                         SEQUENCE LISTING

<110>  Array BioPharma, Inc.
 
<120>  2-ARYL- AND 2-HETEROARYL-SUBSTITUTED 2-PYRIDAZIN-3(2H)-ONE 
       COMPOUNDS AS INHIBITORS OF FGFR TYROSINE KINASES

<130>  40449-0035WO1

<150>  62/245,956
<151>  2015-10-23

<160>  8     

<170>  PatentIn version 3.5

<210>  1
<211>  822
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Trp Ser Trp Lys Cys Leu Leu Phe Trp Ala Val Leu Val Thr Ala 
1               5                   10                  15      


Thr Leu Cys Thr Ala Arg Pro Ser Pro Thr Leu Pro Glu Gln Ala Gln 
            20                  25                  30          


Pro Trp Gly Ala Pro Val Glu Val Glu Ser Phe Leu Val His Pro Gly 
        35                  40                  45              


Asp Leu Leu Gln Leu Arg Cys Arg Leu Arg Asp Asp Val Gln Ser Ile 
    50                  55                  60                  


Asn Trp Leu Arg Asp Gly Val Gln Leu Ala Glu Ser Asn Arg Thr Arg 
65                  70                  75                  80  


Ile Thr Gly Glu Glu Val Glu Val Gln Asp Ser Val Pro Ala Asp Ser 
                85                  90                  95      


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


Tyr Phe Ser Val Asn Val Ser Asp Ala Leu Pro Ser Ser Glu Asp Asp 
        115                 120                 125             


Asp Asp Asp Asp Asp Ser Ser Ser Glu Glu Lys Glu Thr Asp Asn Thr 
    130                 135                 140                 


Lys Pro Asn Arg Met Pro Val Ala Pro Tyr Trp Thr Ser Pro Glu Lys 
145                 150                 155                 160 


Met Glu Lys Lys Leu His Ala Val Pro Ala Ala Lys Thr Val Lys Phe 
                165                 170                 175     


Lys Cys Pro Ser Ser Gly Thr Pro Asn Pro Thr Leu Arg Trp Leu Lys 
            180                 185                 190         


Asn Gly Lys Glu Phe Lys Pro Asp His Arg Ile Gly Gly Tyr Lys Val 
        195                 200                 205             


Arg Tyr Ala Thr Trp Ser Ile Ile Met Asp Ser Val Val Pro Ser Asp 
    210                 215                 220                 


Lys Gly Asn Tyr Thr Cys Ile Val Glu Asn Glu Tyr Gly Ser Ile Asn 
225                 230                 235                 240 


His Thr Tyr Gln Leu Asp Val Val Glu Arg Ser Pro His Arg Pro Ile 
                245                 250                 255     


Leu Gln Ala Gly Leu Pro Ala Asn Lys Thr Val Ala Leu Gly Ser Asn 
            260                 265                 270         


Val Glu Phe Met Cys Lys Val Tyr Ser Asp Pro Gln Pro His Ile Gln 
        275                 280                 285             


Trp Leu Lys His Ile Glu Val Asn Gly Ser Lys Ile Gly Pro Asp Asn 
    290                 295                 300                 


Leu Pro Tyr Val Gln Ile Leu Lys Thr Ala Gly Val Asn Thr Thr Asp 
305                 310                 315                 320 


Lys Glu Met Glu Val Leu His Leu Arg Asn Val Ser Phe Glu Asp Ala 
                325                 330                 335     


Gly Glu Tyr Thr Cys Leu Ala Gly Asn Ser Ile Gly Leu Ser His His 
            340                 345                 350         


Ser Ala Trp Leu Thr Val Leu Glu Ala Leu Glu Glu Arg Pro Ala Val 
        355                 360                 365             


Met Thr Ser Pro Leu Tyr Leu Glu Ile Ile Ile Tyr Cys Thr Gly Ala 
    370                 375                 380                 


Phe Leu Ile Ser Cys Met Val Gly Ser Val Ile Val Tyr Lys Met Lys 
385                 390                 395                 400 


Ser Gly Thr Lys Lys Ser Asp Phe His Ser Gln Met Ala Val His Lys 
                405                 410                 415     


Leu Ala Lys Ser Ile Pro Leu Arg Arg Gln Val Thr Val Ser Ala Asp 
            420                 425                 430         


Ser Ser Ala Ser Met Asn Ser Gly Val Leu Leu Val Arg Pro Ser Arg 
        435                 440                 445             


Leu Ser Ser Ser Gly Thr Pro Met Leu Ala Gly Val Ser Glu Tyr Glu 
    450                 455                 460                 


Leu Pro Glu Asp Pro Arg Trp Glu Leu Pro Arg Asp Arg Leu Val Leu 
465                 470                 475                 480 


Gly Lys Pro Leu Gly Glu Gly Cys Phe Gly Gln Val Val Leu Ala Glu 
                485                 490                 495     


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


Val Lys Met Leu Lys Ser Asp Ala Thr Glu Lys Asp Leu Ser Asp Leu 
        515                 520                 525             


Ile Ser Glu Met Glu Met Met Lys Met Ile Gly Lys His Lys Asn Ile 
    530                 535                 540                 


Ile Asn Leu Leu Gly Ala Cys Thr Gln Asp Gly Pro Leu Tyr Val Ile 
545                 550                 555                 560 


Val Glu Tyr Ala Ser Lys Gly Asn Leu Arg Glu Tyr Leu Gln Ala Arg 
                565                 570                 575     


Arg Pro Pro Gly Leu Glu Tyr Cys Tyr Asn Pro Ser His Asn Pro Glu 
            580                 585                 590         


Glu Gln Leu Ser Ser Lys Asp Leu Val Ser Cys Ala Tyr Gln Val Ala 
        595                 600                 605             


Arg Gly Met Glu Tyr Leu Ala Ser Lys Lys Cys Ile His Arg Asp Leu 
    610                 615                 620                 


Ala Ala Arg Asn Val Leu Val Thr Glu Asp Asn Val Met Lys Ile Ala 
625                 630                 635                 640 


Asp Phe Gly Leu Ala Arg Asp Ile His His Ile Asp Tyr Tyr Lys Lys 
                645                 650                 655     


Thr Thr Asn Gly Arg Leu Pro Val Lys Trp Met Ala Pro Glu Ala Leu 
            660                 665                 670         


Phe Asp Arg Ile Tyr Thr His Gln Ser Asp Val Trp Ser Phe Gly Val 
        675                 680                 685             


Leu Leu Trp Glu Ile Phe Thr Leu Gly Gly Ser Pro Tyr Pro Gly Val 
    690                 695                 700                 


Pro Val Glu Glu Leu Phe Lys Leu Leu Lys Glu Gly His Arg Met Asp 
705                 710                 715                 720 


Lys Pro Ser Asn Cys Thr Asn Glu Leu Tyr Met Met Met Arg Asp Cys 
                725                 730                 735     


Trp His Ala Val Pro Ser Gln Arg Pro Thr Phe Lys Gln Leu Val Glu 
            740                 745                 750         


Asp Leu Asp Arg Ile Val Ala Leu Thr Ser Asn Gln Glu Tyr Leu Asp 
        755                 760                 765             


Leu Ser Met Pro Leu Asp Gln Tyr Ser Pro Ser Phe Pro Asp Thr Arg 
    770                 775                 780                 


Ser Ser Thr Cys Ser Ser Gly Glu Asp Ser Val Phe Ser His Glu Pro 
785                 790                 795                 800 


Leu Pro Glu Glu Pro Cys Leu Pro Arg His Pro Ala Gln Leu Ala Asn 
                805                 810                 815     


Gly Gly Leu Lys Arg Arg 
            820         


<210>  2
<211>  820
<212>  PRT
<213>  Homo sapiens

<400>  2

Met Trp Ser Trp Lys Cys Leu Leu Phe Trp Ala Val Leu Val Thr Ala 
1               5                   10                  15      


Thr Leu Cys Thr Ala Arg Pro Ser Pro Thr Leu Pro Glu Gln Ala Gln 
            20                  25                  30          


Pro Trp Gly Ala Pro Val Glu Val Glu Ser Phe Leu Val His Pro Gly 
        35                  40                  45              


Asp Leu Leu Gln Leu Arg Cys Arg Leu Arg Asp Asp Val Gln Ser Ile 
    50                  55                  60                  


Asn Trp Leu Arg Asp Gly Val Gln Leu Ala Glu Ser Asn Arg Thr Arg 
65                  70                  75                  80  


Ile Thr Gly Glu Glu Val Glu Val Gln Asp Ser Val Pro Ala Asp Ser 
                85                  90                  95      


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


Tyr Phe Ser Val Asn Val Ser Asp Ala Leu Pro Ser Ser Glu Asp Asp 
        115                 120                 125             


Asp Asp Asp Asp Asp Ser Ser Ser Glu Glu Lys Glu Thr Asp Asn Thr 
    130                 135                 140                 


Lys Pro Asn Pro Val Ala Pro Tyr Trp Thr Ser Pro Glu Lys Met Glu 
145                 150                 155                 160 


Lys Lys Leu His Ala Val Pro Ala Ala Lys Thr Val Lys Phe Lys Cys 
                165                 170                 175     


Pro Ser Ser Gly Thr Pro Asn Pro Thr Leu Arg Trp Leu Lys Asn Gly 
            180                 185                 190         


Lys Glu Phe Lys Pro Asp His Arg Ile Gly Gly Tyr Lys Val Arg Tyr 
        195                 200                 205             


Ala Thr Trp Ser Ile Ile Met Asp Ser Val Val Pro Ser Asp Lys Gly 
    210                 215                 220                 


Asn Tyr Thr Cys Ile Val Glu Asn Glu Tyr Gly Ser Ile Asn His Thr 
225                 230                 235                 240 


Tyr Gln Leu Asp Val Val Glu Arg Ser Pro His Arg Pro Ile Leu Gln 
                245                 250                 255     


Ala Gly Leu Pro Ala Asn Lys Thr Val Ala Leu Gly Ser Asn Val Glu 
            260                 265                 270         


Phe Met Cys Lys Val Tyr Ser Asp Pro Gln Pro His Ile Gln Trp Leu 
        275                 280                 285             


Lys His Ile Glu Val Asn Gly Ser Lys Ile Gly Pro Asp Asn Leu Pro 
    290                 295                 300                 


Tyr Val Gln Ile Leu Lys Thr Ala Gly Val Asn Thr Thr Asp Lys Glu 
305                 310                 315                 320 


Met Glu Val Leu His Leu Arg Asn Val Ser Phe Glu Asp Ala Gly Glu 
                325                 330                 335     


Tyr Thr Cys Leu Ala Gly Asn Ser Ile Gly Leu Ser His His Ser Ala 
            340                 345                 350         


Trp Leu Thr Val Leu Glu Ala Leu Glu Glu Arg Pro Ala Val Met Thr 
        355                 360                 365             


Ser Pro Leu Tyr Leu Glu Ile Ile Ile Tyr Cys Thr Gly Ala Phe Leu 
    370                 375                 380                 


Ile Ser Cys Met Val Gly Ser Val Ile Val Tyr Lys Met Lys Ser Gly 
385                 390                 395                 400 


Thr Lys Lys Ser Asp Phe His Ser Gln Met Ala Val His Lys Leu Ala 
                405                 410                 415     


Lys Ser Ile Pro Leu Arg Arg Gln Val Thr Val Ser Ala Asp Ser Ser 
            420                 425                 430         


Ala Ser Met Asn Ser Gly Val Leu Leu Val Arg Pro Ser Arg Leu Ser 
        435                 440                 445             


Ser Ser Gly Thr Pro Met Leu Ala Gly Val Ser Glu Tyr Glu Leu Pro 
    450                 455                 460                 


Glu Asp Pro Arg Trp Glu Leu Pro Arg Asp Arg Leu Val Leu Gly Lys 
465                 470                 475                 480 


Pro Leu Gly Glu Gly Cys Phe Gly Gln Val Val Leu Ala Glu Ala Ile 
                485                 490                 495     


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


Met Leu Lys Ser Asp Ala Thr Glu Lys Asp Leu Ser Asp Leu Ile Ser 
        515                 520                 525             


Glu Met Glu Met Met Lys Met Ile Gly Lys His Lys Asn Ile Ile Asn 
    530                 535                 540                 


Leu Leu Gly Ala Cys Thr Gln Asp Gly Pro Leu Tyr Val Ile Val Glu 
545                 550                 555                 560 


Tyr Ala Ser Lys Gly Asn Leu Arg Glu Tyr Leu Gln Ala Arg Arg Pro 
                565                 570                 575     


Pro Gly Leu Glu Tyr Cys Tyr Asn Pro Ser His Asn Pro Glu Glu Gln 
            580                 585                 590         


Leu Ser Ser Lys Asp Leu Val Ser Cys Ala Tyr Gln Val Ala Arg Gly 
        595                 600                 605             


Met Glu Tyr Leu Ala Ser Lys Lys Cys Ile His Arg Asp Leu Ala Ala 
    610                 615                 620                 


Arg Asn Val Leu Val Thr Glu Asp Asn Val Met Lys Ile Ala Asp Phe 
625                 630                 635                 640 


Gly Leu Ala Arg Asp Ile His His Ile Asp Tyr Tyr Lys Lys Thr Thr 
                645                 650                 655     


Asn Gly Arg Leu Pro Val Lys Trp Met Ala Pro Glu Ala Leu Phe Asp 
            660                 665                 670         


Arg Ile Tyr Thr His Gln Ser Asp Val Trp Ser Phe Gly Val Leu Leu 
        675                 680                 685             


Trp Glu Ile Phe Thr Leu Gly Gly Ser Pro Tyr Pro Gly Val Pro Val 
    690                 695                 700                 


Glu Glu Leu Phe Lys Leu Leu Lys Glu Gly His Arg Met Asp Lys Pro 
705                 710                 715                 720 


Ser Asn Cys Thr Asn Glu Leu Tyr Met Met Met Arg Asp Cys Trp His 
                725                 730                 735     


Ala Val Pro Ser Gln Arg Pro Thr Phe Lys Gln Leu Val Glu Asp Leu 
            740                 745                 750         


Asp Arg Ile Val Ala Leu Thr Ser Asn Gln Glu Tyr Leu Asp Leu Ser 
        755                 760                 765             


Met Pro Leu Asp Gln Tyr Ser Pro Ser Phe Pro Asp Thr Arg Ser Ser 
    770                 775                 780                 


Thr Cys Ser Ser Gly Glu Asp Ser Val Phe Ser His Glu Pro Leu Pro 
785                 790                 795                 800 


Glu Glu Pro Cys Leu Pro Arg His Pro Ala Gln Leu Ala Asn Gly Gly 
                805                 810                 815     


Leu Lys Arg Arg 
            820 


<210>  3
<211>  821
<212>  PRT
<213>  Homo sapiens

<400>  3

Met Val Ser Trp Gly Arg Phe Ile Cys Leu Val Val Val Thr Met Ala 
1               5                   10                  15      


Thr Leu Ser Leu Ala Arg Pro Ser Phe Ser Leu Val Glu Asp Thr Thr 
            20                  25                  30          


Leu Glu Pro Glu Glu Pro Pro Thr Lys Tyr Gln Ile Ser Gln Pro Glu 
        35                  40                  45              


Val Tyr Val Ala Ala Pro Gly Glu Ser Leu Glu Val Arg Cys Leu Leu 
    50                  55                  60                  


Lys Asp Ala Ala Val Ile Ser Trp Thr Lys Asp Gly Val His Leu Gly 
65                  70                  75                  80  


Pro Asn Asn Arg Thr Val Leu Ile Gly Glu Tyr Leu Gln Ile Lys Gly 
                85                  90                  95      


Ala Thr Pro Arg Asp Ser Gly Leu Tyr Ala Cys Thr Ala Ser Arg Thr 
            100                 105                 110         


Val Asp Ser Glu Thr Trp Tyr Phe Met Val Asn Val Thr Asp Ala Ile 
        115                 120                 125             


Ser Ser Gly Asp Asp Glu Asp Asp Thr Asp Gly Ala Glu Asp Phe Val 
    130                 135                 140                 


Ser Glu Asn Ser Asn Asn Lys Arg Ala Pro Tyr Trp Thr Asn Thr Glu 
145                 150                 155                 160 


Lys Met Glu Lys Arg Leu His Ala Val Pro Ala Ala Asn Thr Val Lys 
                165                 170                 175     


Phe Arg Cys Pro Ala Gly Gly Asn Pro Met Pro Thr Met Arg Trp Leu 
            180                 185                 190         


Lys Asn Gly Lys Glu Phe Lys Gln Glu His Arg Ile Gly Gly Tyr Lys 
        195                 200                 205             


Val Arg Asn Gln His Trp Ser Leu Ile Met Glu Ser Val Val Pro Ser 
    210                 215                 220                 


Asp Lys Gly Asn Tyr Thr Cys Val Val Glu Asn Glu Tyr Gly Ser Ile 
225                 230                 235                 240 


Asn His Thr Tyr His Leu Asp Val Val Glu Arg Ser Pro His Arg Pro 
                245                 250                 255     


Ile Leu Gln Ala Gly Leu Pro Ala Asn Ala Ser Thr Val Val Gly Gly 
            260                 265                 270         


Asp Val Glu Phe Val Cys Lys Val Tyr Ser Asp Ala Gln Pro His Ile 
        275                 280                 285             


Gln Trp Ile Lys His Val Glu Lys Asn Gly Ser Lys Tyr Gly Pro Asp 
    290                 295                 300                 


Gly Leu Pro Tyr Leu Lys Val Leu Lys Ala Ala Gly Val Asn Thr Thr 
305                 310                 315                 320 


Asp Lys Glu Ile Glu Val Leu Tyr Ile Arg Asn Val Thr Phe Glu Asp 
                325                 330                 335     


Ala Gly Glu Tyr Thr Cys Leu Ala Gly Asn Ser Ile Gly Ile Ser Phe 
            340                 345                 350         


His Ser Ala Trp Leu Thr Val Leu Pro Ala Pro Gly Arg Glu Lys Glu 
        355                 360                 365             


Ile Thr Ala Ser Pro Asp Tyr Leu Glu Ile Ala Ile Tyr Cys Ile Gly 
    370                 375                 380                 


Val Phe Leu Ile Ala Cys Met Val Val Thr Val Ile Leu Cys Arg Met 
385                 390                 395                 400 


Lys Asn Thr Thr Lys Lys Pro Asp Phe Ser Ser Gln Pro Ala Val His 
                405                 410                 415     


Lys Leu Thr Lys Arg Ile Pro Leu Arg Arg Gln Val Thr Val Ser Ala 
            420                 425                 430         


Glu Ser Ser Ser Ser Met Asn Ser Asn Thr Pro Leu Val Arg Ile Thr 
        435                 440                 445             


Thr Arg Leu Ser Ser Thr Ala Asp Thr Pro Met Leu Ala Gly Val Ser 
    450                 455                 460                 


Glu Tyr Glu Leu Pro Glu Asp Pro Lys Trp Glu Phe Pro Arg Asp Lys 
465                 470                 475                 480 


Leu Thr Leu Gly Lys Pro Leu Gly Glu Gly Cys Phe Gly Gln Val Val 
                485                 490                 495     


Met Ala Glu Ala Val Gly Ile Asp Lys Asp Lys Pro Lys Glu Ala Val 
            500                 505                 510         


Thr Val Ala Val Lys Met Leu Lys Asp Asp Ala Thr Glu Lys Asp Leu 
        515                 520                 525             


Ser Asp Leu Val Ser Glu Met Glu Met Met Lys Met Ile Gly Lys His 
    530                 535                 540                 


Lys Asn Ile Ile Asn Leu Leu Gly Ala Cys Thr Gln Asp Gly Pro Leu 
545                 550                 555                 560 


Tyr Val Ile Val Glu Tyr Ala Ser Lys Gly Asn Leu Arg Glu Tyr Leu 
                565                 570                 575     


Arg Ala Arg Arg Pro Pro Gly Met Glu Tyr Ser Tyr Asp Ile Asn Arg 
            580                 585                 590         


Val Pro Glu Glu Gln Met Thr Phe Lys Asp Leu Val Ser Cys Thr Tyr 
        595                 600                 605             


Gln Leu Ala Arg Gly Met Glu Tyr Leu Ala Ser Gln Lys Cys Ile His 
    610                 615                 620                 


Arg Asp Leu Ala Ala Arg Asn Val Leu Val Thr Glu Asn Asn Val Met 
625                 630                 635                 640 


Lys Ile Ala Asp Phe Gly Leu Ala Arg Asp Ile Asn Asn Ile Asp Tyr 
                645                 650                 655     


Tyr Lys Lys Thr Thr Asn Gly Arg Leu Pro Val Lys Trp Met Ala Pro 
            660                 665                 670         


Glu Ala Leu Phe Asp Arg Val Tyr Thr His Gln Ser Asp Val Trp Ser 
        675                 680                 685             


Phe Gly Val Leu Met Trp Glu Ile Phe Thr Leu Gly Gly Ser Pro Tyr 
    690                 695                 700                 


Pro Gly Ile Pro Val Glu Glu Leu Phe Lys Leu Leu Lys Glu Gly His 
705                 710                 715                 720 


Arg Met Asp Lys Pro Ala Asn Cys Thr Asn Glu Leu Tyr Met Met Met 
                725                 730                 735     


Arg Asp Cys Trp His Ala Val Pro Ser Gln Arg Pro Thr Phe Lys Gln 
            740                 745                 750         


Leu Val Glu Asp Leu Asp Arg Ile Leu Thr Leu Thr Thr Asn Glu Glu 
        755                 760                 765             


Tyr Leu Asp Leu Ser Gln Pro Leu Glu Gln Tyr Ser Pro Ser Tyr Pro 
    770                 775                 780                 


Asp Thr Arg Ser Ser Cys Ser Ser Gly Asp Asp Ser Val Phe Ser Pro 
785                 790                 795                 800 


Asp Pro Met Pro Tyr Glu Pro Cys Leu Pro Gln Tyr Pro His Ile Asn 
                805                 810                 815     


Gly Ser Val Lys Thr 
            820     


<210>  4
<211>  822
<212>  PRT
<213>  Homo sapiens

<400>  4

Met Val Ser Trp Gly Arg Phe Ile Cys Leu Val Val Val Thr Met Ala 
1               5                   10                  15      


Thr Leu Ser Leu Ala Arg Pro Ser Phe Ser Leu Val Glu Asp Thr Thr 
            20                  25                  30          


Leu Glu Pro Glu Glu Pro Pro Thr Lys Tyr Gln Ile Ser Gln Pro Glu 
        35                  40                  45              


Val Tyr Val Ala Ala Pro Gly Glu Ser Leu Glu Val Arg Cys Leu Leu 
    50                  55                  60                  


Lys Asp Ala Ala Val Ile Ser Trp Thr Lys Asp Gly Val His Leu Gly 
65                  70                  75                  80  


Pro Asn Asn Arg Thr Val Leu Ile Gly Glu Tyr Leu Gln Ile Lys Gly 
                85                  90                  95      


Ala Thr Pro Arg Asp Ser Gly Leu Tyr Ala Cys Thr Ala Ser Arg Thr 
            100                 105                 110         


Val Asp Ser Glu Thr Trp Tyr Phe Met Val Asn Val Thr Asp Ala Ile 
        115                 120                 125             


Ser Ser Gly Asp Asp Glu Asp Asp Thr Asp Gly Ala Glu Asp Phe Val 
    130                 135                 140                 


Ser Glu Asn Ser Asn Asn Lys Arg Ala Pro Tyr Trp Thr Asn Thr Glu 
145                 150                 155                 160 


Lys Met Glu Lys Arg Leu His Ala Val Pro Ala Ala Asn Thr Val Lys 
                165                 170                 175     


Phe Arg Cys Pro Ala Gly Gly Asn Pro Met Pro Thr Met Arg Trp Leu 
            180                 185                 190         


Lys Asn Gly Lys Glu Phe Lys Gln Glu His Arg Ile Gly Gly Tyr Lys 
        195                 200                 205             


Val Arg Asn Gln His Trp Ser Leu Ile Met Glu Ser Val Val Pro Ser 
    210                 215                 220                 


Asp Lys Gly Asn Tyr Thr Cys Val Val Glu Asn Glu Tyr Gly Ser Ile 
225                 230                 235                 240 


Asn His Thr Tyr His Leu Asp Val Val Glu Arg Ser Pro His Arg Pro 
                245                 250                 255     


Ile Leu Gln Ala Gly Leu Pro Ala Asn Ala Ser Thr Val Val Gly Gly 
            260                 265                 270         


Asp Val Glu Phe Val Cys Lys Val Tyr Ser Asp Ala Gln Pro His Ile 
        275                 280                 285             


Gln Trp Ile Lys His Val Glu Lys Asn Gly Ser Lys Tyr Gly Pro Asp 
    290                 295                 300                 


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


Asn Ala Glu Val Leu Ala Leu Phe Asn Val Thr Glu Ala Asp Ala Gly 
                325                 330                 335     


Glu Tyr Ile Cys Lys Val Ser Asn Tyr Ile Gly Gln Ala Asn Gln Ser 
            340                 345                 350         


Ala Trp Leu Thr Val Leu Pro Lys Gln Gln Ala Pro Gly Arg Glu Lys 
        355                 360                 365             


Glu Ile Thr Ala Ser Pro Asp Tyr Leu Glu Ile Ala Ile Tyr Cys Ile 
    370                 375                 380                 


Gly Val Phe Leu Ile Ala Cys Met Val Val Thr Val Ile Leu Cys Arg 
385                 390                 395                 400 


Met Lys Asn Thr Thr Lys Lys Pro Asp Phe Ser Ser Gln Pro Ala Val 
                405                 410                 415     


His Lys Leu Thr Lys Arg Ile Pro Leu Arg Arg Gln Val Thr Val Ser 
            420                 425                 430         


Ala Glu Ser Ser Ser Ser Met Asn Ser Asn Thr Pro Leu Val Arg Ile 
        435                 440                 445             


Thr Thr Arg Leu Ser Ser Thr Ala Asp Thr Pro Met Leu Ala Gly Val 
    450                 455                 460                 


Ser Glu Tyr Glu Leu Pro Glu Asp Pro Lys Trp Glu Phe Pro Arg Asp 
465                 470                 475                 480 


Lys Leu Thr Leu Gly Lys Pro Leu Gly Glu Gly Cys Phe Gly Gln Val 
                485                 490                 495     


Val Met Ala Glu Ala Val Gly Ile Asp Lys Asp Lys Pro Lys Glu Ala 
            500                 505                 510         


Val Thr Val Ala Val Lys Met Leu Lys Asp Asp Ala Thr Glu Lys Asp 
        515                 520                 525             


Leu Ser Asp Leu Val Ser Glu Met Glu Met Met Lys Met Ile Gly Lys 
    530                 535                 540                 


His Lys Asn Ile Ile Asn Leu Leu Gly Ala Cys Thr Gln Asp Gly Pro 
545                 550                 555                 560 


Leu Tyr Val Ile Val Glu Tyr Ala Ser Lys Gly Asn Leu Arg Glu Tyr 
                565                 570                 575     


Leu Arg Ala Arg Arg Pro Pro Gly Met Glu Tyr Ser Tyr Asp Ile Asn 
            580                 585                 590         


Arg Val Pro Glu Glu Gln Met Thr Phe Lys Asp Leu Val Ser Cys Thr 
        595                 600                 605             


Tyr Gln Leu Ala Arg Gly Met Glu Tyr Leu Ala Ser Gln Lys Cys Ile 
    610                 615                 620                 


His Arg Asp Leu Ala Ala Arg Asn Val Leu Val Thr Glu Asn Asn Val 
625                 630                 635                 640 


Met Lys Ile Ala Asp Phe Gly Leu Ala Arg Asp Ile Asn Asn Ile Asp 
                645                 650                 655     


Tyr Tyr Lys Lys Thr Thr Asn Gly Arg Leu Pro Val Lys Trp Met Ala 
            660                 665                 670         


Pro Glu Ala Leu Phe Asp Arg Val Tyr Thr His Gln Ser Asp Val Trp 
        675                 680                 685             


Ser Phe Gly Val Leu Met Trp Glu Ile Phe Thr Leu Gly Gly Ser Pro 
    690                 695                 700                 


Tyr Pro Gly Ile Pro Val Glu Glu Leu Phe Lys Leu Leu Lys Glu Gly 
705                 710                 715                 720 


His Arg Met Asp Lys Pro Ala Asn Cys Thr Asn Glu Leu Tyr Met Met 
                725                 730                 735     


Met Arg Asp Cys Trp His Ala Val Pro Ser Gln Arg Pro Thr Phe Lys 
            740                 745                 750         


Gln Leu Val Glu Asp Leu Asp Arg Ile Leu Thr Leu Thr Thr Asn Glu 
        755                 760                 765             


Glu Tyr Leu Asp Leu Ser Gln Pro Leu Glu Gln Tyr Ser Pro Ser Tyr 
    770                 775                 780                 


Pro Asp Thr Arg Ser Ser Cys Ser Ser Gly Asp Asp Ser Val Phe Ser 
785                 790                 795                 800 


Pro Asp Pro Met Pro Tyr Glu Pro Cys Leu Pro Gln Tyr Pro His Ile 
                805                 810                 815     


Asn Gly Ser Val Lys Thr 
            820         


<210>  5
<211>  806
<212>  PRT
<213>  Homo sapien

<400>  5

Met Gly Ala Pro Ala Cys Ala Leu Ala Leu Cys Val Ala Val Ala Ile 
1               5                   10                  15      


Val Ala Gly Ala Ser Ser Glu Ser Leu Gly Thr Glu Gln Arg Val Val 
            20                  25                  30          


Gly Arg Ala Ala Glu Val Pro Gly Pro Glu Pro Gly Gln Gln Glu Gln 
        35                  40                  45              


Leu Val Phe Gly Ser Gly Asp Ala Val Glu Leu Ser Cys Pro Pro Pro 
    50                  55                  60                  


Gly Gly Gly Pro Met Gly Pro Thr Val Trp Val Lys Asp Gly Thr Gly 
65                  70                  75                  80  


Leu Val Pro Ser Glu Arg Val Leu Val Gly Pro Gln Arg Leu Gln Val 
                85                  90                  95      


Leu Asn Ala Ser His Glu Asp Ser Gly Ala Tyr Ser Cys Arg Gln Arg 
            100                 105                 110         


Leu Thr Gln Arg Val Leu Cys His Phe Ser Val Arg Val Thr Asp Ala 
        115                 120                 125             


Pro Ser Ser Gly Asp Asp Glu Asp Gly Glu Asp Glu Ala Glu Asp Thr 
    130                 135                 140                 


Gly Val Asp Thr Gly Ala Pro Tyr Trp Thr Arg Pro Glu Arg Met Asp 
145                 150                 155                 160 


Lys Lys Leu Leu Ala Val Pro Ala Ala Asn Thr Val Arg Phe Arg Cys 
                165                 170                 175     


Pro Ala Ala Gly Asn Pro Thr Pro Ser Ile Ser Trp Leu Lys Asn Gly 
            180                 185                 190         


Arg Glu Phe Arg Gly Glu His Arg Ile Gly Gly Ile Lys Leu Arg His 
        195                 200                 205             


Gln Gln Trp Ser Leu Val Met Glu Ser Val Val Pro Ser Asp Arg Gly 
    210                 215                 220                 


Asn Tyr Thr Cys Val Val Glu Asn Lys Phe Gly Ser Ile Arg Gln Thr 
225                 230                 235                 240 


Tyr Thr Leu Asp Val Leu Glu Arg Ser Pro His Arg Pro Ile Leu Gln 
                245                 250                 255     


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


Phe His Cys Lys Val Tyr Ser Asp Ala Gln Pro His Ile Gln Trp Leu 
        275                 280                 285             


Lys His Val Glu Val Asn Gly Ser Lys Val Gly Pro Asp Gly Thr Pro 
    290                 295                 300                 


Tyr Val Thr Val Leu Lys Thr Ala Gly Ala Asn Thr Thr Asp Lys Glu 
305                 310                 315                 320 


Leu Glu Val Leu Ser Leu His Asn Val Thr Phe Glu Asp Ala Gly Glu 
                325                 330                 335     


Tyr Thr Cys Leu Ala Gly Asn Ser Ile Gly Phe Ser His His Ser Ala 
            340                 345                 350         


Trp Leu Val Val Leu Pro Ala Glu Glu Glu Leu Val Glu Ala Asp Glu 
        355                 360                 365             


Ala Gly Ser Val Tyr Ala Gly Ile Leu Ser Tyr Gly Val Gly Phe Phe 
    370                 375                 380                 


Leu Phe Ile Leu Val Val Ala Ala Val Thr Leu Cys Arg Leu Arg Ser 
385                 390                 395                 400 


Pro Pro Lys Lys Gly Leu Gly Ser Pro Thr Val His Lys Ile Ser Arg 
                405                 410                 415     


Phe Pro Leu Lys Arg Gln Val Ser Leu Glu Ser Asn Ala Ser Met Ser 
            420                 425                 430         


Ser Asn Thr Pro Leu Val Arg Ile Ala Arg Leu Ser Ser Gly Glu Gly 
        435                 440                 445             


Pro Thr Leu Ala Asn Val Ser Glu Leu Glu Leu Pro Ala Asp Pro Lys 
    450                 455                 460                 


Trp Glu Leu Ser Arg Ala Arg Leu Thr Leu Gly Lys Pro Leu Gly Glu 
465                 470                 475                 480 


Gly Cys Phe Gly Gln Val Val Met Ala Glu Ala Ile Gly Ile Asp Lys 
                485                 490                 495     


Asp Arg Ala Ala Lys Pro Val Thr Val Ala Val Lys Met Leu Lys Asp 
            500                 505                 510         


Asp Ala Thr Asp Lys Asp Leu Ser Asp Leu Val Ser Glu Met Glu Met 
        515                 520                 525             


Met Lys Met Ile Gly Lys His Lys Asn Ile Ile Asn Leu Leu Gly Ala 
    530                 535                 540                 


Cys Thr Gln Gly Gly Pro Leu Tyr Val Leu Val Glu Tyr Ala Ala Lys 
545                 550                 555                 560 


Gly Asn Leu Arg Glu Phe Leu Arg Ala Arg Arg Pro Pro Gly Leu Asp 
                565                 570                 575     


Tyr Ser Phe Asp Thr Cys Lys Pro Pro Glu Glu Gln Leu Thr Phe Lys 
            580                 585                 590         


Asp Leu Val Ser Cys Ala Tyr Gln Val Ala Arg Gly Met Glu Tyr Leu 
        595                 600                 605             


Ala Ser Gln Lys Cys Ile His Arg Asp Leu Ala Ala Arg Asn Val Leu 
    610                 615                 620                 


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


Asp Val His Asn Leu Asp Tyr Tyr Lys Lys Thr Thr Asn Gly Arg Leu 
                645                 650                 655     


Pro Val Lys Trp Met Ala Pro Glu Ala Leu Phe Asp Arg Val Tyr Thr 
            660                 665                 670         


His Gln Ser Asp Val Trp Ser Phe Gly Val Leu Leu Trp Glu Ile Phe 
        675                 680                 685             


Thr Leu Gly Gly Ser Pro Tyr Pro Gly Ile Pro Val Glu Glu Leu Phe 
    690                 695                 700                 


Lys Leu Leu Lys Glu Gly His Arg Met Asp Lys Pro Ala Asn Cys Thr 
705                 710                 715                 720 


His Asp Leu Tyr Met Ile Met Arg Glu Cys Trp His Ala Ala Pro Ser 
                725                 730                 735     


Gln Arg Pro Thr Phe Lys Gln Leu Val Glu Asp Leu Asp Arg Val Leu 
            740                 745                 750         


Thr Val Thr Ser Thr Asp Glu Tyr Leu Asp Leu Ser Ala Pro Phe Glu 
        755                 760                 765             


Gln Tyr Ser Pro Gly Gly Gln Asp Thr Pro Ser Ser Ser Ser Ser Gly 
    770                 775                 780                 


Asp Asp Ser Val Phe Ala His Asp Leu Leu Pro Pro Ala Pro Pro Ser 
785                 790                 795                 800 


Ser Gly Gly Ser Arg Thr 
                805     


<210>  6
<211>  808
<212>  PRT
<213>  Homo sapiens

<400>  6

Met Gly Ala Pro Ala Cys Ala Leu Ala Leu Cys Val Ala Val Ala Ile 
1               5                   10                  15      


Val Ala Gly Ala Ser Ser Glu Ser Leu Gly Thr Glu Gln Arg Val Val 
            20                  25                  30          


Gly Arg Ala Ala Glu Val Pro Gly Pro Glu Pro Gly Gln Gln Glu Gln 
        35                  40                  45              


Leu Val Phe Gly Ser Gly Asp Ala Val Glu Leu Ser Cys Pro Pro Pro 
    50                  55                  60                  


Gly Gly Gly Pro Met Gly Pro Thr Val Trp Val Lys Asp Gly Thr Gly 
65                  70                  75                  80  


Leu Val Pro Ser Glu Arg Val Leu Val Gly Pro Gln Arg Leu Gln Val 
                85                  90                  95      


Leu Asn Ala Ser His Glu Asp Ser Gly Ala Tyr Ser Cys Arg Gln Arg 
            100                 105                 110         


Leu Thr Gln Arg Val Leu Cys His Phe Ser Val Arg Val Thr Asp Ala 
        115                 120                 125             


Pro Ser Ser Gly Asp Asp Glu Asp Gly Glu Asp Glu Ala Glu Asp Thr 
    130                 135                 140                 


Gly Val Asp Thr Gly Ala Pro Tyr Trp Thr Arg Pro Glu Arg Met Asp 
145                 150                 155                 160 


Lys Lys Leu Leu Ala Val Pro Ala Ala Asn Thr Val Arg Phe Arg Cys 
                165                 170                 175     


Pro Ala Ala Gly Asn Pro Thr Pro Ser Ile Ser Trp Leu Lys Asn Gly 
            180                 185                 190         


Arg Glu Phe Arg Gly Glu His Arg Ile Gly Gly Ile Lys Leu Arg His 
        195                 200                 205             


Gln Gln Trp Ser Leu Val Met Glu Ser Val Val Pro Ser Asp Arg Gly 
    210                 215                 220                 


Asn Tyr Thr Cys Val Val Glu Asn Lys Phe Gly Ser Ile Arg Gln Thr 
225                 230                 235                 240 


Tyr Thr Leu Asp Val Leu Glu Arg Ser Pro His Arg Pro Ile Leu Gln 
                245                 250                 255     


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


Phe His Cys Lys Val Tyr Ser Asp Ala Gln Pro His Ile Gln Trp Leu 
        275                 280                 285             


Lys His Val Glu Val Asn Gly Ser Lys Val Gly Pro Asp Gly Thr Pro 
    290                 295                 300                 


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


Val Arg Leu Arg Leu Ala Asn Val Ser Glu Arg Asp Gly Gly Glu Tyr 
                325                 330                 335     


Leu Cys Arg Ala Thr Asn Phe Ile Gly Val Ala Glu Lys Ala Phe Trp 
            340                 345                 350         


Leu Ser Val His Gly Pro Arg Ala Ala Glu Glu Glu Leu Val Glu Ala 
        355                 360                 365             


Asp Glu Ala Gly Ser Val Tyr Ala Gly Ile Leu Ser Tyr Gly Val Gly 
    370                 375                 380                 


Phe Phe Leu Phe Ile Leu Val Val Ala Ala Val Thr Leu Cys Arg Leu 
385                 390                 395                 400 


Arg Ser Pro Pro Lys Lys Gly Leu Gly Ser Pro Thr Val His Lys Ile 
                405                 410                 415     


Ser Arg Phe Pro Leu Lys Arg Gln Val Ser Leu Glu Ser Asn Ala Ser 
            420                 425                 430         


Met Ser Ser Asn Thr Pro Leu Val Arg Ile Ala Arg Leu Ser Ser Gly 
        435                 440                 445             


Glu Gly Pro Thr Leu Ala Asn Val Ser Glu Leu Glu Leu Pro Ala Asp 
    450                 455                 460                 


Pro Lys Trp Glu Leu Ser Arg Ala Arg Leu Thr Leu Gly Lys Pro Leu 
465                 470                 475                 480 


Gly Glu Gly Cys Phe Gly Gln Val Val Met Ala Glu Ala Ile Gly Ile 
                485                 490                 495     


Asp Lys Asp Arg Ala Ala Lys Pro Val Thr Val Ala Val Lys Met Leu 
            500                 505                 510         


Lys Asp Asp Ala Thr Asp Lys Asp Leu Ser Asp Leu Val Ser Glu Met 
        515                 520                 525             


Glu Met Met Lys Met Ile Gly Lys His Lys Asn Ile Ile Asn Leu Leu 
    530                 535                 540                 


Gly Ala Cys Thr Gln Gly Gly Pro Leu Tyr Val Leu Val Glu Tyr Ala 
545                 550                 555                 560 


Ala Lys Gly Asn Leu Arg Glu Phe Leu Arg Ala Arg Arg Pro Pro Gly 
                565                 570                 575     


Leu Asp Tyr Ser Phe Asp Thr Cys Lys Pro Pro Glu Glu Gln Leu Thr 
            580                 585                 590         


Phe Lys Asp Leu Val Ser Cys Ala Tyr Gln Val Ala Arg Gly Met Glu 
        595                 600                 605             


Tyr Leu Ala Ser Gln Lys Cys Ile His Arg Asp Leu Ala Ala Arg Asn 
    610                 615                 620                 


Val Leu Val Thr Glu Asp Asn Val Met Lys Ile Ala Asp Phe Gly Leu 
625                 630                 635                 640 


Ala Arg Asp Val His Asn Leu Asp Tyr Tyr Lys Lys Thr Thr Asn Gly 
                645                 650                 655     


Arg Leu Pro Val Lys Trp Met Ala Pro Glu Ala Leu Phe Asp Arg Val 
            660                 665                 670         


Tyr Thr His Gln Ser Asp Val Trp Ser Phe Gly Val Leu Leu Trp Glu 
        675                 680                 685             


Ile Phe Thr Leu Gly Gly Ser Pro Tyr Pro Gly Ile Pro Val Glu Glu 
    690                 695                 700                 


Leu Phe Lys Leu Leu Lys Glu Gly His Arg Met Asp Lys Pro Ala Asn 
705                 710                 715                 720 


Cys Thr His Asp Leu Tyr Met Ile Met Arg Glu Cys Trp His Ala Ala 
                725                 730                 735     


Pro Ser Gln Arg Pro Thr Phe Lys Gln Leu Val Glu Asp Leu Asp Arg 
            740                 745                 750         


Val Leu Thr Val Thr Ser Thr Asp Glu Tyr Leu Asp Leu Ser Ala Pro 
        755                 760                 765             


Phe Glu Gln Tyr Ser Pro Gly Gly Gln Asp Thr Pro Ser Ser Ser Ser 
    770                 775                 780                 


Ser Gly Asp Asp Ser Val Phe Ala His Asp Leu Leu Pro Pro Ala Pro 
785                 790                 795                 800 


Pro Ser Ser Gly Gly Ser Arg Thr 
                805             


<210>  7
<211>  802
<212>  PRT
<213>  Homo sapiens

<400>  7

Met Arg Leu Leu Leu Ala Leu Leu Gly Val Leu Leu Ser Val Pro Gly 
1               5                   10                  15      


Pro Pro Val Leu Ser Leu Glu Ala Ser Glu Glu Val Glu Leu Glu Pro 
            20                  25                  30          


Cys Leu Ala Pro Ser Leu Glu Gln Gln Glu Gln Glu Leu Thr Val Ala 
        35                  40                  45              


Leu Gly Gln Pro Val Arg Leu Cys Cys Gly Arg Ala Glu Arg Gly Gly 
    50                  55                  60                  


His Trp Tyr Lys Glu Gly Ser Arg Leu Ala Pro Ala Gly Arg Val Arg 
65                  70                  75                  80  


Gly Trp Arg Gly Arg Leu Glu Ile Ala Ser Phe Leu Pro Glu Asp Ala 
                85                  90                  95      


Gly Arg Tyr Leu Cys Leu Ala Arg Gly Ser Met Ile Val Leu Gln Asn 
            100                 105                 110         


Leu Thr Leu Ile Thr Gly Asp Ser Leu Thr Ser Ser Asn Asp Asp Glu 
        115                 120                 125             


Asp Pro Lys Ser His Arg Asp Pro Ser Asn Arg His Ser Tyr Pro Gln 
    130                 135                 140                 


Gln Ala Pro Tyr Trp Thr His Pro Gln Arg Met Glu Lys Lys Leu His 
145                 150                 155                 160 


Ala Val Pro Ala Gly Asn Thr Val Lys Phe Arg Cys Pro Ala Ala Gly 
                165                 170                 175     


Asn Pro Thr Pro Thr Ile Arg Trp Leu Lys Asp Gly Gln Ala Phe His 
            180                 185                 190         


Gly Glu Asn Arg Ile Gly Gly Ile Arg Leu Arg His Gln His Trp Ser 
        195                 200                 205             


Leu Val Met Glu Ser Val Val Pro Ser Asp Arg Gly Thr Tyr Thr Cys 
    210                 215                 220                 


Leu Val Glu Asn Ala Val Gly Ser Ile Arg Tyr Asn Tyr Leu Leu Asp 
225                 230                 235                 240 


Val Leu Glu Arg Ser Pro His Arg Pro Ile Leu Gln Ala Gly Leu Pro 
                245                 250                 255     


Ala Asn Thr Thr Ala Val Val Gly Ser Asp Val Glu Leu Leu Cys Lys 
            260                 265                 270         


Val Tyr Ser Asp Ala Gln Pro His Ile Gln Trp Leu Lys His Ile Val 
        275                 280                 285             


Ile Asn Gly Ser Ser Phe Gly Ala Asp Gly Phe Pro Tyr Val Gln Val 
    290                 295                 300                 


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


Arg Asn Val Ser Ala Glu Asp Ala Gly Glu Tyr Thr Cys Leu Ala Gly 
                325                 330                 335     


Asn Ser Ile Gly Leu Ser Tyr Gln Ser Ala Trp Leu Thr Val Leu Pro 
            340                 345                 350         


Glu Glu Asp Pro Thr Trp Thr Ala Ala Ala Pro Glu Ala Arg Tyr Thr 
        355                 360                 365             


Asp Ile Ile Leu Tyr Ala Ser Gly Ser Leu Ala Leu Ala Val Leu Leu 
    370                 375                 380                 


Leu Leu Ala Gly Leu Tyr Arg Gly Gln Ala Leu His Gly Arg His Pro 
385                 390                 395                 400 


Arg Pro Pro Ala Thr Val Gln Lys Leu Ser Arg Phe Pro Leu Ala Arg 
                405                 410                 415     


Gln Phe Ser Leu Glu Ser Gly Ser Ser Gly Lys Ser Ser Ser Ser Leu 
            420                 425                 430         


Val Arg Gly Val Arg Leu Ser Ser Ser Gly Pro Ala Leu Leu Ala Gly 
        435                 440                 445             


Leu Val Ser Leu Asp Leu Pro Leu Asp Pro Leu Trp Glu Phe Pro Arg 
    450                 455                 460                 


Asp Arg Leu Val Leu Gly Lys Pro Leu Gly Glu Gly Cys Phe Gly Gln 
465                 470                 475                 480 


Val Val Arg Ala Glu Ala Phe Gly Met Asp Pro Ala Arg Pro Asp Gln 
                485                 490                 495     


Ala Ser Thr Val Ala Val Lys Met Leu Lys Asp Asn Ala Ser Asp Lys 
            500                 505                 510         


Asp Leu Ala Asp Leu Val Ser Glu Met Glu Val Met Lys Leu Ile Gly 
        515                 520                 525             


Arg His Lys Asn Ile Ile Asn Leu Leu Gly Val Cys Thr Gln Glu Gly 
    530                 535                 540                 


Pro Leu Tyr Val Ile Val Glu Cys Ala Ala Lys Gly Asn Leu Arg Glu 
545                 550                 555                 560 


Phe Leu Arg Ala Arg Arg Pro Pro Gly Pro Asp Leu Ser Pro Asp Gly 
                565                 570                 575     


Pro Arg Ser Ser Glu Gly Pro Leu Ser Phe Pro Val Leu Val Ser Cys 
            580                 585                 590         


Ala Tyr Gln Val Ala Arg Gly Met Gln Tyr Leu Glu Ser Arg Lys Cys 
        595                 600                 605             


Ile His Arg Asp Leu Ala Ala Arg Asn Val Leu Val Thr Glu Asp Asn 
    610                 615                 620                 


Val Met Lys Ile Ala Asp Phe Gly Leu Ala Arg Gly Val His His Ile 
625                 630                 635                 640 


Asp Tyr Tyr Lys Lys Thr Ser Asn Gly Arg Leu Pro Val Lys Trp Met 
                645                 650                 655     


Ala Pro Glu Ala Leu Phe Asp Arg Val Tyr Thr His Gln Ser Asp Val 
            660                 665                 670         


Trp Ser Phe Gly Ile Leu Leu Trp Glu Ile Phe Thr Leu Gly Gly Ser 
        675                 680                 685             


Pro Tyr Pro Gly Ile Pro Val Glu Glu Leu Phe Ser Leu Leu Arg Glu 
    690                 695                 700                 


Gly His Arg Met Asp Arg Pro Pro His Cys Pro Pro Glu Leu Tyr Gly 
705                 710                 715                 720 


Leu Met Arg Glu Cys Trp His Ala Ala Pro Ser Gln Arg Pro Thr Phe 
                725                 730                 735     


Lys Gln Leu Val Glu Ala Leu Asp Lys Val Leu Leu Ala Val Ser Glu 
            740                 745                 750         


Glu Tyr Leu Asp Leu Arg Leu Thr Phe Gly Pro Tyr Ser Pro Ser Gly 
        755                 760                 765             


Gly Asp Ala Ser Ser Thr Cys Ser Ser Ser Asp Ser Val Phe Ser His 
    770                 775                 780                 


Asp Pro Leu Pro Leu Gly Ser Ser Ser Phe Pro Phe Gly Ser Gly Val 
785                 790                 795                 800 


Gln Thr 
        


<210>  8
<211>  762
<212>  PRT
<213>  Homo sapiens

<400>  8

Met Arg Leu Leu Leu Ala Leu Leu Gly Val Leu Leu Ser Val Pro Gly 
1               5                   10                  15      


Pro Pro Val Leu Ser Leu Glu Ala Ser Glu Glu Val Glu Leu Glu Pro 
            20                  25                  30          


Cys Leu Ala Pro Ser Leu Glu Gln Gln Glu Gln Glu Leu Thr Val Ala 
        35                  40                  45              


Leu Gly Gln Pro Val Arg Leu Cys Cys Gly Arg Ala Glu Arg Gly Gly 
    50                  55                  60                  


His Trp Tyr Lys Glu Gly Ser Arg Leu Ala Pro Ala Gly Arg Val Arg 
65                  70                  75                  80  


Gly Trp Arg Gly Arg Leu Glu Ile Ala Ser Phe Leu Pro Glu Asp Ala 
                85                  90                  95      


Gly Arg Tyr Leu Cys Leu Ala Arg Gly Ser Met Ile Val Leu Gln Asn 
            100                 105                 110         


Leu Thr Leu Ile Thr Gly Asp Ser Leu Thr Ser Ser Asn Asp Asp Glu 
        115                 120                 125             


Asp Pro Lys Ser His Arg Asp Pro Ser Asn Arg His Ser Tyr Pro Gln 
    130                 135                 140                 


Gln Ala Pro Tyr Trp Thr His Pro Gln Arg Met Glu Lys Lys Leu His 
145                 150                 155                 160 


Ala Val Pro Ala Gly Asn Thr Val Lys Phe Arg Cys Pro Ala Ala Gly 
                165                 170                 175     


Asn Pro Thr Pro Thr Ile Arg Trp Leu Lys Asp Gly Gln Ala Phe His 
            180                 185                 190         


Gly Glu Asn Arg Ile Gly Gly Ile Arg Leu Arg His Gln His Trp Ser 
        195                 200                 205             


Leu Val Met Glu Ser Val Val Pro Ser Asp Arg Gly Thr Tyr Thr Cys 
    210                 215                 220                 


Leu Val Glu Asn Ala Val Gly Ser Ile Arg Tyr Asn Tyr Leu Leu Asp 
225                 230                 235                 240 


Val Leu Glu Arg Ser Pro His Arg Pro Ile Leu Gln Ala Gly Leu Pro 
                245                 250                 255     


Ala Asn Thr Thr Ala Val Val Gly Ser Asp Val Glu Leu Leu Cys Lys 
            260                 265                 270         


Val Tyr Ser Asp Ala Gln Pro His Ile Gln Trp Leu Lys His Ile Val 
        275                 280                 285             


Ile Asn Gly Ser Ser Phe Gly Ala Asp Gly Phe Pro Tyr Val Gln Val 
    290                 295                 300                 


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


Arg Asn Val Ser Ala Glu Asp Ala Gly Glu Tyr Thr Cys Leu Ala Gly 
                325                 330                 335     


Asn Ser Ile Gly Leu Ser Tyr Gln Ser Ala Trp Leu Thr Val Leu Pro 
            340                 345                 350         


Gly Thr Gly Arg Ile Pro His Leu Thr Cys Asp Ser Leu Thr Pro Ala 
        355                 360                 365             


Gly Arg Thr Lys Ser Pro Thr Leu Gln Phe Ser Leu Glu Ser Gly Ser 
    370                 375                 380                 


Ser Gly Lys Ser Ser Ser Ser Leu Val Arg Gly Val Arg Leu Ser Ser 
385                 390                 395                 400 


Ser Gly Pro Ala Leu Leu Ala Gly Leu Val Ser Leu Asp Leu Pro Leu 
                405                 410                 415     


Asp Pro Leu Trp Glu Phe Pro Arg Asp Arg Leu Val Leu Gly Lys Pro 
            420                 425                 430         


Leu Gly Glu Gly Cys Phe Gly Gln Val Val Arg Ala Glu Ala Phe Gly 
        435                 440                 445             


Met Asp Pro Ala Arg Pro Asp Gln Ala Ser Thr Val Ala Val Lys Met 
    450                 455                 460                 


Leu Lys Asp Asn Ala Ser Asp Lys Asp Leu Ala Asp Leu Val Ser Glu 
465                 470                 475                 480 


Met Glu Val Met Lys Leu Ile Gly Arg His Lys Asn Ile Ile Asn Leu 
                485                 490                 495     


Leu Gly Val Cys Thr Gln Glu Gly Pro Leu Tyr Val Ile Val Glu Cys 
            500                 505                 510         


Ala Ala Lys Gly Asn Leu Arg Glu Phe Leu Arg Ala Arg Arg Pro Pro 
        515                 520                 525             


Gly Pro Asp Leu Ser Pro Asp Gly Pro Arg Ser Ser Glu Gly Pro Leu 
    530                 535                 540                 


Ser Phe Pro Val Leu Val Ser Cys Ala Tyr Gln Val Ala Arg Gly Met 
545                 550                 555                 560 


Gln Tyr Leu Glu Ser Arg Lys Cys Ile His Arg Asp Leu Ala Ala Arg 
                565                 570                 575     


Asn Val Leu Val Thr Glu Asp Asn Val Met Lys Ile Ala Asp Phe Gly 
            580                 585                 590         


Leu Ala Arg Gly Val His His Ile Asp Tyr Tyr Lys Lys Thr Ser Asn 
        595                 600                 605             


Gly Arg Leu Pro Val Lys Trp Met Ala Pro Glu Ala Leu Phe Asp Arg 
    610                 615                 620                 


Val Tyr Thr His Gln Ser Asp Val Trp Ser Phe Gly Ile Leu Leu Trp 
625                 630                 635                 640 


Glu Ile Phe Thr Leu Gly Gly Ser Pro Tyr Pro Gly Ile Pro Val Glu 
                645                 650                 655     


Glu Leu Phe Ser Leu Leu Arg Glu Gly His Arg Met Asp Arg Pro Pro 
            660                 665                 670         


His Cys Pro Pro Glu Leu Tyr Gly Leu Met Arg Glu Cys Trp His Ala 
        675                 680                 685             


Ala Pro Ser Gln Arg Pro Thr Phe Lys Gln Leu Val Glu Ala Leu Asp 
    690                 695                 700                 


Lys Val Leu Leu Ala Val Ser Glu Glu Tyr Leu Asp Leu Arg Leu Thr 
705                 710                 715                 720 


Phe Gly Pro Tyr Ser Pro Ser Gly Gly Asp Ala Ser Ser Thr Cys Ser 
                725                 730                 735     


Ser Ser Asp Ser Val Phe Ser His Asp Pro Leu Pro Leu Gly Ser Ser 
            740                 745                 750         


Ser Phe Pro Phe Gly Ser Gly Val Gln Thr 
        755                 760         


