aat gag       7515
Thr Met Ser His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu           
                770                 775                 780               

aag aag ccc agt agc gtg agg gct ctg tcc att gtc ctc ccc atc gtg       7563
Lys Lys Pro Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val           
            785                 790                 795                   

ctc ctc gtc ttc ctt tgc ctg ggg gtc ttc ctt cta tgg aag aac tgg       7611
Leu Leu Val Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp           
        800                 805                 810                       

cgg ctt aag aac atc aac agc atc aac ttt gac aac ccc gtc tat cag       7659
Arg Leu Lys Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln           
    815                 820                 825                           

agg acc aca gag gat gag gtc cac att gcc cac aac cag gac ggc tac       7707
Arg Thr Thr Glu Asp Glu Val His Ile Ala His Asn Gln Asp Gly Tyr           
830                 835                 840                 845           

agc tac ccc tcg aga cag atg gtc agt ctg gag gat gac gtg gcg tga a     7756
Ser Tyr Pro Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala               
                850                 855                 860               


<210>  11
<211>  860
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Construct

<400>  11

Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu 
1               5                   10                  15      


Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe 
            20                  25                  30          


Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly 
        35                  40                  45              


Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu 
    50                  55                  60                  


Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn 
65                  70                  75                  80  


Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp 
                85                  90                  95      


Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp 
            100                 105                 110         


Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys 
        115                 120                 125             


Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro 
    130                 135                 140                 


Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys 
145                 150                 155                 160 


Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly 
                165                 170                 175     


Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly 
            180                 185                 190         


Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu 
        195                 200                 205             


Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp 
    210                 215                 220                 


Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu 
225                 230                 235                 240 


Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp 
                245                 250                 255     


Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn 
            260                 265                 270         


Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu 
        275                 280                 285             


Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp 
    290                 295                 300                 


Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp 
305                 310                 315                 320 


Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Leu Lys Ile Gly Tyr 
                325                 330                 335     


Glu Cys Leu Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys 
            340                 345                 350         


Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys 
        355                 360                 365             


Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln 
    370                 375                 380                 


Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr 
385                 390                 395                 400 


Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg 
                405                 410                 415     


Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu 
            420                 425                 430         


Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln 
        435                 440                 445             


Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser 
    450                 455                 460                 


Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala 
465                 470                 475                 480 


Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly 
                485                 490                 495     


Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe 
            500                 505                 510         


Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His 
        515                 520                 525             


Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys 
    530                 535                 540                 


Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile 
545                 550                 555                 560 


Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr 
                565                 570                 575     


Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly 
            580                 585                 590         


Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro 
        595                 600                 605             


Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile 
    610                 615                 620                 


Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn 
625                 630                 635                 640 


Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His 
                645                 650                 655     


Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu 
            660                 665                 670         


Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn 
        675                 680                 685             


Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu 
    690                 695                 700                 


Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala 
705                 710                 715                 720 


Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val 
                725                 730                 735     


Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu 
            740                 745                 750         


Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser 
        755                 760                 765             


His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro 
    770                 775                 780                 


Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val 
785                 790                 795                 800 


Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys 
                805                 810                 815     


Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Arg Thr Thr 
            820                 825                 830         


Glu Asp Glu Val His Ile Ala His Asn Gln Asp Gly Tyr Ser Tyr Pro 
        835                 840                 845             


Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala 
    850                 855                 860 


<210>  12
<211>  7059
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Synthetic pAAV.TBG.PI.hLDLR


<220>
<221>  repeat_region
<222>  (1)..(130)
<223>  5' ITR

<220>
<221>  enhancer
<222>  (221)..(320)
<223>  alpha mic/bik

<220>
<221>  enhancer
<222>  (327)..(426)
<223>  alpha mic/bik

<220>
<221>  promoter
<222>  (442)..(901)
<223>  TBG

<220>
<221>  TATA_signal
<222>  (885)..(888)

<220>
<221>  Intron
<222>  (1027)..(1159)
<223>  intron 1

<220>
<221>  CDS
<222>  (1245)..(3827)
<223>  hLDLR variant

<220>
<221>  misc_feature
<222>  (2256)..(2258)
<223>  C before L318D

<220>
<221>  misc_feature
<222>  (2259)..(2261)
<223>  L318D mutation

<220>
<221>  misc_feature
<222>  (3673)..(3710)
<223>  K6 R primter

<220>
<221>  misc_feature
<222>  (3675)..(3773)
<223>  IDOL mutations

<220>
<221>  misc_feature
<222>  (3690)..(3692)
<223>  K6-mutation

<220>
<221>  misc_feature
<222>  (3716)..(3749)
<223>  K20 R primter

<220>
<221>  misc_feature
<222>  (3732)..(3734)
<223>  K20 mutations

<220>
<221>  misc_feature
<222>  (3744)..(3776)
<223>  C29 A Primer

<220>
<221>  misc_feature
<222>  (3761)..(3761)
<223>  C29 mutation

<220>
<221>  polyA_signal
<222>  (3894)..(4020)
<223>  rabbit globulin polyA

<220>
<221>  repeat_region
<222>  (4109)..(4238)
<223>  3' ITR (complementary strand)

<220>
<221>  rep_origin
<222>  (4415)..(4870)
<223>  (located on complementary strand)

<220>
<221>  rep_origin
<222>  (6032)..(6620)

<400>  12
ctgcgcgctc gctcgctcac tgaggccgcc cgggcaaagc ccgggcgtcg ggcgaccttt       60

ggtcgcccgg cctcagtgag cgagcgagcg cgcagagagg gagtggccaa ctccatcact      120

aggggttcct tgtagttaat gattaacccg ccatgctact tatctaccag ggtaatgggg      180

atcctctaga actatagcta gaattcgccc ttaagctagc aggttaattt ttaaaaagca      240

gtcaaaagtc caagtggccc ttggcagcat ttactctctc tgtttgctct ggttaataat      300

ctcaggagca caaacattcc agatccaggt taatttttaa aaagcagtca aaagtccaag      360

tggcccttgg cagcatttac tctctctgtt tgctctggtt aataatctca ggagcacaaa      420

cattccagat ccggcgcgcc agggctggaa gctacctttg acatcatttc ctctgcgaat      480

gcatgtataa tttctacaga acctattaga aaggatcacc cagcctctgc ttttgtacaa      540

ctttccctta aaaaactgcc aattccactg ctgtttggcc caatagtgag aactttttcc      600

tgctgcctct tggtgctttt gcctatggcc cctattctgc ctgctgaaga cactcttgcc      660

agcatggact taaacccctc cagctctgac aatcctcttt ctcttttgtt ttacatgaag      720

ggtctggcag ccaaagcaat cactcaaagt tcaaacctta tcattttttg ctttgttcct      780

cttggccttg gttttgtaca tcagctttga aaataccatc ccagggttaa tgctggggtt      840

aatttataac taagagtgct ctagttttgc aatacaggac atgctataaa aatggaaaga      900

tgttgctttc tgagagacag ctttattgcg gtagtttatc acagttaaat tgctaacgca      960

gtcagtgctt ctgacacaac agtctcgaac ttaagctgca gaagttggtc gtgaggcact     1020

gggcaggtaa gtatcaaggt tacaagacag gtttaaggag accaatagaa actgggcttg     1080

tcgagacaga gaagactctt gcgtttctga taggcaccta ttggtcttac tgacatccac     1140

tttgcctttc tctccacagg tgtccactcc cagttcaatt acagctctta aggctagagt     1200

acttaatacg actcactata ggctagcctc gagaattcac gcgt atg ggg ccc tgg      1256
                                                 Met Gly Pro Trp          
                                                 1                        

ggc tgg aaa ttg cgc tgg acc gtc gcc ttg ctc ctc gcc gcg gcg ggg       1304
Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu Ala Ala Ala Gly           
5                   10                  15                  20            

act gca gtg ggc gac aga tgt gaa aga aac gag ttc cag tgc caa gac       1352
Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe Gln Cys Gln Asp           
                25                  30                  35                

ggg aaa tgc atc tcc tac aag tgg gtc tgc gat ggc agc gct gag tgc       1400
Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly Ser Ala Glu Cys           
            40                  45                  50                    

cag gat ggc tct gat gag tcc cag gag acg tgc ttg tct gtc acc tgc       1448
Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu Ser Val Thr Cys           
        55                  60                  65                        

aaa tcc ggg gac ttc agc tgt ggg ggc cgt gtc aac cgc tgc att cct       1496
Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn Arg Cys Ile Pro           
    70                  75                  80                            

cag ttc tgg agg tgc gat ggc caa gtg gac tgc gac aac ggc tca gac       1544
Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp Asn Gly Ser Asp           
85                  90                  95                  100           

gag caa ggc tgt ccc ccc aag acg tgc tcc cag gac gag ttt cgc tgc       1592
Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp Glu Phe Arg Cys           
                105                 110                 115               

cac gat ggg aag tgc atc tct cgg cag ttc gtc tgt gac tca gac cgg       1640
His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys Asp Ser Asp Arg           
            120                 125                 130                   

gac tgc ttg gac ggc tca gac gag gcc tcc tgc ccg gtg ctc acc tgt       1688
Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro Val Leu Thr Cys           
        135                 140                 145                       

ggt ccc gcc agc ttc cag tgc aac agc tcc acc tgc atc ccc cag ctg       1736
Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys Ile Pro Gln Leu           
    150                 155                 160                           

tgg gcc tgc gac aac gac ccc gac tgc gaa gat ggc tcg gat gag tgg       1784
Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly Ser Asp Glu Trp           
165                 170                 175                 180           

ccg cag cgc tgt agg ggt ctt tac gtg ttc caa ggg gac agt agc ccc       1832
Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly Asp Ser Ser Pro           
                185                 190                 195               

tgc tcg gcc ttc gag ttc cac tgc cta agt ggc gag tgc atc cac tcc       1880
Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu Cys Ile His Ser           
            200                 205                 210                   

agc tgg cgc tgt gat ggt ggc ccc gac tgc aag gac aaa tct gac gag       1928
Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp Lys Ser Asp Glu           
        215                 220                 225                       

gaa aac tgc gct gtg gcc acc tgt cgc cct gac gaa ttc cag tgc tct       1976
Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu Phe Gln Cys Ser           
    230                 235                 240                           

gat gga aac tgc atc cat ggc agc cgg cag tgt gac cgg gaa tat gac       2024
Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp Arg Glu Tyr Asp           
245                 250                 255                 260           

tgc aag gac atg agc gat gaa gtt ggc tgc gtt aat gtg aca ctc tgc       2072
Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn Val Thr Leu Cys           
                265                 270                 275               

gag gga ccc aac aag ttc aag tgt cac agc ggc gaa tgc atc acc ctg       2120
Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu Cys Ile Thr Leu           
            280                 285                 290                   

gac aaa gtc tgc aac atg gct aga gac tgc cgg gac tgg tca gat gaa       2168
Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp Trp Ser Asp Glu           
        295                 300                 305                       

ccc atc aaa gag tgc ggg acc aac gaa tgc ttg gac aac aac ggc ggc       2216
Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp Asn Asn Gly Gly           
    310                 315                 320                           

tgt tcc cac gtc tgc aat gac ctt aag atc ggc tac gag tgc gac tgc       2264
Cys Ser His Val Cys Asn Asp Leu Lys Ile Gly Tyr Glu Cys Asp Cys           
325                 330                 335                 340           

ccc gac ggc ttc cag ctg gtg gcc cag cga aga tgc gaa gat atc gat       2312
Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys Glu Asp Ile Asp           
                345                 350                 355               

gag tgt cag gat ccc gac acc tgc agc cag ctc tgc gtg aac ctg gag       2360
Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys Val Asn Leu Glu           
            360                 365                 370                   

ggt ggc tac aag tgc cag tgt gag gaa ggc ttc cag ctg gac ccc cac       2408
Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln Leu Asp Pro His           
        375                 380                 385                       

acg aag gcc tgc aag gct gtg ggc tcc atc gcc tac ctc ttc ttc acc       2456
Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr Leu Phe Phe Thr           
    390                 395                 400                           

aac cgg cac gag gtc agg aag atg acg ctg gac cgg agc gag tac acc       2504
Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg Ser Glu Tyr Thr           
405                 410                 415                 420           

agc ctc atc ccc aac ctg agg aac gtg gtc gct ctg gac acg gag gtg       2552
Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu Asp Thr Glu Val           
                425                 430                 435               

gcc agc aat aga atc tac tgg tct gac ctg tcc cag aga atg atc tgc       2600
Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln Arg Met Ile Cys           
            440                 445                 450                   

agc acc cag ctt gac aga gcc cac ggc gtc tct tcc tat gac acc gtc       2648
Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser Tyr Asp Thr Val           
        455                 460                 465                       

atc agc agg gac atc cag gcc ccc gac ggg ctg gct gtg gac tgg atc       2696
Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala Val Asp Trp Ile           
    470                 475                 480                           

cac agc aac atc tac tgg acc gac tct gtc ctg ggc act gtc tct gtt       2744
His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly Thr Val Ser Val           
485                 490                 495                 500           

gcg gat acc aag ggc gtg aag agg aaa acg tta ttc agg gag aac ggc       2792
Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe Arg Glu Asn Gly           
                505                 510                 515               

tcc aag cca agg gcc atc gtg gtg gat cct gtt cat ggc ttc atg tac       2840
Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His Gly Phe Met Tyr           
            520                 525                 530                   

tgg act gac tgg gga act ccc gcc aag atc aag aaa ggg ggc ctg aat       2888
Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys Gly Gly Leu Asn           
        535                 540                 545                       

ggt gtg gac atc tac tcg ctg gtg act gaa aac att cag tgg ccc aat       2936
Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile Gln Trp Pro Asn           
    550                 555                 560                           

ggc atc acc cta gat ctc ctc agt ggc cgc ctc tac tgg gtt gac tcc       2984
Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr Trp Val Asp Ser           
565                 570                 575                 580           

aaa ctt cac tcc atc tca agc atc gat gtc aat ggg ggc aac cgg aag       3032
Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly Gly Asn Arg Lys           
                585                 590                 595               

acc atc ttg gag gat gaa aag agg ctg gcc cac ccc ttc tcc ttg gcc       3080
Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro Phe Ser Leu Ala           
            600                 605                 610                   

gtc ttt gag gac aaa gta ttt tgg aca gat atc atc aac gaa gcc att       3128
Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile Asn Glu Ala Ile           
        615                 620                 625                       

ttc agt gcc aac cgc ctc aca ggt tcc gat gtc aac ttg ttg gct gaa       3176
Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn Leu Leu Ala Glu           
    630                 635                 640                           

aac cta ctg tcc cca gag gat atg gtc ctc ttc cac aac ctc acc cag       3224
Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His Asn Leu Thr Gln           
645                 650                 655                 660           

cca aga gga gtg aac tgg tgt gag agg acc acc ctg agc aat ggc ggc       3272
Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu Ser Asn Gly Gly           
                665                 670                 675               

tgc cag tat ctg tgc ctc cct gcc ccg cag atc aac ccc cac tcg ccc       3320
Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn Pro His Ser Pro           
            680                 685                 690                   

aag ttt acc tgc gcc tgc ccg gac ggc atg ctg ctg gcc agg gac atg       3368
Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu Ala Arg Asp Met           
        695                 700                 705                       

agg agc tgc ctc aca gag gct gag gct gca gtg gcc acc cag gag aca       3416
Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala Thr Gln Glu Thr           
    710                 715                 720                           

tcc acc gtc agg cta aag gtc agc tcc aca gcc gta agg aca cag cac       3464
Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val Arg Thr Gln His           
725                 730                 735                 740           

aca acc acc cgg cct gtt ccc gac acc tcc cgg ctg cct ggg gcc acc       3512
Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu Pro Gly Ala Thr           
                745                 750                 755               

cct ggg ctc acc acg gtg gag ata gtg aca atg tct cac caa gct ctg       3560
Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser His Gln Ala Leu           
            760                 765                 770                   

ggc gac gtt gct ggc aga gga aat gag aag aag ccc agt agc gtg agg       3608
Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro Ser Ser Val Arg           
        775                 780                 785                       

gct ctg tcc att gtc ctc ccc atc gtg ctc ctc gtc ttc ctt tgc ctg       3656
Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val Phe Leu Cys Leu           
    790                 795                 800                           

ggg gtc ttc ctt cta tgg aag aac tgg cgg ctt aag aac atc aac agc       3704
Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys Asn Ile Asn Ser           
805                 810                 815                 820           

atc aac ttt gac aac ccc gtc tat cag agg acc aca gag gat gag gtc       3752
Ile Asn Phe Asp Asn Pro Val Tyr Gln Arg Thr Thr Glu Asp Glu Val           
                825                 830                 835               

cac att gcc cac aac cag gac ggc tac agc tac ccc tcg aga cag atg       3800
His Ile Ala His Asn Gln Asp Gly Tyr Ser Tyr Pro Ser Arg Gln Met           
            840                 845                 850                   

gtc agt ctg gag gat gac gtg gcg tga acgcgtggta cctctagagt             3847
Val Ser Leu Glu Asp Asp Val Ala                                           
        855                 860                                           

cgacccgggc ggcctcgagg acggggtgaa ctacgcctga ggatccgatc tttttccctc     3907

tgccaaaaat tatggggaca tcatgaagcc ccttgagcat ctgacttctg gctaataaag     3967

gaaatttatt ttcattgcaa tagtgtgttg gaattttttg tgtctctcac tcggaagcaa     4027

ttcgttgatc tgaatttcga ccacccataa tacccattac cctggtagat aagtagcatg     4087

gcgggttaat cattaactac aaggaacccc tagtgatgga gttggccact ccctctctgc     4147

gcgctcgctc gctcactgag gccgggcgac caaaggtcgc ccgacgcccg ggctttgccc     4207

gggcggcctc agtgagcgag cgagcgcgca gccttaatta acctaattca ctggccgtcg     4267

ttttacaacg tcgtgactgg gaaaaccctg gcgttaccca acttaatcgc cttgcagcac     4327

atcccccttt cgccagctgg cgtaatagcg aagaggcccg caccgatcgc ccttcccaac     4387

agttgcgcag cctgaatggc gaatgggacg cgccctgtag cggcgcatta agcgcggcgg     4447

gtgtggtggt tacgcgcagc gtgaccgcta cacttgccag cgccctagcg cccgctcctt     4507

tcgctttctt cccttccttt ctcgccacgt tcgccggctt tccccgtcaa gctctaaatc     4567

gggggctccc tttagggttc cgatttagtg ctttacggca cctcgacccc aaaaaacttg     4627

attagggtga tggttcacgt agtgggccat cgccctgata gacggttttt cgccctttga     4687

cgttggagtc cacgttcttt aatagtggac tcttgttcca aactggaaca acactcaacc     4747

ctatctcggt ctattctttt gatttataag ggattttgcc gatttcggcc tattggttaa     4807

aaaatgagct gatttaacaa aaatttaacg cgaattttaa caaaatatta acgcttacaa     4867

tttaggtggc acttttcggg gaaatgtgcg cggaacccct atttgtttat ttttctaaat     4927

acattcaaat atgtatccgc tcatgagaca ataaccctga taaatgcttc aataatattg     4987

aaaaaggaag agtatgagta ttcaacattt ccgtgtcgcc cttattccct tttttgcggc     5047

attttgcctt cctgtttttg ctcacccaga aacgctggtg aaagtaaaag atgctgaaga     5107

tcagttgggt gcacgagtgg gttacatcga actggatctc aacagcggta agatccttga     5167

gagttttcgc cccgaagaac gttttccaat gatgagcact tttaaagttc tgctatgtgg     5227

cgcggtatta tcccgtattg acgccgggca agagcaactc ggtcgccgca tacactattc     5287

tcagaatgac ttggttgagt actcaccagt cacagaaaag catcttacgg atggcatgac     5347

agtaagagaa ttatgcagtg ctgccataac catgagtgat aacactgcgg ccaacttact     5407

tctgacaacg atcggaggac cgaaggagct aaccgctttt ttgcacaaca tgggggatca     5467

tgtaactcgc cttgatcgtt gggaaccgga gctgaatgaa gccataccaa acgacgagcg     5527

tgacaccacg atgcctgtag caatggcaac aacgttgcgc aaactattaa ctggcgaact     5587

acttactcta gcttcccggc aacaattaat agactggatg gaggcggata aagttgcagg     5647

accacttctg cgctcggccc ttccggctgg ctggtttatt gctgataaat ctggagccgg     5707

tgagcgtggg tctcgcggta tcattgcagc actggggcca gatggtaagc cctcccgtat     5767

cgtagttatc tacacgacgg ggagtcaggc aactatggat gaacgaaata gacagatcgc     5827

tgagataggt gcctcactga ttaagcattg gtaactgtca gaccaagttt actcatatat     5887

actttagatt gatttaaaac ttcattttta atttaaaagg atctaggtga agatcctttt     5947

tgataatctc atgaccaaaa tcccttaacg tgagttttcg ttccactgag cgtcagaccc     6007

cgtagaaaag atcaaaggat cttcttgaga tccttttttt ctgcgcgtaa tctgctgctt     6067

gcaaacaaaa aaaccaccgc taccagcggt ggtttgtttg ccggatcaag agctaccaac     6127

tctttttccg aaggtaactg gcttcagcag agcgcagata ccaaatactg ttcttctagt     6187

gtagccgtag ttaggccacc acttcaagaa ctctgtagca ccgcctacat acctcgctct     6247

gctaatcctg ttaccagtgg ctgctgccag tggcgataag tcgtgtctta ccgggttgga     6307

ctcaagacga tagttaccgg ataaggcgca gcggtcgggc tgaacggggg gttcgtgcac     6367

acagcccagc ttggagcgaa cgacctacac cgaactgaga tacctacagc gtgagctatg     6427

agaaagcgcc acgcttcccg aagggagaaa ggcggacagg tatccggtaa gcggcagggt     6487

cggaacagga gagcgcacga gggagcttcc agggggaaac gcctggtatc tttatagtcc     6547

tgtcgggttt cgccacctct gacttgagcg tcgatttttg tgatgctcgt caggggggcg     6607

gagcctatgg aaaaacgcca gcaacgcggc ctttttacgg ttcctggcct tttgctggcc     6667

ttttgctcac atgttctttc ctgcgttatc ccctgattct gtggataacc gtattaccgc     6727

ctttgagtga gctgataccg ctcgccgcag ccgaacgacc gagcgcagcg agtcagtgag     6787

cgaggaagcg gaagagcgcc caatacgcaa accgcctctc cccgcgcgtt ggccgattca     6847

ttaatgcagc tggcacgaca ggtttcccga ctggaaagcg ggcagtgagc gcaacgcaat     6907

taatgtgagt tagctcactc attaggcacc ccaggcttta cactttatgc ttccggctcg     6967

tatgttgtgt ggaattgtga gcggataaca atttcacaca ggaaacagct atgaccatga     7027

ttacgccaga tttaattaag gccttaatta gg                                   7059


<210>  13
<211>  860
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Construct

<400>  13

Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu 
1               5                   10                  15      


Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe 
            20                  25                  30          


Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly 
        35                  40                  45              


Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu 
    50                  55                  60                  


Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn 
65                  70                  75                  80  


Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp 
                85                  90                  95      


Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp 
            100                 105                 110         


Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys 
        115                 120                 125             


Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro 
    130                 135                 140                 


Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys 
145                 150                 155                 160 


Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly 
                165                 170                 175     


Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly 
            180                 185                 190         


Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu 
        195                 200                 205             


Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp 
    210                 215                 220                 


Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu 
225                 230                 235                 240 


Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp 
                245                 250                 255     


Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn 
            260                 265                 270         


Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu 
        275                 280                 285             


Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp 
    290                 295                 300                 


Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp 
305                 310                 315                 320 


Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Leu Lys Ile Gly Tyr 
                325                 330                 335     


Glu Cys Asp Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys 
            340                 345                 350         


Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys 
        355                 360                 365             


Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln 
    370                 375                 380                 


Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr 
385                 390                 395                 400 


Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg 
                405                 410                 415     


Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu 
            420                 425                 430         


Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln 
        435                 440                 445             


Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser 
    450                 455                 460                 


Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala 
465                 470                 475                 480 


Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly 
                485                 490                 495     


Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe 
            500                 505                 510         


Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His 
        515                 520                 525             


Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys 
    530                 535                 540                 


Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile 
545                 550                 555                 560 


Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr 
                565                 570                 575     


Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly 
            580                 585                 590         


Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro 
        595                 600                 605             


Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile 
    610                 615                 620                 


Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn 
625                 630                 635                 640 


Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His 
                645                 650                 655     


Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu 
            660                 665                 670         


Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn 
        675                 680                 685             


Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu 
    690                 695                 700                 


Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala 
705                 710                 715                 720 


Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val 
                725                 730                 735     


Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu 
            740                 745                 750         


Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser 
        755                 760                 765             


His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro 
    770                 775                 780                 


Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val 
785                 790                 795                 800 


Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys 
                805                 810                 815     


Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Arg Thr Thr 
            820                 825                 830         


Glu Asp Glu Val His Ile Ala His Asn Gln Asp Gly Tyr Ser Tyr Pro 
        835                 840                 845             


Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala 
    850                 855                 860 


<210>  14
<211>  7059
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic plasmid with hLDLR (K25K, C29A).PGT(P2701)Q


<220>
<221>  repeat_region
<222>  (1)..(130)
<223>  5' ITR

<220>
<221>  enhancer
<222>  (221)..(320)
<223>  alpha mic/bik

<220>
<221>  enhancer
<222>  (327)..(426)
<223>  alpha mic/bik

<220>
<221>  promoter
<222>  (442)..(901)
<223>  TBG promoter

<220>
<221>  TATA_signal
<222>  (885)..(888)

<220>
<221>  Intron
<222>  (1027)..(1159)
<223>  Intron 1

<220>
<221>  CDS
<222>  (1245)..(3827)
<223>  hLDLR with K25R-C29A variants

<220>
<221>  misc_feature
<222>  (2259)..(2261)
<223>  site of L318D mutatoin affecctign PCSK9 binding

<220>
<221>  misc_feature
<222>  (3673)..(3710)
<223>  K6 \R\Primter

<220>
<221>  misc_feature
<222>  (3675)..(3773)
<223>  IDOL mutations

<220>
<221>  misc_feature
<222>  (3690)..(3692)
<223>  K796 (K6) mutation

<220>
<221>  misc_feature
<222>  (3716)..(3749)
<223>  K20 R Primer

<220>
<221>  misc_feature
<222>  (3732)..(3732)
<223>  K20 mutation

<220>
<221>  misc_feature
<222>  (3744)..(3776)
<223>  C29 A primer

<220>
<221>  misc_feature
<222>  (3761)..(3761)
<223>  C29 mutation

<220>
<221>  polyA_signal
<222>  (3894)..(4020)
<223>  rabbit globulin polyA

<220>
<221>  repeat_region
<222>  (4109)..(4238)
<223>  3' ITR (complement)

<220>
<221>  rep_origin
<222>  (4415)..(4870)
<223>  complement f1 ori

<220>
<221>  misc_feature
<222>  (5001)..(5858)
<223>  AP(R) marker

<220>
<221>  rep_origin
<222>  (6032)..(6620)
<223>  origin of replication

<400>  14
ctgcgcgctc gctcgctcac tgaggccgcc cgggcaaagc ccgggcgtcg ggcgaccttt       60

ggtcgcccgg cctcagtgag cgagcgagcg cgcagagagg gagtggccaa ctccatcact      120

aggggttcct tgtagttaat gattaacccg ccatgctact tatctaccag ggtaatgggg      180

atcctctaga actatagcta gaattcgccc ttaagctagc aggttaattt ttaaaaagca      240

gtcaaaagtc caagtggccc ttggcagcat ttactctctc tgtttgctct ggttaataat      300

ctcaggagca caaacattcc agatccaggt taatttttaa aaagcagtca aaagtccaag      360

tggcccttgg cagcatttac tctctctgtt tgctctggtt aataatctca ggagcacaaa      420

cattccagat ccggcgcgcc agggctggaa gctacctttg acatcatttc ctctgcgaat      480

gcatgtataa tttctacaga acctattaga aaggatcacc cagcctctgc ttttgtacaa      540

ctttccctta aaaaactgcc aattccactg ctgtttggcc caatagtgag aactttttcc      600

tgctgcctct tggtgctttt gcctatggcc cctattctgc ctgctgaaga cactcttgcc      660

agcatggact taaacccctc cagctctgac aatcctcttt ctcttttgtt ttacatgaag      720

ggtctggcag ccaaagcaat cactcaaagt tcaaacctta tcattttttg ctttgttcct      780

cttggccttg gttttgtaca tcagctttga aaataccatc ccagggttaa tgctggggtt      840

aatttataac taagagtgct ctagttttgc aatacaggac atgctataaa aatggaaaga      900

tgttgctttc tgagagacag ctttattgcg gtagtttatc acagttaaat tgctaacgca      960

gtcagtgctt ctgacacaac agtctcgaac ttaagctgca gaagttggtc gtgaggcact     1020

gggcaggtaa gtatcaaggt tacaagacag gtttaaggag accaatagaa actgggcttg     1080

tcgagacaga gaagactctt gcgtttctga taggcaccta ttggtcttac tgacatccac     1140

tttgcctttc tctccacagg tgtccactcc cagttcaatt acagctctta aggctagagt     1200

acttaatacg actcactata ggctagcctc gagaattcac gcgt atg ggg ccc tgg      1256
                                                 Met Gly Pro Trp          
                                                 1                        

ggc tgg aaa ttg cgc tgg acc gtc gcc ttg ctc ctc gcc gcg gcg ggg       1304
Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu Ala Ala Ala Gly           
5                   10                  15                  20            

act gca gtg ggc gac aga tgt gaa aga aac gag ttc cag tgc caa gac       1352
Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe Gln Cys Gln Asp           
                25                  30                  35                

ggg aaa tgc atc tcc tac aag tgg gtc tgc gat ggc agc gct gag tgc       1400
Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly Ser Ala Glu Cys           
            40                  45                  50                    

cag gat ggc tct gat gag tcc cag gag acg tgc ttg tct gtc acc tgc       1448
Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu Ser Val Thr Cys           
        55                  60                  65                        

aaa tcc ggg gac ttc agc tgt ggg ggc cgt gtc aac cgc tgc att cct       1496
Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn Arg Cys Ile Pro           
    70                  75                  80                            

cag ttc tgg agg tgc gat ggc caa gtg gac tgc gac aac ggc tca gac       1544
Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp Asn Gly Ser Asp           
85                  90                  95                  100           

gag caa ggc tgt ccc ccc aag acg tgc tcc cag gac gag ttt cgc tgc       1592
Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp Glu Phe Arg Cys           
                105                 110                 115               

cac gat ggg aag tgc atc tct cgg cag ttc gtc tgt gac tca gac cgg       1640
His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys Asp Ser Asp Arg           
            120                 125                 130                   

gac tgc ttg gac ggc tca gac gag gcc tcc tgc ccg gtg ctc acc tgt       1688
Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro Val Leu Thr Cys           
        135                 140                 145                       

ggt ccc gcc agc ttc cag tgc aac agc tcc acc tgc atc ccc cag ctg       1736
Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys Ile Pro Gln Leu           
    150                 155                 160                           

tgg gcc tgc gac aac gac ccc gac tgc gaa gat ggc tcg gat gag tgg       1784
Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly Ser Asp Glu Trp           
165                 170                 175                 180           

ccg cag cgc tgt agg ggt ctt tac gtg ttc caa ggg gac agt agc ccc       1832
Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly Asp Ser Ser Pro           
                185                 190                 195               

tgc tcg gcc ttc gag ttc cac tgc cta agt ggc gag tgc atc cac tcc       1880
Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu Cys Ile His Ser           
            200                 205                 210                   

agc tgg cgc tgt gat ggt ggc ccc gac tgc aag gac aaa tct gac gag       1928
Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp Lys Ser Asp Glu           
        215                 220                 225                       

gaa aac tgc gct gtg gcc acc tgt cgc cct gac gaa ttc cag tgc tct       1976
Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu Phe Gln Cys Ser           
    230                 235                 240                           

gat gga aac tgc atc cat ggc agc cgg cag tgt gac cgg gaa tat gac       2024
Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp Arg Glu Tyr Asp           
245                 250                 255                 260           

tgc aag gac atg agc gat gaa gtt ggc tgc gtt aat gtg aca ctc tgc       2072
Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn Val Thr Leu Cys           
                265                 270                 275               

gag gga ccc aac aag ttc aag tgt cac agc ggc gaa tgc atc acc ctg       2120
Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu Cys Ile Thr Leu           
            280                 285                 290                   

gac aaa gtc tgc aac atg gct aga gac tgc cgg gac tgg tca gat gaa       2168
Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp Trp Ser Asp Glu           
        295                 300                 305                       

ccc atc aaa gag tgc ggg acc aac gaa tgc ttg gac aac aac ggc ggc       2216
Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp Asn Asn Gly Gly           
    310                 315                 320                           

tgt tcc cac gtc tgc aat gac ctt aag atc ggc tac gag tgc ctg tgc       2264
Cys Ser His Val Cys Asn Asp Leu Lys Ile Gly Tyr Glu Cys Leu Cys           
325                 330                 335                 340           

ccc gac ggc ttc cag ctg gtg gcc cag cga aga tgc gaa gat atc gat       2312
Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys Glu Asp Ile Asp           
                345                 350                 355               

gag tgt cag gat ccc gac acc tgc agc cag ctc tgc gtg aac ctg gag       2360
Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys Val Asn Leu Glu           
            360                 365                 370                   

ggt ggc tac aag tgc cag tgt gag gaa ggc ttc cag ctg gac ccc cac       2408
Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln Leu Asp Pro His           
        375                 380                 385                       

acg aag gcc tgc aag gct gtg ggc tcc atc gcc tac ctc ttc ttc acc       2456
Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr Leu Phe Phe Thr           
    390                 395                 400                           

aac cgg cac gag gtc agg aag atg acg ctg gac cgg agc gag tac acc       2504
Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg Ser Glu Tyr Thr           
405                 410                 415                 420           

agc ctc atc ccc aac ctg agg aac gtg gtc gct ctg gac acg gag gtg       2552
Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu Asp Thr Glu Val           
                425                 430                 435               

gcc agc aat aga atc tac tgg tct gac ctg tcc cag aga atg atc tgc       2600
Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln Arg Met Ile Cys           
            440                 445                 450                   

agc acc cag ctt gac aga gcc cac ggc gtc tct tcc tat gac acc gtc       2648
Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser Tyr Asp Thr Val           
        455                 460                 465                       

atc agc agg gac atc cag gcc ccc gac ggg ctg gct gtg gac tgg atc       2696
Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala Val Asp Trp Ile           
    470                 475                 480                           

cac agc aac atc tac tgg acc gac tct gtc ctg ggc act gtc tct gtt       2744
His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly Thr Val Ser Val           
485                 490                 495                 500           

gcg gat acc aag ggc gtg aag agg aaa acg tta ttc agg gag aac ggc       2792
Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe Arg Glu Asn Gly           
                505                 510                 515               

tcc aag cca agg gcc atc gtg gtg gat cct gtt cat ggc ttc atg tac       2840
Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His Gly Phe Met Tyr           
            520                 525                 530                   

tgg act gac tgg gga act ccc gcc aag atc aag aaa ggg ggc ctg aat       2888
Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys Gly Gly Leu Asn           
        535                 540                 545                       

ggt gtg gac atc tac tcg ctg gtg act gaa aac att cag tgg ccc aat       2936
Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile Gln Trp Pro Asn           
    550                 555                 560                           

ggc atc acc cta gat ctc ctc agt ggc cgc ctc tac tgg gtt gac tcc       2984
Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr Trp Val Asp Ser           
565                 570                 575                 580           

aaa ctt cac tcc atc tca agc atc gat gtc aat ggg ggc aac cgg aag       3032
Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly Gly Asn Arg Lys           
                585                 590                 595               

acc atc ttg gag gat gaa aag agg ctg gcc cac ccc ttc tcc ttg gcc       3080
Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro Phe Ser Leu Ala           
            600                 605                 610                   

gtc ttt gag gac aaa gta ttt tgg aca gat atc atc aac gaa gcc att       3128
Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile Asn Glu Ala Ile           
        615                 620                 625                       

ttc agt gcc aac cgc ctc aca ggt tcc gat gtc aac ttg ttg gct gaa       3176
Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn Leu Leu Ala Glu           
    630                 635                 640                           

aac cta ctg tcc cca gag gat atg gtc ctc ttc cac aac ctc acc cag       3224
Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His Asn Leu Thr Gln           
645                 650                 655                 660           

cca aga gga gtg aac tgg tgt gag agg acc acc ctg agc aat ggc ggc       3272
Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu Ser Asn Gly Gly           
                665                 670                 675               

tgc cag tat ctg tgc ctc cct gcc ccg cag atc aac ccc cac tcg ccc       3320
Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn Pro His Ser Pro           
            680                 685                 690                   

aag ttt acc tgc gcc tgc ccg gac ggc atg ctg ctg gcc agg gac atg       3368
Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu Ala Arg Asp Met           
        695                 700                 705                       

agg agc tgc ctc aca gag gct gag gct gca gtg gcc acc cag gag aca       3416
Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala Thr Gln Glu Thr           
    710                 715                 720                           

tcc acc gtc agg cta aag gtc agc tcc aca gcc gta agg aca cag cac       3464
Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val Arg Thr Gln His           
725                 730                 735                 740           

aca acc acc cgg cct gtt ccc gac acc tcc cgg ctg cct ggg gcc acc       3512
Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu Pro Gly Ala Thr           
                745                 750                 755               

cct ggg ctc acc acg gtg gag ata gtg aca atg tct cac caa gct ctg       3560
Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser His Gln Ala Leu           
            760                 765                 770                   

ggc gac gtt gct ggc aga gga aat gag aag aag ccc agt agc gtg agg       3608
Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro Ser Ser Val Arg           
        775                 780                 785                       

gct ctg tcc att gtc ctc ccc atc gtg ctc ctc gtc ttc ctt tgc ctg       3656
Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val Phe Leu Cys Leu           
    790                 795                 800                           

ggg gtc ttc ctt cta tgg aag aac tgg cgg ctt aag aac atc aac agc       3704
Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys Asn Ile Asn Ser           
805                 810                 815                 820           

atc aac ttt gac aac ccc gtc tat cag agg acc aca gag gat gag gtc       3752
Ile Asn Phe Asp Asn Pro Val Tyr Gln Arg Thr Thr Glu Asp Glu Val           
                825                 830                 835               

cac att gcc cac aac cag gac ggc tac agc tac ccc tcg aga cag atg       3800
His Ile Ala His Asn Gln Asp Gly Tyr Ser Tyr Pro Ser Arg Gln Met           
            840                 845                 850                   

gtc agt ctg gag gat gac gtg gcg tga acgcgtggta cctctagagt             3847
Val Ser Leu Glu Asp Asp Val Ala                                           
        855                 860                                           

cgacccgggc ggcctcgagg acggggtgaa ctacgcctga ggatccgatc tttttccctc     3907

tgccaaaaat tatggggaca tcatgaagcc ccttgagcat ctgacttctg gctaataaag     3967

gaaatttatt ttcattgcaa tagtgtgttg gaattttttg tgtctctcac tcggaagcaa     4027

ttcgttgatc tgaatttcga ccacccataa tacccattac cctggtagat aagtagcatg     4087

gcgggttaat cattaactac aaggaacccc tagtgatgga gttggccact ccctctctgc     4147

gcgctcgctc gctcactgag gccgggcgac caaaggtcgc ccgacgcccg ggctttgccc     4207

gggcggcctc agtgagcgag cgagcgcgca gccttaatta acctaattca ctggccgtcg     4267

ttttacaacg tcgtgactgg gaaaaccctg gcgttaccca acttaatcgc cttgcagcac     4327

atcccccttt cgccagctgg cgtaatagcg aagaggcccg caccgatcgc ccttcccaac     4387

agttgcgcag cctgaatggc gaatgggacg cgccctgtag cggcgcatta agcgcggcgg     4447

gtgtggtggt tacgcgcagc gtgaccgcta cacttgccag cgccctagcg cccgctcctt     4507

tcgctttctt cccttccttt ctcgccacgt tcgccggctt tccccgtcaa gctctaaatc     4567

gggggctccc tttagggttc cgatttagtg ctttacggca cctcgacccc aaaaaacttg     4627

attagggtga tggttcacgt agtgggccat cgccctgata gacggttttt cgccctttga     4687

cgttggagtc cacgttcttt aatagtggac tcttgttcca aactggaaca acactcaacc     4747

ctatctcggt ctattctttt gatttataag ggattttgcc gatttcggcc tattggttaa     4807

aaaatgagct gatttaacaa aaatttaacg cgaattttaa caaaatatta acgcttacaa     4867

tttaggtggc acttttcggg gaaatgtgcg cggaacccct atttgtttat ttttctaaat     4927

acattcaaat atgtatccgc tcatgagaca ataaccctga taaatgcttc aataatattg     4987

aaaaaggaag agtatgagta ttcaacattt ccgtgtcgcc cttattccct tttttgcggc     5047

attttgcctt cctgtttttg ctcacccaga aacgctggtg aaagtaaaag atgctgaaga     5107

tcagttgggt gcacgagtgg gttacatcga actggatctc aacagcggta agatccttga     5167

gagttttcgc cccgaagaac gttttccaat gatgagcact tttaaagttc tgctatgtgg     5227

cgcggtatta tcccgtattg acgccgggca agagcaactc ggtcgccgca tacactattc     5287

tcagaatgac ttggttgagt actcaccagt cacagaaaag catcttacgg atggcatgac     5347

agtaagagaa ttatgcagtg ctgccataac catgagtgat aacactgcgg ccaacttact     5407

tctgacaacg atcggaggac cgaaggagct aaccgctttt ttgcacaaca tgggggatca     5467

tgtaactcgc cttgatcgtt gggaaccgga gctgaatgaa gccataccaa acgacgagcg     5527

tgacaccacg atgcctgtag caatggcaac aacgttgcgc aaactattaa ctggcgaact     5587

acttactcta gcttcccggc aacaattaat agactggatg gaggcggata aagttgcagg     5647

accacttctg cgctcggccc ttccggctgg ctggtttatt gctgataaat ctggagccgg     5707

tgagcgtggg tctcgcggta tcattgcagc actggggcca gatggtaagc cctcccgtat     5767

cgtagttatc tacacgacgg ggagtcaggc aactatggat gaacgaaata gacagatcgc     5827

tgagataggt gcctcactga ttaagcattg gtaactgtca gaccaagttt actcatatat     5887

actttagatt gatttaaaac ttcattttta atttaaaagg atctaggtga agatcctttt     5947

tgataatctc atgaccaaaa tcccttaacg tgagttttcg ttccactgag cgtcagaccc     6007

cgtagaaaag atcaaaggat cttcttgaga tccttttttt ctgcgcgtaa tctgctgctt     6067

gcaaacaaaa aaaccaccgc taccagcggt ggtttgtttg ccggatcaag agctaccaac     6127

tctttttccg aaggtaactg gcttcagcag agcgcagata ccaaatactg ttcttctagt     6187

gtagccgtag ttaggccacc acttcaagaa ctctgtagca ccgcctacat acctcgctct     6247

gctaatcctg ttaccagtgg ctgctgccag tggcgataag tcgtgtctta ccgggttgga     6307

ctcaagacga tagttaccgg ataaggcgca gcggtcgggc tgaacggggg gttcgtgcac     6367

acagcccagc ttggagcgaa cgacctacac cgaactgaga tacctacagc gtgagctatg     6427

agaaagcgcc acgcttcccg aagggagaaa ggcggacagg tatccggtaa gcggcagggt     6487

cggaacagga gagcgcacga gggagcttcc agggggaaac gcctggtatc tttatagtcc     6547

tgtcgggttt cgccacctct gacttgagcg tcgatttttg tgatgctcgt caggggggcg     6607

gagcctatgg aaaaacgcca gcaacgcggc ctttttacgg ttcctggcct tttgctggcc     6667

ttttgctcac atgttctttc ctgcgttatc ccctgattct gtggataacc gtattaccgc     6727

ctttgagtga gctgataccg ctcgccgcag ccgaacgacc gagcgcagcg agtcagtgag     6787

cgaggaagcg gaagagcgcc caatacgcaa accgcctctc cccgcgcgtt ggccgattca     6847

ttaatgcagc tggcacgaca ggtttcccga ctggaaagcg ggcagtgagc gcaacgcaat     6907

taatgtgagt tagctcactc attaggcacc ccaggcttta cactttatgc ttccggctcg     6967

tatgttgtgt ggaattgtga gcggataaca atttcacaca ggaaacagct atgaccatga     7027

ttacgccaga tttaattaag gccttaatta gg                                   7059


<210>  15
<211>  860
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  15

Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu 
1               5                   10                  15      


Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe 
            20                  25                  30          


Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly 
        35                  40                  45              


Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu 
    50                  55                  60                  


Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn 
65                  70                  75                  80  


Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp 
                85                  90                  95      


Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp 
            100                 105                 110         


Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys 
        115                 120                 125             


Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro 
    130                 135                 140                 


Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys 
145                 150                 155                 160 


Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly 
                165                 170                 175     


Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly 
            180                 185                 190         


Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu 
        195                 200                 205             


Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp 
    210                 215                 220                 


Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu 
225                 230                 235                 240 


Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp 
                245                 250                 255     


Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn 
            260                 265                 270         


Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu 
        275                 280                 285             


Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp 
    290                 295                 300                 


Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp 
305                 310                 315                 320 


Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Leu Lys Ile Gly Tyr 
                325                 330                 335     


Glu Cys Leu Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys 
            340                 345                 350         


Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys 
        355                 360                 365             


Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln 
    370                 375                 380                 


Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr 
385                 390                 395                 400 


Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg 
                405                 410                 415     


Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu 
            420                 425                 430         


Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln 
        435                 440                 445             


Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser 
    450                 455                 460                 


Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala 
465                 470                 475                 480 


Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly 
                485                 490                 495     


Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe 
            500                 505                 510         


Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His 
        515                 520                 525             


Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys 
    530                 535                 540                 


Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile 
545                 550                 555                 560 


Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr 
                565                 570                 575     


Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly 
            580                 585                 590         


Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro 
        595                 600                 605             


Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile 
    610                 615                 620                 


Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn 
625                 630                 635                 640 


Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His 
                645                 650                 655     


Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu 
            660                 665                 670         


Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn 
        675                 680                 685             


Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu 
    690                 695                 700                 


Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala 
705                 710                 715                 720 


Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val 
                725                 730                 735     


Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu 
            740                 745                 750         


Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser 
        755                 760                 765             


His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro 
    770                 775                 780                 


Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val 
785                 790                 795                 800 


Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys 
                805                 810                 815     


Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Arg Thr Thr 
            820                 825                 830         


Glu Asp Glu Val His Ile Ala His Asn Gln Asp Gly Tyr Ser Tyr Pro 
        835                 840                 845             


Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala 
    850                 855                 860 


<210>  16
<211>  2583
<212>  DNA
<213>  Artificial sequence

<220>
<223>  hLDLR varient D299N with leader


<220>
<221>  CDS
<222>  (1)..(2583)

<400>  16
atg ggg ccc tgg ggc tgg aaa ttg cgc tgg acc gtc gcc ttg ctc ctc         48
Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu           
1               5                   10                  15                

gcc gcg gcg ggg act gca gtg ggc gac aga tgt gaa aga aac gag ttc         96
Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe           
            20                  25                  30                    

cag tgc caa gac ggg aaa tgc atc tcc tac aag tgg gtc tgc gat ggc        144
Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly           
        35                  40                  45                        

agc gct gag tgc cag gat ggc tct gat gag tcc cag gag acg tgc ttg        192
Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu           
    50                  55                  60                            

tct gtc acc tgc aaa tcc ggg gac ttc agc tgt ggg ggc cgt gtc aac        240
Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn           
65                  70                  75                  80            

cgc tgc att cct cag ttc tgg agg tgc gat ggc caa gtg gac tgc gac        288
Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp           
                85                  90                  95                

aac ggc tca gac gag caa ggc tgt ccc ccc aag acg tgc tcc cag gac        336
Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp           
            100                 105                 110                   

gag ttt cgc tgc cac gat ggg aag tgc atc tct cgg cag ttc gtc tgt        384
Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys           
        115                 120                 125                       

gac tca gac cgg gac tgc ttg gac ggc tca gac gag gcc tcc tgc ccg        432
Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro           
    130                 135                 140                           

gtg ctc acc tgt ggt ccc gcc agc ttc cag tgc aac agc tcc acc tgc        480
Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys           
145                 150                 155                 160           

atc ccc cag ctg tgg gcc tgc gac aac gac ccc gac tgc gaa gat ggc        528
Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly           
                165                 170                 175               

tcg gat gag tgg ccg cag cgc tgt agg ggt ctt tac gtg ttc caa ggg        576
Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly           
            180                 185                 190                   

gac agt agc ccc tgc tcg gcc ttc gag ttc cac tgc cta agt ggc gag        624
Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu           
        195                 200                 205                       

tgc atc cac tcc agc tgg cgc tgt gat ggt ggc ccc gac tgc aag gac        672
Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp           
    210                 215                 220                           

aaa tct gac gag gaa aac tgc gct gtg gcc acc tgt cgc cct gac gaa        720
Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu           
225                 230                 235                 240           

ttc cag tgc tct gat gga aac tgc atc cat ggc agc cgg cag tgt gac        768
Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp           
                245                 250                 255               

cgg gaa tat gac tgc aag gac atg agc gat gaa gtt ggc tgc gtt aat        816
Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn           
            260                 265                 270                   

gtg aca ctc tgc gag gga ccc aac aag ttc aag tgt cac agc ggc gaa        864
Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu           
        275                 280                 285                       

tgc atc acc ctg gac aaa gtc tgc aac atg gct aga gac tgc cgg gac        912
Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp           
    290                 295                 300                           

tgg tca gat gaa ccc atc aaa gag tgc ggg acc aac gaa tgc ttg aac        960
Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asn           
305                 310                 315                 320           

aac aac ggc ggc tgt tcc cac gtc tgc aat gac ctt aag atc ggc tac       1008
Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Leu Lys Ile Gly Tyr           
                325                 330                 335               

gag tgc ctg tgc ccc gac ggc ttc cag ctg gtg gcc cag cga aga tgc       1056
Glu Cys Leu Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys           
            340                 345                 350                   

gaa gat atc gat gag tgt cag gat ccc gac acc tgc agc cag ctc tgc       1104
Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys           
        355                 360                 365                       

gtg aac ctg gag ggt ggc tac aag tgc cag tgt gag gaa ggc ttc cag       1152
Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln           
    370                 375                 380                           

ctg gac ccc cac acg aag gcc tgc aag gct gtg ggc tcc atc gcc tac       1200
Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr           
385                 390                 395                 400           

ctc ttc ttc acc aac cgg cac gag gtc agg aag atg acg ctg gac cgg       1248
Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg           
                405                 410                 415               

agc gag tac acc agc ctc atc ccc aac ctg agg aac gtg gtc gct ctg       1296
Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu           
            420                 425                 430                   

gac acg gag gtg gcc agc aat aga atc tac tgg tct gac ctg tcc cag       1344
Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln           
        435                 440                 445                       

aga atg atc tgc agc acc cag ctt gac aga gcc cac ggc gtc tct tcc       1392
Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser           
    450                 455                 460                           

tat gac acc gtc atc agc agg gac atc cag gcc ccc gac ggg ctg gct       1440
Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala           
465                 470                 475                 480           

gtg gac tgg atc cac agc aac atc tac tgg acc gac tct gtc ctg ggc       1488
Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly           
                485                 490                 495               

act gtc tct gtt gcg gat acc aag ggc gtg aag agg aaa acg tta ttc       1536
Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe           
            500                 505                 510                   

agg gag aac ggc tcc aag cca agg gcc atc gtg gtg gat cct gtt cat       1584
Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His           
        515                 520                 525                       

ggc ttc atg tac tgg act gac tgg gga act ccc gcc aag atc aag aaa       1632
Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys           
    530                 535                 540                           

ggg ggc ctg aat ggt gtg gac atc tac tcg ctg gtg act gaa aac att       1680
Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile           
545                 550                 555                 560           

cag tgg ccc aat ggc atc acc cta gat ctc ctc agt ggc cgc ctc tac       1728
Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr           
                565                 570                 575               

tgg gtt gac tcc aaa ctt cac tcc atc tca agc atc gat gtc aat ggg       1776
Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly           
            580                 585                 590                   

ggc aac cgg aag acc atc ttg gag gat gaa aag agg ctg gcc cac ccc       1824
Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro           
        595                 600                 605                       

ttc tcc ttg gcc gtc ttt gag gac aaa gta ttt tgg aca gat atc atc       1872
Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile           
    610                 615                 620                           

aac gaa gcc att ttc agt gcc aac cgc ctc aca ggt tcc gat gtc aac       1920
Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn           
625                 630                 635                 640           

ttg ttg gct gaa aac cta ctg tcc cca gag gat atg gtc ctc ttc cac       1968
Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His           
                645                 650                 655               

aac ctc acc cag cca aga gga gtg aac tgg tgt gag agg acc acc ctg       2016
Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu           
            660                 665                 670                   

agc aat ggc ggc tgc cag tat ctg tgc ctc cct gcc ccg cag atc aac       2064
Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn           
        675                 680                 685                       

ccc cac tcg ccc aag ttt acc tgc gcc tgc ccg gac ggc atg ctg ctg       2112
Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu           
    690                 695                 700                           

gcc agg gac atg agg agc tgc ctc aca gag gct gag gct gca gtg gcc       2160
Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala           
705                 710                 715                 720           

acc cag gag aca tcc acc gtc agg cta aag gtc agc tcc aca gcc gta       2208
Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val           
                725                 730                 735               

agg aca cag cac aca acc acc cgg cct gtt ccc gac acc tcc cgg ctg       2256
Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu           
            740                 745                 750                   

cct ggg gcc acc cct ggg ctc acc acg gtg gag ata gtg aca atg tct       2304
Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser           
        755                 760                 765                       

cac caa gct ctg ggc gac gtt gct ggc aga gga aat gag aag aag ccc       2352
His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro           
    770                 775                 780                           

agt agc gtg agg gct ctg tcc att gtc ctc ccc atc gtg ctc ctc gtc       2400
Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val           
785                 790                 795                 800           

ttc ctt tgc ctg ggg gtc ttc ctt cta tgg aag aac tgg cgg ctt aag       2448
Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys           
                805                 810                 815               

aac atc aac agc atc aac ttt gac aac ccc gtc tat cag aag acc aca       2496
Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Lys Thr Thr           
            820                 825                 830                   

gag gat gag gtc cac att tgc cac aac cag gac ggc tac agc tac ccc       2544
Glu Asp Glu Val His Ile Cys His Asn Gln Asp Gly Tyr Ser Tyr Pro           
        835                 840                 845                       

tcg aga cag atg gtc agt ctg gag gat gac gtg gcg tga                   2583
Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala                           
    850                 855                 860                           


<210>  17
<211>  860
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Construct

<400>  17

Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu 
1               5                   10                  15      


Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe 
            20                  25                  30          


Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly 
        35                  40                  45              


Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu 
    50                  55                  60                  


Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn 
65                  70                  75                  80  


Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp 
                85                  90                  95      


Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp 
            100                 105                 110         


Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys 
        115                 120                 125             


Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro 
    130                 135                 140                 


Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys 
145                 150                 155                 160 


Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly 
                165                 170                 175     


Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly 
            180                 185                 190         


Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu 
        195                 200                 205             


Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp 
    210                 215                 220                 


Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu 
225                 230                 235                 240 


Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp 
                245                 250                 255     


Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn 
            260                 265                 270         


Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu 
        275                 280                 285             


Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp 
    290                 295                 300                 


Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asn 
305                 310                 315                 320 


Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Leu Lys Ile Gly Tyr 
                325                 330                 335     


Glu Cys Leu Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys 
            340                 345                 350         


Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys 
        355                 360                 365             


Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln 
    370                 375                 380                 


Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr 
385                 390                 395                 400 


Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg 
                405                 410                 415     


Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu 
            420                 425                 430         


Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln 
        435                 440                 445             


Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser 
    450                 455                 460                 


Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala 
465                 470                 475                 480 


Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly 
                485                 490                 495     


Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe 
            500                 505                 510         


Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His 
        515                 520                 525             


Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys 
    530                 535                 540                 


Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile 
545                 550                 555                 560 


Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr 
                565                 570                 575     


Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly 
            580                 585                 590         


Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro 
        595                 600                 605             


Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile 
    610                 615                 620                 


Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn 
625                 630                 635                 640 


Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His 
                645                 650                 655     


Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu 
            660                 665                 670         


Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn 
        675                 680                 685             


Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu 
    690                 695                 700                 


Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala 
705                 710                 715                 720 


Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val 
                725                 730                 735     


Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu 
            740                 745                 750         


Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser 
        755                 760                 765             


His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro 
    770                 775                 780                 


Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val 
785                 790                 795                 800 


Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys 
                805                 810                 815     


Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Lys Thr Thr 
            820                 825                 830         


Glu Asp Glu Val His Ile Cys His Asn Gln Asp Gly Tyr Ser Tyr Pro 
        835                 840                 845             


Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala 
    850                 855                 860 


<210>  18
<211>  2583
<212>  DNA
<213>  Artificial sequence

<220>
<223>  hLDLR variant D310N with leader


<220>
<221>  CDS
<222>  (1)..(2583)

<400>  18
atg ggg ccc tgg ggc tgg aaa ttg cgc tgg acc gtc gcc ttg ctc ctc         48
Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu           
1               5                   10                  15                

gcc gcg gcg ggg act gca gtg ggc gac aga tgt gaa aga aac gag ttc         96
Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe           
            20                  25                  30                    

cag tgc caa gac ggg aaa tgc atc tcc tac aag tgg gtc tgc gat ggc        144
Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly           
        35                  40                  45                        

agc gct gag tgc cag gat ggc tct gat gag tcc cag gag acg tgc ttg        192
Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu           
    50                  55                  60                            

tct gtc acc tgc aaa tcc ggg gac ttc agc tgt ggg ggc cgt gtc aac        240
Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn           
65                  70                  75                  80            

cgc tgc att cct cag ttc tgg agg tgc gat ggc caa gtg gac tgc gac        288
Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp           
                85                  90                  95                

aac ggc tca gac gag caa ggc tgt ccc ccc aag acg tgc tcc cag gac        336
Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp           
            100                 105                 110                   

gag ttt cgc tgc cac gat ggg aag tgc atc tct cgg cag ttc gtc tgt        384
Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys           
        115                 120                 125                       

gac tca gac cgg gac tgc ttg gac ggc tca gac gag gcc tcc tgc ccg        432
Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro           
    130                 135                 140                           

gtg ctc acc tgt ggt ccc gcc agc ttc cag tgc aac agc tcc acc tgc        480
Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys           
145                 150                 155                 160           

atc ccc cag ctg tgg gcc tgc gac aac gac ccc gac tgc gaa gat ggc        528
Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly           
                165                 170                 175               

tcg gat gag tgg ccg cag cgc tgt agg ggt ctt tac gtg ttc caa ggg        576
Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly           
            180                 185                 190                   

gac agt agc ccc tgc tcg gcc ttc gag ttc cac tgc cta agt ggc gag        624
Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu           
        195                 200                 205                       

tgc atc cac tcc agc tgg cgc tgt gat ggt ggc ccc gac tgc aag gac        672
Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp           
    210                 215                 220                           

aaa tct gac gag gaa aac tgc gct gtg gcc acc tgt cgc cct gac gaa        720
Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu           
225                 230                 235                 240           

ttc cag tgc tct gat gga aac tgc atc cat ggc agc cgg cag tgt gac        768
Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp           
                245                 250                 255               

cgg gaa tat gac tgc aag gac atg agc gat gaa gtt ggc tgc gtt aat        816
Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn           
            260                 265                 270                   

gtg aca ctc tgc gag gga ccc aac aag ttc aag tgt cac agc ggc gaa        864
Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu           
        275                 280                 285                       

tgc atc acc ctg gac aaa gtc tgc aac atg gct aga gac tgc cgg gac        912
Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp           
    290                 295                 300                           

tgg tca gat gaa ccc atc aaa gag tgc ggg acc aac gaa tgc ttg gac        960
Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp           
305                 310                 315                 320           

aac aac ggc ggc tgt tcc cac gtc tgc aat aac ctt aag atc ggc tac       1008
Asn Asn Gly Gly Cys Ser His Val Cys Asn Asn Leu Lys Ile Gly Tyr           
                325                 330                 335               

gag tgc ctg tgc ccc gac ggc ttc cag ctg gtg gcc cag cga aga tgc       1056
Glu Cys Leu Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys           
            340                 345                 350                   

gaa gat atc gat gag tgt cag gat ccc gac acc tgc agc cag ctc tgc       1104
Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys           
        355                 360                 365                       

gtg aac ctg gag ggt ggc tac aag tgc cag tgt gag gaa ggc ttc cag       1152
Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln           
    370                 375                 380                           

ctg gac ccc cac acg aag gcc tgc aag gct gtg ggc tcc atc gcc tac       1200
Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr           
385                 390                 395                 400           

ctc ttc ttc acc aac cgg cac gag gtc agg aag atg acg ctg gac cgg       1248
Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg           
                405                 410                 415               

agc gag tac acc agc ctc atc ccc aac ctg agg aac gtg gtc gct ctg       1296
Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu           
            420                 425                 430                   

gac acg gag gtg gcc agc aat aga atc tac tgg tct gac ctg tcc cag       1344
Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln           
        435                 440                 445                       

aga atg atc tgc agc acc cag ctt gac aga gcc cac ggc gtc tct tcc       1392
Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser           
    450                 455                 460                           

tat gac acc gtc atc agc agg gac atc cag gcc ccc gac ggg ctg gct       1440
Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala           
465                 470                 475                 480           

gtg gac tgg atc cac agc aac atc tac tgg acc gac tct gtc ctg ggc       1488
Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly           
                485                 490                 495               

act gtc tct gtt gcg gat acc aag ggc gtg aag agg aaa acg tta ttc       1536
Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe           
            500                 505                 510                   

agg gag aac ggc tcc aag cca agg gcc atc gtg gtg gat cct gtt cat       1584
Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His           
        515                 520                 525                       

ggc ttc atg tac tgg act gac tgg gga act ccc gcc aag atc aag aaa       1632
Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys           
    530                 535                 540                           

ggg ggc ctg aat ggt gtg gac atc tac tcg ctg gtg act gaa aac att       1680
Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile           
545                 550                 555                 560           

cag tgg ccc aat ggc atc acc cta gat ctc ctc agt ggc cgc ctc tac       1728
Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr           
                565                 570                 575               

tgg gtt gac tcc aaa ctt cac tcc atc tca agc atc gat gtc aat ggg       1776
Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly           
            580                 585                 590                   

ggc aac cgg aag acc atc ttg gag gat gaa aag agg ctg gcc cac ccc       1824
Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro           
        595                 600                 605                       

ttc tcc ttg gcc gtc ttt gag gac aaa gta ttt tgg aca gat atc atc       1872
Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile           
    610                 615                 620                           

aac gaa gcc att ttc agt gcc aac cgc ctc aca ggt tcc gat gtc aac       1920
Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn           
625                 630                 635                 640           

ttg ttg gct gaa aac cta ctg tcc cca gag gat atg gtc ctc ttc cac       1968
Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His           
                645                 650                 655               

aac ctc acc cag cca aga gga gtg aac tgg tgt gag agg acc acc ctg       2016
Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu           
            660                 665                 670                   

agc aat ggc ggc tgc cag tat ctg tgc ctc cct gcc ccg cag atc aac       2064
Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn           
        675                 680                 685                       

ccc cac tcg ccc aag ttt acc tgc gcc tgc ccg gac ggc atg ctg ctg       2112
Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu           
    690                 695                 700                           

gcc agg gac atg agg agc tgc ctc aca gag gct gag gct gca gtg gcc       2160
Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala           
705                 710                 715                 720           

acc cag gag aca tcc acc gtc agg cta aag gtc agc tcc aca gcc gta       2208
Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val           
                725                 730                 735               

agg aca cag cac aca acc acc cgg cct gtt ccc gac acc tcc cgg ctg       2256
Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu           
            740                 745                 750                   

cct ggg gcc acc cct ggg ctc acc acg gtg gag ata gtg aca atg tct       2304
Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser           
        755                 760                 765                       

cac caa gct ctg ggc gac gtt gct ggc aga gga aat gag aag aag ccc       2352
His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro           
    770                 775                 780                           

agt agc gtg agg gct ctg tcc att gtc ctc ccc atc gtg ctc ctc gtc       2400
Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val           
785                 790                 795                 800           

ttc ctt tgc ctg ggg gtc ttc ctt cta tgg aag aac tgg cgg ctt aag       2448
Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys           
                805                 810                 815               

aac atc aac agc atc aac ttt gac aac ccc gtc tat cag aag acc aca       2496
Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Lys Thr Thr           
            820                 825                 830                   

gag gat gag gtc cac att tgc cac aac cag gac ggc tac agc tac ccc       2544
Glu Asp Glu Val His Ile Cys His Asn Gln Asp Gly Tyr Ser Tyr Pro           
        835                 840                 845                       

tcg aga cag atg gtc agt ctg gag gat gac gtg gcg tga                   2583
Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala                           
    850                 855                 860                           


<210>  19
<211>  860
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Construct

<400>  19

Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu 
1               5                   10                  15      


Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe 
            20                  25                  30          


Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly 
        35                  40                  45              


Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu 
    50                  55                  60                  


Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn 
65                  70                  75                  80  


Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp 
                85                  90                  95      


Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp 
            100                 105                 110         


Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys 
        115                 120                 125             


Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro 
    130                 135                 140                 


Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys 
145                 150                 155                 160 


Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly 
                165                 170                 175     


Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly 
            180                 185                 190         


Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu 
        195                 200                 205             


Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp 
    210                 215                 220                 


Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu 
225                 230                 235                 240 


Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp 
                245                 250                 255     


Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn 
            260                 265                 270         


Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu 
        275                 280                 285             


Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp 
    290                 295                 300                 


Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp 
305                 310                 315                 320 


Asn Asn Gly Gly Cys Ser His Val Cys Asn Asn Leu Lys Ile Gly Tyr 
                325                 330                 335     


Glu Cys Leu Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys 
            340                 345                 350         


Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys 
        355                 360                 365             


Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln 
    370                 375                 380                 


Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr 
385                 390                 395                 400 


Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg 
                405                 410                 415     


Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu 
            420                 425                 430         


Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln 
        435                 440                 445             


Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser 
    450                 455                 460                 


Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala 
465                 470                 475                 480 


Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly 
                485                 490                 495     


Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe 
            500                 505                 510         


Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His 
        515                 520                 525             


Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys 
    530                 535                 540                 


Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile 
545                 550                 555                 560 


Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr 
                565                 570                 575     


Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly 
            580                 585                 590         


Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro 
        595                 600                 605             


Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile 
    610                 615                 620                 


Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn 
625                 630                 635                 640 


Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His 
                645                 650                 655     


Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu 
            660                 665                 670         


Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn 
        675                 680                 685             


Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu 
    690                 695                 700                 


Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala 
705                 710                 715                 720 


Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val 
                725                 730                 735     


Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu 
            740                 745                 750         


Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser 
        755                 760                 765             


His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro 
    770                 775                 780                 


Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val 
785                 790                 795                 800 


Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys 
                805                 810                 815     


Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Lys Thr Thr 
            820                 825                 830         


Glu Asp Glu Val His Ile Cys His Asn Gln Asp Gly Tyr Ser Tyr Pro 
        835                 840                 845             


Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala 
    850                 855                 860 


<210>  20
<211>  2583
<212>  DNA
<213>  Artificial sequence

<220>
<223>  hLDLR variant H306G with leader


<220>
<221>  CDS
<222>  (1)..(2583)

<400>  20
atg ggg ccc tgg ggc tgg aaa ttg cgc tgg acc gtc gcc ttg ctc ctc         48
Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu           
1               5                   10                  15                

gcc gcg gcg ggg act gca gtg ggc gac aga tgt gaa aga aac gag ttc         96
Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe           
            20                  25                  30                    

cag tgc caa gac ggg aaa tgc atc tcc tac aag tgg gtc tgc gat ggc        144
Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly           
        35                  40                  45                        

agc gct gag tgc cag gat ggc tct gat gag tcc cag gag acg tgc ttg        192
Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu           
    50                  55                  60                            

tct gtc acc tgc aaa tcc ggg gac ttc agc tgt ggg ggc cgt gtc aac        240
Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn           
65                  70                  75                  80            

cgc tgc att cct cag ttc tgg agg tgc gat ggc caa gtg gac tgc gac        288
Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp           
                85                  90                  95                

aac ggc tca gac gag caa ggc tgt ccc ccc aag acg tgc tcc cag gac        336
Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp           
            100                 105                 110                   

gag ttt cgc tgc cac gat ggg aag tgc atc tct cgg cag ttc gtc tgt        384
Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys           
        115                 120                 125                       

gac tca gac cgg gac tgc ttg gac ggc tca gac gag gcc tcc tgc ccg        432
Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro           
    130                 135                 140                           

gtg ctc acc tgt ggt ccc gcc agc ttc cag tgc aac agc tcc acc tgc        480
Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys           
145                 150                 155                 160           

atc ccc cag ctg tgg gcc tgc gac aac gac ccc gac tgc gaa gat ggc        528
Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly           
                165                 170                 175               

tcg gat gag tgg ccg cag cgc tgt agg ggt ctt tac gtg ttc caa ggg        576
Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly           
            180                 185                 190                   

gac agt agc ccc tgc tcg gcc ttc gag ttc cac tgc cta agt ggc gag        624
Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu           
        195                 200                 205                       

tgc atc cac tcc agc tgg cgc tgt gat ggt ggc ccc gac tgc aag gac        672
Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp           
    210                 215                 220                           

aaa tct gac gag gaa aac tgc gct gtg gcc acc tgt cgc cct gac gaa        720
Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu           
225                 230                 235                 240           

ttc cag tgc tct gat gga aac tgc atc cat ggc agc cgg cag tgt gac        768
Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp           
                245                 250                 255               

cgg gaa tat gac tgc aag gac atg agc gat gaa gtt ggc tgc gtt aat        816
Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn           
            260                 265                 270                   

gtg aca ctc tgc gag gga ccc aac aag ttc aag tgt cac agc ggc gaa        864
Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu           
        275                 280                 285                       

tgc atc acc ctg gac aaa gtc tgc aac atg gct aga gac tgc cgg gac        912
Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp           
    290                 295                 300                           

tgg tca gat gaa ccc atc aaa gag tgc ggg acc aac gaa tgc ttg gac        960
Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp           
305                 310                 315                 320           

aac aac ggc ggc tgt tcc ggc gtc tgc aat gac ctt aag atc ggc tac       1008
Asn Asn Gly Gly Cys Ser Gly Val Cys Asn Asp Leu Lys Ile Gly Tyr           
                325                 330                 335               

gag tgc ctg tgc ccc gac ggc ttc cag ctg gtg gcc cag cga aga tgc       1056
Glu Cys Leu Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys           
            340                 345                 350                   

gaa gat atc gat gag tgt cag gat ccc gac acc tgc agc cag ctc tgc       1104
Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys           
        355                 360                 365                       

gtg aac ctg gag ggt ggc tac aag tgc cag tgt gag gaa ggc ttc cag       1152
Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln           
    370                 375                 380                           

ctg gac ccc cac acg aag gcc tgc aag gct gtg ggc tcc atc gcc tac       1200
Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr           
385                 390                 395                 400           

ctc ttc ttc acc aac cgg cac gag gtc agg aag atg acg ctg gac cgg       1248
Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg           
                405                 410                 415               

agc gag tac acc agc ctc atc ccc aac ctg agg aac gtg gtc gct ctg       1296
Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu           
            420                 425                 430                   

gac acg gag gtg gcc agc aat aga atc tac tgg tct gac ctg tcc cag       1344
Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln           
        435                 440                 445                       

aga atg atc tgc agc acc cag ctt gac aga gcc cac ggc gtc tct tcc       1392
Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser           
    450                 455                 460                           

tat gac acc gtc atc agc agg gac atc cag gcc ccc gac ggg ctg gct       1440
Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala           
465                 470                 475                 480           

gtg gac tgg atc cac agc aac atc tac tgg acc gac tct gtc ctg ggc       1488
Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly           
                485                 490                 495               

act gtc tct gtt gcg gat acc aag ggc gtg aag agg aaa acg tta ttc       1536
Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe           
            500                 505                 510                   

agg gag aac ggc tcc aag cca agg gcc atc gtg gtg gat cct gtt cat       1584
Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His           
        515                 520                 525                       

ggc ttc atg tac tgg act gac tgg gga act ccc gcc aag atc aag aaa       1632
Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys           
    530                 535                 540                           

ggg ggc ctg aat ggt gtg gac atc tac tcg ctg gtg act gaa aac att       1680
Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile           
545                 550                 555                 560           

cag tgg ccc aat ggc atc acc cta gat ctc ctc agt ggc cgc ctc tac       1728
Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr           
                565                 570                 575               

tgg gtt gac tcc aaa ctt cac tcc atc tca agc atc gat gtc aat ggg       1776
Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly           
            580                 585                 590                   

ggc aac cgg aag acc atc ttg gag gat gaa aag agg ctg gcc cac ccc       1824
Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro           
        595                 600                 605                       

ttc tcc ttg gcc gtc ttt gag gac aaa gta ttt tgg aca gat atc atc       1872
Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile           
    610                 615                 620                           

aac gaa gcc att ttc agt gcc aac cgc ctc aca ggt tcc gat gtc aac       1920
Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn           
625                 630                 635                 640           

ttg ttg gct gaa aac cta ctg tcc cca gag gat atg gtc ctc ttc cac       1968
Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His           
                645                 650                 655               

aac ctc acc cag cca aga gga gtg aac tgg tgt gag agg acc acc ctg       2016
Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu           
            660                 665                 670                   

agc aat ggc ggc tgc cag tat ctg tgc ctc cct gcc ccg cag atc aac       2064
Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn           
        675                 680                 685                       

ccc cac tcg ccc aag ttt acc tgc gcc tgc ccg gac ggc atg ctg ctg       2112
Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu           
    690                 695                 700                           

gcc agg gac atg agg agc tgc ctc aca gag gct gag gct gca gtg gcc       2160
Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala           
705                 710                 715                 720           

acc cag gag aca tcc acc gtc agg cta aag gtc agc tcc aca gcc gta       2208
Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val           
                725                 730                 735               

agg aca cag cac aca acc acc cgg cct gtt ccc gac acc tcc cgg ctg       2256
Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu           
            740                 745                 750                   

cct ggg gcc acc cct ggg ctc acc acg gtg gag ata gtg aca atg tct       2304
Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser           
        755                 760                 765                       

cac caa gct ctg ggc gac gtt gct ggc aga gga aat gag aag aag ccc       2352
His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro           
    770                 775                 780                           

agt agc gtg agg gct ctg tcc att gtc ctc ccc atc gtg ctc ctc gtc       2400
Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val           
785                 790                 795                 800           

ttc ctt tgc ctg ggg gtc ttc ctt cta tgg aag aac tgg cgg ctt aag       2448
Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys           
                805                 810                 815               

aac atc aac agc atc aac ttt gac aac ccc gtc tat cag aag acc aca       2496
Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Lys Thr Thr           
            820                 825                 830                   

gag gat gag gtc cac att tgc cac aac cag gac ggc tac agc tac ccc       2544
Glu Asp Glu Val His Ile Cys His Asn Gln Asp Gly Tyr Ser Tyr Pro           
        835                 840                 845                       

tcg aga cag atg gtc agt ctg gag gat gac gtg gcg tga                   2583
Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala                           
    850                 855                 860                           


<210>  21
<211>  860
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Construct

<400>  21

Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu 
1               5                   10                  15      


Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe 
            20                  25                  30          


Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly 
        35                  40                  45              


Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu 
    50                  55                  60                  


Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn 
65                  70                  75                  80  


Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp 
                85                  90                  95      


Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp 
            100                 105                 110         


Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys 
        115                 120                 125             


Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro 
    130                 135                 140                 


Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys 
145                 150                 155                 160 


Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly 
                165                 170                 175     


Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly 
            180                 185                 190         


Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu 
        195                 200                 205             


Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp 
    210                 215                 220                 


Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu 
225                 230                 235                 240 


Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp 
                245                 250                 255     


Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn 
            260                 265                 270         


Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu 
        275                 280                 285             


Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp 
    290                 295                 300                 


Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp 
305                 310                 315                 320 


Asn Asn Gly Gly Cys Ser Gly Val Cys Asn Asp Leu Lys Ile Gly Tyr 
                325                 330                 335     


Glu Cys Leu Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys 
            340                 345                 350         


Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys 
        355                 360                 365             


Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln 
    370                 375                 380                 


Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr 
385                 390                 395                 400 


Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg 
                405                 410                 415     


Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu 
            420                 425                 430         


Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln 
        435                 440                 445             


Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser 
    450                 455                 460                 


Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala 
465                 470                 475                 480 


Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly 
                485                 490                 495     


Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe 
            500                 505                 510         


Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His 
        515                 520                 525             


Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys 
    530                 535                 540                 


Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile 
545                 550                 555                 560 


Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr 
                565                 570                 575     


Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly 
            580                 585                 590         


Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro 
        595                 600                 605             


Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile 
    610                 615                 620                 


Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn 
625                 630                 635                 640 


Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His 
                645                 650                 655     


Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu 
            660                 665                 670         


Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn 
        675                 680                 685             


Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu 
    690                 695                 700                 


Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala 
705                 710                 715                 720 


Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val 
                725                 730                 735     


Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu 
            740                 745                 750         


Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser 
        755                 760                 765             


His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro 
    770                 775                 780                 


Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val 
785                 790                 795                 800 


Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys 
                805                 810                 815     


Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Lys Thr Thr 
            820                 825                 830         


Glu Asp Glu Val His Ile Cys His Asn Gln Asp Gly Tyr Ser Tyr Pro 
        835                 840                 845             


Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala 
    850                 855                 860 


<210>  22
<211>  2583
<212>  DNA
<213>  Artificial sequence

<220>
<223>  hLDLR variant L311T with leader


<220>
<221>  CDS
<222>  (1)..(2583)

<400>  22
atg ggg ccc tgg ggc tgg aaa ttg cgc tgg acc gtc gcc ttg ctc ctc         48
Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu           
1               5                   10                  15                

gcc gcg gcg ggg act gca gtg ggc gac aga tgt gaa aga aac gag ttc         96
Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe           
            20                  25                  30                    

cag tgc caa gac ggg aaa tgc atc tcc tac aag tgg gtc tgc gat ggc        144
Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly           
        35                  40                  45                        

agc gct gag tgc cag gat ggc tct gat gag tcc cag gag acg tgc ttg        192
Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu           
    50                  55                  60                            

tct gtc acc tgc aaa tcc ggg gac ttc agc tgt ggg ggc cgt gtc aac        240
Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn           
65                  70                  75                  80            

cgc tgc att cct cag ttc tgg agg tgc gat ggc caa gtg gac tgc gac        288
Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp           
                85                  90                  95                

aac ggc tca gac gag caa ggc tgt ccc ccc aag acg tgc tcc cag gac        336
Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp           
            100                 105                 110                   

gag ttt cgc tgc cac gat ggg aag tgc atc tct cgg cag ttc gtc tgt        384
Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys           
        115                 120                 125                       

gac tca gac cgg gac tgc ttg gac ggc tca gac gag gcc tcc tgc ccg        432
Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro           
    130                 135                 140                           

gtg ctc acc tgt ggt ccc gcc agc ttc cag tgc aac agc tcc acc tgc        480
Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys           
145                 150                 155                 160           

atc ccc cag ctg tgg gcc tgc gac aac gac ccc gac tgc gaa gat ggc        528
Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly           
                165                 170                 175               

tcg gat gag tgg ccg cag cgc tgt agg ggt ctt tac gtg ttc caa ggg        576
Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly           
            180                 185                 190                   

gac agt agc ccc tgc tcg gcc ttc gag ttc cac tgc cta agt ggc gag        624
Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu           
        195                 200                 205                       

tgc atc cac tcc agc tgg cgc tgt gat ggt ggc ccc gac tgc aag gac        672
Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp           
    210                 215                 220                           

aaa tct gac gag gaa aac tgc gct gtg gcc acc tgt cgc cct gac gaa        720
Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu           
225                 230                 235                 240           

ttc cag tgc tct gat gga aac tgc atc cat ggc agc cgg cag tgt gac        768
Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp           
                245                 250                 255               

cgg gaa tat gac tgc aag gac atg agc gat gaa gtt ggc tgc gtt aat        816
Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn           
            260                 265                 270                   

gtg aca ctc tgc gag gga ccc aac aag ttc aag tgt cac agc ggc gaa        864
Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu           
        275                 280                 285                       

tgc atc acc ctg gac aaa gtc tgc aac atg gct aga gac tgc cgg gac        912
Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp           
    290                 295                 300                           

tgg tca gat gaa ccc atc aaa gag tgc ggg acc aac gaa tgc ttg gac        960
Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp           
305                 310                 315                 320           

aac aac ggc ggc tgt tcc cac gtc tgc aat gac act aag atc ggc tac       1008
Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Thr Lys Ile Gly Tyr           
                325                 330                 335               

gag tgc ctg tgc ccc gac ggc ttc cag ctg gtg gcc cag cga aga tgc       1056
Glu Cys Leu Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys           
            340                 345                 350                   

gaa gat atc gat gag tgt cag gat ccc gac acc tgc agc cag ctc tgc       1104
Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys           
        355                 360                 365                       

gtg aac ctg gag ggt ggc tac aag tgc cag tgt gag gaa ggc ttc cag       1152
Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln           
    370                 375                 380                           

ctg gac ccc cac acg aag gcc tgc aag gct gtg ggc tcc atc gcc tac       1200
Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr           
385                 390                 395                 400           

ctc ttc ttc acc aac cgg cac gag gtc agg aag atg acg ctg gac cgg       1248
Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg           
                405                 410                 415               

agc gag tac acc agc ctc atc ccc aac ctg agg aac gtg gtc gct ctg       1296
Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu           
            420                 425                 430                   

gac acg gag gtg gcc agc aat aga atc tac tgg tct gac ctg tcc cag       1344
Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln           
        435                 440                 445                       

aga atg atc tgc agc acc cag ctt gac aga gcc cac ggc gtc tct tcc       1392
Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser           
    450                 455                 460                           

tat gac acc gtc atc agc agg gac atc cag gcc ccc gac ggg ctg gct       1440
Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala           
465                 470                 475                 480           

gtg gac tgg atc cac agc aac atc tac tgg acc gac tct gtc ctg ggc       1488
Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly           
                485                 490                 495               

act gtc tct gtt gcg gat acc aag ggc gtg aag agg aaa acg tta ttc       1536
Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe           
            500                 505                 510                   

agg gag aac ggc tcc aag cca agg gcc atc gtg gtg gat cct gtt cat       1584
Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His           
        515                 520                 525                       

ggc ttc atg tac tgg act gac tgg gga act ccc gcc aag atc aag aaa       1632
Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys           
    530                 535                 540                           

ggg ggc ctg aat ggt gtg gac atc tac tcg ctg gtg act gaa aac att       1680
Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile           
545                 550                 555                 560           

cag tgg ccc aat ggc atc acc cta gat ctc ctc agt ggc cgc ctc tac       1728
Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr           
                565                 570                 575               

tgg gtt gac tcc aaa ctt cac tcc atc tca agc atc gat gtc aat ggg       1776
Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly           
            580                 585                 590                   

ggc aac cgg aag acc atc ttg gag gat gaa aag agg ctg gcc cac ccc       1824
Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro           
        595                 600                 605                       

ttc tcc ttg gcc gtc ttt gag gac aaa gta ttt tgg aca gat atc atc       1872
Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile           
    610                 615                 620                           

aac gaa gcc att ttc agt gcc aac cgc ctc aca ggt tcc gat gtc aac       1920
Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn           
625                 630                 635                 640           

ttg ttg gct gaa aac cta ctg tcc cca gag gat atg gtc ctc ttc cac       1968
Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His           
                645                 650                 655               

aac ctc acc cag cca aga gga gtg aac tgg tgt gag agg acc acc ctg       2016
Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu           
            660                 665                 670                   

agc aat ggc ggc tgc cag tat ctg tgc ctc cct gcc ccg cag atc aac       2064
Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn           
        675                 680                 685                       

ccc cac tcg ccc aag ttt acc tgc gcc tgc ccg gac ggc atg ctg ctg       2112
Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu           
    690                 695                 700                           

gcc agg gac atg agg agc tgc ctc aca gag gct gag gct gca gtg gcc       2160
Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala           
705                 710                 715                 720           

acc cag gag aca tcc acc gtc agg cta aag gtc agc tcc aca gcc gta       2208
Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val           
                725                 730                 735               

agg aca cag cac aca acc acc cgg cct gtt ccc gac acc tcc cgg ctg       2256
Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu           
            740                 745                 750                   

cct ggg gcc acc cct ggg ctc acc acg gtg gag ata gtg aca atg tct       2304
Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser           
        755                 760                 765                       

cac caa gct ctg ggc gac gtt gct ggc aga gga aat gag aag aag ccc       2352
His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro           
    770                 775                 780                           

agt agc gtg agg gct ctg tcc att gtc ctc ccc atc gtg ctc ctc gtc       2400
Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val           
785                 790                 795                 800           

ttc ctt tgc ctg ggg gtc ttc ctt cta tgg aag aac tgg cgg ctt aag       2448
Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys           
                805                 810                 815               

aac atc aac agc atc aac ttt gac aac ccc gtc tat cag aag acc aca       2496
Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Lys Thr Thr           
            820                 825                 830                   

gag gat gag gtc cac att tgc cac aac cag gac ggc tac agc tac ccc       2544
Glu Asp Glu Val His Ile Cys His Asn Gln Asp Gly Tyr Ser Tyr Pro           
        835                 840                 845                       

tcg aga cag atg gtc agt ctg gag gat gac gtg gcg tga                   2583
Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala                           
    850                 855                 860                           


<210>  23
<211>  860
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Construct

<400>  23

Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu 
1               5                   10                  15      


Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe 
            20                  25                  30          


Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly 
        35                  40                  45              


Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu 
    50                  55                  60                  


Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn 
65                  70                  75                  80  


Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp 
                85                  90                  95      


Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp 
            100                 105                 110         


Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys 
        115                 120                 125             


Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro 
    130                 135                 140                 


Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys 
145                 150                 155                 160 


Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly 
                165                 170                 175     


Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly 
            180                 185                 190         


Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu 
        195                 200                 205             


Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp 
    210                 215                 220                 


Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu 
225                 230                 235                 240 


Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp 
                245                 250                 255     


Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn 
            260                 265                 270         


Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu 
        275                 280                 285             


Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp 
    290                 295                 300                 


Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp 
305                 310                 315                 320 


Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Thr Lys Ile Gly Tyr 
                325                 330                 335     


Glu Cys Leu Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys 
            340                 345                 350         


Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys 
        355                 360                 365             


Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln 
    370                 375                 380                 


Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr 
385                 390                 395                 400 


Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg 
                405                 410                 415     


Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu 
            420                 425                 430         


Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln 
        435                 440                 445             


Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser 
    450                 455                 460                 


Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala 
465                 470                 475                 480 


Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly 
                485                 490                 495     


Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe 
            500                 505                 510         


Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His 
        515                 520                 525             


Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys 
    530                 535                 540                 


Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile 
545                 550                 555                 560 


Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr 
                565                 570                 575     


Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly 
            580                 585                 590         


Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro 
        595                 600                 605             


Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile 
    610                 615                 620                 


Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn 
625                 630                 635                 640 


Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His 
                645                 650                 655     


Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu 
            660                 665                 670         


Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn 
        675                 680                 685             


Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu 
    690                 695                 700                 


Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala 
705                 710                 715                 720 


Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val 
                725                 730                 735     


Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu 
            740                 745                 750         


Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser 
        755                 760                 765             


His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro 
    770                 775                 780                 


Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val 
785                 790                 795                 800 


Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys 
                805                 810                 815     


Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Lys Thr Thr 
            820                 825                 830         


Glu Asp Glu Val His Ile Cys His Asn Gln Asp Gly Tyr Ser Tyr Pro 
        835                 840                 845             


Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala 
    850                 855                 860 


<210>  24
<211>  2583
<212>  DNA
<213>  Artificial sequence

<220>
<223>  hLDLR variant L318D with leader


<220>
<221>  CDS
<222>  (1)..(2583)

<400>  24
atg ggg ccc tgg ggc tgg aaa ttg cgc tgg acc gtc gcc ttg ctc ctc         48
Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu           
1               5                   10                  15                

gcc gcg gcg ggg act gca gtg ggc gac aga tgt gaa aga aac gag ttc         96
Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe           
            20                  25                  30                    

cag tgc caa gac ggg aaa tgc atc tcc tac aag tgg gtc tgc gat ggc        144
Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly           
        35                  40                  45                        

agc gct gag tgc cag gat ggc tct gat gag tcc cag gag acg tgc ttg        192
Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu           
    50                  55                  60                            

tct gtc acc tgc aaa tcc ggg gac ttc agc tgt ggg ggc cgt gtc aac        240
Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn           
65                  70                  75                  80            

cgc tgc att cct cag ttc tgg agg tgc gat ggc caa gtg gac tgc gac        288
Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp           
                85                  90                  95                

aac ggc tca gac gag caa ggc tgt ccc ccc aag acg tgc tcc cag gac        336
Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp           
            100                 105                 110                   

gag ttt cgc tgc cac gat ggg aag tgc atc tct cgg cag ttc gtc tgt        384
Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys           
        115                 120                 125                       

gac tca gac cgg gac tgc ttg gac ggc tca gac gag gcc tcc tgc ccg        432
Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro           
    130                 135                 140                           

gtg ctc acc tgt ggt ccc gcc agc ttc cag tgc aac agc tcc acc tgc        480
Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys           
145                 150                 155                 160           

atc ccc cag ctg tgg gcc tgc gac aac gac ccc gac tgc gaa gat ggc        528
Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly           
                165                 170                 175               

tcg gat gag tgg ccg cag cgc tgt agg ggt ctt tac gtg ttc caa ggg        576
Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly           
            180                 185                 190                   

gac agt agc ccc tgc tcg gcc ttc gag ttc cac tgc cta agt ggc gag        624
Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu           
        195                 200                 205                       

tgc atc cac tcc agc tgg cgc tgt gat ggt ggc ccc gac tgc aag gac        672
Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp           
    210                 215                 220                           

aaa tct gac gag gaa aac tgc gct gtg gcc acc tgt cgc cct gac gaa        720
Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu           
225                 230                 235                 240           

ttc cag tgc tct gat gga aac tgc atc cat ggc agc cgg cag tgt gac        768
Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp           
                245                 250                 255               

cgg gaa tat gac tgc aag gac atg agc gat gaa gtt ggc tgc gtt aat        816
Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn           
            260                 265                 270                   

gtg aca ctc tgc gag gga ccc aac aag ttc aag tgt cac agc ggc gaa        864
Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu           
        275                 280                 285                       

tgc atc acc ctg gac aaa gtc tgc aac atg gct aga gac tgc cgg gac        912
Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp           
    290                 295                 300                           

tgg tca gat gaa ccc atc aaa gag tgc ggg acc aac gaa tgc ttg gac        960
Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp           
305                 310                 315                 320           

aac aac ggc ggc tgt tcc cac gtc tgc aat gac ctt aag atc ggc tac       1008
Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Leu Lys Ile Gly Tyr           
                325                 330                 335               

gag tgc gac tgc ccc gac ggc ttc cag ctg gtg gcc cag cga aga tgc       1056
Glu Cys Asp Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys           
            340                 345                 350                   

gaa gat atc gat gag tgt cag gat ccc gac acc tgc agc cag ctc tgc       1104
Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys           
        355                 360                 365                       

gtg aac ctg gag ggt ggc tac aag tgc cag tgt gag gaa ggc ttc cag       1152
Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln           
    370                 375                 380                           

ctg gac ccc cac acg aag gcc tgc aag gct gtg ggc tcc atc gcc tac       1200
Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr           
385                 390                 395                 400           

ctc ttc ttc acc aac cgg cac gag gtc agg aag atg acg ctg gac cgg       1248
Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg           
                405                 410                 415               

agc gag tac acc agc ctc atc ccc aac ctg agg aac gtg gtc gct ctg       1296
Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu           
            420                 425                 430                   

gac acg gag gtg gcc agc aat aga atc tac tgg tct gac ctg tcc cag       1344
Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln           
        435                 440                 445                       

aga atg atc tgc agc acc cag ctt gac aga gcc cac ggc gtc tct tcc       1392
Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser           
    450                 455                 460                           

tat gac acc gtc atc agc agg gac atc cag gcc ccc gac ggg ctg gct       1440
Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala           
465                 470                 475                 480           

gtg gac tgg atc cac agc aac atc tac tgg acc gac tct gtc ctg ggc       1488
Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly           
                485                 490                 495               

act gtc tct gtt gcg gat acc aag ggc gtg aag agg aaa acg tta ttc       1536
Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe           
            500                 505                 510                   

agg gag aac ggc tcc aag cca agg gcc atc gtg gtg gat cct gtt cat       1584
Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His           
        515                 520                 525                       

ggc ttc atg tac tgg act gac tgg gga act ccc gcc aag atc aag aaa       1632
Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys           
    530                 535                 540                           

ggg ggc ctg aat ggt gtg gac atc tac tcg ctg gtg act gaa aac att       1680
Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile           
545                 550                 555                 560           

cag tgg ccc aat ggc atc acc cta gat ctc ctc agt ggc cgc ctc tac       1728
Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr           
                565                 570                 575               

tgg gtt gac tcc aaa ctt cac tcc atc tca agc atc gat gtc aat ggg       1776
Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly           
            580                 585                 590                   

ggc aac cgg aag acc atc ttg gag gat gaa aag agg ctg gcc cac ccc       1824
Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro           
        595                 600                 605                       

ttc tcc ttg gcc gtc ttt gag gac aaa gta ttt tgg aca gat atc atc       1872
Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile           
    610                 615                 620                           

aac gaa gcc att ttc agt gcc aac cgc ctc aca ggt tcc gat gtc aac       1920
Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn           
625                 630                 635                 640           

ttg ttg gct gaa aac cta ctg tcc cca gag gat atg gtc ctc ttc cac       1968
Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His           
                645                 650                 655               

aac ctc acc cag cca aga gga gtg aac tgg tgt gag agg acc acc ctg       2016
Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu           
            660                 665                 670                   

agc aat ggc ggc tgc cag tat ctg tgc ctc cct gcc ccg cag atc aac       2064
Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn           
        675                 680                 685                       

ccc cac tcg ccc aag ttt acc tgc gcc tgc ccg gac ggc atg ctg ctg       2112
Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu           
    690                 695                 700                           

gcc agg gac atg agg agc tgc ctc aca gag gct gag gct gca gtg gcc       2160
Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala           
705                 710                 715                 720           

acc cag gag aca tcc acc gtc agg cta aag gtc agc tcc aca gcc gta       2208
Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val           
                725                 730                 735               

agg aca cag cac aca acc acc cgg cct gtt ccc gac acc tcc cgg ctg       2256
Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu           
            740                 745                 750                   

cct ggg gcc acc cct ggg ctc acc acg gtg gag ata gtg aca atg tct       2304
Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser           
        755                 760                 765                       

cac caa gct ctg ggc gac gtt gct ggc aga gga aat gag aag aag ccc       2352
His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro           
    770                 775                 780                           

agt agc gtg agg gct ctg tcc att gtc ctc ccc atc gtg ctc ctc gtc       2400
Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val           
785                 790                 795                 800           

ttc ctt tgc ctg ggg gtc ttc ctt cta tgg aag aac tgg cgg ctt aag       2448
Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys           
                805                 810                 815               

aac atc aac agc atc aac ttt gac aac ccc gtc tat cag aag acc aca       2496
Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Lys Thr Thr           
            820                 825                 830                   

gag gat gag gtc cac att tgc cac aac cag gac ggc tac agc tac ccc       2544
Glu Asp Glu Val His Ile Cys His Asn Gln Asp Gly Tyr Ser Tyr Pro           
        835                 840                 845                       

tcg aga cag atg gtc agt ctg gag gat gac gtg gcg tga                   2583
Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala                           
    850                 855                 860                           


<210>  25
<211>  860
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Construct

<400>  25

Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu 
1               5                   10                  15      


Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe 
            20                  25                  30          


Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly 
        35                  40                  45              


Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu 
    50                  55                  60                  


Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn 
65                  70                  75                  80  


Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp 
                85                  90                  95      


Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp 
            100                 105                 110         


Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys 
        115                 120                 125             


Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro 
    130                 135                 140                 


Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys 
145                 150                 155                 160 


Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly 
                165                 170                 175     


Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly 
            180                 185                 190         


Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu 
        195                 200                 205             


Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp 
    210                 215                 220                 


Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu 
225                 230                 235                 240 


Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp 
                245                 250                 255     


Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn 
            260                 265                 270         


Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu 
        275                 280                 285             


Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp 
    290                 295                 300                 


Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp 
305                 310                 315                 320 


Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Leu Lys Ile Gly Tyr 
                325                 330                 335     


Glu Cys Asp Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys 
            340                 345                 350         


Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys 
        355                 360                 365             


Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln 
    370                 375                 380                 


Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr 
385                 390                 395                 400 


Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg 
                405                 410                 415     


Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu 
            420                 425                 430         


Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln 
        435                 440                 445             


Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser 
    450                 455                 460                 


Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala 
465                 470                 475                 480 


Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly 
                485                 490                 495     


Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe 
            500                 505                 510         


Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His 
        515                 520                 525             


Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys 
    530                 535                 540                 


Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile 
545                 550                 555                 560 


Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr 
                565                 570                 575     


Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly 
            580                 585                 590         


Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro 
        595                 600                 605             


Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile 
    610                 615                 620                 


Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn 
625                 630                 635                 640 


Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His 
                645                 650                 655     


Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu 
            660                 665                 670         


Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn 
        675                 680                 685             


Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu 
    690                 695                 700                 


Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala 
705                 710                 715                 720 


Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val 
                725                 730                 735     


Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu 
            740                 745                 750         


Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser 
        755                 760                 765             


His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro 
    770                 775                 780                 


Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val 
785                 790                 795                 800 


Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys 
                805                 810                 815     


Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Lys Thr Thr 
            820                 825                 830         


Glu Asp Glu Val His Ile Cys His Asn Gln Asp Gly Tyr Ser Tyr Pro 
        835                 840                 845             


Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala 
    850                 855                 860 


<210>  26
<211>  2583
<212>  DNA
<213>  Artificial sequence

<220>
<223>  hLDLR varient L318H with leader


<220>
<221>  CDS
<222>  (1)..(2583)

<400>  26
atg ggg ccc tgg ggc tgg aaa ttg cgc tgg acc gtc gcc ttg ctc ctc         48
Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu           
1               5                   10                  15                

gcc gcg gcg ggg act gca gtg ggc gac aga tgt gaa aga aac gag ttc         96
Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe           
            20                  25                  30                    

cag tgc caa gac ggg aaa tgc atc tcc tac aag tgg gtc tgc gat ggc        144
Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly           
        35                  40                  45                        

agc gct gag tgc cag gat ggc tct gat gag tcc cag gag acg tgc ttg        192
Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu           
    50                  55                  60                            

tct gtc acc tgc aaa tcc ggg gac ttc agc tgt ggg ggc cgt gtc aac        240
Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn           
65                  70                  75                  80            

cgc tgc att cct cag ttc tgg agg tgc gat ggc caa gtg gac tgc gac        288
Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp           
                85                  90                  95                

aac ggc tca gac gag caa ggc tgt ccc ccc aag acg tgc tcc cag gac        336
Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp           
            100                 105                 110                   

gag ttt cgc tgc cac gat ggg aag tgc atc tct cgg cag ttc gtc tgt        384
Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys           
        115                 120                 125                       

gac tca gac cgg gac tgc ttg gac ggc tca gac gag gcc tcc tgc ccg        432
Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro           
    130                 135                 140                           

gtg ctc acc tgt ggt ccc gcc agc ttc cag tgc aac agc tcc acc tgc        480
Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys           
145                 150                 155                 160           

atc ccc cag ctg tgg gcc tgc gac aac gac ccc gac tgc gaa gat ggc        528
Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly           
                165                 170                 175               

tcg gat gag tgg ccg cag cgc tgt agg ggt ctt tac gtg ttc caa ggg        576
Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly           
            180                 185                 190                   

gac agt agc ccc tgc tcg gcc ttc gag ttc cac tgc cta agt ggc gag        624
Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu           
        195                 200                 205                       

tgc atc cac tcc agc tgg cgc tgt gat ggt ggc ccc gac tgc aag gac        672
Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp           
    210                 215                 220                           

aaa tct gac gag gaa aac tgc gct gtg gcc acc tgt cgc cct gac gaa        720
Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu           
225                 230                 235                 240           

ttc cag tgc tct gat gga aac tgc atc cat ggc agc cgg cag tgt gac        768
Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp           
                245                 250                 255               

cgg gaa tat gac tgc aag gac atg agc gat gaa gtt ggc tgc gtt aat        816
Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn           
            260                 265                 270                   

gtg aca ctc tgc gag gga ccc aac aag ttc aag tgt cac agc ggc gaa        864
Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu           
        275                 280                 285                       

tgc atc acc ctg gac aaa gtc tgc aac atg gct aga gac tgc cgg gac        912
Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp           
    290                 295                 300                           

tgg tca gat gaa ccc atc aaa gag tgc ggg acc aac gaa tgc ttg gac        960
Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp           
305                 310                 315                 320           

aac aac ggc ggc tgt tcc cac gtc tgc aat gac ctt aag atc ggc tac       1008
Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Leu Lys Ile Gly Tyr           
                325                 330                 335               

gag tgc gac tgc ccc gac ggc ttc cag ctg gtg gcc cag cga aga tgc       1056
Glu Cys Asp Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys           
            340                 345                 350                   

gaa gat atc gat gag tgt cag gat ccc gac acc tgc agc cag ctc tgc       1104
Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys           
        355                 360                 365                       

gtg aac ctg gag ggt ggc tac aag tgc cag tgt gag gaa ggc ttc cag       1152
Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln           
    370                 375                 380                           

ctg gac ccc cac acg aag gcc tgc aag gct gtg ggc tcc atc gcc tac       1200
Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr           
385                 390                 395                 400           

ctc ttc ttc acc aac cgg cac gag gtc agg aag atg acg ctg gac cgg       1248
Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg           
                405                 410                 415               

agc gag tac acc agc ctc atc ccc aac ctg agg aac gtg gtc gct ctg       1296
Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu           
            420                 425                 430                   

gac acg gag gtg gcc agc aat aga atc tac tgg tct gac ctg tcc cag       1344
Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln           
        435                 440                 445                       

aga atg atc tgc agc acc cag ctt gac aga gcc cac ggc gtc tct tcc       1392
Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser           
    450                 455                 460                           

tat gac acc gtc atc agc agg gac atc cag gcc ccc gac ggg ctg gct       1440
Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala           
465                 470                 475                 480           

gtg gac tgg atc cac agc aac atc tac tgg acc gac tct gtc ctg ggc       1488
Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly           
                485                 490                 495               

act gtc tct gtt gcg gat acc aag ggc gtg aag agg aaa acg tta ttc       1536
Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe           
            500                 505                 510                   

agg gag aac ggc tcc aag cca agg gcc atc gtg gtg gat cct gtt cat       1584
Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His           
        515                 520                 525                       

ggc ttc atg tac tgg act gac tgg gga act ccc gcc aag atc aag aaa       1632
Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys           
    530                 535                 540                           

ggg ggc ctg aat ggt gtg gac atc tac tcg ctg gtg act gaa aac att       1680
Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile           
545                 550                 555                 560           

cag tgg ccc aat ggc atc acc cta gat ctc ctc agt ggc cgc ctc tac       1728
Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr           
                565                 570                 575               

tgg gtt gac tcc aaa ctt cac tcc atc tca agc atc gat gtc aat ggg       1776
Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly           
            580                 585                 590                   

ggc aac cgg aag acc atc ttg gag gat gaa aag agg ctg gcc cac ccc       1824
Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro           
        595                 600                 605                       

ttc tcc ttg gcc gtc ttt gag gac aaa gta ttt tgg aca gat atc atc       1872
Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile           
    610                 615                 620                           

aac gaa gcc att ttc agt gcc aac cgc ctc aca ggt tcc gat gtc aac       1920
Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn           
625                 630                 635                 640           

ttg ttg gct gaa aac cta ctg tcc cca gag gat atg gtc ctc ttc cac       1968
Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His           
                645                 650                 655               

aac ctc acc cag cca aga gga gtg aac tgg tgt gag agg acc acc ctg       2016
Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu           
            660                 665                 670                   

agc aat ggc ggc tgc cag tat ctg tgc ctc cct gcc ccg cag atc aac       2064
Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn           
        675                 680                 685                       

ccc cac tcg ccc aag ttt acc tgc gcc tgc ccg gac ggc atg ctg ctg       2112
Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu           
    690                 695                 700                           

gcc agg gac atg agg agc tgc ctc aca gag gct gag gct gca gtg gcc       2160
Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala           
705                 710                 715                 720           

acc cag gag aca tcc acc gtc agg cta aag gtc agc tcc aca gcc gta       2208
Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val           
                725                 730                 735               

agg aca cag cac aca acc acc cgg cct gtt ccc gac acc tcc cgg ctg       2256
Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu           
            740                 745                 750                   

cct ggg gcc acc cct ggg ctc acc acg gtg gag ata gtg aca atg tct       2304
Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser           
        755                 760                 765                       

cac caa gct ctg ggc gac gtt gct ggc aga gga aat gag aag aag ccc       2352
His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro           
    770                 775                 780                           

agt agc gtg agg gct ctg tcc att gtc ctc ccc atc gtg ctc ctc gtc       2400
Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val           
785                 790                 795                 800           

ttc ctt tgc ctg ggg gtc ttc ctt cta tgg aag aac tgg cgg ctt aag       2448
Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys           
                805                 810                 815               

aac atc aac agc atc aac ttt gac aac ccc gtc tat cag aag acc aca       2496
Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Lys Thr Thr           
            820                 825                 830                   

gag gat gag gtc cac att tgc cac aac cag gac ggc tac agc tac ccc       2544
Glu Asp Glu Val His Ile Cys His Asn Gln Asp Gly Tyr Ser Tyr Pro           
        835                 840                 845                       

tcg aga cag atg gtc agt ctg gag gat gac gtg gcg tga                   2583
Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala                           
    850                 855                 860                           


<210>  27
<211>  860
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Construct

<400>  27

Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu 
1               5                   10                  15      


Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe 
            20                  25                  30          


Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly 
        35                  40                  45              


Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu 
    50                  55                  60                  


Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn 
65                  70                  75                  80  


Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp 
                85                  90                  95      


Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp 
            100                 105                 110         


Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys 
        115                 120                 125             


Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro 
    130                 135                 140                 


Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys 
145                 150                 155                 160 


Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly 
                165                 170                 175     


Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly 
            180                 185                 190         


Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu 
        195                 200                 205             


Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp 
    210                 215                 220                 


Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu 
225                 230                 235                 240 


Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp 
                245                 250                 255     


Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn 
            260                 265                 270         


Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu 
        275                 280                 285             


Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp 
    290                 295                 300                 


Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp 
305                 310                 315                 320 


Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Leu Lys Ile Gly Tyr 
                325                 330                 335     


Glu Cys Asp Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys 
            340                 345                 350         


Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys 
        355                 360                 365             


Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln 
    370                 375                 380                 


Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr 
385                 390                 395                 400 


Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg 
                405                 410                 415     


Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu 
            420                 425                 430         


Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln 
        435                 440                 445             


Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser 
    450                 455                 460                 


Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala 
465                 470                 475                 480 


Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly 
                485                 490                 495     


Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe 
            500                 505                 510         


Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His 
        515                 520                 525             


Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys 
    530                 535                 540                 


Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile 
545                 550                 555                 560 


Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr 
                565                 570                 575     


Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly 
            580                 585                 590         


Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro 
        595                 600                 605             


Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile 
    610                 615                 620                 


Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn 
625                 630                 635                 640 


Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His 
                645                 650                 655     


Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu 
            660                 665                 670         


Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn 
        675                 680                 685             


Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu 
    690                 695                 700                 


Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala 
705                 710                 715                 720 


Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val 
                725                 730                 735     


Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu 
            740                 745                 750         


Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser 
        755                 760                 765             


His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro 
    770                 775                 780                 


Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val 
785                 790                 795                 800 


Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys 
                805                 810                 815     


Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Lys Thr Thr 
            820                 825                 830         


Glu Asp Glu Val His Ile Cys His Asn Gln Asp Gly Tyr Ser Tyr Pro 
        835                 840                 845             


Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala 
    850                 855                 860 


<210>  28
<211>  2583
<212>  DNA
<213>  Artificial sequence with leader sequence

<220>
<223>  hLDLR N295D with leader


<220>
<221>  CDS
<222>  (1)..(2583)

<400>  28
atg ggg ccc tgg ggc tgg aaa ttg cgc tgg acc gtc gcc ttg ctc ctc         48
Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu           
1               5                   10                  15                

gcc gcg gcg ggg act gca gtg ggc gac aga tgt gaa aga aac gag ttc         96
Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe           
            20                  25                  30                    

cag tgc caa gac ggg aaa tgc atc tcc tac aag tgg gtc tgc gat ggc        144
Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly           
        35                  40                  45                        

agc gct gag tgc cag gat ggc tct gat gag tcc cag gag acg tgc ttg        192
Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu           
    50                  55                  60                            

tct gtc acc tgc aaa tcc ggg gac ttc agc tgt ggg ggc cgt gtc aac        240
Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn           
65                  70                  75                  80            

cgc tgc att cct cag ttc tgg agg tgc gat ggc caa gtg gac tgc gac        288
Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp           
                85                  90                  95                

aac ggc tca gac gag caa ggc tgt ccc ccc aag acg tgc tcc cag gac        336
Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp           
            100                 105                 110                   

gag ttt cgc tgc cac gat ggg aag tgc atc tct cgg cag ttc gtc tgt        384
Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys           
        115                 120                 125                       

gac tca gac cgg gac tgc ttg gac ggc tca gac gag gcc tcc tgc ccg        432
Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro           
    130                 135                 140                           

gtg ctc acc tgt ggt ccc gcc agc ttc cag tgc aac agc tcc acc tgc        480
Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys           
145                 150                 155                 160           

atc ccc cag ctg tgg gcc tgc gac aac gac ccc gac tgc gaa gat ggc        528
Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly           
                165                 170                 175               

tcg gat gag tgg ccg cag cgc tgt agg ggt ctt tac gtg ttc caa ggg        576
Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly           
            180                 185                 190                   

gac agt agc ccc tgc tcg gcc ttc gag ttc cac tgc cta agt ggc gag        624
Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu           
        195                 200                 205                       

tgc atc cac tcc agc tgg cgc tgt gat ggt ggc ccc gac tgc aag gac        672
Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp           
    210                 215                 220                           

aaa tct gac gag gaa aac tgc gct gtg gcc acc tgt cgc cct gac gaa        720
Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu           
225                 230                 235                 240           

ttc cag tgc tct gat gga aac tgc atc cat ggc agc cgg cag tgt gac        768
Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp           
                245                 250                 255               

cgg gaa tat gac tgc aag gac atg agc gat gaa gtt ggc tgc gtt aat        816
Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn           
            260                 265                 270                   

gtg aca ctc tgc gag gga ccc aac aag ttc aag tgt cac agc ggc gaa        864
Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu           
        275                 280                 285                       

tgc atc acc ctg gac aaa gtc tgc aac atg gct aga gac tgc cgg gac        912
Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp           
    290                 295                 300                           

tgg tca gat gaa ccc atc aaa gag tgc ggg acc gac gaa tgc ttg gac        960
Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asp Glu Cys Leu Asp           
305                 310                 315                 320           

aac aac ggc ggc tgt tcc cac gtc tgc aat gac ctt aag atc ggc tac       1008
Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Leu Lys Ile Gly Tyr           
                325                 330                 335               

gag tgc ctg tgc ccc gac ggc ttc cag ctg gtg gcc cag cga aga tgc       1056
Glu Cys Leu Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys           
            340                 345                 350                   

gaa gat atc gat gag tgt cag gat ccc gac acc tgc agc cag ctc tgc       1104
Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys           
        355                 360                 365                       

gtg aac ctg gag ggt ggc tac aag tgc cag tgt gag gaa ggc ttc cag       1152
Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln           
    370                 375                 380                           

ctg gac ccc cac acg aag gcc tgc aag gct gtg ggc tcc atc gcc tac       1200
Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr           
385                 390                 395                 400           

ctc ttc ttc acc aac cgg cac gag gtc agg aag atg acg ctg gac cgg       1248
Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg           
                405                 410                 415               

agc gag tac acc agc ctc atc ccc aac ctg agg aac gtg gtc gct ctg       1296
Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu           
            420                 425                 430                   

gac acg gag gtg gcc agc aat aga atc tac tgg tct gac ctg tcc cag       1344
Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln           
        435                 440                 445                       

aga atg atc tgc agc acc cag ctt gac aga gcc cac ggc gtc tct tcc       1392
Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser           
    450                 455                 460                           

tat gac acc gtc atc agc agg gac atc cag gcc ccc gac ggg ctg gct       1440
Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala           
465                 470                 475                 480           

gtg gac tgg atc cac agc aac atc tac tgg acc gac tct gtc ctg ggc       1488
Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly           
                485                 490                 495               

act gtc tct gtt gcg gat acc aag ggc gtg aag agg aaa acg tta ttc       1536
Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe           
            500                 505                 510                   

agg gag aac ggc tcc aag cca agg gcc atc gtg gtg gat cct gtt cat       1584
Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His           
        515                 520                 525                       

ggc ttc atg tac tgg act gac tgg gga act ccc gcc aag atc aag aaa       1632
Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys           
    530                 535                 540                           

ggg ggc ctg aat ggt gtg gac atc tac tcg ctg gtg act gaa aac att       1680
Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile           
545                 550                 555                 560           

cag tgg ccc aat ggc atc acc cta gat ctc ctc agt ggc cgc ctc tac       1728
Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr           
                565                 570                 575               

tgg gtt gac tcc aaa ctt cac tcc atc tca agc atc gat gtc aat ggg       1776
Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly           
            580                 585                 590                   

ggc aac cgg aag acc atc ttg gag gat gaa aag agg ctg gcc cac ccc       1824
Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro           
        595                 600                 605                       

ttc tcc ttg gcc gtc ttt gag gac aaa gta ttt tgg aca gat atc atc       1872
Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile           
    610                 615                 620                           

aac gaa gcc att ttc agt gcc aac cgc ctc aca ggt tcc gat gtc aac       1920
Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn           
625                 630                 635                 640           

ttg ttg gct gaa aac cta ctg tcc cca gag gat atg gtc ctc ttc cac       1968
Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His           
                645                 650                 655               

aac ctc acc cag cca aga gga gtg aac tgg tgt gag agg acc acc ctg       2016
Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu           
            660                 665                 670                   

agc aat ggc ggc tgc cag tat ctg tgc ctc cct gcc ccg cag atc aac       2064
Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn           
        675                 680                 685                       

ccc cac tcg ccc aag ttt acc tgc gcc tgc ccg gac ggc atg ctg ctg       2112
Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu           
    690                 695                 700                           

gcc agg gac atg agg agc tgc ctc aca gag gct gag gct gca gtg gcc       2160
Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala           
705                 710                 715                 720           

acc cag gag aca tcc acc gtc agg cta aag gtc agc tcc aca gcc gta       2208
Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val           
                725                 730                 735               

agg aca cag cac aca acc acc cgg cct gtt ccc gac acc tcc cgg ctg       2256
Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu           
            740                 745                 750                   

cct ggg gcc acc cct ggg ctc acc acg gtg gag ata gtg aca atg tct       2304
Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser           
        755                 760                 765                       

cac caa gct ctg ggc gac gtt gct ggc aga gga aat gag aag aag ccc       2352
His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro           
    770                 775                 780                           

agt agc gtg agg gct ctg tcc att gtc ctc ccc atc gtg ctc ctc gtc       2400
Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val           
785                 790                 795                 800           

ttc ctt tgc ctg ggg gtc ttc ctt cta tgg aag aac tgg cgg ctt aag       2448
Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys           
                805                 810                 815               

aac atc aac agc atc aac ttt gac aac ccc gtc tat cag aag acc aca       2496
Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Lys Thr Thr           
            820                 825                 830                   

gag gat gag gtc cac att tgc cac aac cag gac ggc tac agc tac ccc       2544
Glu Asp Glu Val His Ile Cys His Asn Gln Asp Gly Tyr Ser Tyr Pro           
        835                 840                 845                       

tcg aga cag atg gtc agt ctg gag gat gac gtg gcg tga                   2583
Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala                           
    850                 855                 860                           


<210>  29
<211>  860
<212>  PRT
<213>  Artificial sequence with leader sequence

<220>
<223>  Synthetic Construct

<400>  29

Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu 
1               5                   10                  15      


Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe 
            20                  25                  30          


Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly 
        35                  40                  45              


Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu 
    50                  55                  60                  


Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn 
65                  70                  75                  80  


Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp 
                85                  90                  95      


Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp 
            100                 105                 110         


Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys 
        115                 120                 125             


Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro 
    130                 135                 140                 


Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys 
145                 150                 155                 160 


Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly 
                165                 170                 175     


Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly 
            180                 185                 190         


Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu 
        195                 200                 205             


Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp 
    210                 215                 220                 


Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu 
225                 230                 235                 240 


Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp 
                245                 250                 255     


Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn 
            260                 265                 270         


Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu 
        275                 280                 285             


Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp 
    290                 295                 300                 


Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asp Glu Cys Leu Asp 
305                 310                 315                 320 


Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Leu Lys Ile Gly Tyr 
                325                 330                 335     


Glu Cys Leu Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys 
            340                 345                 350         


Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys 
        355                 360                 365             


Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln 
    370                 375                 380                 


Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr 
385                 390                 395                 400 


Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg 
                405                 410                 415     


Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu 
            420                 425                 430         


Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln 
        435                 440                 445             


Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser 
    450                 455                 460                 


Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala 
465                 470                 475                 480 


Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly 
                485                 490                 495     


Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe 
            500                 505                 510         


Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His 
        515                 520                 525             


Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys 
    530                 535                 540                 


Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile 
545                 550                 555                 560 


Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr 
                565                 570                 575     


Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly 
            580                 585                 590         


Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro 
        595                 600                 605             


Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile 
    610                 615                 620                 


Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn 
625                 630                 635                 640 


Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His 
                645                 650                 655     


Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu 
            660                 665                 670         


Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn 
        675                 680                 685             


Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu 
    690                 695                 700                 


Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala 
705                 710                 715                 720 


Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val 
                725                 730                 735     


Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu 
            740                 745                 750         


Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser 
        755                 760                 765             


His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro 
    770                 775                 780                 


Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val 
785                 790                 795                 800 


Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys 
                805                 810                 815     


Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Lys Thr Thr 
            820                 825                 830         


Glu Asp Glu Val His Ile Cys His Asn Gln Asp Gly Tyr Ser Tyr Pro 
        835                 840                 845             


Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala 
    850                 855                 860 


<210>  30
<211>  2583
<212>  DNA
<213>  Artificial sequence

<220>
<223>  synthetic hLDLR variant N309A with leader


<220>
<221>  CDS
<222>  (1)..(2583)

<400>  30
atg ggg ccc tgg ggc tgg aaa ttg cgc tgg acc gtc gcc ttg ctc ctc         48
Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu           
1               5                   10                  15                

gcc gcg gcg ggg act gca gtg ggc gac aga tgt gaa aga aac gag ttc         96
Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe           
            20                  25                  30                    

cag tgc caa gac ggg aaa tgc atc tcc tac aag tgg gtc tgc gat ggc        144
Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly           
        35                  40                  45                        

agc gct gag tgc cag gat ggc tct gat gag tcc cag gag acg tgc ttg        192
Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu           
    50                  55                  60                            

tct gtc acc tgc aaa tcc ggg gac ttc agc tgt ggg ggc cgt gtc aac        240
Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn           
65                  70                  75                  80            

cgc tgc att cct cag ttc tgg agg tgc gat ggc caa gtg gac tgc gac        288
Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp           
                85                  90                  95                

aac ggc tca gac gag caa ggc tgt ccc ccc aag acg tgc tcc cag gac        336
Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp           
            100                 105                 110                   

gag ttt cgc tgc cac gat ggg aag tgc atc tct cgg cag ttc gtc tgt        384
Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys           
        115                 120                 125                       

gac tca gac cgg gac tgc ttg gac ggc tca gac gag gcc tcc tgc ccg        432
Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro           
    130                 135                 140                           

gtg ctc acc tgt ggt ccc gcc agc ttc cag tgc aac agc tcc acc tgc        480
Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys           
145                 150                 155                 160           

atc ccc cag ctg tgg gcc tgc gac aac gac ccc gac tgc gaa gat ggc        528
Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly           
                165                 170                 175               

tcg gat gag tgg ccg cag cgc tgt agg ggt ctt tac gtg ttc caa ggg        576
Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly           
            180                 185                 190                   

gac agt agc ccc tgc tcg gcc ttc gag ttc cac tgc cta agt ggc gag        624
Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu           
        195                 200                 205                       

tgc atc cac tcc agc tgg cgc tgt gat ggt ggc ccc gac tgc aag gac        672
Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp           
    210                 215                 220                           

aaa tct gac gag gaa aac tgc gct gtg gcc acc tgt cgc cct gac gaa        720
Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu           
225                 230                 235                 240           

ttc cag tgc tct gat gga aac tgc atc cat ggc agc cgg cag tgt gac        768
Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp           
                245                 250                 255               

cgg gaa tat gac tgc aag gac atg agc gat gaa gtt ggc tgc gtt aat        816
Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn           
            260                 265                 270                   

gtg aca ctc tgc gag gga ccc aac aag ttc aag tgt cac agc ggc gaa        864
Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu           
        275                 280                 285                       

tgc atc acc ctg gac aaa gtc tgc aac atg gct aga gac tgc cgg gac        912
Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp           
    290                 295                 300                           

tgg tca gat gaa ccc atc aaa gag tgc ggg acc aac gaa tgc ttg gac        960
Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp           
305                 310                 315                 320           

aac aac ggc ggc tgt tcc cac gtc tgc gct gac ctt aag atc ggc tac       1008
Asn Asn Gly Gly Cys Ser His Val Cys Ala Asp Leu Lys Ile Gly Tyr           
                325                 330                 335               

gag tgc ctg tgc ccc gac ggc ttc cag ctg gtg gcc cag cga aga tgc       1056
Glu Cys Leu Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys           
            340                 345                 350                   

gaa gat atc gat gag tgt cag gat ccc gac acc tgc agc cag ctc tgc       1104
Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys           
        355                 360                 365                       

gtg aac ctg gag ggt ggc tac aag tgc cag tgt gag gaa ggc ttc cag       1152
Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln           
    370                 375                 380                           

ctg gac ccc cac acg aag gcc tgc aag gct gtg ggc tcc atc gcc tac       1200
Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr           
385                 390                 395                 400           

ctc ttc ttc acc aac cgg cac gag gtc agg aag atg acg ctg gac cgg       1248
Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg           
                405                 410                 415               

agc gag tac acc agc ctc atc ccc aac ctg agg aac gtg gtc gct ctg       1296
Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu           
            420                 425                 430                   

gac acg gag gtg gcc agc aat aga atc tac tgg tct gac ctg tcc cag       1344
Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln           
        435                 440                 445                       

aga atg atc tgc agc acc cag ctt gac aga gcc cac ggc gtc tct tcc       1392
Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser           
    450                 455                 460                           

tat gac acc gtc atc agc agg gac atc cag gcc ccc gac ggg ctg gct       1440
Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala           
465                 470                 475                 480           

gtg gac tgg atc cac agc aac atc tac tgg acc gac tct gtc ctg ggc       1488
Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly           
                485                 490                 495               

act gtc tct gtt gcg gat acc aag ggc gtg aag agg aaa acg tta ttc       1536
Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe           
            500                 505                 510                   

agg gag aac ggc tcc aag cca agg gcc atc gtg gtg gat cct gtt cat       1584
Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His           
        515                 520                 525                       

ggc ttc atg tac tgg act gac tgg gga act ccc gcc aag atc aag aaa       1632
Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys           
    530                 535                 540                           

ggg ggc ctg aat ggt gtg gac atc tac tcg ctg gtg act gaa aac att       1680
Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile           
545                 550                 555                 560           

cag tgg ccc aat ggc atc acc cta gat ctc ctc agt ggc cgc ctc tac       1728
Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr           
                565                 570                 575               

tgg gtt gac tcc aaa ctt cac tcc atc tca agc atc gat gtc aat ggg       1776
Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly           
            580                 585                 590                   

ggc aac cgg aag acc atc ttg gag gat gaa aag agg ctg gcc cac ccc       1824
Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro           
        595                 600                 605                       

ttc tcc ttg gcc gtc ttt gag gac aaa gta ttt tgg aca gat atc atc       1872
Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile           
    610                 615                 620                           

aac gaa gcc att ttc agt gcc aac cgc ctc aca ggt tcc gat gtc aac       1920
Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn           
625                 630                 635                 640           

ttg ttg gct gaa aac cta ctg tcc cca gag gat atg gtc ctc ttc cac       1968
Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His           
                645                 650                 655               

aac ctc acc cag cca aga gga gtg aac tgg tgt gag agg acc acc ctg       2016
Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu           
            660                 665                 670                   

agc aat ggc ggc tgc cag tat ctg tgc ctc cct gcc ccg cag atc aac       2064
Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn           
        675                 680                 685                       

ccc cac tcg ccc aag ttt acc tgc gcc tgc ccg gac ggc atg ctg ctg       2112
Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu           
    690                 695                 700                           

gcc agg gac atg agg agc tgc ctc aca gag gct gag gct gca gtg gcc       2160
Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala           
705                 710                 715                 720           

acc cag gag aca tcc acc gtc agg cta aag gtc agc tcc aca gcc gta       2208
Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val           
                725                 730                 735               

agg aca cag cac aca acc acc cgg cct gtt ccc gac acc tcc cgg ctg       2256
Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu           
            740                 745                 750                   

cct ggg gcc acc cct ggg ctc acc acg gtg gag ata gtg aca atg tct       2304
Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser           
        755                 760                 765                       

cac caa gct ctg ggc gac gtt gct ggc aga gga aat gag aag aag ccc       2352
His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro           
    770                 775                 780                           

agt agc gtg agg gct ctg tcc att gtc ctc ccc atc gtg ctc ctc gtc       2400
Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val           
785                 790                 795                 800           

ttc ctt tgc ctg ggg gtc ttc ctt cta tgg aag aac tgg cgg ctt aag       2448
Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys           
                805                 810                 815               

aac atc aac agc atc aac ttt gac aac ccc gtc tat cag aag acc aca       2496
Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Lys Thr Thr           
            820                 825                 830                   

gag gat gag gtc cac att tgc cac aac cag gac ggc tac agc tac ccc       2544
Glu Asp Glu Val His Ile Cys His Asn Gln Asp Gly Tyr Ser Tyr Pro           
        835                 840                 845                       

tcg aga cag atg gtc agt ctg gag gat gac gtg gcg tga                   2583
Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala                           
    850                 855                 860                           


<210>  31
<211>  860
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Construct

<400>  31

Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu 
1               5                   10                  15      


Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe 
            20                  25                  30          


Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly 
        35                  40                  45              


Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu 
    50                  55                  60                  


Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn 
65                  70                  75                  80  


Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp 
                85                  90                  95      


Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp 
            100                 105                 110         


Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys 
        115                 120                 125             


Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro 
    130                 135                 140                 


Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys 
145                 150                 155                 160 


Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly 
                165                 170                 175     


Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly 
            180                 185                 190         


Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu 
        195                 200                 205             


Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp 
    210                 215                 220                 


Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu 
225                 230                 235                 240 


Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp 
                245                 250                 255     


Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn 
            260                 265                 270         


Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu 
        275                 280                 285             


Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp 
    290                 295                 300                 


Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp 
305                 310                 315                 320 


Asn Asn Gly Gly Cys Ser His Val Cys Ala Asp Leu Lys Ile Gly Tyr 
                325                 330                 335     


Glu Cys Leu Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys 
            340                 345                 350         


Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys 
        355                 360                 365             


Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln 
    370                 375                 380                 


Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr 
385                 390                 395                 400 


Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg 
                405                 410                 415     


Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu 
            420                 425                 430         


Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln 
        435                 440                 445             


Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser 
    450                 455                 460                 


Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala 
465                 470                 475                 480 


Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly 
                485                 490                 495     


Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe 
            500                 505                 510         


Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His 
        515                 520                 525             


Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys 
    530                 535                 540                 


Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile 
545                 550                 555                 560 


Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr 
                565                 570                 575     


Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly 
            580                 585                 590         


Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro 
        595                 600                 605             


Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile 
    610                 615                 620                 


Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn 
625                 630                 635                 640 


Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His 
                645                 650                 655     


Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu 
            660                 665                 670         


Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn 
        675                 680                 685             


Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu 
    690                 695                 700                 


Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala 
705                 710                 715                 720 


Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val 
                725                 730                 735     


Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu 
            740                 745                 750         


Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser 
        755                 760                 765             


His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro 
    770                 775                 780                 


Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val 
785                 790                 795                 800 


Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys 
                805                 810                 815     


Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Lys Thr Thr 
            820                 825                 830         


Glu Asp Glu Val His Ile Cys His Asn Gln Asp Gly Tyr Ser Tyr Pro 
        835                 840                 845             


Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala 
    850                 855                 860 


<210>  32
<211>  2583
<212>  DNA
<213>  Artificial sequence

<220>
<223>  synthetic hLDLR V307D with leader

<400>  32
atggggccct ggggctggaa attgcgctgg accgtcgcct tgctcctcgc cgcggcgggg       60

actgcagtgg gcgacagatg tgaaagaaac gagttccagt gccaagacgg gaaatgcatc      120

tcctacaagt gggtctgcga tggcagcgct gagtgccagg atggctctga tgagtcccag      180

gagacgtgct tgtctgtcac ctgcaaatcc ggggacttca gctgtggggg ccgtgtcaac      240

cgctgcattc ctcagttctg gaggtgcgat ggccaagtgg actgcgacaa cggctcagac      300

gagcaaggct gtccccccaa gacgtgctcc caggacgagt ttcgctgcca cgatgggaag      360

tgcatctctc ggcagttcgt ctgtgactca gaccgggact gcttggacgg ctcagacgag      420

gcctcctgcc cggtgctcac ctgtggtccc gccagcttcc agtgcaacag ctccacctgc      480

atcccccagc tgtgggcctg cgacaacgac cccgactgcg aagatggctc ggatgagtgg      540

ccgcagcgct gtaggggtct ttacgtgttc caaggggaca gtagcccctg ctcggccttc      600

gagttccact gcctaagtgg cgagtgcatc cactccagct ggcgctgtga tggtggcccc      660

gactgcaagg acaaatctga cgaggaaaac tgcgctgtgg ccacctgtcg ccctgacgaa      720

ttccagtgct ctgatggaaa ctgcatccat ggcagccggc agtgtgaccg ggaatatgac      780

tgcaaggaca tgagcgatga agttggctgc gttaatgtga cactctgcga gggacccaac      840

aagttcaagt gtcacagcgg cgaatgcatc accctggaca aagtctgcaa catggctaga      900

gactgccggg actggtcaga tgaacccatc aaagagtgcg ggaccaacga atgcttggac      960

aacaacggcg gctgttccca cgactgcaat gaccttaaga tcggctacga gtgcctgtgc     1020

cccgacggct tccagctggt ggcccagcga agatgcgaag atatcgatga gtgtcaggat     1080

cccgacacct gcagccagct ctgcgtgaac ctggagggtg gctacaagtg ccagtgtgag     1140

gaaggcttcc agctggaccc ccacacgaag gcctgcaagg ctgtgggctc catcgcctac     1200

ctcttcttca ccaaccggca cgaggtcagg aagatgacgc tggaccggag cgagtacacc     1260

agcctcatcc ccaacctgag gaacgtggtc gctctggaca cggaggtggc cagcaataga     1320

atctactggt ctgacctgtc ccagagaatg atctgcagca cccagcttga cagagcccac     1380

ggcgtctctt cctatgacac cgtcatcagc agggacatcc aggcccccga cgggctggct     1440

gtggactgga tccacagcaa catctactgg accgactctg tcctgggcac tgtctctgtt     1500

gcggatacca agggcgtgaa gaggaaaacg ttattcaggg agaacggctc caagccaagg     1560

gccatcgtgg tggatcctgt tcatggcttc atgtactgga ctgactgggg aactcccgcc     1620

aagatcaaga aagggggcct gaatggtgtg gacatctact cgctggtgac tgaaaacatt     1680

cagtggccca atggcatcac cctagatctc ctcagtggcc gcctctactg ggttgactcc     1740

aaacttcact ccatctcaag catcgatgtc aatgggggca accggaagac catcttggag     1800

gatgaaaaga ggctggccca ccccttctcc ttggccgtct ttgaggacaa agtattttgg     1860

acagatatca tcaacgaagc cattttcagt gccaaccgcc tcacaggttc cgatgtcaac     1920

ttgttggctg aaaacctact gtccccagag gatatggtcc tcttccacaa cctcacccag     1980

ccaagaggag tgaactggtg tgagaggacc accctgagca atggcggctg ccagtatctg     2040

tgcctccctg ccccgcagat caacccccac tcgcccaagt ttacctgcgc ctgcccggac     2100

ggcatgctgc tggccaggga catgaggagc tgcctcacag aggctgaggc tgcagtggcc     2160

acccaggaga catccaccgt caggctaaag gtcagctcca cagccgtaag gacacagcac     2220

acaaccaccc ggcctgttcc cgacacctcc cggctgcctg gggccacccc tgggctcacc     2280

acggtggaga tagtgacaat gtctcaccaa gctctgggcg acgttgctgg cagaggaaat     2340

gagaagaagc ccagtagcgt gagggctctg tccattgtcc tccccatcgt gctcctcgtc     2400

ttcctttgcc tgggggtctt ccttctatgg aagaactggc ggcttaagaa catcaacagc     2460

atcaactttg acaaccccgt ctatcagaag accacagagg atgaggtcca catttgccac     2520

aaccaggacg gctacagcta cccctcgaga cagatggtca gtctggagga tgacgtggcg     2580

tga                                                                   2583


<210>  33
<211>  2583
<212>  DNA
<213>  Artificial sequence

<220>
<223>  synthetic hLDLR-IDOL-K796R, K809R, C818A with leader


<220>
<221>  CDS
<222>  (1)..(2583)

<400>  33
atg ggg ccc tgg ggc tgg aaa ttg cgc tgg acc gtc gcc ttg ctc ctc         48
Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu           
1               5                   10                  15                

gcc gcg gcg ggg act gca gtg ggc gac aga tgt gaa aga aac gag ttc         96
Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe           
            20                  25                  30                    

cag tgc caa gac ggg aaa tgc atc tcc tac aag tgg gtc tgc gat ggc        144
Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly           
        35                  40                  45                        

agc gct gag tgc cag gat ggc tct gat gag tcc cag gag acg tgc ttg        192
Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu           
    50                  55                  60                            

tct gtc acc tgc aaa tcc ggg gac ttc agc tgt ggg ggc cgt gtc aac        240
Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn           
65                  70                  75                  80            

cgc tgc att cct cag ttc tgg agg tgc gat ggc caa gtg gac tgc gac        288
Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp           
                85                  90                  95                

aac ggc tca gac gag caa ggc tgt ccc ccc aag acg tgc tcc cag gac        336
Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp           
            100                 105                 110                   

gag ttt cgc tgc cac gat ggg aag tgc atc tct cgg cag ttc gtc tgt        384
Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys           
        115                 120                 125                       

gac tca gac cgg gac tgc ttg gac ggc tca gac gag gcc tcc tgc ccg        432
Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro           
    130                 135                 140                           

gtg ctc acc tgt ggt ccc gcc agc ttc cag tgc aac agc tcc acc tgc        480
Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys           
145                 150                 155                 160           

atc ccc cag ctg tgg gcc tgc gac aac gac ccc gac tgc gaa gat ggc        528
Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly           
                165                 170                 175               

tcg gat gag tgg ccg cag cgc tgt agg ggt ctt tac gtg ttc caa ggg        576
Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly           
            180                 185                 190                   

gac agt agc ccc tgc tcg gcc ttc gag ttc cac tgc cta agt ggc gag        624
Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu           
        195                 200                 205                       

tgc atc cac tcc agc tgg cgc tgt gat ggt ggc ccc gac tgc aag gac        672
Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp           
    210                 215                 220                           

aaa tct gac gag gaa aac tgc gct gtg gcc acc tgt cgc cct gac gaa        720
Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu           
225                 230                 235                 240           

ttc cag tgc tct gat gga aac tgc atc cat ggc agc cgg cag tgt gac        768
Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp           
                245                 250                 255               

cgg gaa tat gac tgc aag gac atg agc gat gaa gtt ggc tgc gtt aat        816
Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn           
            260                 265                 270                   

gtg aca ctc tgc gag gga ccc aac aag ttc aag tgt cac agc ggc gaa        864
Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu           
        275                 280                 285                       

tgc atc acc ctg gac aaa gtc tgc aac atg gct aga gac tgc cgg gac        912
Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp           
    290                 295                 300                           

tgg tca gat gaa ccc atc aaa gag tgc ggg acc aac gaa tgc ttg gac        960
Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp           
305                 310                 315                 320           

aac aac ggc ggc tgt tcc cac gtc tgc aat gac ctt aag atc ggc tac       1008
Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Leu Lys Ile Gly Tyr           
                325                 330                 335               

gag tgc ctg tgc ccc gac ggc ttc cag ctg gtg gcc cag cga aga tgc       1056
Glu Cys Leu Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys           
            340                 345                 350                   

gaa gat atc gat gag tgt cag gat ccc gac acc tgc agc cag ctc tgc       1104
Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys           
        355                 360                 365                       

gtg aac ctg gag ggt ggc tac aag tgc cag tgt gag gaa ggc ttc cag       1152
Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln           
    370                 375                 380                           

ctg gac ccc cac acg aag gcc tgc aag gct gtg ggc tcc atc gcc tac       1200
Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr           
385                 390                 395                 400           

ctc ttc ttc acc aac cgg cac gag gtc agg aag atg acg ctg gac cgg       1248
Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg           
                405                 410                 415               

agc gag tac acc agc ctc atc ccc aac ctg agg aac gtg gtc gct ctg       1296
Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu           
            420                 425                 430                   

gac acg gag gtg gcc agc aat aga atc tac tgg tct gac ctg tcc cag       1344
Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln           
        435                 440                 445                       

aga atg atc tgc agc acc cag ctt gac aga gcc cac ggc gtc tct tcc       1392
Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser           
    450                 455                 460                           

tat gac acc gtc atc agc agg gac atc cag gcc ccc gac ggg ctg gct       1440
Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala           
465                 470                 475                 480           

gtg gac tgg atc cac agc aac atc tac tgg acc gac tct gtc ctg ggc       1488
Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly           
                485                 490                 495               

act gtc tct gtt gcg gat acc aag ggc gtg aag agg aaa acg tta ttc       1536
Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe           
            500                 505                 510                   

agg gag aac ggc tcc aag cca agg gcc atc gtg gtg gat cct gtt cat       1584
Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His           
        515                 520                 525                       

ggc ttc atg tac tgg act gac tgg gga act ccc gcc aag atc aag aaa       1632
Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys           
    530                 535                 540                           

ggg ggc ctg aat ggt gtg gac atc tac tcg ctg gtg act gaa aac att       1680
Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile           
545                 550                 555                 560           

cag tgg ccc aat ggc atc acc cta gat ctc ctc agt ggc cgc ctc tac       1728
Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr           
                565                 570                 575               

tgg gtt gac tcc aaa ctt cac tcc atc tca agc atc gat gtc aat ggg       1776
Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly           
            580                 585                 590                   

ggc aac cgg aag acc atc ttg gag gat gaa aag agg ctg gcc cac ccc       1824
Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro           
        595                 600                 605                       

ttc tcc ttg gcc gtc ttt gag gac aaa gta ttt tgg aca gat atc atc       1872
Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile           
    610                 615                 620                           

aac gaa gcc att ttc agt gcc aac cgc ctc aca ggt tcc gat gtc aac       1920
Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn           
625                 630                 635                 640           

ttg ttg gct gaa aac cta ctg tcc cca gag gat atg gtc ctc ttc cac       1968
Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His           
                645                 650                 655               

aac ctc acc cag cca aga gga gtg aac tgg tgt gag agg acc acc ctg       2016
Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu           
            660                 665                 670                   

agc aat ggc ggc tgc cag tat ctg tgc ctc cct gcc ccg cag atc aac       2064
Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn           
        675                 680                 685                       

ccc cac tcg ccc aag ttt acc tgc gcc tgc ccg gac ggc atg ctg ctg       2112
Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu           
    690                 695                 700                           

gcc agg gac atg agg agc tgc ctc aca gag gct gag gct gca gtg gcc       2160
Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala           
705                 710                 715                 720           

acc cag gag aca tcc acc gtc agg cta aag gtc agc tcc aca gcc gta       2208
Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val           
                725                 730                 735               

agg aca cag cac aca acc acc cgg cct gtt ccc gac acc tcc cgg ctg       2256
Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu           
            740                 745                 750                   

cct ggg gcc acc cct ggg ctc acc acg gtg gag ata gtg aca atg tct       2304
Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser           
        755                 760                 765                       

cac caa gct ctg ggc gac gtt gct ggc aga gga aat gag aag aag ccc       2352
His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro           
    770                 775                 780                           

agt agc gtg agg gct ctg tcc att gtc ctc ccc atc gtg ctc ctc gtc       2400
Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val           
785                 790                 795                 800           

ttc ctt tgc ctg ggg gtc ttc ctt cta tgg aag aac tgg cgg ctt agg       2448
Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Arg           
                805                 810                 815               

aac atc aac agc atc aac ttt gac aac ccc gtc tat cag agg acc aca       2496
Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Arg Thr Thr           
            820                 825                 830                   

gag gat gag gtc cac att gcc cac aac cag gac ggc tac agc tac ccc       2544
Glu Asp Glu Val His Ile Ala His Asn Gln Asp Gly Tyr Ser Tyr Pro           
        835                 840                 845                       

tcg aga cag atg gtc agt ctg gag gat gac gtg gcg tga                   2583
Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala                           
    850                 855                 860                           


<210>  34
<211>  860
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Construct

<400>  34

Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu 
1               5                   10                  15      


Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe 
            20                  25                  30          


Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly 
        35                  40                  45              


Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu 
    50                  55                  60                  


Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn 
65                  70                  75                  80  


Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp 
                85                  90                  95      


Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp 
            100                 105                 110         


Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys 
        115                 120                 125             


Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro 
    130                 135                 140                 


Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys 
145                 150                 155                 160 


Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly 
                165                 170                 175     


Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly 
            180                 185                 190         


Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu 
        195                 200                 205             


Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp 
    210                 215                 220                 


Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu 
225                 230                 235                 240 


Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp 
                245                 250                 255     


Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn 
            260                 265                 270         


Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu 
        275                 280                 285             


Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp 
    290                 295                 300                 


Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp 
305                 310                 315                 320 


Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Leu Lys Ile Gly Tyr 
                325                 330                 335     


Glu Cys Leu Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys 
            340                 345                 350         


Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys 
        355                 360                 365             


Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln 
    370                 375                 380                 


Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr 
385                 390                 395                 400 


Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg 
                405                 410                 415     


Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu 
            420                 425                 430         


Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln 
        435                 440                 445             


Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser 
    450                 455                 460                 


Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala 
465                 470                 475                 480 


Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly 
                485                 490                 495     


Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe 
            500                 505                 510         


Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His 
        515                 520                 525             


Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys 
    530                 535                 540                 


Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile 
545                 550                 555                 560 


Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr 
                565                 570                 575     


Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly 
            580                 585                 590         


Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro 
        595                 600                 605             


Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile 
    610                 615                 620                 


Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn 
625                 630                 635                 640 


Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His 
                645                 650                 655     


Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu 
            660                 665                 670         


Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn 
        675                 680                 685             


Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu 
    690                 695                 700                 


Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala 
705                 710                 715                 720 


Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val 
                725                 730                 735     


Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu 
            740                 745                 750         


Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser 
        755                 760                 765             


His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro 
    770                 775                 780                 


Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val 
785                 790                 795                 800 


Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Arg 
                805                 810                 815     


Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Arg Thr Thr 
            820                 825                 830         


Glu Asp Glu Val His Ile Ala His Asn Gln Asp Gly Tyr Ser Tyr Pro 
        835                 840                 845             


Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala 
    850                 855                 860 


<210>  35
<211>  2583
<212>  DNA
<213>  Artificial sequence

<220>
<223>  synthetic hLDLR.K809R-818A with leader


<220>
<221>  CDS
<222>  (1)..(2583)

<400>  35
atg ggg ccc tgg ggc tgg aaa ttg cgc tgg acc gtc gcc ttg ctc ctc         48
Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu           
1               5                   10                  15                

gcc gcg gcg ggg act gca gtg ggc gac aga tgt gaa aga aac gag ttc         96
Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe           
            20                  25                  30                    

cag tgc caa gac ggg aaa tgc atc tcc tac aag tgg gtc tgc gat ggc        144
Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly           
        35                  40                  45                        

agc gct gag tgc cag gat ggc tct gat gag tcc cag gag acg tgc ttg        192
Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu           
    50                  55                  60                            

tct gtc acc tgc aaa tcc ggg gac ttc agc tgt ggg ggc cgt gtc aac        240
Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn           
65                  70                  75                  80            

cgc tgc att cct cag ttc tgg agg tgc gat ggc caa gtg gac tgc gac        288
Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp           
                85                  90                  95                

aac ggc tca gac gag caa ggc tgt ccc ccc aag acg tgc tcc cag gac        336
Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp           
            100                 105                 110                   

gag ttt cgc tgc cac gat ggg aag tgc atc tct cgg cag ttc gtc tgt        384
Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys           
        115                 120                 125                       

gac tca gac cgg gac tgc ttg gac ggc tca gac gag gcc tcc tgc ccg        432
Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro           
    130                 135                 140                           

gtg ctc acc tgt ggt ccc gcc agc ttc cag tgc aac agc tcc acc tgc        480
Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys           
145                 150                 155                 160           

atc ccc cag ctg tgg gcc tgc gac aac gac ccc gac tgc gaa gat ggc        528
Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly           
                165                 170                 175               

tcg gat gag tgg ccg cag cgc tgt agg ggt ctt tac gtg ttc caa ggg        576
Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly           
            180                 185                 190                   

gac agt agc ccc tgc tcg gcc ttc gag ttc cac tgc cta agt ggc gag        624
Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu           
        195                 200                 205                       

tgc atc cac tcc agc tgg cgc tgt gat ggt ggc ccc gac tgc aag gac        672
Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp           
    210                 215                 220                           

aaa tct gac gag gaa aac tgc gct gtg gcc acc tgt cgc cct gac gaa        720
Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu           
225                 230                 235                 240           

ttc cag tgc tct gat gga aac tgc atc cat ggc agc cgg cag tgt gac        768
Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp           
                245                 250                 255               

cgg gaa tat gac tgc aag gac atg agc gat gaa gtt ggc tgc gtt aat        816
Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn           
            260                 265                 270                   

gtg aca ctc tgc gag gga ccc aac aag ttc aag tgt cac agc ggc gaa        864
Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu           
        275                 280                 285                       

tgc atc acc ctg gac aaa gtc tgc aac atg gct aga gac tgc cgg gac        912
Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp           
    290                 295                 300                           

tgg tca gat gaa ccc atc aaa gag tgc ggg acc aac gaa tgc ttg gac        960
Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp           
305                 310                 315                 320           

aac aac ggc ggc tgt tcc cac gtc tgc aat gac ctt aag atc ggc tac       1008
Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Leu Lys Ile Gly Tyr           
                325                 330                 335               

gag tgc ctg tgc ccc gac ggc ttc cag ctg gtg gcc cag cga aga tgc       1056
Glu Cys Leu Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys           
            340                 345                 350                   

gaa gat atc gat gag tgt cag gat ccc gac acc tgc agc cag ctc tgc       1104
Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys           
        355                 360                 365                       

gtg aac ctg gag ggt ggc tac aag tgc cag tgt gag gaa ggc ttc cag       1152
Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln           
    370                 375                 380                           

ctg gac ccc cac acg aag gcc tgc aag gct gtg ggc tcc atc gcc tac       1200
Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr           
385                 390                 395                 400           

ctc ttc ttc acc aac cgg cac gag gtc agg aag atg acg ctg gac cgg       1248
Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg           
                405                 410                 415               

agc gag tac acc agc ctc atc ccc aac ctg agg aac gtg gtc gct ctg       1296
Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu           
            420                 425                 430                   

gac acg gag gtg gcc agc aat aga atc tac tgg tct gac ctg tcc cag       1344
Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln           
        435                 440                 445                       

aga atg atc tgc agc acc cag ctt gac aga gcc cac ggc gtc tct tcc       1392
Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser           
    450                 455                 460                           

tat gac acc gtc atc agc agg gac atc cag gcc ccc gac ggg ctg gct       1440
Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala           
465                 470                 475                 480           

gtg gac tgg atc cac agc aac atc tac tgg acc gac tct gtc ctg ggc       1488
Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly           
                485                 490                 495               

act gtc tct gtt gcg gat acc aag ggc gtg aag agg aaa acg tta ttc       1536
Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe           
            500                 505                 510                   

agg gag aac ggc tcc aag cca agg gcc atc gtg gtg gat cct gtt cat       1584
Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His           
        515                 520                 525                       

ggc ttc atg tac tgg act gac tgg gga act ccc gcc aag atc aag aaa       1632
Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys           
    530                 535                 540                           

ggg ggc ctg aat ggt gtg gac atc tac tcg ctg gtg act gaa aac att       1680
Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile           
545                 550                 555                 560           

cag tgg ccc aat ggc atc acc cta gat ctc ctc agt ggc cgc ctc tac       1728
Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr           
                565                 570                 575               

tgg gtt gac tcc aaa ctt cac tcc atc tca agc atc gat gtc aat ggg       1776
Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly           
            580                 585                 590                   

ggc aac cgg aag acc atc ttg gag gat gaa aag agg ctg gcc cac ccc       1824
Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro           
        595                 600                 605                       

ttc tcc ttg gcc gtc ttt gag gac aaa gta ttt tgg aca gat atc atc       1872
Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile           
    610                 615                 620                           

aac gaa gcc att ttc agt gcc aac cgc ctc aca ggt tcc gat gtc aac       1920
Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn           
625                 630                 635                 640           

ttg ttg gct gaa aac cta ctg tcc cca gag gat atg gtc ctc ttc cac       1968
Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His           
                645                 650                 655               

aac ctc acc cag cca aga gga gtg aac tgg tgt gag agg acc acc ctg       2016
Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu           
            660                 665                 670                   

agc aat ggc ggc tgc cag tat ctg tgc ctc cct gcc ccg cag atc aac       2064
Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn           
        675                 680                 685                       

ccc cac tcg ccc aag ttt acc tgc gcc tgc ccg gac ggc atg ctg ctg       2112
Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu           
    690                 695                 700                           

gcc agg gac atg agg agc tgc ctc aca gag gct gag gct gca gtg gcc       2160
Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala           
705                 710                 715                 720           

acc cag gag aca tcc acc gtc agg cta aag gtc agc tcc aca gcc gta       2208
Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val           
                725                 730                 735               

agg aca cag cac aca acc acc cgg cct gtt ccc gac acc tcc cgg ctg       2256
Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu           
            740                 745                 750                   

cct ggg gcc acc cct ggg ctc acc acg gtg gag ata gtg aca atg tct       2304
Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser           
        755                 760                 765                       

cac caa gct ctg ggc gac gtt gct ggc aga gga aat gag aag aag ccc       2352
His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro           
    770                 775                 780                           

agt agc gtg agg gct ctg tcc att gtc ctc ccc atc gtg ctc ctc gtc       2400
Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val           
785                 790                 795                 800           

ttc ctt tgc ctg ggg gtc ttc ctt cta tgg aag aac tgg cgg ctt aag       2448
Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys           
                805                 810                 815               

aac atc aac agc atc aac ttt gac aac ccc gtc tat cag agg acc aca       2496
Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Arg Thr Thr           
            820                 825                 830                   

gag gat gag gtc cac att gcc cac aac cag gac ggc tac agc tac ccc       2544
Glu Asp Glu Val His Ile Ala His Asn Gln Asp Gly Tyr Ser Tyr Pro           
        835                 840                 845                       

tcg aga cag atg gtc agt ctg gag gat gac gtg gcg tga                   2583
Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala                           
    850                 855                 860                           


<210>  36
<211>  860
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Construct

<400>  36

Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu 
1               5                   10                  15      


Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe 
            20                  25                  30          


Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly 
        35                  40                  45              


Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu 
    50                  55                  60                  


Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn 
65                  70                  75                  80  


Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp 
                85                  90                  95      


Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp 
            100                 105                 110         


Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys 
        115                 120                 125             


Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro 
    130                 135                 140                 


Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys 
145                 150                 155                 160 


Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly 
                165                 170                 175     


Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly 
            180                 185                 190         


Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu 
        195                 200                 205             


Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp 
    210                 215                 220                 


Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu 
225                 230                 235                 240 


Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp 
                245                 250                 255     


Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn 
            260                 265                 270         


Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu 
        275                 280                 285             


Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp 
    290                 295                 300                 


Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp 
305                 310                 315                 320 


Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Leu Lys Ile Gly Tyr 
                325                 330                 335     


Glu Cys Leu Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys 
            340                 345                 350         


Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys 
        355                 360                 365             


Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln 
    370                 375                 380                 


Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr 
385                 390                 395                 400 


Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg 
                405                 410                 415     


Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu 
            420                 425                 430         


Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln 
        435                 440                 445             


Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser 
    450                 455                 460                 


Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala 
465                 470                 475                 480 


Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly 
                485                 490                 495     


Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe 
            500                 505                 510         


Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His 
        515                 520                 525             


Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys 
    530                 535                 540                 


Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile 
545                 550                 555                 560 


Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr 
                565                 570                 575     


Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly 
            580                 585                 590         


Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro 
        595                 600                 605             


Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile 
    610                 615                 620                 


Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn 
625                 630                 635                 640 


Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His 
                645                 650                 655     


Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu 
            660                 665                 670         


Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn 
        675                 680                 685             


Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu 
    690                 695                 700                 


Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala 
705                 710                 715                 720 


Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val 
                725                 730                 735     


Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu 
            740                 745                 750         


Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser 
        755                 760                 765             


His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro 
    770                 775                 780                 


Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val 
785                 790                 795                 800 


Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys 
                805                 810                 815     


Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Arg Thr Thr 
            820                 825                 830         


Glu Asp Glu Val His Ile Ala His Asn Gln Asp Gly Tyr Ser Tyr Pro 
        835                 840                 845             


Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala 
    850                 855                 860 


<210>  37
<211>  2583
<212>  DNA
<213>  Artificial sequence

<220>
<223>  synthetic hLDLR (K25R, C29A, L318D) with leader


<220>
<221>  CDS
<222>  (1)..(2583)

<400>  37
atg ggg ccc tgg ggc tgg aaa ttg cgc tgg acc gtc gcc ttg ctc ctc         48
Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu           
1               5                   10                  15                

gcc gcg gcg ggg act gca gtg ggc gac aga tgt gaa aga aac gag ttc         96
Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe           
            20                  25                  30                    

cag tgc caa gac ggg aaa tgc atc tcc tac aag tgg gtc tgc gat ggc        144
Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly           
        35                  40                  45                        

agc gct gag tgc cag gat ggc tct gat gag tcc cag gag acg tgc ttg        192
Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu           
    50                  55                  60                            

tct gtc acc tgc aaa tcc ggg gac ttc agc tgt ggg ggc cgt gtc aac        240
Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn           
65                  70                  75                  80            

cgc tgc att cct cag ttc tgg agg tgc gat ggc caa gtg gac tgc gac        288
Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp           
                85                  90                  95                

aac ggc tca gac gag caa ggc tgt ccc ccc aag acg tgc tcc cag gac        336
Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp           
            100                 105                 110                   

gag ttt cgc tgc cac gat ggg aag tgc atc tct cgg cag ttc gtc tgt        384
Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys           
        115                 120                 125                       

gac tca gac cgg gac tgc ttg gac ggc tca gac gag gcc tcc tgc ccg        432
Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro           
    130                 135                 140                           

gtg ctc acc tgt ggt ccc gcc agc ttc cag tgc aac agc tcc acc tgc        480
Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys           
145                 150                 155                 160           

atc ccc cag ctg tgg gcc tgc gac aac gac ccc gac tgc gaa gat ggc        528
Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly           
                165                 170                 175               

tcg gat gag tgg ccg cag cgc tgt agg ggt ctt tac gtg ttc caa ggg        576
Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly           
            180                 185                 190                   

gac agt agc ccc tgc tcg gcc ttc gag ttc cac tgc cta agt ggc gag        624
Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu           
        195                 200                 205                       

tgc atc cac tcc agc tgg cgc tgt gat ggt ggc ccc gac tgc aag gac        672
Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp           
    210                 215                 220                           

aaa tct gac gag gaa aac tgc gct gtg gcc acc tgt cgc cct gac gaa        720
Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu           
225                 230                 235                 240           

ttc cag tgc tct gat gga aac tgc atc cat ggc agc cgg cag tgt gac        768
Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp           
                245                 250                 255               

cgg gaa tat gac tgc aag gac atg agc gat gaa gtt ggc tgc gtt aat        816
Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn           
            260                 265                 270                   

gtg aca ctc tgc gag gga ccc aac aag ttc aag tgt cac agc ggc gaa        864
Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu           
        275                 280                 285                       

tgc atc acc ctg gac aaa gtc tgc aac atg gct aga gac tgc cgg gac        912
Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp           
    290                 295                 300                           

tgg tca gat gaa ccc atc aaa gag tgc ggg acc aac gaa tgc ttg gac        960
Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp           
305                 310                 315                 320           

aac aac ggc ggc tgt tcc cac gtc tgc aat gac ctt aag atc ggc tac       1008
Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Leu Lys Ile Gly Tyr           
                325                 330                 335               

gag tgc gac tgc ccc gac ggc ttc cag ctg gtg gcc cag cga aga tgc       1056
Glu Cys Asp Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys           
            340                 345                 350                   

gaa gat atc gat gag tgt cag gat ccc gac acc tgc agc cag ctc tgc       1104
Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys           
        355                 360                 365                       

gtg aac ctg gag ggt ggc tac aag tgc cag tgt gag gaa ggc ttc cag       1152
Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln           
    370                 375                 380                           

ctg gac ccc cac acg aag gcc tgc aag gct gtg ggc tcc atc gcc tac       1200
Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr           
385                 390                 395                 400           

ctc ttc ttc acc aac cgg cac gag gtc agg aag atg acg ctg gac cgg       1248
Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg           
                405                 410                 415               

agc gag tac acc agc ctc atc ccc aac ctg agg aac gtg gtc gct ctg       1296
Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu           
            420                 425                 430                   

gac acg gag gtg gcc agc aat aga atc tac tgg tct gac ctg tcc cag       1344
Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln           
        435                 440                 445                       

aga atg atc tgc agc acc cag ctt gac aga gcc cac ggc gtc tct tcc       1392
Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser           
    450                 455                 460                           

tat gac acc gtc atc agc agg gac atc cag gcc ccc gac ggg ctg gct       1440
Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala           
465                 470                 475                 480           

gtg gac tgg atc cac agc aac atc tac tgg acc gac tct gtc ctg ggc       1488
Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly           
                485                 490                 495               

act gtc tct gtt gcg gat acc aag ggc gtg aag agg aaa acg tta ttc       1536
Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe           
            500                 505                 510                   

agg gag aac ggc tcc aag cca agg gcc atc gtg gtg gat cct gtt cat       1584
Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His           
        515                 520                 525                       

ggc ttc atg tac tgg act gac tgg gga act ccc gcc aag atc aag aaa       1632
Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys           
    530                 535                 540                           

ggg ggc ctg aat ggt gtg gac atc tac tcg ctg gtg act gaa aac att       1680
Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile           
545                 550                 555                 560           

cag tgg ccc aat ggc atc acc cta gat ctc ctc agt ggc cgc ctc tac       1728
Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr           
                565                 570                 575               

tgg gtt gac tcc aaa ctt cac tcc atc tca agc atc gat gtc aat ggg       1776
Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly           
            580                 585                 590                   

ggc aac cgg aag acc atc ttg gag gat gaa aag agg ctg gcc cac ccc       1824
Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro           
        595                 600                 605                       

ttc tcc ttg gcc gtc ttt gag gac aaa gta ttt tgg aca gat atc atc       1872
Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile           
    610                 615                 620                           

aac gaa gcc att ttc agt gcc aac cgc ctc aca ggt tcc gat gtc aac       1920
Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn           
625                 630                 635                 640           

ttg ttg gct gaa aac cta ctg tcc cca gag gat atg gtc ctc ttc cac       1968
Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His           
                645                 650                 655               

aac ctc acc cag cca aga gga gtg aac tgg tgt gag agg acc acc ctg       2016
Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu           
            660                 665                 670                   

agc aat ggc ggc tgc cag tat ctg tgc ctc cct gcc ccg cag atc aac       2064
Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn           
        675                 680                 685                       

ccc cac tcg ccc aag ttt acc tgc gcc tgc ccg gac ggc atg ctg ctg       2112
Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu           
    690                 695                 700                           

gcc agg gac atg agg agc tgc ctc aca gag gct gag gct gca gtg gcc       2160
Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala           
705                 710                 715                 720           

acc cag gag aca tcc acc gtc agg cta aag gtc agc tcc aca gcc gta       2208
Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val           
                725                 730                 735               

agg aca cag cac aca acc acc cgg cct gtt ccc gac acc tcc cgg ctg       2256
Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu           
            740                 745                 750                   

cct ggg gcc acc cct ggg ctc acc acg gtg gag ata gtg aca atg tct       2304
Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser           
        755                 760                 765                       

cac caa gct ctg ggc gac gtt gct ggc aga gga aat gag aag aag ccc       2352
His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro           
    770                 775                 780                           

agt agc gtg agg gct ctg tcc att gtc ctc ccc atc gtg ctc ctc gtc       2400
Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val           
785                 790                 795                 800           

ttc ctt tgc ctg ggg gtc ttc ctt cta tgg aag aac tgg cgg ctt aag       2448
Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys           
                805                 810                 815               

aac atc aac agc atc aac ttt gac aac ccc gtc tat cag agg acc aca       2496
Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Arg Thr Thr           
            820                 825                 830                   

gag gat gag gtc cac att gcc cac aac cag gac ggc tac agc tac ccc       2544
Glu Asp Glu Val His Ile Ala His Asn Gln Asp Gly Tyr Ser Tyr Pro           
        835                 840                 845                       

tcg aga cag atg gtc agt ctg gag gat gac gtg gcg tga                   2583
Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala                           
    850                 855                 860                           


<210>  38
<211>  860
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Construct

<400>  38

Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu 
1               5                   10                  15      


Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe 
            20                  25                  30          


Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly 
        35                  40                  45              


Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu 
    50                  55                  60                  


Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn 
65                  70                  75                  80  


Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp 
                85                  90                  95      


Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp 
            100                 105                 110         


Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys 
        115                 120                 125             


Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro 
    130                 135                 140                 


Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys 
145                 150                 155                 160 


Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly 
                165                 170                 175     


Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly 
            180                 185                 190         


Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu 
        195                 200                 205             


Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp 
    210                 215                 220                 


Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu 
225                 230                 235                 240 


Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp 
                245                 250                 255     


Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn 
            260                 265                 270         


Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu 
        275                 280                 285             


Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp 
    290                 295                 300                 


Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp 
305                 310                 315                 320 


Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Leu Lys Ile Gly Tyr 
                325                 330                 335     


Glu Cys Asp Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys 
            340                 345                 350         


Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys 
        355                 360                 365             


Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln 
    370                 375                 380                 


Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr 
385                 390                 395                 400 


Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg 
                405                 410                 415     


Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu 
            420                 425                 430         


Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln 
        435                 440                 445             


Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser 
    450                 455                 460                 


Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala 
465                 470                 475                 480 


Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly 
                485                 490                 495     


Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe 
            500                 505                 510         


Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His 
        515                 520                 525             


Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys 
    530                 535                 540                 


Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile 
545                 550                 555                 560 


Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr 
                565                 570                 575     


Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly 
            580                 585                 590         


Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro 
        595                 600                 605             


Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile 
    610                 615                 620                 


Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn 
625                 630                 635                 640 


Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His 
                645                 650                 655     


Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu 
            660                 665                 670         


Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn 
        675                 680                 685             


Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu 
    690                 695                 700                 


Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala 
705                 710                 715                 720 


Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val 
                725                 730                 735     


Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu 
            740                 745                 750         


Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser 
        755                 760                 765             


His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro 
    770                 775                 780                 


Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val 
785                 790                 795                 800 


Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys 
                805                 810                 815     


Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Arg Thr Thr 
            820                 825                 830         


Glu Asp Glu Val His Ile Ala His Asn Gln Asp Gly Tyr Ser Tyr Pro 
        835                 840                 845             


Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala 
    850                 855                 860 


<210>  39
<211>  2583
<212>  DNA
<213>  Artificial sequence

<220>
<223>  synthetic K809R, C818A, L318D with leader


<220>
<221>  CDS
<222>  (1)..(2583)

<400>  39
atg ggg ccc tgg ggc tgg aaa ttg cgc tgg acc gtc gcc ttg ctc ctc         48
Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu           
1               5                   10                  15                

gcc gcg gcg ggg act gca gtg ggc gac aga tgt gaa aga aac gag ttc         96
Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe           
            20                  25                  30                    

cag tgc caa gac ggg aaa tgc atc tcc tac aag tgg gtc tgc gat ggc        144
Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly           
        35                  40                  45                        

agc gct gag tgc cag gat ggc tct gat gag tcc cag gag acg tgc ttg        192
Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu           
    50                  55                  60                            

tct gtc acc tgc aaa tcc ggg gac ttc agc tgt ggg ggc cgt gtc aac        240
Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn           
65                  70                  75                  80            

cgc tgc att cct cag ttc tgg agg tgc gat ggc caa gtg gac tgc gac        288
Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp           
                85                  90                  95                

aac ggc tca gac gag caa ggc tgt ccc ccc aag acg tgc tcc cag gac        336
Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp           
            100                 105                 110                   

gag ttt cgc tgc cac gat ggg aag tgc atc tct cgg cag ttc gtc tgt        384
Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys           
        115                 120                 125                       

gac tca gac cgg gac tgc ttg gac ggc tca gac gag gcc tcc tgc ccg        432
Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro           
    130                 135                 140                           

gtg ctc acc tgt ggt ccc gcc agc ttc cag tgc aac agc tcc acc tgc        480
Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys           
145                 150                 155                 160           

atc ccc cag ctg tgg gcc tgc gac aac gac ccc gac tgc gaa gat ggc        528
Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly           
                165                 170                 175               

tcg gat gag tgg ccg cag cgc tgt agg ggt ctt tac gtg ttc caa ggg        576
Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly           
            180                 185                 190                   

gac agt agc ccc tgc tcg gcc ttc gag ttc cac tgc cta agt ggc gag        624
Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu           
        195                 200                 205                       

tgc atc cac tcc agc tgg cgc tgt gat ggt ggc ccc gac tgc aag gac        672
Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp           
    210                 215                 220                           

aaa tct gac gag gaa aac tgc gct gtg gcc acc tgt cgc cct gac gaa        720
Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu           
225                 230                 235                 240           

ttc cag tgc tct gat gga aac tgc atc cat ggc agc cgg cag tgt gac        768
Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp           
                245                 250                 255               

cgg gaa tat gac tgc aag gac atg agc gat gaa gtt ggc tgc gtt aat        816
Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn           
            260                 265                 270                   

gtg aca ctc tgc gag gga ccc aac aag ttc aag tgt cac agc ggc gaa        864
Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu           
        275                 280                 285                       

tgc atc acc ctg gac aaa gtc tgc aac atg gct aga gac tgc cgg gac        912
Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp           
    290                 295                 300                           

tgg tca gat gaa ccc atc aaa gag tgc ggg acc aac gaa tgc ttg gac        960
Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp           
305                 310                 315                 320           

aac aac ggc ggc tgt tcc cac gtc tgc aat gac ctt aag atc ggc tac       1008
Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Leu Lys Ile Gly Tyr           
                325                 330                 335               

gag tgc gac tgc ccc gac ggc ttc cag ctg gtg gcc cag cga aga tgc       1056
Glu Cys Asp Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys           
            340                 345                 350                   

gaa gat atc gat gag tgt cag gat ccc gac acc tgc agc cag ctc tgc       1104
Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys           
        355                 360                 365                       

gtg aac ctg gag ggt ggc tac aag tgc cag tgt gag gaa ggc ttc cag       1152
Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln           
    370                 375                 380                           

ctg gac ccc cac acg aag gcc tgc aag gct gtg ggc tcc atc gcc tac       1200
Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr           
385                 390                 395                 400           

ctc ttc ttc acc aac cgg cac gag gtc agg aag atg acg ctg gac cgg       1248
Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg           
                405                 410                 415               

agc gag tac acc agc ctc atc ccc aac ctg agg aac gtg gtc gct ctg       1296
Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu           
            420                 425                 430                   

gac acg gag gtg gcc agc aat aga atc tac tgg tct gac ctg tcc cag       1344
Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln           
        435                 440                 445                       

aga atg atc tgc agc acc cag ctt gac aga gcc cac ggc gtc tct tcc       1392
Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser           
    450                 455                 460                           

tat gac acc gtc atc agc agg gac atc cag gcc ccc gac ggg ctg gct       1440
Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala           
465                 470                 475                 480           

gtg gac tgg atc cac agc aac atc tac tgg acc gac tct gtc ctg ggc       1488
Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly           
                485                 490                 495               

act gtc tct gtt gcg gat acc aag ggc gtg aag agg aaa acg tta ttc       1536
Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe           
            500                 505                 510                   

agg gag aac ggc tcc aag cca agg gcc atc gtg gtg gat cct gtt cat       1584
Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His           
        515                 520                 525                       

ggc ttc atg tac tgg act gac tgg gga act ccc gcc aag atc aag aaa       1632
Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys           
    530                 535                 540                           

ggg ggc ctg aat ggt gtg gac atc tac tcg ctg gtg act gaa aac att       1680
Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile           
545                 550                 555                 560           

cag tgg ccc aat ggc atc acc cta gat ctc ctc agt ggc cgc ctc tac       1728
Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr           
                565                 570                 575               

tgg gtt gac tcc aaa ctt cac tcc atc tca agc atc gat gtc aat ggg       1776
Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly           
            580                 585                 590                   

ggc aac cgg aag acc atc ttg gag gat gaa aag agg ctg gcc cac ccc       1824
Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro           
        595                 600                 605                       

ttc tcc ttg gcc gtc ttt gag gac aaa gta ttt tgg aca gat atc atc       1872
Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile           
    610                 615                 620                           

aac gaa gcc att ttc agt gcc aac cgc ctc aca ggt tcc gat gtc aac       1920
Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn           
625                 630                 635                 640           

ttg ttg gct gaa aac cta ctg tcc cca gag gat atg gtc ctc ttc cac       1968
Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His           
                645                 650                 655               

aac ctc acc cag cca aga gga gtg aac tgg tgt gag agg acc acc ctg       2016
Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu           
            660                 665                 670                   

agc aat ggc ggc tgc cag tat ctg tgc ctc cct gcc ccg cag atc aac       2064
Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn           
        675                 680                 685                       

ccc cac tcg ccc aag ttt acc tgc gcc tgc ccg gac ggc atg ctg ctg       2112
Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu           
    690                 695                 700                           

gcc agg gac atg agg agc tgc ctc aca gag gct gag gct gca gtg gcc       2160
Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala           
705                 710                 715                 720           

acc cag gag aca tcc acc gtc agg cta aag gtc agc tcc aca gcc gta       2208
Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val           
                725                 730                 735               

agg aca cag cac aca acc acc cgg cct gtt ccc gac acc tcc cgg ctg       2256
Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu           
            740                 745                 750                   

cct ggg gcc acc cct ggg ctc acc acg gtg gag ata gtg aca atg tct       2304
Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser           
        755                 760                 765                       

cac caa gct ctg ggc gac gtt gct ggc aga gga aat gag aag aag ccc       2352
His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro           
    770                 775                 780                           

agt agc gtg agg gct ctg tcc att gtc ctc ccc atc gtg ctc ctc gtc       2400
Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val           
785                 790                 795                 800           

ttc ctt tgc ctg ggg gtc ttc ctt cta tgg aag aac tgg cgg ctt aag       2448
Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys           
                805                 810                 815               

aac atc aac agc atc aac ttt gac aac ccc gtc tat cag agg acc aca       2496
Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Arg Thr Thr           
            820                 825                 830                   

gag gat gag gtc cac att gcc cac aac cag gac ggc tac agc tac ccc       2544
Glu Asp Glu Val His Ile Ala His Asn Gln Asp Gly Tyr Ser Tyr Pro           
        835                 840                 845                       

tcg aga cag atg gtc agt ctg gag gat gac gtg gcg tga                   2583
Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala                           
    850                 855                 860                           


<210>  40
<211>  860
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Synthetic Construct

<400>  40

Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu 
1               5                   10                  15      


Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe 
            20                  25                  30          


Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly 
        35                  40                  45              


Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu 
    50                  55                  60                  


Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn 
65                  70                  75                  80  


Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp 
                85                  90                  95      


Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp 
            100                 105                 110         


Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys 
        115                 120                 125             


Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro 
    130                 135                 140                 


Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys 
145                 150                 155                 160 


Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly 
                165                 170                 175     


Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly 
            180                 185                 190         


Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu 
        195                 200                 205             


Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp 
    210                 215                 220                 


Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu 
225                 230                 235                 240 


Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp 
                245                 250                 255     


Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn 
            260                 265                 270         


Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu 
        275                 280                 285             


Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp 
    290                 295                 300                 


Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp 
305                 310                 315                 320 


Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Leu Lys Ile Gly Tyr 
                325                 330                 335     


Glu Cys Asp Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys 
            340                 345                 350         


Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys 
        355                 360                 365             


Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln 
    370                 375                 380                 


Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr 
385                 390                 395                 400 


Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg 
                405                 410                 415     


Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu 
            420                 425                 430         


Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln 
        435                 440                 445             


Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser 
    450                 455                 460                 


Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala 
465                 470                 475                 480 


Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly 
                485                 490                 495     


Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe 
            500                 505                 510         


Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His 
        515                 520                 525             


Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys 
    530                 535                 540                 


Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile 
545                 550                 555                 560 


Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr 
                565                 570                 575     


Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly 
            580                 585                 590         


Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro 
        595                 600                 605             


Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile 
    610                 615                 620                 


Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn 
625                 630                 635                 640 


Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His 
                645                 650                 655     


Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu 
            660                 665                 670         


Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn 
        675                 680                 685             


Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu 
    690                 695                 700                 


Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala 
705                 710                 715                 720 


Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val 
                725                 730                 735     


Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu 
            740                 745                 750         


Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser 
        755                 760                 765             


His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro 
    770                 775                 780                 


Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val 
785                 790                 795                 800 


Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys 
                805                 810                 815     


Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Arg Thr Thr 
            820                 825                 830         


Glu Asp Glu Val His Ile Ala His Asn Gln Asp Gly Tyr Ser Tyr Pro 
        835                 840                 845             


Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala 
    850                 855                 860 


