                         SEQUENCE LISTING

<110>  bluebird bio, Inc.
       Leung, Wai-Hang
 
<120>  DARIC INTERLEUKIN RECEPTORS

<130>  BLBD-092/01WO 315698-2768

<150>  US 62/598,923
<151>  2017-12-14

<160>  43    

<170>  PatentIn version 3.5

<210>  1
<211>  333
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized IL-18R DARIC signaling component

<400>  1

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu 
1               5                   10                  15      


His Ala Ala Arg Pro Gly Ser Ile Leu Trp His Glu Met Trp His Glu 
            20                  25                  30          


Gly Leu Glu Glu Ala Ser Arg Leu Tyr Phe Gly Glu Arg Asn Val Lys 
        35                  40                  45              


Gly Met Phe Glu Val Leu Glu Pro Leu His Ala Met Met Glu Arg Gly 
    50                  55                  60                  


Pro Gln Thr Leu Lys Glu Thr Ser Phe Asn Gln Ala Tyr Gly Arg Asp 
65                  70                  75                  80  


Leu Met Glu Ala Gln Glu Trp Cys Arg Lys Tyr Met Lys Ser Gly Asn 
                85                  90                  95      


Val Lys Asp Leu Leu Gln Ala Trp Asp Leu Tyr Tyr His Val Phe Arg 
            100                 105                 110         


Arg Ile Ser Lys Ala Ser Gly Met Ile Ile Ala Val Leu Ile Leu Val 
        115                 120                 125             


Ala Val Val Cys Leu Val Thr Val Cys Val Ile Tyr Arg Val Asp Leu 
    130                 135                 140                 


Val Leu Phe Tyr Arg His Leu Thr Arg Arg Asp Glu Thr Leu Thr Asp 
145                 150                 155                 160 


Gly Lys Thr Tyr Asp Ala Phe Val Ser Tyr Leu Lys Glu Cys Arg Pro 
                165                 170                 175     


Glu Asn Gly Glu Glu His Thr Phe Ala Val Glu Ile Leu Pro Arg Val 
            180                 185                 190         


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


Val Pro Gly Gly Ala Val Val Asp Glu Ile His Ser Leu Ile Glu Lys 
    210                 215                 220                 


Ser Arg Arg Leu Ile Ile Val Leu Ser Lys Ser Tyr Met Ser Asn Glu 
225                 230                 235                 240 


Val Arg Tyr Glu Leu Glu Ser Gly Leu His Glu Ala Leu Val Glu Arg 
                245                 250                 255     


Lys Ile Lys Ile Ile Leu Ile Glu Phe Thr Pro Val Thr Asp Phe Thr 
            260                 265                 270         


Phe Leu Pro Gln Ser Leu Lys Leu Leu Lys Ser His Arg Val Leu Lys 
        275                 280                 285             


Trp Lys Ala Asp Lys Ser Leu Ser Tyr Asn Ser Arg Phe Trp Lys Asn 
    290                 295                 300                 


Leu Leu Tyr Leu Met Pro Ala Lys Thr Val Lys Pro Gly Arg Asp Glu 
305                 310                 315                 320 


Pro Glu Val Leu Pro Val Leu Ser Glu Ser Pro Arg Ser 
                325                 330             


<210>  2
<211>  354
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized IL-18R DARIC signaling component

<400>  2

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu 
1               5                   10                  15      


His Ala Ala Arg Pro Gly Ser Ile Leu Trp His Glu Met Trp His Glu 
            20                  25                  30          


Gly Leu Glu Glu Ala Ser Arg Leu Tyr Phe Gly Glu Arg Asn Val Lys 
        35                  40                  45              


Gly Met Phe Glu Val Leu Glu Pro Leu His Ala Met Met Glu Arg Gly 
    50                  55                  60                  


Pro Gln Thr Leu Lys Glu Thr Ser Phe Asn Gln Ala Tyr Gly Arg Asp 
65                  70                  75                  80  


Leu Met Glu Ala Gln Glu Trp Cys Arg Lys Tyr Met Lys Ser Gly Asn 
                85                  90                  95      


Val Lys Asp Leu Leu Gln Ala Trp Asp Leu Tyr Tyr His Val Phe Arg 
            100                 105                 110         


Arg Ile Ser Lys Ala Ser Gly Met Ile Ile Ala Val Leu Ile Leu Val 
        115                 120                 125             


Ala Val Val Cys Leu Val Thr Val Cys Val Ile Tyr Arg Val Asp Leu 
    130                 135                 140                 


Val Leu Phe Tyr Arg His Leu Thr Arg Arg Asp Glu Thr Leu Thr Asp 
145                 150                 155                 160 


Gly Lys Thr Tyr Asp Ala Phe Val Ser Tyr Leu Lys Glu Cys Arg Pro 
                165                 170                 175     


Glu Asn Gly Glu Glu His Thr Phe Ala Val Glu Ile Leu Pro Arg Val 
            180                 185                 190         


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


Val Pro Gly Gly Ala Val Val Asp Glu Ile His Ser Leu Ile Glu Lys 
    210                 215                 220                 


Ser Arg Arg Leu Ile Ile Val Leu Ser Lys Ser Tyr Met Ser Asn Glu 
225                 230                 235                 240 


Val Arg Tyr Glu Leu Glu Ser Gly Leu His Glu Ala Leu Val Glu Arg 
                245                 250                 255     


Lys Ile Lys Ile Ile Leu Ile Glu Phe Thr Pro Val Thr Asp Phe Thr 
            260                 265                 270         


Phe Leu Pro Gln Ser Leu Lys Leu Leu Lys Ser His Arg Val Leu Lys 
        275                 280                 285             


Trp Lys Ala Asp Lys Ser Leu Ser Tyr Asn Ser Arg Phe Trp Lys Asn 
    290                 295                 300                 


Leu Leu Tyr Leu Met Pro Ala Lys Thr Val Lys Pro Gly Arg Asp Glu 
305                 310                 315                 320 


Pro Glu Val Leu Pro Val Leu Ser Glu Ser Pro Arg Ser Gly Ser Gly 
                325                 330                 335     


Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val Glu Glu Asn 
            340                 345                 350         


Pro Gly 
        


<210>  3
<211>  373
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized IL-18R DARIC binding component

<400>  3

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
1               5                   10                  15      


Gly Ser Thr Gly Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly 
            20                  25                  30          


Arg Thr Phe Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly 
        35                  40                  45              


Met Leu Glu Asp Gly Lys Lys Phe Asp Ser Ser Arg Asp Arg Asn Lys 
    50                  55                  60                  


Pro Phe Lys Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu 
65                  70                  75                  80  


Glu Gly Val Ala Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile 
                85                  90                  95      


Ser Pro Asp Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro 
            100                 105                 110         


Pro His Ala Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu Gly 
        115                 120                 125             


Gly Arg Gly Val Val Leu Leu Tyr Ile Leu Leu Gly Thr Ile Gly Thr 
    130                 135                 140                 


Leu Val Ala Val Leu Ala Ala Ser Ala Leu Leu Tyr Arg His Trp Ile 
145                 150                 155                 160 


Glu Ile Val Leu Leu Tyr Arg Thr Tyr Gln Ser Lys Asp Gln Thr Leu 
                165                 170                 175     


Gly Asp Lys Lys Asp Phe Asp Ala Phe Val Ser Tyr Ala Lys Trp Ser 
            180                 185                 190         


Ser Phe Pro Ser Glu Ala Thr Ser Ser Leu Ser Glu Glu His Leu Ala 
        195                 200                 205             


Leu Ser Leu Phe Pro Asp Val Leu Glu Asn Lys Tyr Gly Tyr Ser Leu 
    210                 215                 220                 


Cys Leu Leu Glu Arg Asp Val Ala Pro Gly Gly Val Tyr Ala Glu Asp 
225                 230                 235                 240 


Ile Val Ser Ile Ile Lys Arg Ser Arg Arg Gly Ile Phe Ile Leu Ser 
                245                 250                 255     


Pro Asn Tyr Val Asn Gly Pro Ser Ile Phe Glu Leu Gln Ala Ala Val 
            260                 265                 270         


Asn Leu Ala Leu Asp Asp Gln Thr Leu Lys Leu Ile Leu Ile Lys Phe 
        275                 280                 285             


Cys Tyr Phe Gln Glu Pro Glu Ser Leu Pro His Leu Val Lys Lys Ala 
    290                 295                 300                 


Leu Arg Val Leu Pro Thr Val Thr Trp Arg Gly Leu Lys Ser Val Pro 
305                 310                 315                 320 


Pro Asn Ser Arg Phe Trp Ala Lys Met Arg Tyr His Met Pro Val Lys 
                325                 330                 335     


Asn Ser Gln Gly Phe Thr Trp Asn Gln Leu Arg Ile Thr Ser Arg Ile 
            340                 345                 350         


Phe Gln Trp Lys Gly Leu Ser Arg Thr Glu Thr Thr Gly Arg Ser Ser 
        355                 360                 365             


Gln Pro Lys Glu Trp 
    370             


<210>  4
<211>  375
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized IL-18R DARIC binding component

<400>  4

Pro Ser Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp 
1               5                   10                  15      


Val Pro Gly Ser Thr Gly Gly Val Gln Val Glu Thr Ile Ser Pro Gly 
            20                  25                  30          


Asp Gly Arg Thr Phe Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr 
        35                  40                  45              


Thr Gly Met Leu Glu Asp Gly Lys Lys Phe Asp Ser Ser Arg Asp Arg 
    50                  55                  60                  


Asn Lys Pro Phe Lys Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly 
65                  70                  75                  80  


Trp Glu Glu Gly Val Ala Gln Met Ser Val Gly Gln Arg Ala Lys Leu 
                85                  90                  95      


Thr Ile Ser Pro Asp Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile 
            100                 105                 110         


Ile Pro Pro His Ala Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu 
        115                 120                 125             


Glu Gly Gly Arg Gly Val Val Leu Leu Tyr Ile Leu Leu Gly Thr Ile 
    130                 135                 140                 


Gly Thr Leu Val Ala Val Leu Ala Ala Ser Ala Leu Leu Tyr Arg His 
145                 150                 155                 160 


Trp Ile Glu Ile Val Leu Leu Tyr Arg Thr Tyr Gln Ser Lys Asp Gln 
                165                 170                 175     


Thr Leu Gly Asp Lys Lys Asp Phe Asp Ala Phe Val Ser Tyr Ala Lys 
            180                 185                 190         


Trp Ser Ser Phe Pro Ser Glu Ala Thr Ser Ser Leu Ser Glu Glu His 
        195                 200                 205             


Leu Ala Leu Ser Leu Phe Pro Asp Val Leu Glu Asn Lys Tyr Gly Tyr 
    210                 215                 220                 


Ser Leu Cys Leu Leu Glu Arg Asp Val Ala Pro Gly Gly Val Tyr Ala 
225                 230                 235                 240 


Glu Asp Ile Val Ser Ile Ile Lys Arg Ser Arg Arg Gly Ile Phe Ile 
                245                 250                 255     


Leu Ser Pro Asn Tyr Val Asn Gly Pro Ser Ile Phe Glu Leu Gln Ala 
            260                 265                 270         


Ala Val Asn Leu Ala Leu Asp Asp Gln Thr Leu Lys Leu Ile Leu Ile 
        275                 280                 285             


Lys Phe Cys Tyr Phe Gln Glu Pro Glu Ser Leu Pro His Leu Val Lys 
    290                 295                 300                 


Lys Ala Leu Arg Val Leu Pro Thr Val Thr Trp Arg Gly Leu Lys Ser 
305                 310                 315                 320 


Val Pro Pro Asn Ser Arg Phe Trp Ala Lys Met Arg Tyr His Met Pro 
                325                 330                 335     


Val Lys Asn Ser Gln Gly Phe Thr Trp Asn Gln Leu Arg Ile Thr Ser 
            340                 345                 350         


Arg Ile Phe Gln Trp Lys Gly Leu Ser Arg Thr Glu Thr Thr Gly Arg 
        355                 360                 365             


Ser Ser Gln Pro Lys Glu Trp 
    370                 375 


<210>  5
<211>  729
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized IL-18R DARIC polyprotein comprising an IL-18R DARIC 
       binding component and signaling component separated by a viral 
       P2A domain

<400>  5

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu 
1               5                   10                  15      


His Ala Ala Arg Pro Gly Ser Ile Leu Trp His Glu Met Trp His Glu 
            20                  25                  30          


Gly Leu Glu Glu Ala Ser Arg Leu Tyr Phe Gly Glu Arg Asn Val Lys 
        35                  40                  45              


Gly Met Phe Glu Val Leu Glu Pro Leu His Ala Met Met Glu Arg Gly 
    50                  55                  60                  


Pro Gln Thr Leu Lys Glu Thr Ser Phe Asn Gln Ala Tyr Gly Arg Asp 
65                  70                  75                  80  


Leu Met Glu Ala Gln Glu Trp Cys Arg Lys Tyr Met Lys Ser Gly Asn 
                85                  90                  95      


Val Lys Asp Leu Leu Gln Ala Trp Asp Leu Tyr Tyr His Val Phe Arg 
            100                 105                 110         


Arg Ile Ser Lys Ala Ser Gly Met Ile Ile Ala Val Leu Ile Leu Val 
        115                 120                 125             


Ala Val Val Cys Leu Val Thr Val Cys Val Ile Tyr Arg Val Asp Leu 
    130                 135                 140                 


Val Leu Phe Tyr Arg His Leu Thr Arg Arg Asp Glu Thr Leu Thr Asp 
145                 150                 155                 160 


Gly Lys Thr Tyr Asp Ala Phe Val Ser Tyr Leu Lys Glu Cys Arg Pro 
                165                 170                 175     


Glu Asn Gly Glu Glu His Thr Phe Ala Val Glu Ile Leu Pro Arg Val 
            180                 185                 190         


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


Val Pro Gly Gly Ala Val Val Asp Glu Ile His Ser Leu Ile Glu Lys 
    210                 215                 220                 


Ser Arg Arg Leu Ile Ile Val Leu Ser Lys Ser Tyr Met Ser Asn Glu 
225                 230                 235                 240 


Val Arg Tyr Glu Leu Glu Ser Gly Leu His Glu Ala Leu Val Glu Arg 
                245                 250                 255     


Lys Ile Lys Ile Ile Leu Ile Glu Phe Thr Pro Val Thr Asp Phe Thr 
            260                 265                 270         


Phe Leu Pro Gln Ser Leu Lys Leu Leu Lys Ser His Arg Val Leu Lys 
        275                 280                 285             


Trp Lys Ala Asp Lys Ser Leu Ser Tyr Asn Ser Arg Phe Trp Lys Asn 
    290                 295                 300                 


Leu Leu Tyr Leu Met Pro Ala Lys Thr Val Lys Pro Gly Arg Asp Glu 
305                 310                 315                 320 


Pro Glu Val Leu Pro Val Leu Ser Glu Ser Pro Arg Ser Gly Ser Gly 
                325                 330                 335     


Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val Glu Glu Asn 
            340                 345                 350         


Pro Gly Pro Ser Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu 
        355                 360                 365             


Leu Trp Val Pro Gly Ser Thr Gly Gly Val Gln Val Glu Thr Ile Ser 
    370                 375                 380                 


Pro Gly Asp Gly Arg Thr Phe Pro Lys Arg Gly Gln Thr Cys Val Val 
385                 390                 395                 400 


His Tyr Thr Gly Met Leu Glu Asp Gly Lys Lys Phe Asp Ser Ser Arg 
                405                 410                 415     


Asp Arg Asn Lys Pro Phe Lys Phe Met Leu Gly Lys Gln Glu Val Ile 
            420                 425                 430         


Arg Gly Trp Glu Glu Gly Val Ala Gln Met Ser Val Gly Gln Arg Ala 
        435                 440                 445             


Lys Leu Thr Ile Ser Pro Asp Tyr Ala Tyr Gly Ala Thr Gly His Pro 
    450                 455                 460                 


Gly Ile Ile Pro Pro His Ala Thr Leu Val Phe Asp Val Glu Leu Leu 
465                 470                 475                 480 


Lys Leu Glu Gly Gly Arg Gly Val Val Leu Leu Tyr Ile Leu Leu Gly 
                485                 490                 495     


Thr Ile Gly Thr Leu Val Ala Val Leu Ala Ala Ser Ala Leu Leu Tyr 
            500                 505                 510         


Arg His Trp Ile Glu Ile Val Leu Leu Tyr Arg Thr Tyr Gln Ser Lys 
        515                 520                 525             


Asp Gln Thr Leu Gly Asp Lys Lys Asp Phe Asp Ala Phe Val Ser Tyr 
    530                 535                 540                 


Ala Lys Trp Ser Ser Phe Pro Ser Glu Ala Thr Ser Ser Leu Ser Glu 
545                 550                 555                 560 


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


Gly Tyr Ser Leu Cys Leu Leu Glu Arg Asp Val Ala Pro Gly Gly Val 
            580                 585                 590         


Tyr Ala Glu Asp Ile Val Ser Ile Ile Lys Arg Ser Arg Arg Gly Ile 
        595                 600                 605             


Phe Ile Leu Ser Pro Asn Tyr Val Asn Gly Pro Ser Ile Phe Glu Leu 
    610                 615                 620                 


Gln Ala Ala Val Asn Leu Ala Leu Asp Asp Gln Thr Leu Lys Leu Ile 
625                 630                 635                 640 


Leu Ile Lys Phe Cys Tyr Phe Gln Glu Pro Glu Ser Leu Pro His Leu 
                645                 650                 655     


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


Lys Ser Val Pro Pro Asn Ser Arg Phe Trp Ala Lys Met Arg Tyr His 
        675                 680                 685             


Met Pro Val Lys Asn Ser Gln Gly Phe Thr Trp Asn Gln Leu Arg Ile 
    690                 695                 700                 


Thr Ser Arg Ile Phe Gln Trp Lys Gly Leu Ser Arg Thr Glu Thr Thr 
705                 710                 715                 720 


Gly Arg Ser Ser Gln Pro Lys Glu Trp 
                725                 


<210>  6
<211>  989
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized IL-18R DARIC -GFP polyprotein comprising an IL-18R 
       DARIC binding component, signaling component, and GFP, each 
       separated by a viral P2A domain

<400>  6

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu 
1               5                   10                  15      


His Ala Ala Arg Pro Gly Ser Ile Leu Trp His Glu Met Trp His Glu 
            20                  25                  30          


Gly Leu Glu Glu Ala Ser Arg Leu Tyr Phe Gly Glu Arg Asn Val Lys 
        35                  40                  45              


Gly Met Phe Glu Val Leu Glu Pro Leu His Ala Met Met Glu Arg Gly 
    50                  55                  60                  


Pro Gln Thr Leu Lys Glu Thr Ser Phe Asn Gln Ala Tyr Gly Arg Asp 
65                  70                  75                  80  


Leu Met Glu Ala Gln Glu Trp Cys Arg Lys Tyr Met Lys Ser Gly Asn 
                85                  90                  95      


Val Lys Asp Leu Leu Gln Ala Trp Asp Leu Tyr Tyr His Val Phe Arg 
            100                 105                 110         


Arg Ile Ser Lys Ala Ser Gly Met Ile Ile Ala Val Leu Ile Leu Val 
        115                 120                 125             


Ala Val Val Cys Leu Val Thr Val Cys Val Ile Tyr Arg Val Asp Leu 
    130                 135                 140                 


Val Leu Phe Tyr Arg His Leu Thr Arg Arg Asp Glu Thr Leu Thr Asp 
145                 150                 155                 160 


Gly Lys Thr Tyr Asp Ala Phe Val Ser Tyr Leu Lys Glu Cys Arg Pro 
                165                 170                 175     


Glu Asn Gly Glu Glu His Thr Phe Ala Val Glu Ile Leu Pro Arg Val 
            180                 185                 190         


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


Val Pro Gly Gly Ala Val Val Asp Glu Ile His Ser Leu Ile Glu Lys 
    210                 215                 220                 


Ser Arg Arg Leu Ile Ile Val Leu Ser Lys Ser Tyr Met Ser Asn Glu 
225                 230                 235                 240 


Val Arg Tyr Glu Leu Glu Ser Gly Leu His Glu Ala Leu Val Glu Arg 
                245                 250                 255     


Lys Ile Lys Ile Ile Leu Ile Glu Phe Thr Pro Val Thr Asp Phe Thr 
            260                 265                 270         


Phe Leu Pro Gln Ser Leu Lys Leu Leu Lys Ser His Arg Val Leu Lys 
        275                 280                 285             


Trp Lys Ala Asp Lys Ser Leu Ser Tyr Asn Ser Arg Phe Trp Lys Asn 
    290                 295                 300                 


Leu Leu Tyr Leu Met Pro Ala Lys Thr Val Lys Pro Gly Arg Asp Glu 
305                 310                 315                 320 


Pro Glu Val Leu Pro Val Leu Ser Glu Ser Pro Arg Ser Gly Ser Gly 
                325                 330                 335     


Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val Glu Glu Asn 
            340                 345                 350         


Pro Gly Pro Ser Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu 
        355                 360                 365             


Leu Trp Val Pro Gly Ser Thr Gly Gly Val Gln Val Glu Thr Ile Ser 
    370                 375                 380                 


Pro Gly Asp Gly Arg Thr Phe Pro Lys Arg Gly Gln Thr Cys Val Val 
385                 390                 395                 400 


His Tyr Thr Gly Met Leu Glu Asp Gly Lys Lys Phe Asp Ser Ser Arg 
                405                 410                 415     


Asp Arg Asn Lys Pro Phe Lys Phe Met Leu Gly Lys Gln Glu Val Ile 
            420                 425                 430         


Arg Gly Trp Glu Glu Gly Val Ala Gln Met Ser Val Gly Gln Arg Ala 
        435                 440                 445             


Lys Leu Thr Ile Ser Pro Asp Tyr Ala Tyr Gly Ala Thr Gly His Pro 
    450                 455                 460                 


Gly Ile Ile Pro Pro His Ala Thr Leu Val Phe Asp Val Glu Leu Leu 
465                 470                 475                 480 


Lys Leu Glu Gly Gly Arg Gly Val Val Leu Leu Tyr Ile Leu Leu Gly 
                485                 490                 495     


Thr Ile Gly Thr Leu Val Ala Val Leu Ala Ala Ser Ala Leu Leu Tyr 
            500                 505                 510         


Arg His Trp Ile Glu Ile Val Leu Leu Tyr Arg Thr Tyr Gln Ser Lys 
        515                 520                 525             


Asp Gln Thr Leu Gly Asp Lys Lys Asp Phe Asp Ala Phe Val Ser Tyr 
    530                 535                 540                 


Ala Lys Trp Ser Ser Phe Pro Ser Glu Ala Thr Ser Ser Leu Ser Glu 
545                 550                 555                 560 


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


Gly Tyr Ser Leu Cys Leu Leu Glu Arg Asp Val Ala Pro Gly Gly Val 
            580                 585                 590         


Tyr Ala Glu Asp Ile Val Ser Ile Ile Lys Arg Ser Arg Arg Gly Ile 
        595                 600                 605             


Phe Ile Leu Ser Pro Asn Tyr Val Asn Gly Pro Ser Ile Phe Glu Leu 
    610                 615                 620                 


Gln Ala Ala Val Asn Leu Ala Leu Asp Asp Gln Thr Leu Lys Leu Ile 
625                 630                 635                 640 


Leu Ile Lys Phe Cys Tyr Phe Gln Glu Pro Glu Ser Leu Pro His Leu 
                645                 650                 655     


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


Lys Ser Val Pro Pro Asn Ser Arg Phe Trp Ala Lys Met Arg Tyr His 
        675                 680                 685             


Met Pro Val Lys Asn Ser Gln Gly Phe Thr Trp Asn Gln Leu Arg Ile 
    690                 695                 700                 


Thr Ser Arg Ile Phe Gln Trp Lys Gly Leu Ser Arg Thr Glu Thr Thr 
705                 710                 715                 720 


Gly Arg Ser Ser Gln Pro Lys Glu Trp Ala Thr Asn Phe Ser Leu Leu 
                725                 730                 735     


Lys Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Ser Gly Met Val 
            740                 745                 750         


Ser Lys Gly Glu Glu Leu Phe Thr Gly Val Val Pro Ile Leu Val Glu 
        755                 760                 765             


Leu Asp Gly Asp Val Asn Gly His Lys Phe Ser Val Ser Gly Glu Gly 
    770                 775                 780                 


Glu Gly Asp Ala Thr Tyr Gly Lys Leu Thr Leu Lys Phe Ile Cys Thr 
785                 790                 795                 800 


Thr Gly Lys Leu Pro Val Pro Trp Pro Thr Leu Val Thr Thr Leu Thr 
                805                 810                 815     


Tyr Gly Val Gln Cys Phe Ser Arg Tyr Pro Asp His Met Lys Gln His 
            820                 825                 830         


Asp Phe Phe Lys Ser Ala Met Pro Glu Gly Tyr Val Gln Glu Arg Thr 
        835                 840                 845             


Ile Phe Phe Lys Asp Asp Gly Asn Tyr Lys Thr Arg Ala Glu Val Lys 
    850                 855                 860                 


Phe Glu Gly Asp Thr Leu Val Asn Arg Ile Glu Leu Lys Gly Ile Asp 
865                 870                 875                 880 


Phe Lys Glu Asp Gly Asn Ile Leu Gly His Lys Leu Glu Tyr Asn Tyr 
                885                 890                 895     


Asn Ser His Asn Val Tyr Ile Met Ala Asp Lys Gln Lys Asn Gly Ile 
            900                 905                 910         


Lys Val Asn Phe Lys Ile Arg His Asn Ile Glu Asp Gly Ser Val Gln 
        915                 920                 925             


Leu Ala Asp His Tyr Gln Gln Asn Thr Pro Ile Gly Asp Gly Pro Val 
    930                 935                 940                 


Leu Leu Pro Asp Asn His Tyr Leu Ser Thr Gln Ser Ala Leu Ser Lys 
945                 950                 955                 960 


Asp Pro Asn Glu Lys Arg Asp His Met Val Leu Leu Glu Phe Val Thr 
                965                 970                 975     


Ala Ala Gly Ile Thr Leu Gly Met Asp Glu Leu Tyr Lys 
            980                 985                 


<210>  7
<211>  3
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  7

Gly Gly Gly 
1           


<210>  8
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  8

Asp Gly Gly Gly Ser 
1               5   


<210>  9
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  9

Thr Gly Glu Lys Pro 
1               5   


<210>  10
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  10

Gly Gly Arg Arg 
1               


<210>  11
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  11

Gly Gly Gly Gly Ser 
1               5   


<210>  12
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  12

Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Val Asp 
1               5                   10                  


<210>  13
<211>  18
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  13

Lys Glu Ser Gly Ser Val Ser Ser Glu Gln Leu Ala Gln Phe Arg Ser 
1               5                   10                  15      


Leu Asp 
        


<210>  14
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  14

Gly Gly Arg Arg Gly Gly Gly Ser 
1               5               


<210>  15
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  15

Leu Arg Gln Arg Asp Gly Glu Arg Pro 
1               5                   


<210>  16
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  16

Leu Arg Gln Lys Asp Gly Gly Gly Ser Glu Arg Pro 
1               5                   10          


<210>  17
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  17

Leu Arg Gln Lys Asp Gly Gly Gly Ser Gly Gly Gly Ser Glu Arg Pro 
1               5                   10                  15      


<210>  18
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Cleavage sequence by TEV protease


<220>
<221>  misc_feature
<222>  (2)..(3)
<223>  Xaa is any amino acid

<220>
<221>  misc_feature
<222>  (5)..(5)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (7)..(7)
<223>  Xaa = Gly or Ser

<400>  18

Glu Xaa Xaa Tyr Xaa Gln Xaa 
1               5           


<210>  19
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Cleavage sequence by TEV protease

<400>  19

Glu Asn Leu Tyr Phe Gln Gly 
1               5           


<210>  20
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Cleavage sequence by TEV protease

<400>  20

Glu Asn Leu Tyr Phe Gln Ser 
1               5           


<210>  21
<211>  22
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  21

Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val 
1               5                   10                  15      


Glu Glu Asn Pro Gly Pro 
            20          


<210>  22
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  22

Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val Glu Glu Asn 
1               5                   10                  15      


Pro Gly Pro 
            


<210>  23
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  23

Leu Leu Lys Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro 
1               5                   10                  


<210>  24
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  24

Gly Ser Gly Glu Gly Arg Gly Ser Leu Leu Thr Cys Gly Asp Val Glu 
1               5                   10                  15      


Glu Asn Pro Gly Pro 
            20      


<210>  25
<211>  18
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  25

Glu Gly Arg Gly Ser Leu Leu Thr Cys Gly Asp Val Glu Glu Asn Pro 
1               5                   10                  15      


Gly Pro 
        


<210>  26
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  26

Leu Leu Thr Cys Gly Asp Val Glu Glu Asn Pro Gly Pro 
1               5                   10              


<210>  27
<211>  23
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  27

Gly Ser Gly Gln Cys Thr Asn Tyr Ala Leu Leu Lys Leu Ala Gly Asp 
1               5                   10                  15      


Val Glu Ser Asn Pro Gly Pro 
            20              


<210>  28
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  28

Gln Cys Thr Asn Tyr Ala Leu Leu Lys Leu Ala Gly Asp Val Glu Ser 
1               5                   10                  15      


Asn Pro Gly Pro 
            20  


<210>  29
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  29

Leu Leu Lys Leu Ala Gly Asp Val Glu Ser Asn Pro Gly Pro 
1               5                   10                  


<210>  30
<211>  25
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  30

Gly Ser Gly Val Lys Gln Thr Leu Asn Phe Asp Leu Leu Lys Leu Ala 
1               5                   10                  15      


Gly Asp Val Glu Ser Asn Pro Gly Pro 
            20                  25  


<210>  31
<211>  22
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  31

Val Lys Gln Thr Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val 
1               5                   10                  15      


Glu Ser Asn Pro Gly Pro 
            20          


<210>  32
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  32

Leu Leu Lys Leu Ala Gly Asp Val Glu Ser Asn Pro Gly Pro 
1               5                   10                  


<210>  33
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  33

Leu Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val Glu Ser Asn 
1               5                   10                  15      


Pro Gly Pro 
            


<210>  34
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  34

Thr Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val Glu Ser Asn 
1               5                   10                  15      


Pro Gly Pro 
            


<210>  35
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  35

Leu Leu Lys Leu Ala Gly Asp Val Glu Ser Asn Pro Gly Pro 
1               5                   10                  


<210>  36
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  36

Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val Glu Ser Asn Pro Gly 
1               5                   10                  15      


Pro 
    


<210>  37
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  37

Gln Leu Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val Glu Ser 
1               5                   10                  15      


Asn Pro Gly Pro 
            20  


<210>  38
<211>  24
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  38

Ala Pro Val Lys Gln Thr Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly 
1               5                   10                  15      


Asp Val Glu Ser Asn Pro Gly Pro 
            20                  


<210>  39
<211>  40
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  39

Val Thr Glu Leu Leu Tyr Arg Met Lys Arg Ala Glu Thr Tyr Cys Pro 
1               5                   10                  15      


Arg Pro Leu Leu Ala Ile His Pro Thr Glu Ala Arg His Lys Gln Lys 
            20                  25                  30          


Ile Val Ala Pro Val Lys Gln Thr 
        35                  40  


<210>  40
<211>  18
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  40

Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val Glu Ser Asn Pro 
1               5                   10                  15      


Gly Pro 
        


<210>  41
<211>  40
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  41

Leu Leu Ala Ile His Pro Thr Glu Ala Arg His Lys Gln Lys Ile Val 
1               5                   10                  15      


Ala Pro Val Lys Gln Thr Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly 
            20                  25                  30          


Asp Val Glu Ser Asn Pro Gly Pro 
        35                  40  


<210>  42
<211>  33
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  42

Glu Ala Arg His Lys Gln Lys Ile Val Ala Pro Val Lys Gln Thr Leu 
1               5                   10                  15      


Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val Glu Ser Asn Pro Gly 
            20                  25                  30          


Pro 
    


<210>  43
<211>  10
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Consensus Kozak sequence

<400>  43
gccrccatgg                                                              10


