                         SEQUENCE LISTING

<110>  CSL Behring Recombinant Facility AG
 
<120>  Modified von Willebrand Factor having improved half-life

<130>  A241

<150>  EP2015158065.1
<151>  2015-03-06

<160>  12    

<170>  PatentIn version 3.5

<210>  1
<211>  8442
<212>  DNA
<213>  Homo sapiens


<220>
<221>  CDS
<222>  (1)..(8442)

<400>  1
atg att cct gcc aga ttt gcc ggg gtg ctg ctt gct ctg gcc ctc att         48
Met Ile Pro Ala Arg Phe Ala Gly Val Leu Leu Ala Leu Ala Leu Ile           
1               5                   10                  15                

ttg cca ggg acc ctt tgt gca gaa gga act cgc ggc agg tca tcc acg         96
Leu Pro Gly Thr Leu Cys Ala Glu Gly Thr Arg Gly Arg Ser Ser Thr           
            20                  25                  30                    

gcc cga tgc agc ctt ttc gga agt gac ttc gtc aac acc ttt gat ggg        144
Ala Arg Cys Ser Leu Phe Gly Ser Asp Phe Val Asn Thr Phe Asp Gly           
        35                  40                  45                        

agc atg tac agc ttt gcg gga tac tgc agt tac ctc ctg gca ggg ggc        192
Ser Met Tyr Ser Phe Ala Gly Tyr Cys Ser Tyr Leu Leu Ala Gly Gly           
    50                  55                  60                            

tgc cag aaa cgc tcc ttc tcg att att ggg gac ttc cag aat ggc aag        240
Cys Gln Lys Arg Ser Phe Ser Ile Ile Gly Asp Phe Gln Asn Gly Lys           
65                  70                  75                  80            

aga gtg agc ctc tcc gtg tat ctt ggg gaa ttt ttt gac atc cat ttg        288
Arg Val Ser Leu Ser Val Tyr Leu Gly Glu Phe Phe Asp Ile His Leu           
                85                  90                  95                

ttt gtc aat ggt acc gtg aca cag ggg gac caa aga gtc tcc atg ccc        336
Phe Val Asn Gly Thr Val Thr Gln Gly Asp Gln Arg Val Ser Met Pro           
            100                 105                 110                   

tat gcc tcc aaa ggg ctg tat cta gaa act gag gct ggg tac tac aag        384
Tyr Ala Ser Lys Gly Leu Tyr Leu Glu Thr Glu Ala Gly Tyr Tyr Lys           
        115                 120                 125                       

ctg tcc ggt gag gcc tat ggc ttt gtg gcc agg atc gat ggc agc ggc        432
Leu Ser Gly Glu Ala Tyr Gly Phe Val Ala Arg Ile Asp Gly Ser Gly           
    130                 135                 140                           

aac ttt caa gtc ctg ctg tca gac aga tac ttc aac aag acc tgc ggg        480
Asn Phe Gln Val Leu Leu Ser Asp Arg Tyr Phe Asn Lys Thr Cys Gly           
145                 150                 155                 160           

ctg tgt ggc aac ttt aac atc ttt gct gaa gat gac ttt atg acc caa        528
Leu Cys Gly Asn Phe Asn Ile Phe Ala Glu Asp Asp Phe Met Thr Gln           
                165                 170                 175               

gaa ggg acc ttg acc tcg gac cct tat gac ttt gcc aac tca tgg gct        576
Glu Gly Thr Leu Thr Ser Asp Pro Tyr Asp Phe Ala Asn Ser Trp Ala           
            180                 185                 190                   

ctg agc agt gga gaa cag tgg tgt gaa cgg gca tct cct ccc agc agc        624
Leu Ser Ser Gly Glu Gln Trp Cys Glu Arg Ala Ser Pro Pro Ser Ser           
        195                 200                 205                       

tca tgc aac atc tcc tct ggg gaa atg cag aag ggc ctg tgg gag cag        672
Ser Cys Asn Ile Ser Ser Gly Glu Met Gln Lys Gly Leu Trp Glu Gln           
    210                 215                 220                           

tgc cag ctt ctg aag agc acc tcg gtg ttt gcc cgc tgc cac cct ctg        720
Cys Gln Leu Leu Lys Ser Thr Ser Val Phe Ala Arg Cys His Pro Leu           
225                 230                 235                 240           

gtg gac ccc gag cct ttt gtg gcc ctg tgt gag aag act ttg tgt gag        768
Val Asp Pro Glu Pro Phe Val Ala Leu Cys Glu Lys Thr Leu Cys Glu           
                245                 250                 255               

tgt gct ggg ggg ctg gag tgc gcc tgc cct gcc ctc ctg gag tac gcc        816
Cys Ala Gly Gly Leu Glu Cys Ala Cys Pro Ala Leu Leu Glu Tyr Ala           
            260                 265                 270                   

cgg acc tgt gcc cag gag gga atg gtg ctg tac ggc tgg acc gac cac        864
Arg Thr Cys Ala Gln Glu Gly Met Val Leu Tyr Gly Trp Thr Asp His           
        275                 280                 285                       

agc gcg tgc agc cca gtg tgc cct gct ggt atg gag tat agg cag tgt        912
Ser Ala Cys Ser Pro Val Cys Pro Ala Gly Met Glu Tyr Arg Gln Cys           
    290                 295                 300                           

gtg tcc cct tgc gcc agg acc tgc cag agc ctg cac atc aat gaa atg        960
Val Ser Pro Cys Ala Arg Thr Cys Gln Ser Leu His Ile Asn Glu Met           
305                 310                 315                 320           

tgt cag gag cga tgc gtg gat ggc tgc agc tgc cct gag gga cag ctc       1008
Cys Gln Glu Arg Cys Val Asp Gly Cys Ser Cys Pro Glu Gly Gln Leu           
                325                 330                 335               

ctg gat gaa ggc ctc tgc gtg gag agc acc gag tgt ccc tgc gtg cat       1056
Leu Asp Glu Gly Leu Cys Val Glu Ser Thr Glu Cys Pro Cys Val His           
            340                 345                 350                   

tcc gga aag cgc tac cct ccc ggc acc tcc ctc tct cga gac tgc aac       1104
Ser Gly Lys Arg Tyr Pro Pro Gly Thr Ser Leu Ser Arg Asp Cys Asn           
        355                 360                 365                       

acc tgc att tgc cga aac agc cag tgg atc tgc agc aat gaa gaa tgt       1152
Thr Cys Ile Cys Arg Asn Ser Gln Trp Ile Cys Ser Asn Glu Glu Cys           
    370                 375                 380                           

cca ggg gag tgc ctt gtc aca ggt caa tca cac ttc aag agc ttt gac       1200
Pro Gly Glu Cys Leu Val Thr Gly Gln Ser His Phe Lys Ser Phe Asp           
385                 390                 395                 400           

aac aga tac ttc acc ttc agt ggg atc tgc cag tac ctg ctg gcc cgg       1248
Asn Arg Tyr Phe Thr Phe Ser Gly Ile Cys Gln Tyr Leu Leu Ala Arg           
                405                 410                 415               

gat tgc cag gac cac tcc ttc tcc att gtc att gag act gtc cag tgt       1296
Asp Cys Gln Asp His Ser Phe Ser Ile Val Ile Glu Thr Val Gln Cys           
            420                 425                 430                   

gct gat gac cgc gac gct gtg tgc acc cgc tcc gtc acc gtc cgg ctg       1344
Ala Asp Asp Arg Asp Ala Val Cys Thr Arg Ser Val Thr Val Arg Leu           
        435                 440                 445                       

cct ggc ctg cac aac agc ctt gtg aaa ctg aag cat ggg gca gga gtt       1392
Pro Gly Leu His Asn Ser Leu Val Lys Leu Lys His Gly Ala Gly Val           
    450                 455                 460                           

gcc atg gat ggc cag gac gtc cag ctc ccc ctc ctg aaa ggt gac ctc       1440
Ala Met Asp Gly Gln Asp Val Gln Leu Pro Leu Leu Lys Gly Asp Leu           
465                 470                 475                 480           

cgc atc cag cat aca gtg acg gcc tcc gtg cgc ctc agc tac ggg gag       1488
Arg Ile Gln His Thr Val Thr Ala Ser Val Arg Leu Ser Tyr Gly Glu           
                485                 490                 495               

gac ctg cag atg gac tgg gat ggc cgc ggg agg ctg ctg gtg aag ctg       1536
Asp Leu Gln Met Asp Trp Asp Gly Arg Gly Arg Leu Leu Val Lys Leu           
            500                 505                 510                   

tcc ccc gtc tat gcc ggg aag acc tgc ggc ctg tgt ggg aat tac aat       1584
Ser Pro Val Tyr Ala Gly Lys Thr Cys Gly Leu Cys Gly Asn Tyr Asn           
        515                 520                 525                       

ggc aac cag ggc gac gac ttc ctt acc ccc tct ggg ctg gcg gag ccc       1632
Gly Asn Gln Gly Asp Asp Phe Leu Thr Pro Ser Gly Leu Ala Glu Pro           
    530                 535                 540                           

cgg gtg gag gac ttc ggg aac gcc tgg aag ctg cac ggg gac tgc cag       1680
Arg Val Glu Asp Phe Gly Asn Ala Trp Lys Leu His Gly Asp Cys Gln           
545                 550                 555                 560           

gac ctg cag aag cag cac agc gat ccc tgc gcc ctc aac ccg cgc atg       1728
Asp Leu Gln Lys Gln His Ser Asp Pro Cys Ala Leu Asn Pro Arg Met           
                565                 570                 575               

acc agg ttc tcc gag gag gcg tgc gcg gtc ctg acg tcc ccc aca ttc       1776
Thr Arg Phe Ser Glu Glu Ala Cys Ala Val Leu Thr Ser Pro Thr Phe           
            580                 585                 590                   

gag gcc tgc cat cgt gcc gtc agc ccg ctg ccc tac ctg cgg aac tgc       1824
Glu Ala Cys His Arg Ala Val Ser Pro Leu Pro Tyr Leu Arg Asn Cys           
        595                 600                 605                       

cgc tac gac gtg tgc tcc tgc tcg gac ggc cgc gag tgc ctg tgc ggc       1872
Arg Tyr Asp Val Cys Ser Cys Ser Asp Gly Arg Glu Cys Leu Cys Gly           
    610                 615                 620                           

gcc ctg gcc agc tat gcc gcg gcc tgc gcg ggg aga ggc gtg cgc gtc       1920
Ala Leu Ala Ser Tyr Ala Ala Ala Cys Ala Gly Arg Gly Val Arg Val           
625                 630                 635                 640           

gcg tgg cgc gag cca ggc cgc tgt gag ctg aac tgc ccg aaa ggc cag       1968
Ala Trp Arg Glu Pro Gly Arg Cys Glu Leu Asn Cys Pro Lys Gly Gln           
                645                 650                 655               

gtg tac ctg cag tgc ggg acc ccc tgc aac ctg acc tgc cgc tct ctc       2016
Val Tyr Leu Gln Cys Gly Thr Pro Cys Asn Leu Thr Cys Arg Ser Leu           
            660                 665                 670                   

tct tac ccg gat gag gaa tgc aat gag gcc tgc ctg gag ggc tgc ttc       2064
Ser Tyr Pro Asp Glu Glu Cys Asn Glu Ala Cys Leu Glu Gly Cys Phe           
        675                 680                 685                       

tgc ccc cca ggg ctc tac atg gat gag agg ggg gac tgc gtg ccc aag       2112
Cys Pro Pro Gly Leu Tyr Met Asp Glu Arg Gly Asp Cys Val Pro Lys           
    690                 695                 700                           

gcc cag tgc ccc tgt tac tat gac ggt gag atc ttc cag cca gaa gac       2160
Ala Gln Cys Pro Cys Tyr Tyr Asp Gly Glu Ile Phe Gln Pro Glu Asp           
705                 710                 715                 720           

atc ttc tca gac cat cac acc atg tgc tac tgt gag gat ggc ttc atg       2208
Ile Phe Ser Asp His His Thr Met Cys Tyr Cys Glu Asp Gly Phe Met           
                725                 730                 735               

cac tgt acc atg agt gga gtc ccc gga agc ttg ctg cct gac gct gtc       2256
His Cys Thr Met Ser Gly Val Pro Gly Ser Leu Leu Pro Asp Ala Val           
            740                 745                 750                   

ctc agc agt ccc ctg tct cat cgc agc aaa agg agc cta tcc tgt cgg       2304
Leu Ser Ser Pro Leu Ser His Arg Ser Lys Arg Ser Leu Ser Cys Arg           
        755                 760                 765                       

ccc ccc atg gtc aag ctg gtg tgt ccc gct gac aac ctg cgg gct gaa       2352
Pro Pro Met Val Lys Leu Val Cys Pro Ala Asp Asn Leu Arg Ala Glu           
    770                 775                 780                           

ggg ctc gag tgt acc aaa acg tgc cag aac tat gac ctg gag tgc atg       2400
Gly Leu Glu Cys Thr Lys Thr Cys Gln Asn Tyr Asp Leu Glu Cys Met           
785                 790                 795                 800           

agc atg ggc tgt gtc tct ggc tgc ctc tgc ccc ccg ggc atg gtc cgg       2448
Ser Met Gly Cys Val Ser Gly Cys Leu Cys Pro Pro Gly Met Val Arg           
                805                 810                 815               

cat gag aac aga tgt gtg gcc ctg gaa agg tgt ccc tgc ttc cat cag       2496
His Glu Asn Arg Cys Val Ala Leu Glu Arg Cys Pro Cys Phe His Gln           
            820                 825                 830                   

ggc aag gag tat gcc cct gga gaa aca gtg aag att ggc tgc aac act       2544
Gly Lys Glu Tyr Ala Pro Gly Glu Thr Val Lys Ile Gly Cys Asn Thr           
        835                 840                 845                       

tgt gtc tgt cgg gac cgg aag tgg aac tgc aca gac cat gtg tgt gat       2592
Cys Val Cys Arg Asp Arg Lys Trp Asn Cys Thr Asp His Val Cys Asp           
    850                 855                 860                           

gcc acg tgc tcc acg atc ggc atg gcc cac tac ctc acc ttc gac ggg       2640
Ala Thr Cys Ser Thr Ile Gly Met Ala His Tyr Leu Thr Phe Asp Gly           
865                 870                 875                 880           

ctc aaa tac ctg ttc ccc ggg gag tgc cag tac gtt ctg gtg cag gat       2688
Leu Lys Tyr Leu Phe Pro Gly Glu Cys Gln Tyr Val Leu Val Gln Asp           
                885                 890                 895               

tac tgc ggc agt aac cct ggg acc ttt cgg atc cta gtg ggg aat aag       2736
Tyr Cys Gly Ser Asn Pro Gly Thr Phe Arg Ile Leu Val Gly Asn Lys           
            900                 905                 910                   

gga tgc agc cac ccc tca gtg aaa tgc aag aaa cgg gtc acc atc ctg       2784
Gly Cys Ser His Pro Ser Val Lys Cys Lys Lys Arg Val Thr Ile Leu           
        915                 920                 925                       

gtg gag gga gga gag att gag ctg ttt gac ggg gag gtg aat gtg aag       2832
Val Glu Gly Gly Glu Ile Glu Leu Phe Asp Gly Glu Val Asn Val Lys           
    930                 935                 940                           

agg ccc atg aag gat gag act cac ttt gag gtg gtg gag tct ggc cgg       2880
Arg Pro Met Lys Asp Glu Thr His Phe Glu Val Val Glu Ser Gly Arg           
945                 950                 955                 960           

tac atc att ctg ctg ctg ggc aaa gcc ctc tcc gtg gtc tgg gac cgc       2928
Tyr Ile Ile Leu Leu Leu Gly Lys Ala Leu Ser Val Val Trp Asp Arg           
                965                 970                 975               

cac ctg agc atc tcc gtg gtc ctg aag cag aca tac cag gag aaa gtg       2976
His Leu Ser Ile Ser Val Val Leu Lys Gln Thr Tyr Gln Glu Lys Val           
            980                 985                 990                   

tgt ggc ctg tgt ggg aat ttt gat  ggc atc cag aac aat  gac ctc acc     3024
Cys Gly Leu Cys Gly Asn Phe Asp  Gly Ile Gln Asn Asn  Asp Leu Thr         
        995                 1000                 1005                     

agc agc  aac ctc caa gtg gag  gaa gac cct gtg gac  ttt ggg aac        3069
Ser Ser  Asn Leu Gln Val Glu  Glu Asp Pro Val Asp  Phe Gly Asn            
    1010                 1015                 1020                        

tcc tgg  aaa gtg agc tcg cag  tgt gct gac acc aga  aaa gtg cct        3114
Ser Trp  Lys Val Ser Ser Gln  Cys Ala Asp Thr Arg  Lys Val Pro            
    1025                 1030                 1035                        

ctg gac  tca tcc cct gcc acc  tgc cat aac aac atc  atg aag cag        3159
Leu Asp  Ser Ser Pro Ala Thr  Cys His Asn Asn Ile  Met Lys Gln            
    1040                 1045                 1050                        

acg atg  gtg gat tcc tcc tgt  aga atc ctt acc agt  gac gtc ttc        3204
Thr Met  Val Asp Ser Ser Cys  Arg Ile Leu Thr Ser  Asp Val Phe            
    1055                 1060                 1065                        

cag gac  tgc aac aag ctg gtg  gac ccc gag cca tat  ctg gat gtc        3249
Gln Asp  Cys Asn Lys Leu Val  Asp Pro Glu Pro Tyr  Leu Asp Val            
    1070                 1075                 1080                        

tgc att  tac gac acc tgc tcc  tgt gag tcc att ggg  gac tgc gcc        3294
Cys Ile  Tyr Asp Thr Cys Ser  Cys Glu Ser Ile Gly  Asp Cys Ala            
    1085                 1090                 1095                        

tgc ttc  tgc gac acc att gct  gcc tat gcc cac gtg  tgt gcc cag        3339
Cys Phe  Cys Asp Thr Ile Ala  Ala Tyr Ala His Val  Cys Ala Gln            
    1100                 1105                 1110                        

cat ggc  aag gtg gtg acc tgg  agg acg gcc aca ttg  tgc ccc cag        3384
His Gly  Lys Val Val Thr Trp  Arg Thr Ala Thr Leu  Cys Pro Gln            
    1115                 1120                 1125                        

agc tgc  gag gag agg aat ctc  cgg gag aac ggg tat  gag tgt gag        3429
Ser Cys  Glu Glu Arg Asn Leu  Arg Glu Asn Gly Tyr  Glu Cys Glu            
    1130                 1135                 1140                        

tgg cgc  tat aac agc tgt gca  cct gcc tgt caa gtc  acg tgt cag        3474
Trp Arg  Tyr Asn Ser Cys Ala  Pro Ala Cys Gln Val  Thr Cys Gln            
    1145                 1150                 1155                        

cac cct  gag cca ctg gcc tgc  cct gtg cag tgt gtg  gag ggc tgc        3519
His Pro  Glu Pro Leu Ala Cys  Pro Val Gln Cys Val  Glu Gly Cys            
    1160                 1165                 1170                        

cat gcc  cac tgc cct cca ggg  aaa atc ctg gat gag  ctt ttg cag        3564
His Ala  His Cys Pro Pro Gly  Lys Ile Leu Asp Glu  Leu Leu Gln            
    1175                 1180                 1185                        

acc tgc  gtt gac cct gaa gac  tgt cca gtg tgt gag  gtg gct ggc        3609
Thr Cys  Val Asp Pro Glu Asp  Cys Pro Val Cys Glu  Val Ala Gly            
    1190                 1195                 1200                        

cgg cgt  ttt gcc tca gga aag  aaa gtc acc ttg aat  ccc agt gac        3654
Arg Arg  Phe Ala Ser Gly Lys  Lys Val Thr Leu Asn  Pro Ser Asp            
    1205                 1210                 1215                        

cct gag  cac tgc cag att tgc  cac tgt gat gtt gtc  aac ctc acc        3699
Pro Glu  His Cys Gln Ile Cys  His Cys Asp Val Val  Asn Leu Thr            
    1220                 1225                 1230                        

tgt gaa  gcc tgc cag gag ccg  gga ggc ctg gtg gtg  cct ccc aca        3744
Cys Glu  Ala Cys Gln Glu Pro  Gly Gly Leu Val Val  Pro Pro Thr            
    1235                 1240                 1245                        

gat gcc  ccg gtg agc ccc acc  act ctg tat gtg gag  gac atc tcg        3789
Asp Ala  Pro Val Ser Pro Thr  Thr Leu Tyr Val Glu  Asp Ile Ser            
    1250                 1255                 1260                        

gaa ccg  ccg ttg cac gat ttc  tac tgc agc agg cta  ctg gac ctg        3834
Glu Pro  Pro Leu His Asp Phe  Tyr Cys Ser Arg Leu  Leu Asp Leu            
    1265                 1270                 1275                        

gtc ttc  ctg ctg gat ggc tcc  tcc agg ctg tcc gag  gct gag ttt        3879
Val Phe  Leu Leu Asp Gly Ser  Ser Arg Leu Ser Glu  Ala Glu Phe            
    1280                 1285                 1290                        

gaa gtg  ctg aag gcc ttt gtg  gtg gac atg atg gag  cgg ctg cgc        3924
Glu Val  Leu Lys Ala Phe Val  Val Asp Met Met Glu  Arg Leu Arg            
    1295                 1300                 1305                        

atc tcc  cag aag tgg gtc cgc  gtg gcc gtg gtg gag  tac cac gac        3969
Ile Ser  Gln Lys Trp Val Arg  Val Ala Val Val Glu  Tyr His Asp            
    1310                 1315                 1320                        

ggc tcc  cac gcc tac atc ggg  ctc aag gac cgg aag  cga ccg tca        4014
Gly Ser  His Ala Tyr Ile Gly  Leu Lys Asp Arg Lys  Arg Pro Ser            
    1325                 1330                 1335                        

gag ctg  cgg cgc att gcc agc  cag gtg aag tat gcg  ggc agc cag        4059
Glu Leu  Arg Arg Ile Ala Ser  Gln Val Lys Tyr Ala  Gly Ser Gln            
    1340                 1345                 1350                        

gtg gcc  tcc acc agc gag gtc  ttg aaa tac aca ctg  ttc caa atc        4104
Val Ala  Ser Thr Ser Glu Val  Leu Lys Tyr Thr Leu  Phe Gln Ile            
    1355                 1360                 1365                        

ttc agc  aag atc gac cgc cct  gaa gcc tcc cgc atc  gcc ctg ctc        4149
Phe Ser  Lys Ile Asp Arg Pro  Glu Ala Ser Arg Ile  Ala Leu Leu            
    1370                 1375                 1380                        

ctg atg  gcc agc cag gag ccc  caa cgg atg tcc cgg  aac ttt gtc        4194
Leu Met  Ala Ser Gln Glu Pro  Gln Arg Met Ser Arg  Asn Phe Val            
    1385                 1390                 1395                        

cgc tac  gtc cag ggc ctg aag  aag aag aag gtc att  gtg atc ccg        4239
Arg Tyr  Val Gln Gly Leu Lys  Lys Lys Lys Val Ile  Val Ile Pro            
    1400                 1405                 1410                        

gtg ggc  att ggg ccc cat gcc  aac ctc aag cag atc  cgc ctc atc        4284
Val Gly  Ile Gly Pro His Ala  Asn Leu Lys Gln Ile  Arg Leu Ile            
    1415                 1420                 1425                        

gag aag  cag gcc cct gag aac  aag gcc ttc gtg ctg  agc agt gtg        4329
Glu Lys  Gln Ala Pro Glu Asn  Lys Ala Phe Val Leu  Ser Ser Val            
    1430                 1435                 1440                        

gat gag  ctg gag cag caa agg  gac gag atc gtt agc  tac ctc tgt        4374
Asp Glu  Leu Glu Gln Gln Arg  Asp Glu Ile Val Ser  Tyr Leu Cys            
    1445                 1450                 1455                        

gac ctt  gcc cct gaa gcc cct  cct cct act ctg ccc  ccc cac atg        4419
Asp Leu  Ala Pro Glu Ala Pro  Pro Pro Thr Leu Pro  Pro His Met            
    1460                 1465                 1470                        

gca caa  gtc act gtg ggc ccg  ggg ctc ttg ggg gtt  tcg acc ctg        4464
Ala Gln  Val Thr Val Gly Pro  Gly Leu Leu Gly Val  Ser Thr Leu            
    1475                 1480                 1485                        

ggg ccc  aag agg aac tcc atg  gtt ctg gat gtg gcg  ttc gtc ctg        4509
Gly Pro  Lys Arg Asn Ser Met  Val Leu Asp Val Ala  Phe Val Leu            
    1490                 1495                 1500                        

gaa gga  tcg gac aaa att ggt  gaa gcc gac ttc aac  agg agc aag        4554
Glu Gly  Ser Asp Lys Ile Gly  Glu Ala Asp Phe Asn  Arg Ser Lys            
    1505                 1510                 1515                        

gag ttc  atg gag gag gtg att  cag cgg atg gat gtg  ggc cag gac        4599
Glu Phe  Met Glu Glu Val Ile  Gln Arg Met Asp Val  Gly Gln Asp            
    1520                 1525                 1530                        

agc atc  cac gtc acg gtg ctg  cag tac tcc tac atg  gtg acc gtg        4644
Ser Ile  His Val Thr Val Leu  Gln Tyr Ser Tyr Met  Val Thr Val            
    1535                 1540                 1545                        

gag tac  ccc ttc agc gag gca  cag tcc aaa ggg gac  atc ctg cag        4689
Glu Tyr  Pro Phe Ser Glu Ala  Gln Ser Lys Gly Asp  Ile Leu Gln            
    1550                 1555                 1560                        

cgg gtg  cga gag atc cgc tac  cag ggc ggc aac agg  acc aac act        4734
Arg Val  Arg Glu Ile Arg Tyr  Gln Gly Gly Asn Arg  Thr Asn Thr            
    1565                 1570                 1575                        

ggg ctg  gcc ctg cgg tac ctc  tct gac cac agc ttc  ttg gtc agc        4779
Gly Leu  Ala Leu Arg Tyr Leu  Ser Asp His Ser Phe  Leu Val Ser            
    1580                 1585                 1590                        

cag ggt  gac cgg gag cag gcg  ccc aac ctg gtc tac  atg gtc acc        4824
Gln Gly  Asp Arg Glu Gln Ala  Pro Asn Leu Val Tyr  Met Val Thr            
    1595                 1600                 1605                        

gga aat  cct gcc tct gat gag  atc aag agg ctg cct  gga gac atc        4869
Gly Asn  Pro Ala Ser Asp Glu  Ile Lys Arg Leu Pro  Gly Asp Ile            
    1610                 1615                 1620                        

cag gtg  gtg ccc att gga gtg  ggc cct aat gcc aac  gtg cag gag        4914
Gln Val  Val Pro Ile Gly Val  Gly Pro Asn Ala Asn  Val Gln Glu            
    1625                 1630                 1635                        

ctg gag  agg att ggc tgg ccc  aat gcc cct atc ctc  atc cag gac        4959
Leu Glu  Arg Ile Gly Trp Pro  Asn Ala Pro Ile Leu  Ile Gln Asp            
    1640                 1645                 1650                        

ttt gag  acg ctc ccc cga gag  gct cct gac ctg gtg  ctg cag agg        5004
Phe Glu  Thr Leu Pro Arg Glu  Ala Pro Asp Leu Val  Leu Gln Arg            
    1655                 1660                 1665                        

tgc tgc  tcc gga gag ggg ctg  cag atc ccc acc ctc  tcc cct gca        5049
Cys Cys  Ser Gly Glu Gly Leu  Gln Ile Pro Thr Leu  Ser Pro Ala            
    1670                 1675                 1680                        

cct gac  tgc agc cag ccc ctg  gac gtg atc ctt ctc  ctg gat ggc        5094
Pro Asp  Cys Ser Gln Pro Leu  Asp Val Ile Leu Leu  Leu Asp Gly            
    1685                 1690                 1695                        

tcc tcc  agt ttc cca gct tct  tat ttt gat gaa atg  aag agt ttc        5139
Ser Ser  Ser Phe Pro Ala Ser  Tyr Phe Asp Glu Met  Lys Ser Phe            
    1700                 1705                 1710                        

gcc aag  gct ttc att tca aaa  gcc aat ata ggg cct  cgt ctc act        5184
Ala Lys  Ala Phe Ile Ser Lys  Ala Asn Ile Gly Pro  Arg Leu Thr            
    1715                 1720                 1725                        

cag gtg  tca gtg ctg cag tat  gga agc atc acc acc  att gac gtg        5229
Gln Val  Ser Val Leu Gln Tyr  Gly Ser Ile Thr Thr  Ile Asp Val            
    1730                 1735                 1740                        

cca tgg  aac gtg gtc ccg gag  aaa gcc cat ttg ctg  agc ctt gtg        5274
Pro Trp  Asn Val Val Pro Glu  Lys Ala His Leu Leu  Ser Leu Val            
    1745                 1750                 1755                        

gac gtc  atg cag cgg gag gga  ggc ccc agc caa atc  ggg gat gcc        5319
Asp Val  Met Gln Arg Glu Gly  Gly Pro Ser Gln Ile  Gly Asp Ala            
    1760                 1765                 1770                        

ttg ggc  ttt gct gtg cga tac  ttg act tca gaa atg  cat ggg gcg        5364
Leu Gly  Phe Ala Val Arg Tyr  Leu Thr Ser Glu Met  His Gly Ala            
    1775                 1780                 1785                        

cgc ccg  gga gcc tca aag gcg  gtg gtc atc ctg gtc  acg gac gtc        5409
Arg Pro  Gly Ala Ser Lys Ala  Val Val Ile Leu Val  Thr Asp Val            
    1790                 1795                 1800                        

tct gtg  gat tca gtg gat gca  gca gct gat gcc gcc  agg tcc aac        5454
Ser Val  Asp Ser Val Asp Ala  Ala Ala Asp Ala Ala  Arg Ser Asn            
    1805                 1810                 1815                        

aga gtg  aca gtg ttc cct att  gga att gga gat cgc  tac gat gca        5499
Arg Val  Thr Val Phe Pro Ile  Gly Ile Gly Asp Arg  Tyr Asp Ala            
    1820                 1825                 1830                        

gcc cag  cta cgg atc ttg gca  ggc cca gca ggc gac  tcc aac gtg        5544
Ala Gln  Leu Arg Ile Leu Ala  Gly Pro Ala Gly Asp  Ser Asn Val            
    1835                 1840                 1845                        

gtg aag  ctc cag cga atc gaa  gac ctc cct acc atg  gtc acc ttg        5589
Val Lys  Leu Gln Arg Ile Glu  Asp Leu Pro Thr Met  Val Thr Leu            
    1850                 1855                 1860                        

ggc aat  tcc ttc ctc cac aaa  ctg tgc tct gga ttt  gtt agg att        5634
Gly Asn  Ser Phe Leu His Lys  Leu Cys Ser Gly Phe  Val Arg Ile            
    1865                 1870                 1875                        

tgc atg  gat gag gat ggg aat  gag aag agg ccc ggg  gac gtc tgg        5679
Cys Met  Asp Glu Asp Gly Asn  Glu Lys Arg Pro Gly  Asp Val Trp            
    1880                 1885                 1890                        

acc ttg  cca gac cag tgc cac  acc gtg act tgc cag  cca gat ggc        5724
Thr Leu  Pro Asp Gln Cys His  Thr Val Thr Cys Gln  Pro Asp Gly            
    1895                 1900                 1905                        

cag acc  ttg ctg aag agt cat  cgg gtc aac tgt gac  cgg ggg ctg        5769
Gln Thr  Leu Leu Lys Ser His  Arg Val Asn Cys Asp  Arg Gly Leu            
    1910                 1915                 1920                        

agg cct  tcg tgc cct aac agc  cag tcc cct gtt aaa  gtg gaa gag        5814
Arg Pro  Ser Cys Pro Asn Ser  Gln Ser Pro Val Lys  Val Glu Glu            
    1925                 1930                 1935                        

acc tgt  ggc tgc cgc tgg acc  tgc ccc tgc gtg tgc  aca ggc agc        5859
Thr Cys  Gly Cys Arg Trp Thr  Cys Pro Cys Val Cys  Thr Gly Ser            
    1940                 1945                 1950                        

tcc act  cgg cac atc gtg acc  ttt gat ggg cag aat  ttc aag ctg        5904
Ser Thr  Arg His Ile Val Thr  Phe Asp Gly Gln Asn  Phe Lys Leu            
    1955                 1960                 1965                        

act ggc  agc tgt tct tat gtc  cta ttt caa aac aag  gag cag gac        5949
Thr Gly  Ser Cys Ser Tyr Val  Leu Phe Gln Asn Lys  Glu Gln Asp            
    1970                 1975                 1980                        

ctg gag  gtg att ctc cat aat  ggt gcc tgc agc cct  gga gca agg        5994
Leu Glu  Val Ile Leu His Asn  Gly Ala Cys Ser Pro  Gly Ala Arg            
    1985                 1990                 1995                        

cag ggc  tgc atg aaa tcc atc  gag gtg aag cac agt  gcc ctc tcc        6039
Gln Gly  Cys Met Lys Ser Ile  Glu Val Lys His Ser  Ala Leu Ser            
    2000                 2005                 2010                        

gtc gag  ctg cac agt gac atg  gag gtg acg gtg aat  ggg aga ctg        6084
Val Glu  Leu His Ser Asp Met  Glu Val Thr Val Asn  Gly Arg Leu            
    2015                 2020                 2025                        

gtc tct  gtt cct tac gtg ggt  ggg aac atg gaa gtc  aac gtt tat        6129
Val Ser  Val Pro Tyr Val Gly  Gly Asn Met Glu Val  Asn Val Tyr            
    2030                 2035                 2040                        

ggt gcc  atc atg cat gag gtc  aga ttc aat cac ctt  ggt cac atc        6174
Gly Ala  Ile Met His Glu Val  Arg Phe Asn His Leu  Gly His Ile            
    2045                 2050                 2055                        

ttc aca  ttc act cca caa aac  aat gag ttc caa ctg  cag ctc agc        6219
Phe Thr  Phe Thr Pro Gln Asn  Asn Glu Phe Gln Leu  Gln Leu Ser            
    2060                 2065                 2070                        

ccc aag  act ttt gct tca aag  acg tat ggt ctg tgt  ggg atc tgt        6264
Pro Lys  Thr Phe Ala Ser Lys  Thr Tyr Gly Leu Cys  Gly Ile Cys            
    2075                 2080                 2085                        

gat gag  aac gga gcc aat gac  ttc atg ctg agg gat  ggc aca gtc        6309
Asp Glu  Asn Gly Ala Asn Asp  Phe Met Leu Arg Asp  Gly Thr Val            
    2090                 2095                 2100                        

acc aca  gac tgg aaa aca ctt  gtt cag gaa tgg act  gtg cag cgg        6354
Thr Thr  Asp Trp Lys Thr Leu  Val Gln Glu Trp Thr  Val Gln Arg            
    2105                 2110                 2115                        

cca ggg  cag acg tgc cag ccc  atc ctg gag gag cag  tgt ctt gtc        6399
Pro Gly  Gln Thr Cys Gln Pro  Ile Leu Glu Glu Gln  Cys Leu Val            
    2120                 2125                 2130                        

ccc gac  agc tcc cac tgc cag  gtc ctc ctc tta cca  ctg ttt gct        6444
Pro Asp  Ser Ser His Cys Gln  Val Leu Leu Leu Pro  Leu Phe Ala            
    2135                 2140                 2145                        

gaa tgc  cac aag gtc ctg gct  cca gcc aca ttc tat  gcc atc tgc        6489
Glu Cys  His Lys Val Leu Ala  Pro Ala Thr Phe Tyr  Ala Ile Cys            
    2150                 2155                 2160                        

cag cag  gac agt tgc cac cag  gag caa gtg tgt gag  gtg atc gcc        6534
Gln Gln  Asp Ser Cys His Gln  Glu Gln Val Cys Glu  Val Ile Ala            
    2165                 2170                 2175                        

tct tat  gcc cac ctc tgt cgg  acc aac ggg gtc tgc  gtt gac tgg        6579
Ser Tyr  Ala His Leu Cys Arg  Thr Asn Gly Val Cys  Val Asp Trp            
    2180                 2185                 2190                        

agg aca  cct gat ttc tgt gct  atg tca tgc cca cca  tct ctg gtt        6624
Arg Thr  Pro Asp Phe Cys Ala  Met Ser Cys Pro Pro  Ser Leu Val            
    2195                 2200                 2205                        

tat aac  cac tgt gag cat ggc  tgt ccc cgg cac tgt  gat ggc aac        6669
Tyr Asn  His Cys Glu His Gly  Cys Pro Arg His Cys  Asp Gly Asn            
    2210                 2215                 2220                        

gtg agc  tcc tgt ggg gac cat  ccc tcc gaa ggc tgt  ttc tgc cct        6714
Val Ser  Ser Cys Gly Asp His  Pro Ser Glu Gly Cys  Phe Cys Pro            
    2225                 2230                 2235                        

cca gat  aaa gtc atg ttg gaa  ggc agc tgt gtc cct  gaa gag gcc        6759
Pro Asp  Lys Val Met Leu Glu  Gly Ser Cys Val Pro  Glu Glu Ala            
    2240                 2245                 2250                        

tgc act  cag tgc att ggt gag  gat gga gtc cag cac  cag ttc ctg        6804
Cys Thr  Gln Cys Ile Gly Glu  Asp Gly Val Gln His  Gln Phe Leu            
    2255                 2260                 2265                        

gaa gcc  tgg gtc ccg gac cac  cag ccc tgt cag atc  tgc aca tgc        6849
Glu Ala  Trp Val Pro Asp His  Gln Pro Cys Gln Ile  Cys Thr Cys            
    2270                 2275                 2280                        

ctc agc  ggg cgg aag gtc aac  tgc aca acg cag ccc  tgc ccc acg        6894
Leu Ser  Gly Arg Lys Val Asn  Cys Thr Thr Gln Pro  Cys Pro Thr            
    2285                 2290                 2295                        

gcc aaa  gct ccc acg tgt ggc  ctg tgt gaa gta gcc  cgc ctc cgc        6939
Ala Lys  Ala Pro Thr Cys Gly  Leu Cys Glu Val Ala  Arg Leu Arg            
    2300                 2305                 2310                        

cag aat  gca gac cag tgc tgc  ccc gag tat gag tgt  gtg tgt gac        6984
Gln Asn  Ala Asp Gln Cys Cys  Pro Glu Tyr Glu Cys  Val Cys Asp            
    2315                 2320                 2325                        

cca gtg  agc tgt gac ctg ccc  cca gtg cct cac tgt  gaa cgt ggc        7029
Pro Val  Ser Cys Asp Leu Pro  Pro Val Pro His Cys  Glu Arg Gly            
    2330                 2335                 2340                        

ctc cag  ccc aca ctg acc aac  cct ggc gag tgc aga  ccc aac ttc        7074
Leu Gln  Pro Thr Leu Thr Asn  Pro Gly Glu Cys Arg  Pro Asn Phe            
    2345                 2350                 2355                        

acc tgc  gcc tgc agg aag gag  gag tgc aaa aga gtg  tcc cca ccc        7119
Thr Cys  Ala Cys Arg Lys Glu  Glu Cys Lys Arg Val  Ser Pro Pro            
    2360                 2365                 2370                        

tcc tgc  ccc ccg cac cgt ttg  ccc acc ctt cgg aag  acc cag tgc        7164
Ser Cys  Pro Pro His Arg Leu  Pro Thr Leu Arg Lys  Thr Gln Cys            
    2375                 2380                 2385                        

tgt gat  gag tat gag tgt gcc  tgc aac tgt gtc aac  tcc aca gtg        7209
Cys Asp  Glu Tyr Glu Cys Ala  Cys Asn Cys Val Asn  Ser Thr Val            
    2390                 2395                 2400                        

agc tgt  ccc ctt ggg tac ttg  gcc tca acc gcc acc  aat gac tgt        7254
Ser Cys  Pro Leu Gly Tyr Leu  Ala Ser Thr Ala Thr  Asn Asp Cys            
    2405                 2410                 2415                        

ggc tgt  acc aca acc acc tgc  ctt ccc gac aag gtg  tgt gtc cac        7299
Gly Cys  Thr Thr Thr Thr Cys  Leu Pro Asp Lys Val  Cys Val His            
    2420                 2425                 2430                        

cga agc  acc atc tac cct gtg  ggc cag ttc tgg gag  gag ggc tgc        7344
Arg Ser  Thr Ile Tyr Pro Val  Gly Gln Phe Trp Glu  Glu Gly Cys            
    2435                 2440                 2445                        

gat gtg  tgc acc tgc acc gac  atg gag gat gcc gtg  atg ggc ctc        7389
Asp Val  Cys Thr Cys Thr Asp  Met Glu Asp Ala Val  Met Gly Leu            
    2450                 2455                 2460                        

cgc gtg  gcc cag tgc tcc cag  aag ccc tgt gag gac  agc tgt cgg        7434
Arg Val  Ala Gln Cys Ser Gln  Lys Pro Cys Glu Asp  Ser Cys Arg            
    2465                 2470                 2475                        

tcg ggc  ttc act tac gtt ctg  cat gaa ggc gag tgc  tgt gga agg        7479
Ser Gly  Phe Thr Tyr Val Leu  His Glu Gly Glu Cys  Cys Gly Arg            
    2480                 2485                 2490                        

tgc ctg  cca tct gcc tgt gag  gtg gtg act ggc tca  ccg cgg ggg        7524
Cys Leu  Pro Ser Ala Cys Glu  Val Val Thr Gly Ser  Pro Arg Gly            
    2495                 2500                 2505                        

gac tcc  cag tct tcc tgg aag  agt gtc ggc tcc cag  tgg gcc tcc        7569
Asp Ser  Gln Ser Ser Trp Lys  Ser Val Gly Ser Gln  Trp Ala Ser            
    2510                 2515                 2520                        

ccg gag  aac ccc tgc ctc atc  aat gag tgt gtc cga  gtg aag gag        7614
Pro Glu  Asn Pro Cys Leu Ile  Asn Glu Cys Val Arg  Val Lys Glu            
    2525                 2530                 2535                        

gag gtc  ttt ata caa caa agg  aac gtc tcc tgc ccc  cag ctg gag        7659
Glu Val  Phe Ile Gln Gln Arg  Asn Val Ser Cys Pro  Gln Leu Glu            
    2540                 2545                 2550                        

gtc cct  gtc tgc ccc tcg ggc  ttt cag ctg agc tgt  aag acc tca        7704
Val Pro  Val Cys Pro Ser Gly  Phe Gln Leu Ser Cys  Lys Thr Ser            
    2555                 2560                 2565                        

gcg tgc  tgc cca agc tgt cgc  tgt gag cgc atg gag  gcc tgc atg        7749
Ala Cys  Cys Pro Ser Cys Arg  Cys Glu Arg Met Glu  Ala Cys Met            
    2570                 2575                 2580                        

ctc aat  ggc act gtc att ggg  ccc ggg aag act gtg  atg atc gat        7794
Leu Asn  Gly Thr Val Ile Gly  Pro Gly Lys Thr Val  Met Ile Asp            
    2585                 2590                 2595                        

gtg tgc  acg acc tgc cgc tgc  atg gtg cag gtg ggg  gtc atc tct        7839
Val Cys  Thr Thr Cys Arg Cys  Met Val Gln Val Gly  Val Ile Ser            
    2600                 2605                 2610                        

gga ttc  aag ctg gag tgc agg  aag acc acc tgc aac  ccc tgc ccc        7884
Gly Phe  Lys Leu Glu Cys Arg  Lys Thr Thr Cys Asn  Pro Cys Pro            
    2615                 2620                 2625                        

ctg ggt  tac aag gaa gaa aat  aac aca ggt gaa tgt  tgt ggg aga        7929
Leu Gly  Tyr Lys Glu Glu Asn  Asn Thr Gly Glu Cys  Cys Gly Arg            
    2630                 2635                 2640                        

tgt ttg  cct acg gct tgc acc  att cag cta aga gga  gga cag atc        7974
Cys Leu  Pro Thr Ala Cys Thr  Ile Gln Leu Arg Gly  Gly Gln Ile            
    2645                 2650                 2655                        

atg aca  ctg aag cgt gat gag  acg ctc cag gat ggc  tgt gat act        8019
Met Thr  Leu Lys Arg Asp Glu  Thr Leu Gln Asp Gly  Cys Asp Thr            
    2660                 2665                 2670                        

cac ttc  tgc aag gtc aat gag  aga gga gag tac ttc  tgg gag aag        8064
His Phe  Cys Lys Val Asn Glu  Arg Gly Glu Tyr Phe  Trp Glu Lys            
    2675                 2680                 2685                        

agg gtc  aca ggc tgc cca ccc  ttt gat gaa cac aag  tgt ctg gct        8109
Arg Val  Thr Gly Cys Pro Pro  Phe Asp Glu His Lys  Cys Leu Ala            
    2690                 2695                 2700                        

gag gga  ggt aaa att atg aaa  att cca ggc acc tgc  tgt gac aca        8154
Glu Gly  Gly Lys Ile Met Lys  Ile Pro Gly Thr Cys  Cys Asp Thr            
    2705                 2710                 2715                        

tgt gag  gag cct gag tgc aac  gac atc act gcc agg  ctg cag tat        8199
Cys Glu  Glu Pro Glu Cys Asn  Asp Ile Thr Ala Arg  Leu Gln Tyr            
    2720                 2725                 2730                        

gtc aag  gtg gga agc tgt aag  tct gaa gta gag gtg  gat atc cac        8244
Val Lys  Val Gly Ser Cys Lys  Ser Glu Val Glu Val  Asp Ile His            
    2735                 2740                 2745                        

tac tgc  cag ggc aaa tgt gcc  agc aaa gcc atg tac  tcc att gac        8289
Tyr Cys  Gln Gly Lys Cys Ala  Ser Lys Ala Met Tyr  Ser Ile Asp            
    2750                 2755                 2760                        

atc aac  gat gtg cag gac cag  tgc tcc tgc tgc tct  ccg aca cgg        8334
Ile Asn  Asp Val Gln Asp Gln  Cys Ser Cys Cys Ser  Pro Thr Arg            
    2765                 2770                 2775                        

acg gag  ccc atg cag gtg gcc  ctg cac tgc acc aat  ggc tct gtt        8379
Thr Glu  Pro Met Gln Val Ala  Leu His Cys Thr Asn  Gly Ser Val            
    2780                 2785                 2790                        

gtg tac  cat gag gtt ctc aat  gcc atg gag tgc aaa  tgc tcc ccc        8424
Val Tyr  His Glu Val Leu Asn  Ala Met Glu Cys Lys  Cys Ser Pro            
    2795                 2800                 2805                        

agg aag  tgc agc aag tga                                              8442
Arg Lys  Cys Ser Lys                                                      
    2810                                                                  


<210>  2
<211>  2813
<212>  PRT
<213>  Homo sapiens

<400>  2

Met Ile Pro Ala Arg Phe Ala Gly Val Leu Leu Ala Leu Ala Leu Ile 
1               5                   10                  15      


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


Ala Arg Cys Ser Leu Phe Gly Ser Asp Phe Val Asn Thr Phe Asp Gly 
        35                  40                  45              


Ser Met Tyr Ser Phe Ala Gly Tyr Cys Ser Tyr Leu Leu Ala Gly Gly 
    50                  55                  60                  


Cys Gln Lys Arg Ser Phe Ser Ile Ile Gly Asp Phe Gln Asn Gly Lys 
65                  70                  75                  80  


Arg Val Ser Leu Ser Val Tyr Leu Gly Glu Phe Phe Asp Ile His Leu 
                85                  90                  95      


Phe Val Asn Gly Thr Val Thr Gln Gly Asp Gln Arg Val Ser Met Pro 
            100                 105                 110         


Tyr Ala Ser Lys Gly Leu Tyr Leu Glu Thr Glu Ala Gly Tyr Tyr Lys 
        115                 120                 125             


Leu Ser Gly Glu Ala Tyr Gly Phe Val Ala Arg Ile Asp Gly Ser Gly 
    130                 135                 140                 


Asn Phe Gln Val Leu Leu Ser Asp Arg Tyr Phe Asn Lys Thr Cys Gly 
145                 150                 155                 160 


Leu Cys Gly Asn Phe Asn Ile Phe Ala Glu Asp Asp Phe Met Thr Gln 
                165                 170                 175     


Glu Gly Thr Leu Thr Ser Asp Pro Tyr Asp Phe Ala Asn Ser Trp Ala 
            180                 185                 190         


Leu Ser Ser Gly Glu Gln Trp Cys Glu Arg Ala Ser Pro Pro Ser Ser 
        195                 200                 205             


Ser Cys Asn Ile Ser Ser Gly Glu Met Gln Lys Gly Leu Trp Glu Gln 
    210                 215                 220                 


Cys Gln Leu Leu Lys Ser Thr Ser Val Phe Ala Arg Cys His Pro Leu 
225                 230                 235                 240 


Val Asp Pro Glu Pro Phe Val Ala Leu Cys Glu Lys Thr Leu Cys Glu 
                245                 250                 255     


Cys Ala Gly Gly Leu Glu Cys Ala Cys Pro Ala Leu Leu Glu Tyr Ala 
            260                 265                 270         


Arg Thr Cys Ala Gln Glu Gly Met Val Leu Tyr Gly Trp Thr Asp His 
        275                 280                 285             


Ser Ala Cys Ser Pro Val Cys Pro Ala Gly Met Glu Tyr Arg Gln Cys 
    290                 295                 300                 


Val Ser Pro Cys Ala Arg Thr Cys Gln Ser Leu His Ile Asn Glu Met 
305                 310                 315                 320 


Cys Gln Glu Arg Cys Val Asp Gly Cys Ser Cys Pro Glu Gly Gln Leu 
                325                 330                 335     


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


Ser Gly Lys Arg Tyr Pro Pro Gly Thr Ser Leu Ser Arg Asp Cys Asn 
        355                 360                 365             


Thr Cys Ile Cys Arg Asn Ser Gln Trp Ile Cys Ser Asn Glu Glu Cys 
    370                 375                 380                 


Pro Gly Glu Cys Leu Val Thr Gly Gln Ser His Phe Lys Ser Phe Asp 
385                 390                 395                 400 


Asn Arg Tyr Phe Thr Phe Ser Gly Ile Cys Gln Tyr Leu Leu Ala Arg 
                405                 410                 415     


Asp Cys Gln Asp His Ser Phe Ser Ile Val Ile Glu Thr Val Gln Cys 
            420                 425                 430         


Ala Asp Asp Arg Asp Ala Val Cys Thr Arg Ser Val Thr Val Arg Leu 
        435                 440                 445             


Pro Gly Leu His Asn Ser Leu Val Lys Leu Lys His Gly Ala Gly Val 
    450                 455                 460                 


Ala Met Asp Gly Gln Asp Val Gln Leu Pro Leu Leu Lys Gly Asp Leu 
465                 470                 475                 480 


Arg Ile Gln His Thr Val Thr Ala Ser Val Arg Leu Ser Tyr Gly Glu 
                485                 490                 495     


Asp Leu Gln Met Asp Trp Asp Gly Arg Gly Arg Leu Leu Val Lys Leu 
            500                 505                 510         


Ser Pro Val Tyr Ala Gly Lys Thr Cys Gly Leu Cys Gly Asn Tyr Asn 
        515                 520                 525             


Gly Asn Gln Gly Asp Asp Phe Leu Thr Pro Ser Gly Leu Ala Glu Pro 
    530                 535                 540                 


Arg Val Glu Asp Phe Gly Asn Ala Trp Lys Leu His Gly Asp Cys Gln 
545                 550                 555                 560 


Asp Leu Gln Lys Gln His Ser Asp Pro Cys Ala Leu Asn Pro Arg Met 
                565                 570                 575     


Thr Arg Phe Ser Glu Glu Ala Cys Ala Val Leu Thr Ser Pro Thr Phe 
            580                 585                 590         


Glu Ala Cys His Arg Ala Val Ser Pro Leu Pro Tyr Leu Arg Asn Cys 
        595                 600                 605             


Arg Tyr Asp Val Cys Ser Cys Ser Asp Gly Arg Glu Cys Leu Cys Gly 
    610                 615                 620                 


Ala Leu Ala Ser Tyr Ala Ala Ala Cys Ala Gly Arg Gly Val Arg Val 
625                 630                 635                 640 


Ala Trp Arg Glu Pro Gly Arg Cys Glu Leu Asn Cys Pro Lys Gly Gln 
                645                 650                 655     


Val Tyr Leu Gln Cys Gly Thr Pro Cys Asn Leu Thr Cys Arg Ser Leu 
            660                 665                 670         


Ser Tyr Pro Asp Glu Glu Cys Asn Glu Ala Cys Leu Glu Gly Cys Phe 
        675                 680                 685             


Cys Pro Pro Gly Leu Tyr Met Asp Glu Arg Gly Asp Cys Val Pro Lys 
    690                 695                 700                 


Ala Gln Cys Pro Cys Tyr Tyr Asp Gly Glu Ile Phe Gln Pro Glu Asp 
705                 710                 715                 720 


Ile Phe Ser Asp His His Thr Met Cys Tyr Cys Glu Asp Gly Phe Met 
                725                 730                 735     


His Cys Thr Met Ser Gly Val Pro Gly Ser Leu Leu Pro Asp Ala Val 
            740                 745                 750         


Leu Ser Ser Pro Leu Ser His Arg Ser Lys Arg Ser Leu Ser Cys Arg 
        755                 760                 765             


Pro Pro Met Val Lys Leu Val Cys Pro Ala Asp Asn Leu Arg Ala Glu 
    770                 775                 780                 


Gly Leu Glu Cys Thr Lys Thr Cys Gln Asn Tyr Asp Leu Glu Cys Met 
785                 790                 795                 800 


Ser Met Gly Cys Val Ser Gly Cys Leu Cys Pro Pro Gly Met Val Arg 
                805                 810                 815     


His Glu Asn Arg Cys Val Ala Leu Glu Arg Cys Pro Cys Phe His Gln 
            820                 825                 830         


Gly Lys Glu Tyr Ala Pro Gly Glu Thr Val Lys Ile Gly Cys Asn Thr 
        835                 840                 845             


Cys Val Cys Arg Asp Arg Lys Trp Asn Cys Thr Asp His Val Cys Asp 
    850                 855                 860                 


Ala Thr Cys Ser Thr Ile Gly Met Ala His Tyr Leu Thr Phe Asp Gly 
865                 870                 875                 880 


Leu Lys Tyr Leu Phe Pro Gly Glu Cys Gln Tyr Val Leu Val Gln Asp 
                885                 890                 895     


Tyr Cys Gly Ser Asn Pro Gly Thr Phe Arg Ile Leu Val Gly Asn Lys 
            900                 905                 910         


Gly Cys Ser His Pro Ser Val Lys Cys Lys Lys Arg Val Thr Ile Leu 
        915                 920                 925             


Val Glu Gly Gly Glu Ile Glu Leu Phe Asp Gly Glu Val Asn Val Lys 
    930                 935                 940                 


Arg Pro Met Lys Asp Glu Thr His Phe Glu Val Val Glu Ser Gly Arg 
945                 950                 955                 960 


Tyr Ile Ile Leu Leu Leu Gly Lys Ala Leu Ser Val Val Trp Asp Arg 
                965                 970                 975     


His Leu Ser Ile Ser Val Val Leu Lys Gln Thr Tyr Gln Glu Lys Val 
            980                 985                 990         


Cys Gly Leu Cys Gly Asn Phe Asp  Gly Ile Gln Asn Asn  Asp Leu Thr 
        995                 1000                 1005             


Ser Ser  Asn Leu Gln Val Glu  Glu Asp Pro Val Asp  Phe Gly Asn 
    1010                 1015                 1020             


Ser Trp  Lys Val Ser Ser Gln  Cys Ala Asp Thr Arg  Lys Val Pro 
    1025                 1030                 1035             


Leu Asp  Ser Ser Pro Ala Thr  Cys His Asn Asn Ile  Met Lys Gln 
    1040                 1045                 1050             


Thr Met  Val Asp Ser Ser Cys  Arg Ile Leu Thr Ser  Asp Val Phe 
    1055                 1060                 1065             


Gln Asp  Cys Asn Lys Leu Val  Asp Pro Glu Pro Tyr  Leu Asp Val 
    1070                 1075                 1080             


Cys Ile  Tyr Asp Thr Cys Ser  Cys Glu Ser Ile Gly  Asp Cys Ala 
    1085                 1090                 1095             


Cys Phe  Cys Asp Thr Ile Ala  Ala Tyr Ala His Val  Cys Ala Gln 
    1100                 1105                 1110             


His Gly  Lys Val Val Thr Trp  Arg Thr Ala Thr Leu  Cys Pro Gln 
    1115                 1120                 1125             


Ser Cys  Glu Glu Arg Asn Leu  Arg Glu Asn Gly Tyr  Glu Cys Glu 
    1130                 1135                 1140             


Trp Arg  Tyr Asn Ser Cys Ala  Pro Ala Cys Gln Val  Thr Cys Gln 
    1145                 1150                 1155             


His Pro  Glu Pro Leu Ala Cys  Pro Val Gln Cys Val  Glu Gly Cys 
    1160                 1165                 1170             


His Ala  His Cys Pro Pro Gly  Lys Ile Leu Asp Glu  Leu Leu Gln 
    1175                 1180                 1185             


Thr Cys  Val Asp Pro Glu Asp  Cys Pro Val Cys Glu  Val Ala Gly 
    1190                 1195                 1200             


Arg Arg  Phe Ala Ser Gly Lys  Lys Val Thr Leu Asn  Pro Ser Asp 
    1205                 1210                 1215             


Pro Glu  His Cys Gln Ile Cys  His Cys Asp Val Val  Asn Leu Thr 
    1220                 1225                 1230             


Cys Glu  Ala Cys Gln Glu Pro  Gly Gly Leu Val Val  Pro Pro Thr 
    1235                 1240                 1245             


Asp Ala  Pro Val Ser Pro Thr  Thr Leu Tyr Val Glu  Asp Ile Ser 
    1250                 1255                 1260             


Glu Pro  Pro Leu His Asp Phe  Tyr Cys Ser Arg Leu  Leu Asp Leu 
    1265                 1270                 1275             


Val Phe  Leu Leu Asp Gly Ser  Ser Arg Leu Ser Glu  Ala Glu Phe 
    1280                 1285                 1290             


Glu Val  Leu Lys Ala Phe Val  Val Asp Met Met Glu  Arg Leu Arg 
    1295                 1300                 1305             


Ile Ser  Gln Lys Trp Val Arg  Val Ala Val Val Glu  Tyr His Asp 
    1310                 1315                 1320             


Gly Ser  His Ala Tyr Ile Gly  Leu Lys Asp Arg Lys  Arg Pro Ser 
    1325                 1330                 1335             


Glu Leu  Arg Arg Ile Ala Ser  Gln Val Lys Tyr Ala  Gly Ser Gln 
    1340                 1345                 1350             


Val Ala  Ser Thr Ser Glu Val  Leu Lys Tyr Thr Leu  Phe Gln Ile 
    1355                 1360                 1365             


Phe Ser  Lys Ile Asp Arg Pro  Glu Ala Ser Arg Ile  Ala Leu Leu 
    1370                 1375                 1380             


Leu Met  Ala Ser Gln Glu Pro  Gln Arg Met Ser Arg  Asn Phe Val 
    1385                 1390                 1395             


Arg Tyr  Val Gln Gly Leu Lys  Lys Lys Lys Val Ile  Val Ile Pro 
    1400                 1405                 1410             


Val Gly  Ile Gly Pro His Ala  Asn Leu Lys Gln Ile  Arg Leu Ile 
    1415                 1420                 1425             


Glu Lys  Gln Ala Pro Glu Asn  Lys Ala Phe Val Leu  Ser Ser Val 
    1430                 1435                 1440             


Asp Glu  Leu Glu Gln Gln Arg  Asp Glu Ile Val Ser  Tyr Leu Cys 
    1445                 1450                 1455             


Asp Leu  Ala Pro Glu Ala Pro  Pro Pro Thr Leu Pro  Pro His Met 
    1460                 1465                 1470             


Ala Gln  Val Thr Val Gly Pro  Gly Leu Leu Gly Val  Ser Thr Leu 
    1475                 1480                 1485             


Gly Pro  Lys Arg Asn Ser Met  Val Leu Asp Val Ala  Phe Val Leu 
    1490                 1495                 1500             


Glu Gly  Ser Asp Lys Ile Gly  Glu Ala Asp Phe Asn  Arg Ser Lys 
    1505                 1510                 1515             


Glu Phe  Met Glu Glu Val Ile  Gln Arg Met Asp Val  Gly Gln Asp 
    1520                 1525                 1530             


Ser Ile  His Val Thr Val Leu  Gln Tyr Ser Tyr Met  Val Thr Val 
    1535                 1540                 1545             


Glu Tyr  Pro Phe Ser Glu Ala  Gln Ser Lys Gly Asp  Ile Leu Gln 
    1550                 1555                 1560             


Arg Val  Arg Glu Ile Arg Tyr  Gln Gly Gly Asn Arg  Thr Asn Thr 
    1565                 1570                 1575             


Gly Leu  Ala Leu Arg Tyr Leu  Ser Asp His Ser Phe  Leu Val Ser 
    1580                 1585                 1590             


Gln Gly  Asp Arg Glu Gln Ala  Pro Asn Leu Val Tyr  Met Val Thr 
    1595                 1600                 1605             


Gly Asn  Pro Ala Ser Asp Glu  Ile Lys Arg Leu Pro  Gly Asp Ile 
    1610                 1615                 1620             


Gln Val  Val Pro Ile Gly Val  Gly Pro Asn Ala Asn  Val Gln Glu 
    1625                 1630                 1635             


Leu Glu  Arg Ile Gly Trp Pro  Asn Ala Pro Ile Leu  Ile Gln Asp 
    1640                 1645                 1650             


Phe Glu  Thr Leu Pro Arg Glu  Ala Pro Asp Leu Val  Leu Gln Arg 
    1655                 1660                 1665             


Cys Cys  Ser Gly Glu Gly Leu  Gln Ile Pro Thr Leu  Ser Pro Ala 
    1670                 1675                 1680             


Pro Asp  Cys Ser Gln Pro Leu  Asp Val Ile Leu Leu  Leu Asp Gly 
    1685                 1690                 1695             


Ser Ser  Ser Phe Pro Ala Ser  Tyr Phe Asp Glu Met  Lys Ser Phe 
    1700                 1705                 1710             


Ala Lys  Ala Phe Ile Ser Lys  Ala Asn Ile Gly Pro  Arg Leu Thr 
    1715                 1720                 1725             


Gln Val  Ser Val Leu Gln Tyr  Gly Ser Ile Thr Thr  Ile Asp Val 
    1730                 1735                 1740             


Pro Trp  Asn Val Val Pro Glu  Lys Ala His Leu Leu  Ser Leu Val 
    1745                 1750                 1755             


Asp Val  Met Gln Arg Glu Gly  Gly Pro Ser Gln Ile  Gly Asp Ala 
    1760                 1765                 1770             


Leu Gly  Phe Ala Val Arg Tyr  Leu Thr Ser Glu Met  His Gly Ala 
    1775                 1780                 1785             


Arg Pro  Gly Ala Ser Lys Ala  Val Val Ile Leu Val  Thr Asp Val 
    1790                 1795                 1800             


Ser Val  Asp Ser Val Asp Ala  Ala Ala Asp Ala Ala  Arg Ser Asn 
    1805                 1810                 1815             


Arg Val  Thr Val Phe Pro Ile  Gly Ile Gly Asp Arg  Tyr Asp Ala 
    1820                 1825                 1830             


Ala Gln  Leu Arg Ile Leu Ala  Gly Pro Ala Gly Asp  Ser Asn Val 
    1835                 1840                 1845             


Val Lys  Leu Gln Arg Ile Glu  Asp Leu Pro Thr Met  Val Thr Leu 
    1850                 1855                 1860             


Gly Asn  Ser Phe Leu His Lys  Leu Cys Ser Gly Phe  Val Arg Ile 
    1865                 1870                 1875             


Cys Met  Asp Glu Asp Gly Asn  Glu Lys Arg Pro Gly  Asp Val Trp 
    1880                 1885                 1890             


Thr Leu  Pro Asp Gln Cys His  Thr Val Thr Cys Gln  Pro Asp Gly 
    1895                 1900                 1905             


Gln Thr  Leu Leu Lys Ser His  Arg Val Asn Cys Asp  Arg Gly Leu 
    1910                 1915                 1920             


Arg Pro  Ser Cys Pro Asn Ser  Gln Ser Pro Val Lys  Val Glu Glu 
    1925                 1930                 1935             


Thr Cys  Gly Cys Arg Trp Thr  Cys Pro Cys Val Cys  Thr Gly Ser 
    1940                 1945                 1950             


Ser Thr  Arg His Ile Val Thr  Phe Asp Gly Gln Asn  Phe Lys Leu 
    1955                 1960                 1965             


Thr Gly  Ser Cys Ser Tyr Val  Leu Phe Gln Asn Lys  Glu Gln Asp 
    1970                 1975                 1980             


Leu Glu  Val Ile Leu His Asn  Gly Ala Cys Ser Pro  Gly Ala Arg 
    1985                 1990                 1995             


Gln Gly  Cys Met Lys Ser Ile  Glu Val Lys His Ser  Ala Leu Ser 
    2000                 2005                 2010             


Val Glu  Leu His Ser Asp Met  Glu Val Thr Val Asn  Gly Arg Leu 
    2015                 2020                 2025             


Val Ser  Val Pro Tyr Val Gly  Gly Asn Met Glu Val  Asn Val Tyr 
    2030                 2035                 2040             


Gly Ala  Ile Met His Glu Val  Arg Phe Asn His Leu  Gly His Ile 
    2045                 2050                 2055             


Phe Thr  Phe Thr Pro Gln Asn  Asn Glu Phe Gln Leu  Gln Leu Ser 
    2060                 2065                 2070             


Pro Lys  Thr Phe Ala Ser Lys  Thr Tyr Gly Leu Cys  Gly Ile Cys 
    2075                 2080                 2085             


Asp Glu  Asn Gly Ala Asn Asp  Phe Met Leu Arg Asp  Gly Thr Val 
    2090                 2095                 2100             


Thr Thr  Asp Trp Lys Thr Leu  Val Gln Glu Trp Thr  Val Gln Arg 
    2105                 2110                 2115             


Pro Gly  Gln Thr Cys Gln Pro  Ile Leu Glu Glu Gln  Cys Leu Val 
    2120                 2125                 2130             


Pro Asp  Ser Ser His Cys Gln  Val Leu Leu Leu Pro  Leu Phe Ala 
    2135                 2140                 2145             


Glu Cys  His Lys Val Leu Ala  Pro Ala Thr Phe Tyr  Ala Ile Cys 
    2150                 2155                 2160             


Gln Gln  Asp Ser Cys His Gln  Glu Gln Val Cys Glu  Val Ile Ala 
    2165                 2170                 2175             


Ser Tyr  Ala His Leu Cys Arg  Thr Asn Gly Val Cys  Val Asp Trp 
    2180                 2185                 2190             


Arg Thr  Pro Asp Phe Cys Ala  Met Ser Cys Pro Pro  Ser Leu Val 
    2195                 2200                 2205             


Tyr Asn  His Cys Glu His Gly  Cys Pro Arg His Cys  Asp Gly Asn 
    2210                 2215                 2220             


Val Ser  Ser Cys Gly Asp His  Pro Ser Glu Gly Cys  Phe Cys Pro 
    2225                 2230                 2235             


Pro Asp  Lys Val Met Leu Glu  Gly Ser Cys Val Pro  Glu Glu Ala 
    2240                 2245                 2250             


Cys Thr  Gln Cys Ile Gly Glu  Asp Gly Val Gln His  Gln Phe Leu 
    2255                 2260                 2265             


Glu Ala  Trp Val Pro Asp His  Gln Pro Cys Gln Ile  Cys Thr Cys 
    2270                 2275                 2280             


Leu Ser  Gly Arg Lys Val Asn  Cys Thr Thr Gln Pro  Cys Pro Thr 
    2285                 2290                 2295             


Ala Lys  Ala Pro Thr Cys Gly  Leu Cys Glu Val Ala  Arg Leu Arg 
    2300                 2305                 2310             


Gln Asn  Ala Asp Gln Cys Cys  Pro Glu Tyr Glu Cys  Val Cys Asp 
    2315                 2320                 2325             


Pro Val  Ser Cys Asp Leu Pro  Pro Val Pro His Cys  Glu Arg Gly 
    2330                 2335                 2340             


Leu Gln  Pro Thr Leu Thr Asn  Pro Gly Glu Cys Arg  Pro Asn Phe 
    2345                 2350                 2355             


Thr Cys  Ala Cys Arg Lys Glu  Glu Cys Lys Arg Val  Ser Pro Pro 
    2360                 2365                 2370             


Ser Cys  Pro Pro His Arg Leu  Pro Thr Leu Arg Lys  Thr Gln Cys 
    2375                 2380                 2385             


Cys Asp  Glu Tyr Glu Cys Ala  Cys Asn Cys Val Asn  Ser Thr Val 
    2390                 2395                 2400             


Ser Cys  Pro Leu Gly Tyr Leu  Ala Ser Thr Ala Thr  Asn Asp Cys 
    2405                 2410                 2415             


Gly Cys  Thr Thr Thr Thr Cys  Leu Pro Asp Lys Val  Cys Val His 
    2420                 2425                 2430             


Arg Ser  Thr Ile Tyr Pro Val  Gly Gln Phe Trp Glu  Glu Gly Cys 
    2435                 2440                 2445             


Asp Val  Cys Thr Cys Thr Asp  Met Glu Asp Ala Val  Met Gly Leu 
    2450                 2455                 2460             


Arg Val  Ala Gln Cys Ser Gln  Lys Pro Cys Glu Asp  Ser Cys Arg 
    2465                 2470                 2475             


Ser Gly  Phe Thr Tyr Val Leu  His Glu Gly Glu Cys  Cys Gly Arg 
    2480                 2485                 2490             


Cys Leu  Pro Ser Ala Cys Glu  Val Val Thr Gly Ser  Pro Arg Gly 
    2495                 2500                 2505             


Asp Ser  Gln Ser Ser Trp Lys  Ser Val Gly Ser Gln  Trp Ala Ser 
    2510                 2515                 2520             


Pro Glu  Asn Pro Cys Leu Ile  Asn Glu Cys Val Arg  Val Lys Glu 
    2525                 2530                 2535             


Glu Val  Phe Ile Gln Gln Arg  Asn Val Ser Cys Pro  Gln Leu Glu 
    2540                 2545                 2550             


Val Pro  Val Cys Pro Ser Gly  Phe Gln Leu Ser Cys  Lys Thr Ser 
    2555                 2560                 2565             


Ala Cys  Cys Pro Ser Cys Arg  Cys Glu Arg Met Glu  Ala Cys Met 
    2570                 2575                 2580             


Leu Asn  Gly Thr Val Ile Gly  Pro Gly Lys Thr Val  Met Ile Asp 
    2585                 2590                 2595             


Val Cys  Thr Thr Cys Arg Cys  Met Val Gln Val Gly  Val Ile Ser 
    2600                 2605                 2610             


Gly Phe  Lys Leu Glu Cys Arg  Lys Thr Thr Cys Asn  Pro Cys Pro 
    2615                 2620                 2625             


Leu Gly  Tyr Lys Glu Glu Asn  Asn Thr Gly Glu Cys  Cys Gly Arg 
    2630                 2635                 2640             


Cys Leu  Pro Thr Ala Cys Thr  Ile Gln Leu Arg Gly  Gly Gln Ile 
    2645                 2650                 2655             


Met Thr  Leu Lys Arg Asp Glu  Thr Leu Gln Asp Gly  Cys Asp Thr 
    2660                 2665                 2670             


His Phe  Cys Lys Val Asn Glu  Arg Gly Glu Tyr Phe  Trp Glu Lys 
    2675                 2680                 2685             


Arg Val  Thr Gly Cys Pro Pro  Phe Asp Glu His Lys  Cys Leu Ala 
    2690                 2695                 2700             


Glu Gly  Gly Lys Ile Met Lys  Ile Pro Gly Thr Cys  Cys Asp Thr 
    2705                 2710                 2715             


Cys Glu  Glu Pro Glu Cys Asn  Asp Ile Thr Ala Arg  Leu Gln Tyr 
    2720                 2725                 2730             


Val Lys  Val Gly Ser Cys Lys  Ser Glu Val Glu Val  Asp Ile His 
    2735                 2740                 2745             


Tyr Cys  Gln Gly Lys Cys Ala  Ser Lys Ala Met Tyr  Ser Ile Asp 
    2750                 2755                 2760             


Ile Asn  Asp Val Gln Asp Gln  Cys Ser Cys Cys Ser  Pro Thr Arg 
    2765                 2770                 2775             


Thr Glu  Pro Met Gln Val Ala  Leu His Cys Thr Asn  Gly Ser Val 
    2780                 2785                 2790             


Val Tyr  His Glu Val Leu Asn  Ala Met Glu Cys Lys  Cys Ser Pro 
    2795                 2800                 2805             


Arg Lys  Cys Ser Lys 
    2810             


<210>  3
<211>  30
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  PCR primer VWF+

<400>  3
ttcgaattcc cgcagccctc atttgcaggg                                        30


<210>  4
<211>  31
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  PCR primer VWF-

<400>  4
tccgaattcc ggcagcagca ggcacccatg c                                      31


<210>  5
<211>  30
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  PCR primer VWFT2298Q+

<400>  5
gcagccctgc ccccaggcca aagctcccac                                        30


<210>  6
<211>  30
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  PCR primer VWFT2298Q-

<400>  6
gtgggagctt tggcctgggg gcagggctgc                                        30


<210>  7
<211>  28
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  PCR primer HA+

<400>  7
ggatccgatg cacacaagag tgaggttg                                          28


<210>  8
<211>  31
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  PCR primer HA-

<400>  8
gcggccgcct ataagcctaa ggcagcttga c                                      31


<210>  9
<211>  686
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Signal peptide (1-22); VWF fragment aa 2276 to 2326 (23 - 73); 
       glycin/serin linker (74 - 101); albumin (102 - 686)

<400>  9

Met Ile Pro Ala Arg Phe Ala Gly Val Leu Leu Ala Leu Ala Leu Ile 
1               5                   10                  15      


Leu Pro Gly Thr Leu Cys Gln Pro Cys Gln Ile Cys Thr Cys Leu Ser 
            20                  25                  30          


Gly Arg Lys Val Asn Cys Thr Thr Gln Pro Cys Pro Thr Ala Lys Ala 
        35                  40                  45              


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


Gln Cys Cys Pro Glu Tyr Glu Cys Val Gly Ser Gly Gly Ser Gly Gly 
65                  70                  75                  80  


Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser 
                85                  90                  95      


Gly Gly Ser Gly Ser Asp Ala His Lys Ser Glu Val Ala His Arg Phe 
            100                 105                 110         


Lys Asp Leu Gly Glu Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe 
        115                 120                 125             


Ala Gln Tyr Leu Gln Gln Cys Pro Phe Glu Asp His Val Lys Leu Val 
    130                 135                 140                 


Asn Glu Val Thr Glu Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala 
145                 150                 155                 160 


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


Thr Val Ala Thr Leu Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys 
            180                 185                 190         


Ala Lys Gln Glu Pro Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp 
        195                 200                 205             


Asp Asn Pro Asn Leu Pro Arg Leu Val Arg Pro Glu Val Asp Val Met 
    210                 215                 220                 


Cys Thr Ala Phe His Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu 
225                 230                 235                 240 


Tyr Glu Ile Ala Arg Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu 
                245                 250                 255     


Phe Phe Ala Lys Arg Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala 
            260                 265                 270         


Ala Asp Lys Ala Ala Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp 
        275                 280                 285             


Glu Gly Lys Ala Ser Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu 
    290                 295                 300                 


Gln Lys Phe Gly Glu Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu 
305                 310                 315                 320 


Ser Gln Arg Phe Pro Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val 
                325                 330                 335     


Thr Asp Leu Thr Lys Val His Thr Glu Cys Cys His Gly Asp Leu Leu 
            340                 345                 350         


Glu Cys Ala Asp Asp Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn 
        355                 360                 365             


Gln Asp Ser Ile Ser Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu 
    370                 375                 380                 


Leu Glu Lys Ser His Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro 
385                 390                 395                 400 


Ala Asp Leu Pro Ser Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val 
                405                 410                 415     


Cys Lys Asn Tyr Ala Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu 
            420                 425                 430         


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


Arg Leu Ala Lys Thr Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala 
    450                 455                 460                 


Ala Asp Pro His Glu Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro 
465                 470                 475                 480 


Leu Val Glu Glu Pro Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe 
                485                 490                 495     


Glu Gln Leu Gly Glu Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr 
            500                 505                 510         


Thr Lys Lys Val Pro Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser 
        515                 520                 525             


Arg Asn Leu Gly Lys Val Gly Ser Lys Cys Cys Lys His Pro Glu Ala 
    530                 535                 540                 


Lys Arg Met Pro Cys Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln 
545                 550                 555                 560 


Leu Cys Val Leu His Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys 
                565                 570                 575     


Cys Cys Thr Glu Ser Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu 
            580                 585                 590         


Glu Val Asp Glu Thr Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe 
        595                 600                 605             


Thr Phe His Ala Asp Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile 
    610                 615                 620                 


Lys Lys Gln Thr Ala Leu Val Glu Leu Val Lys His Lys Pro Lys Ala 
625                 630                 635                 640 


Thr Lys Glu Gln Leu Lys Ala Val Met Asp Asp Phe Ala Ala Phe Val 
                645                 650                 655     


Glu Lys Cys Cys Lys Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu 
            660                 665                 670         


Gly Lys Lys Leu Val Ala Ala Ser Gln Ala Ala Leu Gly Leu 
        675                 680                 685     


<210>  10
<211>  74
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C1 domain of modified VWF having a mutation at T2298


<220>
<221>  MISC_FEATURE
<222>  (44)..(44)
<223>  Xaa is absent or an amino acid other than threonine and serine

<400>  10

Thr Gln Cys Ile Gly Glu Asp Gly Val Gln His Gln Phe Leu Glu Ala 
1               5                   10                  15      


Trp Val Pro Asp His Gln Pro Cys Gln Ile Cys Thr Cys Leu Ser Gly 
            20                  25                  30          


Arg Lys Val Asn Cys Thr Thr Gln Pro Cys Pro Xaa Ala Lys Ala Pro 
        35                  40                  45              


Thr Cys Gly Leu Cys Glu Val Ala Arg Leu Arg Gln Asn Ala Asp Gln 
    50                  55                  60                  


Cys Cys Pro Glu Tyr Glu Cys Val Cys Asp 
65                  70                  


<210>  11
<211>  2050
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Mature form of modified VWF having a mutation of T2298


<220>
<221>  MISC_FEATURE
<222>  (1535)..(1535)
<223>  Xaa is absent or an amino acid other than threonine and serine

<400>  11

Ser Leu Ser Cys Arg Pro Pro Met Val Lys Leu Val Cys Pro Ala Asp 
1               5                   10                  15      


Asn Leu Arg Ala Glu Gly Leu Glu Cys Thr Lys Thr Cys Gln Asn Tyr 
            20                  25                  30          


Asp Leu Glu Cys Met Ser Met Gly Cys Val Ser Gly Cys Leu Cys Pro 
        35                  40                  45              


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


Pro Cys Phe His Gln Gly Lys Glu Tyr Ala Pro Gly Glu Thr Val Lys 
65                  70                  75                  80  


Ile Gly Cys Asn Thr Cys Val Cys Arg Asp Arg Lys Trp Asn Cys Thr 
                85                  90                  95      


Asp His Val Cys Asp Ala Thr Cys Ser Thr Ile Gly Met Ala His Tyr 
            100                 105                 110         


Leu Thr Phe Asp Gly Leu Lys Tyr Leu Phe Pro Gly Glu Cys Gln Tyr 
        115                 120                 125             


Val Leu Val Gln Asp Tyr Cys Gly Ser Asn Pro Gly Thr Phe Arg Ile 
    130                 135                 140                 


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


Arg Val Thr Ile Leu Val Glu Gly Gly Glu Ile Glu Leu Phe Asp Gly 
                165                 170                 175     


Glu Val Asn Val Lys Arg Pro Met Lys Asp Glu Thr His Phe Glu Val 
            180                 185                 190         


Val Glu Ser Gly Arg Tyr Ile Ile Leu Leu Leu Gly Lys Ala Leu Ser 
        195                 200                 205             


Val Val Trp Asp Arg His Leu Ser Ile Ser Val Val Leu Lys Gln Thr 
    210                 215                 220                 


Tyr Gln Glu Lys Val Cys Gly Leu Cys Gly Asn Phe Asp Gly Ile Gln 
225                 230                 235                 240 


Asn Asn Asp Leu Thr Ser Ser Asn Leu Gln Val Glu Glu Asp Pro Val 
                245                 250                 255     


Asp Phe Gly Asn Ser Trp Lys Val Ser Ser Gln Cys Ala Asp Thr Arg 
            260                 265                 270         


Lys Val Pro Leu Asp Ser Ser Pro Ala Thr Cys His Asn Asn Ile Met 
        275                 280                 285             


Lys Gln Thr Met Val Asp Ser Ser Cys Arg Ile Leu Thr Ser Asp Val 
    290                 295                 300                 


Phe Gln Asp Cys Asn Lys Leu Val Asp Pro Glu Pro Tyr Leu Asp Val 
305                 310                 315                 320 


Cys Ile Tyr Asp Thr Cys Ser Cys Glu Ser Ile Gly Asp Cys Ala Cys 
                325                 330                 335     


Phe Cys Asp Thr Ile Ala Ala Tyr Ala His Val Cys Ala Gln His Gly 
            340                 345                 350         


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


Glu Arg Asn Leu Arg Glu Asn Gly Tyr Glu Cys Glu Trp Arg Tyr Asn 
    370                 375                 380                 


Ser Cys Ala Pro Ala Cys Gln Val Thr Cys Gln His Pro Glu Pro Leu 
385                 390                 395                 400 


Ala Cys Pro Val Gln Cys Val Glu Gly Cys His Ala His Cys Pro Pro 
                405                 410                 415     


Gly Lys Ile Leu Asp Glu Leu Leu Gln Thr Cys Val Asp Pro Glu Asp 
            420                 425                 430         


Cys Pro Val Cys Glu Val Ala Gly Arg Arg Phe Ala Ser Gly Lys Lys 
        435                 440                 445             


Val Thr Leu Asn Pro Ser Asp Pro Glu His Cys Gln Ile Cys His Cys 
    450                 455                 460                 


Asp Val Val Asn Leu Thr Cys Glu Ala Cys Gln Glu Pro Gly Gly Leu 
465                 470                 475                 480 


Val Val Pro Pro Thr Asp Ala Pro Val Ser Pro Thr Thr Leu Tyr Val 
                485                 490                 495     


Glu Asp Ile Ser Glu Pro Pro Leu His Asp Phe Tyr Cys Ser Arg Leu 
            500                 505                 510         


Leu Asp Leu Val Phe Leu Leu Asp Gly Ser Ser Arg Leu Ser Glu Ala 
        515                 520                 525             


Glu Phe Glu Val Leu Lys Ala Phe Val Val Asp Met Met Glu Arg Leu 
    530                 535                 540                 


Arg Ile Ser Gln Lys Trp Val Arg Val Ala Val Val Glu Tyr His Asp 
545                 550                 555                 560 


Gly Ser His Ala Tyr Ile Gly Leu Lys Asp Arg Lys Arg Pro Ser Glu 
                565                 570                 575     


Leu Arg Arg Ile Ala Ser Gln Val Lys Tyr Ala Gly Ser Gln Val Ala 
            580                 585                 590         


Ser Thr Ser Glu Val Leu Lys Tyr Thr Leu Phe Gln Ile Phe Ser Lys 
        595                 600                 605             


Ile Asp Arg Pro Glu Ala Ser Arg Ile Ala Leu Leu Leu Met Ala Ser 
    610                 615                 620                 


Gln Glu Pro Gln Arg Met Ser Arg Asn Phe Val Arg Tyr Val Gln Gly 
625                 630                 635                 640 


Leu Lys Lys Lys Lys Val Ile Val Ile Pro Val Gly Ile Gly Pro His 
                645                 650                 655     


Ala Asn Leu Lys Gln Ile Arg Leu Ile Glu Lys Gln Ala Pro Glu Asn 
            660                 665                 670         


Lys Ala Phe Val Leu Ser Ser Val Asp Glu Leu Glu Gln Gln Arg Asp 
        675                 680                 685             


Glu Ile Val Ser Tyr Leu Cys Asp Leu Ala Pro Glu Ala Pro Pro Pro 
    690                 695                 700                 


Thr Leu Pro Pro His Met Ala Gln Val Thr Val Gly Pro Gly Leu Leu 
705                 710                 715                 720 


Gly Val Ser Thr Leu Gly Pro Lys Arg Asn Ser Met Val Leu Asp Val 
                725                 730                 735     


Ala Phe Val Leu Glu Gly Ser Asp Lys Ile Gly Glu Ala Asp Phe Asn 
            740                 745                 750         


Arg Ser Lys Glu Phe Met Glu Glu Val Ile Gln Arg Met Asp Val Gly 
        755                 760                 765             


Gln Asp Ser Ile His Val Thr Val Leu Gln Tyr Ser Tyr Met Val Thr 
    770                 775                 780                 


Val Glu Tyr Pro Phe Ser Glu Ala Gln Ser Lys Gly Asp Ile Leu Gln 
785                 790                 795                 800 


Arg Val Arg Glu Ile Arg Tyr Gln Gly Gly Asn Arg Thr Asn Thr Gly 
                805                 810                 815     


Leu Ala Leu Arg Tyr Leu Ser Asp His Ser Phe Leu Val Ser Gln Gly 
            820                 825                 830         


Asp Arg Glu Gln Ala Pro Asn Leu Val Tyr Met Val Thr Gly Asn Pro 
        835                 840                 845             


Ala Ser Asp Glu Ile Lys Arg Leu Pro Gly Asp Ile Gln Val Val Pro 
    850                 855                 860                 


Ile Gly Val Gly Pro Asn Ala Asn Val Gln Glu Leu Glu Arg Ile Gly 
865                 870                 875                 880 


Trp Pro Asn Ala Pro Ile Leu Ile Gln Asp Phe Glu Thr Leu Pro Arg 
                885                 890                 895     


Glu Ala Pro Asp Leu Val Leu Gln Arg Cys Cys Ser Gly Glu Gly Leu 
            900                 905                 910         


Gln Ile Pro Thr Leu Ser Pro Ala Pro Asp Cys Ser Gln Pro Leu Asp 
        915                 920                 925             


Val Ile Leu Leu Leu Asp Gly Ser Ser Ser Phe Pro Ala Ser Tyr Phe 
    930                 935                 940                 


Asp Glu Met Lys Ser Phe Ala Lys Ala Phe Ile Ser Lys Ala Asn Ile 
945                 950                 955                 960 


Gly Pro Arg Leu Thr Gln Val Ser Val Leu Gln Tyr Gly Ser Ile Thr 
                965                 970                 975     


Thr Ile Asp Val Pro Trp Asn Val Val Pro Glu Lys Ala His Leu Leu 
            980                 985                 990         


Ser Leu Val Asp Val Met Gln Arg  Glu Gly Gly Pro Ser  Gln Ile Gly 
        995                 1000                 1005             


Asp Ala  Leu Gly Phe Ala Val  Arg Tyr Leu Thr Ser  Glu Met His 
    1010                 1015                 1020             


Gly Ala  Arg Pro Gly Ala Ser  Lys Ala Val Val Ile  Leu Val Thr 
    1025                 1030                 1035             


Asp Val  Ser Val Asp Ser Val  Asp Ala Ala Ala Asp  Ala Ala Arg 
    1040                 1045                 1050             


Ser Asn  Arg Val Thr Val Phe  Pro Ile Gly Ile Gly  Asp Arg Tyr 
    1055                 1060                 1065             


Asp Ala  Ala Gln Leu Arg Ile  Leu Ala Gly Pro Ala  Gly Asp Ser 
    1070                 1075                 1080             


Asn Val  Val Lys Leu Gln Arg  Ile Glu Asp Leu Pro  Thr Met Val 
    1085                 1090                 1095             


Thr Leu  Gly Asn Ser Phe Leu  His Lys Leu Cys Ser  Gly Phe Val 
    1100                 1105                 1110             


Arg Ile  Cys Met Asp Glu Asp  Gly Asn Glu Lys Arg  Pro Gly Asp 
    1115                 1120                 1125             


Val Trp  Thr Leu Pro Asp Gln  Cys His Thr Val Thr  Cys Gln Pro 
    1130                 1135                 1140             


Asp Gly  Gln Thr Leu Leu Lys  Ser His Arg Val Asn  Cys Asp Arg 
    1145                 1150                 1155             


Gly Leu  Arg Pro Ser Cys Pro  Asn Ser Gln Ser Pro  Val Lys Val 
    1160                 1165                 1170             


Glu Glu  Thr Cys Gly Cys Arg  Trp Thr Cys Pro Cys  Val Cys Thr 
    1175                 1180                 1185             


Gly Ser  Ser Thr Arg His Ile  Val Thr Phe Asp Gly  Gln Asn Phe 
    1190                 1195                 1200             


Lys Leu  Thr Gly Ser Cys Ser  Tyr Val Leu Phe Gln  Asn Lys Glu 
    1205                 1210                 1215             


Gln Asp  Leu Glu Val Ile Leu  His Asn Gly Ala Cys  Ser Pro Gly 
    1220                 1225                 1230             


Ala Arg  Gln Gly Cys Met Lys  Ser Ile Glu Val Lys  His Ser Ala 
    1235                 1240                 1245             


Leu Ser  Val Glu Leu His Ser  Asp Met Glu Val Thr  Val Asn Gly 
    1250                 1255                 1260             


Arg Leu  Val Ser Val Pro Tyr  Val Gly Gly Asn Met  Glu Val Asn 
    1265                 1270                 1275             


Val Tyr  Gly Ala Ile Met His  Glu Val Arg Phe Asn  His Leu Gly 
    1280                 1285                 1290             


His Ile  Phe Thr Phe Thr Pro  Gln Asn Asn Glu Phe  Gln Leu Gln 
    1295                 1300                 1305             


Leu Ser  Pro Lys Thr Phe Ala  Ser Lys Thr Tyr Gly  Leu Cys Gly 
    1310                 1315                 1320             


Ile Cys  Asp Glu Asn Gly Ala  Asn Asp Phe Met Leu  Arg Asp Gly 
    1325                 1330                 1335             


Thr Val  Thr Thr Asp Trp Lys  Thr Leu Val Gln Glu  Trp Thr Val 
    1340                 1345                 1350             


Gln Arg  Pro Gly Gln Thr Cys  Gln Pro Ile Leu Glu  Glu Gln Cys 
    1355                 1360                 1365             


Leu Val  Pro Asp Ser Ser His  Cys Gln Val Leu Leu  Leu Pro Leu 
    1370                 1375                 1380             


Phe Ala  Glu Cys His Lys Val  Leu Ala Pro Ala Thr  Phe Tyr Ala 
    1385                 1390                 1395             


Ile Cys  Gln Gln Asp Ser Cys  His Gln Glu Gln Val  Cys Glu Val 
    1400                 1405                 1410             


Ile Ala  Ser Tyr Ala His Leu  Cys Arg Thr Asn Gly  Val Cys Val 
    1415                 1420                 1425             


Asp Trp  Arg Thr Pro Asp Phe  Cys Ala Met Ser Cys  Pro Pro Ser 
    1430                 1435                 1440             


Leu Val  Tyr Asn His Cys Glu  His Gly Cys Pro Arg  His Cys Asp 
    1445                 1450                 1455             


Gly Asn  Val Ser Ser Cys Gly  Asp His Pro Ser Glu  Gly Cys Phe 
    1460                 1465                 1470             


Cys Pro  Pro Asp Lys Val Met  Leu Glu Gly Ser Cys  Val Pro Glu 
    1475                 1480                 1485             


Glu Ala  Cys Thr Gln Cys Ile  Gly Glu Asp Gly Val  Gln His Gln 
    1490                 1495                 1500             


Phe Leu  Glu Ala Trp Val Pro  Asp His Gln Pro Cys  Gln Ile Cys 
    1505                 1510                 1515             


Thr Cys  Leu Ser Gly Arg Lys  Val Asn Cys Thr Thr  Gln Pro Cys 
    1520                 1525                 1530             


Pro Xaa  Ala Lys Ala Pro Thr  Cys Gly Leu Cys Glu  Val Ala Arg 
    1535                 1540                 1545             


Leu Arg  Gln Asn Ala Asp Gln  Cys Cys Pro Glu Tyr  Glu Cys Val 
    1550                 1555                 1560             


Cys Asp  Pro Val Ser Cys Asp  Leu Pro Pro Val Pro  His Cys Glu 
    1565                 1570                 1575             


Arg Gly  Leu Gln Pro Thr Leu  Thr Asn Pro Gly Glu  Cys Arg Pro 
    1580                 1585                 1590             


Asn Phe  Thr Cys Ala Cys Arg  Lys Glu Glu Cys Lys  Arg Val Ser 
    1595                 1600                 1605             


Pro Pro  Ser Cys Pro Pro His  Arg Leu Pro Thr Leu  Arg Lys Thr 
    1610                 1615                 1620             


Gln Cys  Cys Asp Glu Tyr Glu  Cys Ala Cys Asn Cys  Val Asn Ser 
    1625                 1630                 1635             


Thr Val  Ser Cys Pro Leu Gly  Tyr Leu Ala Ser Thr  Ala Thr Asn 
    1640                 1645                 1650             


Asp Cys  Gly Cys Thr Thr Thr  Thr Cys Leu Pro Asp  Lys Val Cys 
    1655                 1660                 1665             


Val His  Arg Ser Thr Ile Tyr  Pro Val Gly Gln Phe  Trp Glu Glu 
    1670                 1675                 1680             


Gly Cys  Asp Val Cys Thr Cys  Thr Asp Met Glu Asp  Ala Val Met 
    1685                 1690                 1695             


Gly Leu  Arg Val Ala Gln Cys  Ser Gln Lys Pro Cys  Glu Asp Ser 
    1700                 1705                 1710             


Cys Arg  Ser Gly Phe Thr Tyr  Val Leu His Glu Gly  Glu Cys Cys 
    1715                 1720                 1725             


Gly Arg  Cys Leu Pro Ser Ala  Cys Glu Val Val Thr  Gly Ser Pro 
    1730                 1735                 1740             


Arg Gly  Asp Ser Gln Ser Ser  Trp Lys Ser Val Gly  Ser Gln Trp 
    1745                 1750                 1755             


Ala Ser  Pro Glu Asn Pro Cys  Leu Ile Asn Glu Cys  Val Arg Val 
    1760                 1765                 1770             


Lys Glu  Glu Val Phe Ile Gln  Gln Arg Asn Val Ser  Cys Pro Gln 
    1775                 1780                 1785             


Leu Glu  Val Pro Val Cys Pro  Ser Gly Phe Gln Leu  Ser Cys Lys 
    1790                 1795                 1800             


Thr Ser  Ala Cys Cys Pro Ser  Cys Arg Cys Glu Arg  Met Glu Ala 
    1805                 1810                 1815             


Cys Met  Leu Asn Gly Thr Val  Ile Gly Pro Gly Lys  Thr Val Met 
    1820                 1825                 1830             


Ile Asp  Val Cys Thr Thr Cys  Arg Cys Met Val Gln  Val Gly Val 
    1835                 1840                 1845             


Ile Ser  Gly Phe Lys Leu Glu  Cys Arg Lys Thr Thr  Cys Asn Pro 
    1850                 1855                 1860             


Cys Pro  Leu Gly Tyr Lys Glu  Glu Asn Asn Thr Gly  Glu Cys Cys 
    1865                 1870                 1875             


Gly Arg  Cys Leu Pro Thr Ala  Cys Thr Ile Gln Leu  Arg Gly Gly 
    1880                 1885                 1890             


Gln Ile  Met Thr Leu Lys Arg  Asp Glu Thr Leu Gln  Asp Gly Cys 
    1895                 1900                 1905             


Asp Thr  His Phe Cys Lys Val  Asn Glu Arg Gly Glu  Tyr Phe Trp 
    1910                 1915                 1920             


Glu Lys  Arg Val Thr Gly Cys  Pro Pro Phe Asp Glu  His Lys Cys 
    1925                 1930                 1935             


Leu Ala  Glu Gly Gly Lys Ile  Met Lys Ile Pro Gly  Thr Cys Cys 
    1940                 1945                 1950             


Asp Thr  Cys Glu Glu Pro Glu  Cys Asn Asp Ile Thr  Ala Arg Leu 
    1955                 1960                 1965             


Gln Tyr  Val Lys Val Gly Ser  Cys Lys Ser Glu Val  Glu Val Asp 
    1970                 1975                 1980             


Ile His  Tyr Cys Gln Gly Lys  Cys Ala Ser Lys Ala  Met Tyr Ser 
    1985                 1990                 1995             


Ile Asp  Ile Asn Asp Val Gln  Asp Gln Cys Ser Cys  Cys Ser Pro 
    2000                 2005                 2010             


Thr Arg  Thr Glu Pro Met Gln  Val Ala Leu His Cys  Thr Asn Gly 
    2015                 2020                 2025             


Ser Val  Val Tyr His Glu Val  Leu Asn Ala Met Glu  Cys Lys Cys 
    2030                 2035                 2040             


Ser Pro  Arg Lys Cys Ser Lys  
    2045                 2050 


<210>  12
<211>  1444
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  single chain FVIII

<400>  12

Ala Thr Arg Arg Tyr Tyr Leu Gly Ala Val Glu Leu Ser Trp Asp Tyr 
1               5                   10                  15      


Met Gln Ser Asp Leu Gly Glu Leu Pro Val Asp Ala Arg Phe Pro Pro 
            20                  25                  30          


Arg Val Pro Lys Ser Phe Pro Phe Asn Thr Ser Val Val Tyr Lys Lys 
        35                  40                  45              


Thr Leu Phe Val Glu Phe Thr Asp His Leu Phe Asn Ile Ala Lys Pro 
    50                  55                  60                  


Arg Pro Pro Trp Met Gly Leu Leu Gly Pro Thr Ile Gln Ala Glu Val 
65                  70                  75                  80  


Tyr Asp Thr Val Val Ile Thr Leu Lys Asn Met Ala Ser His Pro Val 
                85                  90                  95      


Ser Leu His Ala Val Gly Val Ser Tyr Trp Lys Ala Ser Glu Gly Ala 
            100                 105                 110         


Glu Tyr Asp Asp Gln Thr Ser Gln Arg Glu Lys Glu Asp Asp Lys Val 
        115                 120                 125             


Phe Pro Gly Gly Ser His Thr Tyr Val Trp Gln Val Leu Lys Glu Asn 
    130                 135                 140                 


Gly Pro Met Ala Ser Asp Pro Leu Cys Leu Thr Tyr Ser Tyr Leu Ser 
145                 150                 155                 160 


His Val Asp Leu Val Lys Asp Leu Asn Ser Gly Leu Ile Gly Ala Leu 
                165                 170                 175     


Leu Val Cys Arg Glu Gly Ser Leu Ala Lys Glu Lys Thr Gln Thr Leu 
            180                 185                 190         


His Lys Phe Ile Leu Leu Phe Ala Val Phe Asp Glu Gly Lys Ser Trp 
        195                 200                 205             


His Ser Glu Thr Lys Asn Ser Leu Met Gln Asp Arg Asp Ala Ala Ser 
    210                 215                 220                 


Ala Arg Ala Trp Pro Lys Met His Thr Val Asn Gly Tyr Val Asn Arg 
225                 230                 235                 240 


Ser Leu Pro Gly Leu Ile Gly Cys His Arg Lys Ser Val Tyr Trp His 
                245                 250                 255     


Val Ile Gly Met Gly Thr Thr Pro Glu Val His Ser Ile Phe Leu Glu 
            260                 265                 270         


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


Ser Pro Ile Thr Phe Leu Thr Ala Gln Thr Leu Leu Met Asp Leu Gly 
    290                 295                 300                 


Gln Phe Leu Leu Phe Cys His Ile Ser Ser His Gln His Asp Gly Met 
305                 310                 315                 320 


Glu Ala Tyr Val Lys Val Asp Ser Cys Pro Glu Glu Pro Gln Leu Arg 
                325                 330                 335     


Met Lys Asn Asn Glu Glu Ala Glu Asp Tyr Asp Asp Asp Leu Thr Asp 
            340                 345                 350         


Ser Glu Met Asp Val Val Arg Phe Asp Asp Asp Asn Ser Pro Ser Phe 
        355                 360                 365             


Ile Gln Ile Arg Ser Val Ala Lys Lys His Pro Lys Thr Trp Val His 
    370                 375                 380                 


Tyr Ile Ala Ala Glu Glu Glu Asp Trp Asp Tyr Ala Pro Leu Val Leu 
385                 390                 395                 400 


Ala Pro Asp Asp Arg Ser Tyr Lys Ser Gln Tyr Leu Asn Asn Gly Pro 
                405                 410                 415     


Gln Arg Ile Gly Arg Lys Tyr Lys Lys Val Arg Phe Met Ala Tyr Thr 
            420                 425                 430         


Asp Glu Thr Phe Lys Thr Arg Glu Ala Ile Gln His Glu Ser Gly Ile 
        435                 440                 445             


Leu Gly Pro Leu Leu Tyr Gly Glu Val Gly Asp Thr Leu Leu Ile Ile 
    450                 455                 460                 


Phe Lys Asn Gln Ala Ser Arg Pro Tyr Asn Ile Tyr Pro His Gly Ile 
465                 470                 475                 480 


Thr Asp Val Arg Pro Leu Tyr Ser Arg Arg Leu Pro Lys Gly Val Lys 
                485                 490                 495     


His Leu Lys Asp Phe Pro Ile Leu Pro Gly Glu Ile Phe Lys Tyr Lys 
            500                 505                 510         


Trp Thr Val Thr Val Glu Asp Gly Pro Thr Lys Ser Asp Pro Arg Cys 
        515                 520                 525             


Leu Thr Arg Tyr Tyr Ser Ser Phe Val Asn Met Glu Arg Asp Leu Ala 
    530                 535                 540                 


Ser Gly Leu Ile Gly Pro Leu Leu Ile Cys Tyr Lys Glu Ser Val Asp 
545                 550                 555                 560 


Gln Arg Gly Asn Gln Ile Met Ser Asp Lys Arg Asn Val Ile Leu Phe 
                565                 570                 575     


Ser Val Phe Asp Glu Asn Arg Ser Trp Tyr Leu Thr Glu Asn Ile Gln 
            580                 585                 590         


Arg Phe Leu Pro Asn Pro Ala Gly Val Gln Leu Glu Asp Pro Glu Phe 
        595                 600                 605             


Gln Ala Ser Asn Ile Met His Ser Ile Asn Gly Tyr Val Phe Asp Ser 
    610                 615                 620                 


Leu Gln Leu Ser Val Cys Leu His Glu Val Ala Tyr Trp Tyr Ile Leu 
625                 630                 635                 640 


Ser Ile Gly Ala Gln Thr Asp Phe Leu Ser Val Phe Phe Ser Gly Tyr 
                645                 650                 655     


Thr Phe Lys His Lys Met Val Tyr Glu Asp Thr Leu Thr Leu Phe Pro 
            660                 665                 670         


Phe Ser Gly Glu Thr Val Phe Met Ser Met Glu Asn Pro Gly Leu Trp 
        675                 680                 685             


Ile Leu Gly Cys His Asn Ser Asp Phe Arg Asn Arg Gly Met Thr Ala 
    690                 695                 700                 


Leu Leu Lys Val Ser Ser Cys Asp Lys Asn Thr Gly Asp Tyr Tyr Glu 
705                 710                 715                 720 


Asp Ser Tyr Glu Asp Ile Ser Ala Tyr Leu Leu Ser Lys Asn Asn Ala 
                725                 730                 735     


Ile Glu Pro Arg Ser Phe Ser Gln Asn Ser Arg His Pro Ser Thr Arg 
            740                 745                 750         


Gln Lys Gln Phe Asn Ala Thr Thr Ile Pro Glu Asn Thr Thr Leu Gln 
        755                 760                 765             


Ser Asp Gln Glu Glu Ile Asp Tyr Asp Asp Thr Ile Ser Val Glu Met 
    770                 775                 780                 


Lys Lys Glu Asp Phe Asp Ile Tyr Asp Glu Asp Glu Asn Gln Ser Pro 
785                 790                 795                 800 


Arg Ser Phe Gln Lys Lys Thr Arg His Tyr Phe Ile Ala Ala Val Glu 
                805                 810                 815     


Arg Leu Trp Asp Tyr Gly Met Ser Ser Ser Pro His Val Leu Arg Asn 
            820                 825                 830         


Arg Ala Gln Ser Gly Ser Val Pro Gln Phe Lys Lys Val Val Phe Gln 
        835                 840                 845             


Glu Phe Thr Asp Gly Ser Phe Thr Gln Pro Leu Tyr Arg Gly Glu Leu 
    850                 855                 860                 


Asn Glu His Leu Gly Leu Leu Gly Pro Tyr Ile Arg Ala Glu Val Glu 
865                 870                 875                 880 


Asp Asn Ile Met Val Thr Phe Arg Asn Gln Ala Ser Arg Pro Tyr Ser 
                885                 890                 895     


Phe Tyr Ser Ser Leu Ile Ser Tyr Glu Glu Asp Gln Arg Gln Gly Ala 
            900                 905                 910         


Glu Pro Arg Lys Asn Phe Val Lys Pro Asn Glu Thr Lys Thr Tyr Phe 
        915                 920                 925             


Trp Lys Val Gln His His Met Ala Pro Thr Lys Asp Glu Phe Asp Cys 
    930                 935                 940                 


Lys Ala Trp Ala Tyr Phe Ser Asp Val Asp Leu Glu Lys Asp Val His 
945                 950                 955                 960 


Ser Gly Leu Ile Gly Pro Leu Leu Val Cys His Thr Asn Thr Leu Asn 
                965                 970                 975     


Pro Ala His Gly Arg Gln Val Thr Val Gln Glu Phe Ala Leu Phe Phe 
            980                 985                 990         


Thr Ile Phe Asp Glu Thr Lys Ser  Trp Tyr Phe Thr Glu  Asn Met Glu 
        995                 1000                 1005             


Arg Asn  Cys Arg Ala Pro Cys  Asn Ile Gln Met Glu  Asp Pro Thr 
    1010                 1015                 1020             


Phe Lys  Glu Asn Tyr Arg Phe  His Ala Ile Asn Gly  Tyr Ile Met 
    1025                 1030                 1035             


Asp Thr  Leu Pro Gly Leu Val  Met Ala Gln Asp Gln  Arg Ile Arg 
    1040                 1045                 1050             


Trp Tyr  Leu Leu Ser Met Gly  Ser Asn Glu Asn Ile  His Ser Ile 
    1055                 1060                 1065             


His Phe  Ser Gly His Val Phe  Thr Val Arg Lys Lys  Glu Glu Tyr 
    1070                 1075                 1080             


Lys Met  Ala Leu Tyr Asn Leu  Tyr Pro Gly Val Phe  Glu Thr Val 
    1085                 1090                 1095             


Glu Met  Leu Pro Ser Lys Ala  Gly Ile Trp Arg Val  Glu Cys Leu 
    1100                 1105                 1110             


Ile Gly  Glu His Leu His Ala  Gly Met Ser Thr Leu  Phe Leu Val 
    1115                 1120                 1125             


Tyr Ser  Asn Lys Cys Gln Thr  Pro Leu Gly Met Ala  Ser Gly His 
    1130                 1135                 1140             


Ile Arg  Asp Phe Gln Ile Thr  Ala Ser Gly Gln Tyr  Gly Gln Trp 
    1145                 1150                 1155             


Ala Pro  Lys Leu Ala Arg Leu  His Tyr Ser Gly Ser  Ile Asn Ala 
    1160                 1165                 1170             


Trp Ser  Thr Lys Glu Pro Phe  Ser Trp Ile Lys Val  Asp Leu Leu 
    1175                 1180                 1185             


Ala Pro  Met Ile Ile His Gly  Ile Lys Thr Gln Gly  Ala Arg Gln 
    1190                 1195                 1200             


Lys Phe  Ser Ser Leu Tyr Ile  Ser Gln Phe Ile Ile  Met Tyr Ser 
    1205                 1210                 1215             


Leu Asp  Gly Lys Lys Trp Gln  Thr Tyr Arg Gly Asn  Ser Thr Gly 
    1220                 1225                 1230             


Thr Leu  Met Val Phe Phe Gly  Asn Val Asp Ser Ser  Gly Ile Lys 
    1235                 1240                 1245             


His Asn  Ile Phe Asn Pro Pro  Ile Ile Ala Arg Tyr  Ile Arg Leu 
    1250                 1255                 1260             


His Pro  Thr His Tyr Ser Ile  Arg Ser Thr Leu Arg  Met Glu Leu 
    1265                 1270                 1275             


Met Gly  Cys Asp Leu Asn Ser  Cys Ser Met Pro Leu  Gly Met Glu 
    1280                 1285                 1290             


Ser Lys  Ala Ile Ser Asp Ala  Gln Ile Thr Ala Ser  Ser Tyr Phe 
    1295                 1300                 1305             


Thr Asn  Met Phe Ala Thr Trp  Ser Pro Ser Lys Ala  Arg Leu His 
    1310                 1315                 1320             


Leu Gln  Gly Arg Ser Asn Ala  Trp Arg Pro Gln Val  Asn Asn Pro 
    1325                 1330                 1335             


Lys Glu  Trp Leu Gln Val Asp  Phe Gln Lys Thr Met  Lys Val Thr 
    1340                 1345                 1350             


Gly Val  Thr Thr Gln Gly Val  Lys Ser Leu Leu Thr  Ser Met Tyr 
    1355                 1360                 1365             


Val Lys  Glu Phe Leu Ile Ser  Ser Ser Gln Asp Gly  His Gln Trp 
    1370                 1375                 1380             


Thr Leu  Phe Phe Gln Asn Gly  Lys Val Lys Val Phe  Gln Gly Asn 
    1385                 1390                 1395             


Gln Asp  Ser Phe Thr Pro Val  Val Asn Ser Leu Asp  Pro Pro Leu 
    1400                 1405                 1410             


Leu Thr  Arg Tyr Leu Arg Ile  His Pro Gln Ser Trp  Val His Gln 
    1415                 1420                 1425             


Ile Ala  Leu Arg Met Glu Val  Leu Gly Cys Glu Ala  Gln Asp Leu 
    1430                 1435                 1440             


Tyr 
    


