                         SEQUENCE LISTING

<110>  Novo Nordisk A/S
 
<120>  TARGETED DELIVERY OF FACTOR VIII PROTEINS TO PLATELETS

<130>  8044.504-WO

<160>  42    

<170>  PatentIn version 3.5

<210>  1
<211>  2351
<212>  PRT
<213>  homo sapiens

<400>  1

Met Gln Ile Glu Leu Ser Thr Cys Phe Phe Leu Cys Leu Leu Arg Phe 
1               5                   10                  15      


Cys Phe Ser Ala Thr Arg Arg Tyr Tyr Leu Gly Ala Val Glu Leu Ser 
            20                  25                  30          


Trp Asp Tyr Met Gln Ser Asp Leu Gly Glu Leu Pro Val Asp Ala Arg 
        35                  40                  45              


Phe Pro Pro Arg Val Pro Lys Ser Phe Pro Phe Asn Thr Ser Val Val 
    50                  55                  60                  


Tyr Lys Lys Thr Leu Phe Val Glu Phe Thr Asp His Leu Phe Asn Ile 
65                  70                  75                  80  


Ala Lys Pro Arg Pro Pro Trp Met Gly Leu Leu Gly Pro Thr Ile Gln 
                85                  90                  95      


Ala Glu Val Tyr Asp Thr Val Val Ile Thr Leu Lys Asn Met Ala Ser 
            100                 105                 110         


His Pro Val Ser Leu His Ala Val Gly Val Ser Tyr Trp Lys Ala Ser 
        115                 120                 125             


Glu Gly Ala Glu Tyr Asp Asp Gln Thr Ser Gln Arg Glu Lys Glu Asp 
    130                 135                 140                 


Asp Lys Val Phe Pro Gly Gly Ser His Thr Tyr Val Trp Gln Val Leu 
145                 150                 155                 160 


Lys Glu Asn Gly Pro Met Ala Ser Asp Pro Leu Cys Leu Thr Tyr Ser 
                165                 170                 175     


Tyr Leu Ser His Val Asp Leu Val Lys Asp Leu Asn Ser Gly Leu Ile 
            180                 185                 190         


Gly Ala Leu Leu Val Cys Arg Glu Gly Ser Leu Ala Lys Glu Lys Thr 
        195                 200                 205             


Gln Thr Leu His Lys Phe Ile Leu Leu Phe Ala Val Phe Asp Glu Gly 
    210                 215                 220                 


Lys Ser Trp His Ser Glu Thr Lys Asn Ser Leu Met Gln Asp Arg Asp 
225                 230                 235                 240 


Ala Ala Ser Ala Arg Ala Trp Pro Lys Met His Thr Val Asn Gly Tyr 
                245                 250                 255     


Val Asn Arg Ser Leu Pro Gly Leu Ile Gly Cys His Arg Lys Ser Val 
            260                 265                 270         


Tyr Trp His Val Ile Gly Met Gly Thr Thr Pro Glu Val His Ser Ile 
        275                 280                 285             


Phe Leu Glu Gly His Thr Phe Leu Val Arg Asn His Arg Gln Ala Ser 
    290                 295                 300                 


Leu Glu Ile Ser Pro Ile Thr Phe Leu Thr Ala Gln Thr Leu Leu Met 
305                 310                 315                 320 


Asp Leu Gly Gln Phe Leu Leu Phe Cys His Ile Ser Ser His Gln His 
                325                 330                 335     


Asp Gly Met Glu Ala Tyr Val Lys Val Asp Ser Cys Pro Glu Glu Pro 
            340                 345                 350         


Gln Leu Arg Met Lys Asn Asn Glu Glu Ala Glu Asp Tyr Asp Asp Asp 
        355                 360                 365             


Leu Thr Asp Ser Glu Met Asp Val Val Arg Phe Asp Asp Asp Asn Ser 
    370                 375                 380                 


Pro Ser Phe Ile Gln Ile Arg Ser Val Ala Lys Lys His Pro Lys Thr 
385                 390                 395                 400 


Trp Val His Tyr Ile Ala Ala Glu Glu Glu Asp Trp Asp Tyr Ala Pro 
                405                 410                 415     


Leu Val Leu Ala Pro Asp Asp Arg Ser Tyr Lys Ser Gln Tyr Leu Asn 
            420                 425                 430         


Asn Gly Pro Gln Arg Ile Gly Arg Lys Tyr Lys Lys Val Arg Phe Met 
        435                 440                 445             


Ala Tyr Thr Asp Glu Thr Phe Lys Thr Arg Glu Ala Ile Gln His Glu 
    450                 455                 460                 


Ser Gly Ile Leu Gly Pro Leu Leu Tyr Gly Glu Val Gly Asp Thr Leu 
465                 470                 475                 480 


Leu Ile Ile Phe Lys Asn Gln Ala Ser Arg Pro Tyr Asn Ile Tyr Pro 
                485                 490                 495     


His Gly Ile Thr Asp Val Arg Pro Leu Tyr Ser Arg Arg Leu Pro Lys 
            500                 505                 510         


Gly Val Lys His Leu Lys Asp Phe Pro Ile Leu Pro Gly Glu Ile Phe 
        515                 520                 525             


Lys Tyr Lys Trp Thr Val Thr Val Glu Asp Gly Pro Thr Lys Ser Asp 
    530                 535                 540                 


Pro Arg Cys Leu Thr Arg Tyr Tyr Ser Ser Phe Val Asn Met Glu Arg 
545                 550                 555                 560 


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


Ser Val Asp Gln Arg Gly Asn Gln Ile Met Ser Asp Lys Arg Asn Val 
            580                 585                 590         


Ile Leu Phe Ser Val Phe Asp Glu Asn Arg Ser Trp Tyr Leu Thr Glu 
        595                 600                 605             


Asn Ile Gln Arg Phe Leu Pro Asn Pro Ala Gly Val Gln Leu Glu Asp 
    610                 615                 620                 


Pro Glu Phe Gln Ala Ser Asn Ile Met His Ser Ile Asn Gly Tyr Val 
625                 630                 635                 640 


Phe Asp Ser Leu Gln Leu Ser Val Cys Leu His Glu Val Ala Tyr Trp 
                645                 650                 655     


Tyr Ile Leu Ser Ile Gly Ala Gln Thr Asp Phe Leu Ser Val Phe Phe 
            660                 665                 670         


Ser Gly Tyr Thr Phe Lys His Lys Met Val Tyr Glu Asp Thr Leu Thr 
        675                 680                 685             


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


Gly Leu Trp Ile Leu Gly Cys His Asn Ser Asp Phe Arg Asn Arg Gly 
705                 710                 715                 720 


Met Thr Ala Leu Leu Lys Val Ser Ser Cys Asp Lys Asn Thr Gly Asp 
                725                 730                 735     


Tyr Tyr Glu Asp Ser Tyr Glu Asp Ile Ser Ala Tyr Leu Leu Ser Lys 
            740                 745                 750         


Asn Asn Ala Ile Glu Pro Arg Ser Phe Ser Gln Asn Ser Arg His Pro 
        755                 760                 765             


Ser Thr Arg Gln Lys Gln Phe Asn Ala Thr Thr Ile Pro Glu Asn Asp 
    770                 775                 780                 


Ile Glu Lys Thr Asp Pro Trp Phe Ala His Arg Thr Pro Met Pro Lys 
785                 790                 795                 800 


Ile Gln Asn Val Ser Ser Ser Asp Leu Leu Met Leu Leu Arg Gln Ser 
                805                 810                 815     


Pro Thr Pro His Gly Leu Ser Leu Ser Asp Leu Gln Glu Ala Lys Tyr 
            820                 825                 830         


Glu Thr Phe Ser Asp Asp Pro Ser Pro Gly Ala Ile Asp Ser Asn Asn 
        835                 840                 845             


Ser Leu Ser Glu Met Thr His Phe Arg Pro Gln Leu His His Ser Gly 
    850                 855                 860                 


Asp Met Val Phe Thr Pro Glu Ser Gly Leu Gln Leu Arg Leu Asn Glu 
865                 870                 875                 880 


Lys Leu Gly Thr Thr Ala Ala Thr Glu Leu Lys Lys Leu Asp Phe Lys 
                885                 890                 895     


Val Ser Ser Thr Ser Asn Asn Leu Ile Ser Thr Ile Pro Ser Asp Asn 
            900                 905                 910         


Leu Ala Ala Gly Thr Asp Asn Thr Ser Ser Leu Gly Pro Pro Ser Met 
        915                 920                 925             


Pro Val His Tyr Asp Ser Gln Leu Asp Thr Thr Leu Phe Gly Lys Lys 
    930                 935                 940                 


Ser Ser Pro Leu Thr Glu Ser Gly Gly Pro Leu Ser Leu Ser Glu Glu 
945                 950                 955                 960 


Asn Asn Asp Ser Lys Leu Leu Glu Ser Gly Leu Met Asn Ser Gln Glu 
                965                 970                 975     


Ser Ser Trp Gly Lys Asn Val Ser Ser Thr Glu Ser Gly Arg Leu Phe 
            980                 985                 990         


Lys Gly Lys Arg Ala His Gly Pro  Ala Leu Leu Thr Lys  Asp Asn Ala 
        995                 1000                 1005             


Leu Phe  Lys Val Ser Ile Ser  Leu Leu Lys Thr Asn  Lys Thr Ser 
    1010                 1015                 1020             


Asn Asn  Ser Ala Thr Asn Arg  Lys Thr His Ile Asp  Gly Pro Ser 
    1025                 1030                 1035             


Leu Leu  Ile Glu Asn Ser Pro  Ser Val Trp Gln Asn  Ile Leu Glu 
    1040                 1045                 1050             


Ser Asp  Thr Glu Phe Lys Lys  Val Thr Pro Leu Ile  His Asp Arg 
    1055                 1060                 1065             


Met Leu  Met Asp Lys Asn Ala  Thr Ala Leu Arg Leu  Asn His Met 
    1070                 1075                 1080             


Ser Asn  Lys Thr Thr Ser Ser  Lys Asn Met Glu Met  Val Gln Gln 
    1085                 1090                 1095             


Lys Lys  Glu Gly Pro Ile Pro  Pro Asp Ala Gln Asn  Pro Asp Met 
    1100                 1105                 1110             


Ser Phe  Phe Lys Met Leu Phe  Leu Pro Glu Ser Ala  Arg Trp Ile 
    1115                 1120                 1125             


Gln Arg  Thr His Gly Lys Asn  Ser Leu Asn Ser Gly  Gln Gly Pro 
    1130                 1135                 1140             


Ser Pro  Lys Gln Leu Val Ser  Leu Gly Pro Glu Lys  Ser Val Glu 
    1145                 1150                 1155             


Gly Gln  Asn Phe Leu Ser Glu  Lys Asn Lys Val Val  Val Gly Lys 
    1160                 1165                 1170             


Gly Glu  Phe Thr Lys Asp Val  Gly Leu Lys Glu Met  Val Phe Pro 
    1175                 1180                 1185             


Ser Ser  Arg Asn Leu Phe Leu  Thr Asn Leu Asp Asn  Leu His Glu 
    1190                 1195                 1200             


Asn Asn  Thr His Asn Gln Glu  Lys Lys Ile Gln Glu  Glu Ile Glu 
    1205                 1210                 1215             


Lys Lys  Glu Thr Leu Ile Gln  Glu Asn Val Val Leu  Pro Gln Ile 
    1220                 1225                 1230             


His Thr  Val Thr Gly Thr Lys  Asn Phe Met Lys Asn  Leu Phe Leu 
    1235                 1240                 1245             


Leu Ser  Thr Arg Gln Asn Val  Glu Gly Ser Tyr Asp  Gly Ala Tyr 
    1250                 1255                 1260             


Ala Pro  Val Leu Gln Asp Phe  Arg Ser Leu Asn Asp  Ser Thr Asn 
    1265                 1270                 1275             


Arg Thr  Lys Lys His Thr Ala  His Phe Ser Lys Lys  Gly Glu Glu 
    1280                 1285                 1290             


Glu Asn  Leu Glu Gly Leu Gly  Asn Gln Thr Lys Gln  Ile Val Glu 
    1295                 1300                 1305             


Lys Tyr  Ala Cys Thr Thr Arg  Ile Ser Pro Asn Thr  Ser Gln Gln 
    1310                 1315                 1320             


Asn Phe  Val Thr Gln Arg Ser  Lys Arg Ala Leu Lys  Gln Phe Arg 
    1325                 1330                 1335             


Leu Pro  Leu Glu Glu Thr Glu  Leu Glu Lys Arg Ile  Ile Val Asp 
    1340                 1345                 1350             


Asp Thr  Ser Thr Gln Trp Ser  Lys Asn Met Lys His  Leu Thr Pro 
    1355                 1360                 1365             


Ser Thr  Leu Thr Gln Ile Asp  Tyr Asn Glu Lys Glu  Lys Gly Ala 
    1370                 1375                 1380             


Ile Thr  Gln Ser Pro Leu Ser  Asp Cys Leu Thr Arg  Ser His Ser 
    1385                 1390                 1395             


Ile Pro  Gln Ala Asn Arg Ser  Pro Leu Pro Ile Ala  Lys Val Ser 
    1400                 1405                 1410             


Ser Phe  Pro Ser Ile Arg Pro  Ile Tyr Leu Thr Arg  Val Leu Phe 
    1415                 1420                 1425             


Gln Asp  Asn Ser Ser His Leu  Pro Ala Ala Ser Tyr  Arg Lys Lys 
    1430                 1435                 1440             


Asp Ser  Gly Val Gln Glu Ser  Ser His Phe Leu Gln  Gly Ala Lys 
    1445                 1450                 1455             


Lys Asn  Asn Leu Ser Leu Ala  Ile Leu Thr Leu Glu  Met Thr Gly 
    1460                 1465                 1470             


Asp Gln  Arg Glu Val Gly Ser  Leu Gly Thr Ser Ala  Thr Asn Ser 
    1475                 1480                 1485             


Val Thr  Tyr Lys Lys Val Glu  Asn Thr Val Leu Pro  Lys Pro Asp 
    1490                 1495                 1500             


Leu Pro  Lys Thr Ser Gly Lys  Val Glu Leu Leu Pro  Lys Val His 
    1505                 1510                 1515             


Ile Tyr  Gln Lys Asp Leu Phe  Pro Thr Glu Thr Ser  Asn Gly Ser 
    1520                 1525                 1530             


Pro Gly  His Leu Asp Leu Val  Glu Gly Ser Leu Leu  Gln Gly Thr 
    1535                 1540                 1545             


Glu Gly  Ala Ile Lys Trp Asn  Glu Ala Asn Arg Pro  Gly Lys Val 
    1550                 1555                 1560             


Pro Phe  Leu Arg Val Ala Thr  Glu Ser Ser Ala Lys  Thr Pro Ser 
    1565                 1570                 1575             


Lys Leu  Leu Asp Pro Leu Ala  Trp Asp Asn His Tyr  Gly Thr Gln 
    1580                 1585                 1590             


Ile Pro  Lys Glu Glu Trp Lys  Ser Gln Glu Lys Ser  Pro Glu Lys 
    1595                 1600                 1605             


Thr Ala  Phe Lys Lys Lys Asp  Thr Ile Leu Ser Leu  Asn Ala Cys 
    1610                 1615                 1620             


Glu Ser  Asn His Ala Ile Ala  Ala Ile Asn Glu Gly  Gln Asn Lys 
    1625                 1630                 1635             


Pro Glu  Ile Glu Val Thr Trp  Ala Lys Gln Gly Arg  Thr Glu Arg 
    1640                 1645                 1650             


Leu Cys  Ser Gln Asn Pro Pro  Val Leu Lys Arg His  Gln Arg Glu 
    1655                 1660                 1665             


Ile Thr  Arg Thr Thr Leu Gln  Ser Asp Gln Glu Glu  Ile Asp Tyr 
    1670                 1675                 1680             


Asp Asp  Thr Ile Ser Val Glu  Met Lys Lys Glu Asp  Phe Asp Ile 
    1685                 1690                 1695             


Tyr Asp  Glu Asp Glu Asn Gln  Ser Pro Arg Ser Phe  Gln Lys Lys 
    1700                 1705                 1710             


Thr Arg  His Tyr Phe Ile Ala  Ala Val Glu Arg Leu  Trp Asp Tyr 
    1715                 1720                 1725             


Gly Met  Ser Ser Ser Pro His  Val Leu Arg Asn Arg  Ala Gln Ser 
    1730                 1735                 1740             


Gly Ser  Val Pro Gln Phe Lys  Lys Val Val Phe Gln  Glu Phe Thr 
    1745                 1750                 1755             


Asp Gly  Ser Phe Thr Gln Pro  Leu Tyr Arg Gly Glu  Leu Asn Glu 
    1760                 1765                 1770             


His Leu  Gly Leu Leu Gly Pro  Tyr Ile Arg Ala Glu  Val Glu Asp 
    1775                 1780                 1785             


Asn Ile  Met Val Thr Phe Arg  Asn Gln Ala Ser Arg  Pro Tyr Ser 
    1790                 1795                 1800             


Phe Tyr  Ser Ser Leu Ile Ser  Tyr Glu Glu Asp Gln  Arg Gln Gly 
    1805                 1810                 1815             


Ala Glu  Pro Arg Lys Asn Phe  Val Lys Pro Asn Glu  Thr Lys Thr 
    1820                 1825                 1830             


Tyr Phe  Trp Lys Val Gln His  His Met Ala Pro Thr  Lys Asp Glu 
    1835                 1840                 1845             


Phe Asp  Cys Lys Ala Trp Ala  Tyr Phe Ser Asp Val  Asp Leu Glu 
    1850                 1855                 1860             


Lys Asp  Val His Ser Gly Leu  Ile Gly Pro Leu Leu  Val Cys His 
    1865                 1870                 1875             


Thr Asn  Thr Leu Asn Pro Ala  His Gly Arg Gln Val  Thr Val Gln 
    1880                 1885                 1890             


Glu Phe  Ala Leu Phe Phe Thr  Ile Phe Asp Glu Thr  Lys Ser Trp 
    1895                 1900                 1905             


Tyr Phe  Thr Glu Asn Met Glu  Arg Asn Cys Arg Ala  Pro Cys Asn 
    1910                 1915                 1920             


Ile Gln  Met Glu Asp Pro Thr  Phe Lys Glu Asn Tyr  Arg Phe His 
    1925                 1930                 1935             


Ala Ile  Asn Gly Tyr Ile Met  Asp Thr Leu Pro Gly  Leu Val Met 
    1940                 1945                 1950             


Ala Gln  Asp Gln Arg Ile Arg  Trp Tyr Leu Leu Ser  Met Gly Ser 
    1955                 1960                 1965             


Asn Glu  Asn Ile His Ser Ile  His Phe Ser Gly His  Val Phe Thr 
    1970                 1975                 1980             


Val Arg  Lys Lys Glu Glu Tyr  Lys Met Ala Leu Tyr  Asn Leu Tyr 
    1985                 1990                 1995             


Pro Gly  Val Phe Glu Thr Val  Glu Met Leu Pro Ser  Lys Ala Gly 
    2000                 2005                 2010             


Ile Trp  Arg Val Glu Cys Leu  Ile Gly Glu His Leu  His Ala Gly 
    2015                 2020                 2025             


Met Ser  Thr Leu Phe Leu Val  Tyr Ser Asn Lys Cys  Gln Thr Pro 
    2030                 2035                 2040             


Leu Gly  Met Ala Ser Gly His  Ile Arg Asp Phe Gln  Ile Thr Ala 
    2045                 2050                 2055             


Ser Gly  Gln Tyr Gly Gln Trp  Ala Pro Lys Leu Ala  Arg Leu His 
    2060                 2065                 2070             


Tyr Ser  Gly Ser Ile Asn Ala  Trp Ser Thr Lys Glu  Pro Phe Ser 
    2075                 2080                 2085             


Trp Ile  Lys Val Asp Leu Leu  Ala Pro Met Ile Ile  His Gly Ile 
    2090                 2095                 2100             


Lys Thr  Gln Gly Ala Arg Gln  Lys Phe Ser Ser Leu  Tyr Ile Ser 
    2105                 2110                 2115             


Gln Phe  Ile Ile Met Tyr Ser  Leu Asp Gly Lys Lys  Trp Gln Thr 
    2120                 2125                 2130             


Tyr Arg  Gly Asn Ser Thr Gly  Thr Leu Met Val Phe  Phe Gly Asn 
    2135                 2140                 2145             


Val Asp  Ser Ser Gly Ile Lys  His Asn Ile Phe Asn  Pro Pro Ile 
    2150                 2155                 2160             


Ile Ala  Arg Tyr Ile Arg Leu  His Pro Thr His Tyr  Ser Ile Arg 
    2165                 2170                 2175             


Ser Thr  Leu Arg Met Glu Leu  Met Gly Cys Asp Leu  Asn Ser Cys 
    2180                 2185                 2190             


Ser Met  Pro Leu Gly Met Glu  Ser Lys Ala Ile Ser  Asp Ala Gln 
    2195                 2200                 2205             


Ile Thr  Ala Ser Ser Tyr Phe  Thr Asn Met Phe Ala  Thr Trp Ser 
    2210                 2215                 2220             


Pro Ser  Lys Ala Arg Leu His  Leu Gln Gly Arg Ser  Asn Ala Trp 
    2225                 2230                 2235             


Arg Pro  Gln Val Asn Asn Pro  Lys Glu Trp Leu Gln  Val Asp Phe 
    2240                 2245                 2250             


Gln Lys  Thr Met Lys Val Thr  Gly Val Thr Thr Gln  Gly Val Lys 
    2255                 2260                 2265             


Ser Leu  Leu Thr Ser Met Tyr  Val Lys Glu Phe Leu  Ile Ser Ser 
    2270                 2275                 2280             


Ser Gln  Asp Gly His Gln Trp  Thr Leu Phe Phe Gln  Asn Gly Lys 
    2285                 2290                 2295             


Val Lys  Val Phe Gln Gly Asn  Gln Asp Ser Phe Thr  Pro Val Val 
    2300                 2305                 2310             


Asn Ser  Leu Asp Pro Pro Leu  Leu Thr Arg Tyr Leu  Arg Ile His 
    2315                 2320                 2325             


Pro Gln  Ser Trp Val His Gln  Ile Ala Leu Arg Met  Glu Val Leu 
    2330                 2335                 2340             


Gly Cys  Glu Ala Gln Asp Leu  Tyr 
    2345                 2350     


<210>  2
<211>  1457
<212>  PRT
<213>  homo sapiens

<400>  2

Met Gln Ile Glu Leu Ser Thr Cys Phe Phe Leu Cys Leu Leu Arg Phe 
1               5                   10                  15      


Cys Phe Ser Ala Thr Arg Arg Tyr Tyr Leu Gly Ala Val Glu Leu Ser 
            20                  25                  30          


Trp Asp Tyr Met Gln Ser Asp Leu Gly Glu Leu Pro Val Asp Ala Arg 
        35                  40                  45              


Phe Pro Pro Arg Val Pro Lys Ser Phe Pro Phe Asn Thr Ser Val Val 
    50                  55                  60                  


Tyr Lys Lys Thr Leu Phe Val Glu Phe Thr Asp His Leu Phe Asn Ile 
65                  70                  75                  80  


Ala Lys Pro Arg Pro Pro Trp Met Gly Leu Leu Gly Pro Thr Ile Gln 
                85                  90                  95      


Ala Glu Val Tyr Asp Thr Val Val Ile Thr Leu Lys Asn Met Ala Ser 
            100                 105                 110         


His Pro Val Ser Leu His Ala Val Gly Val Ser Tyr Trp Lys Ala Ser 
        115                 120                 125             


Glu Gly Ala Glu Tyr Asp Asp Gln Thr Ser Gln Arg Glu Lys Glu Asp 
    130                 135                 140                 


Asp Lys Val Phe Pro Gly Gly Ser His Thr Tyr Val Trp Gln Val Leu 
145                 150                 155                 160 


Lys Glu Asn Gly Pro Met Ala Ser Asp Pro Leu Cys Leu Thr Tyr Ser 
                165                 170                 175     


Tyr Leu Ser His Val Asp Leu Val Lys Asp Leu Asn Ser Gly Leu Ile 
            180                 185                 190         


Gly Ala Leu Leu Val Cys Arg Glu Gly Ser Leu Ala Lys Glu Lys Thr 
        195                 200                 205             


Gln Thr Leu His Lys Phe Ile Leu Leu Phe Ala Val Phe Asp Glu Gly 
    210                 215                 220                 


Lys Ser Trp His Ser Glu Thr Lys Asn Ser Leu Met Gln Asp Arg Asp 
225                 230                 235                 240 


Ala Ala Ser Ala Arg Ala Trp Pro Lys Met His Thr Val Asn Gly Tyr 
                245                 250                 255     


Val Asn Arg Ser Leu Pro Gly Leu Ile Gly Cys His Arg Lys Ser Val 
            260                 265                 270         


Tyr Trp His Val Ile Gly Met Gly Thr Thr Pro Glu Val His Ser Ile 
        275                 280                 285             


Phe Leu Glu Gly His Thr Phe Leu Val Arg Asn His Arg Gln Ala Ser 
    290                 295                 300                 


Leu Glu Ile Ser Pro Ile Thr Phe Leu Thr Ala Gln Thr Leu Leu Met 
305                 310                 315                 320 


Asp Leu Gly Gln Phe Leu Leu Phe Cys His Ile Ser Ser His Gln His 
                325                 330                 335     


Asp Gly Met Glu Ala Tyr Val Lys Val Asp Ser Cys Pro Glu Glu Pro 
            340                 345                 350         


Gln Leu Arg Met Lys Asn Asn Glu Glu Ala Glu Asp Tyr Asp Asp Asp 
        355                 360                 365             


Leu Thr Asp Ser Glu Met Asp Val Val Arg Phe Asp Asp Asp Asn Ser 
    370                 375                 380                 


Pro Ser Phe Ile Gln Ile Arg Ser Val Ala Lys Lys His Pro Lys Thr 
385                 390                 395                 400 


Trp Val His Tyr Ile Ala Ala Glu Glu Glu Asp Trp Asp Tyr Ala Pro 
                405                 410                 415     


Leu Val Leu Ala Pro Asp Asp Arg Ser Tyr Lys Ser Gln Tyr Leu Asn 
            420                 425                 430         


Asn Gly Pro Gln Arg Ile Gly Arg Lys Tyr Lys Lys Val Arg Phe Met 
        435                 440                 445             


Ala Tyr Thr Asp Glu Thr Phe Lys Thr Arg Glu Ala Ile Gln His Glu 
    450                 455                 460                 


Ser Gly Ile Leu Gly Pro Leu Leu Tyr Gly Glu Val Gly Asp Thr Leu 
465                 470                 475                 480 


Leu Ile Ile Phe Lys Asn Gln Ala Ser Arg Pro Tyr Asn Ile Tyr Pro 
                485                 490                 495     


His Gly Ile Thr Asp Val Arg Pro Leu Tyr Ser Arg Arg Leu Pro Lys 
            500                 505                 510         


Gly Val Lys His Leu Lys Asp Phe Pro Ile Leu Pro Gly Glu Ile Phe 
        515                 520                 525             


Lys Tyr Lys Trp Thr Val Thr Val Glu Asp Gly Pro Thr Lys Ser Asp 
    530                 535                 540                 


Pro Arg Cys Leu Thr Arg Tyr Tyr Ser Ser Phe Val Asn Met Glu Arg 
545                 550                 555                 560 


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


Ser Val Asp Gln Arg Gly Asn Gln Ile Met Ser Asp Lys Arg Asn Val 
            580                 585                 590         


Ile Leu Phe Ser Val Phe Asp Glu Asn Arg Ser Trp Tyr Leu Thr Glu 
        595                 600                 605             


Asn Ile Gln Arg Phe Leu Pro Asn Pro Ala Gly Val Gln Leu Glu Asp 
    610                 615                 620                 


Pro Glu Phe Gln Ala Ser Asn Ile Met His Ser Ile Asn Gly Tyr Val 
625                 630                 635                 640 


Phe Asp Ser Leu Gln Leu Ser Val Cys Leu His Glu Val Ala Tyr Trp 
                645                 650                 655     


Tyr Ile Leu Ser Ile Gly Ala Gln Thr Asp Phe Leu Ser Val Phe Phe 
            660                 665                 670         


Ser Gly Tyr Thr Phe Lys His Lys Met Val Tyr Glu Asp Thr Leu Thr 
        675                 680                 685             


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


Gly Leu Trp Ile Leu Gly Cys His Asn Ser Asp Phe Arg Asn Arg Gly 
705                 710                 715                 720 


Met Thr Ala Leu Leu Lys Val Ser Ser Cys Asp Lys Asn Thr Gly Asp 
                725                 730                 735     


Tyr Tyr Glu Asp Ser Tyr Glu Asp Ile Ser Ala Tyr Leu Leu Ser Lys 
            740                 745                 750         


Asn Asn Ala Ile Glu Pro Arg Ser Phe Ser Gln Asn Pro Pro Val Leu 
        755                 760                 765             


Lys Arg His Gln Arg Glu Ile Thr Arg Thr Thr Leu Gln Ser Asp Gln 
    770                 775                 780                 


Glu Glu Ile Asp Tyr Asp Asp Thr Ile Ser Val Glu Met Lys Lys Glu 
785                 790                 795                 800 


Asp Phe Asp Ile Tyr Asp Glu Asp Glu Asn Gln Ser Pro Arg Ser Phe 
                805                 810                 815     


Gln Lys Lys Thr Arg His Tyr Phe Ile Ala Ala Val Glu Arg Leu Trp 
            820                 825                 830         


Asp Tyr Gly Met Ser Ser Ser Pro His Val Leu Arg Asn Arg Ala Gln 
        835                 840                 845             


Ser Gly Ser Val Pro Gln Phe Lys Lys Val Val Phe Gln Glu Phe Thr 
    850                 855                 860                 


Asp Gly Ser Phe Thr Gln Pro Leu Tyr Arg Gly Glu Leu Asn Glu His 
865                 870                 875                 880 


Leu Gly Leu Leu Gly Pro Tyr Ile Arg Ala Glu Val Glu Asp Asn Ile 
                885                 890                 895     


Met Val Thr Phe Arg Asn Gln Ala Ser Arg Pro Tyr Ser Phe Tyr Ser 
            900                 905                 910         


Ser Leu Ile Ser Tyr Glu Glu Asp Gln Arg Gln Gly Ala Glu Pro Arg 
        915                 920                 925             


Lys Asn Phe Val Lys Pro Asn Glu Thr Lys Thr Tyr Phe Trp Lys Val 
    930                 935                 940                 


Gln His His Met Ala Pro Thr Lys Asp Glu Phe Asp Cys Lys Ala Trp 
945                 950                 955                 960 


Ala Tyr Phe Ser Asp Val Asp Leu Glu Lys Asp Val His Ser Gly Leu 
                965                 970                 975     


Ile Gly Pro Leu Leu Val Cys His Thr Asn Thr Leu Asn Pro Ala His 
            980                 985                 990         


Gly Arg Gln Val Thr Val Gln Glu  Phe Ala Leu Phe Phe  Thr Ile Phe 
        995                 1000                 1005             


Asp Glu  Thr Lys Ser Trp Tyr  Phe Thr Glu Asn Met  Glu Arg Asn 
    1010                 1015                 1020             


Cys Arg  Ala Pro Cys Asn Ile  Gln Met Glu Asp Pro  Thr Phe Lys 
    1025                 1030                 1035             


Glu Asn  Tyr Arg Phe His Ala  Ile Asn Gly Tyr Ile  Met Asp Thr 
    1040                 1045                 1050             


Leu Pro  Gly Leu Val Met Ala  Gln Asp Gln Arg Ile  Arg Trp Tyr 
    1055                 1060                 1065             


Leu Leu  Ser Met Gly Ser Asn  Glu Asn Ile His Ser  Ile His Phe 
    1070                 1075                 1080             


Ser Gly  His Val Phe Thr Val  Arg Lys Lys Glu Glu  Tyr Lys Met 
    1085                 1090                 1095             


Ala Leu  Tyr Asn Leu Tyr Pro  Gly Val Phe Glu Thr  Val Glu Met 
    1100                 1105                 1110             


Leu Pro  Ser Lys Ala Gly Ile  Trp Arg Val Glu Cys  Leu Ile Gly 
    1115                 1120                 1125             


Glu His  Leu His Ala Gly Met  Ser Thr Leu Phe Leu  Val Tyr Ser 
    1130                 1135                 1140             


Asn Lys  Cys Gln Thr Pro Leu  Gly Met Ala Ser Gly  His Ile Arg 
    1145                 1150                 1155             


Asp Phe  Gln Ile Thr Ala Ser  Gly Gln Tyr Gly Gln  Trp Ala Pro 
    1160                 1165                 1170             


Lys Leu  Ala Arg Leu His Tyr  Ser Gly Ser Ile Asn  Ala Trp Ser 
    1175                 1180                 1185             


Thr Lys  Glu Pro Phe Ser Trp  Ile Lys Val Asp Leu  Leu Ala Pro 
    1190                 1195                 1200             


Met Ile  Ile His Gly Ile Lys  Thr Gln Gly Ala Arg  Gln Lys Phe 
    1205                 1210                 1215             


Ser Ser  Leu Tyr Ile Ser Gln  Phe Ile Ile Met Tyr  Ser Leu Asp 
    1220                 1225                 1230             


Gly Lys  Lys Trp Gln Thr Tyr  Arg Gly Asn Ser Thr  Gly Thr Leu 
    1235                 1240                 1245             


Met Val  Phe Phe Gly Asn Val  Asp Ser Ser Gly Ile  Lys His Asn 
    1250                 1255                 1260             


Ile Phe  Asn Pro Pro Ile Ile  Ala Arg Tyr Ile Arg  Leu His Pro 
    1265                 1270                 1275             


Thr His  Tyr Ser Ile Arg Ser  Thr Leu Arg Met Glu  Leu Met Gly 
    1280                 1285                 1290             


Cys Asp  Leu Asn Ser Cys Ser  Met Pro Leu Gly Met  Glu Ser Lys 
    1295                 1300                 1305             


Ala Ile  Ser Asp Ala Gln Ile  Thr Ala Ser Ser Tyr  Phe Thr Asn 
    1310                 1315                 1320             


Met Phe  Ala Thr Trp Ser Pro  Ser Lys Ala Arg Leu  His Leu Gln 
    1325                 1330                 1335             


Gly Arg  Ser Asn Ala Trp Arg  Pro Gln Val Asn Asn  Pro Lys Glu 
    1340                 1345                 1350             


Trp Leu  Gln Val Asp Phe Gln  Lys Thr Met Lys Val  Thr Gly Val 
    1355                 1360                 1365             


Thr Thr  Gln Gly Val Lys Ser  Leu Leu Thr Ser Met  Tyr Val Lys 
    1370                 1375                 1380             


Glu Phe  Leu Ile Ser Ser Ser  Gln Asp Gly His Gln  Trp Thr Leu 
    1385                 1390                 1395             


Phe Phe  Gln Asn Gly Lys Val  Lys Val Phe Gln Gly  Asn Gln Asp 
    1400                 1405                 1410             


Ser Phe  Thr Pro Val Val Asn  Ser Leu Asp Pro Pro  Leu Leu Thr 
    1415                 1420                 1425             


Arg Tyr  Leu Arg Ile His Pro  Gln Ser Trp Val His  Gln Ile Ala 
    1430                 1435                 1440             


Leu Arg  Met Glu Val Leu Gly  Cys Glu Ala Gln Asp  Leu Tyr 
    1445                 1450                 1455         


<210>  3
<211>  1464
<212>  PRT
<213>  homo sapiens

<400>  3

Met Gln Ile Glu Leu Ser Thr Cys Phe Phe Leu Cys Leu Leu Arg Phe 
1               5                   10                  15      


Cys Phe Ser Ala Thr Arg Arg Tyr Tyr Leu Gly Ala Val Glu Leu Ser 
            20                  25                  30          


Trp Asp Tyr Met Gln Ser Asp Leu Gly Glu Leu Pro Val Asp Ala Arg 
        35                  40                  45              


Phe Pro Pro Arg Val Pro Lys Ser Phe Pro Phe Asn Thr Ser Val Val 
    50                  55                  60                  


Tyr Lys Lys Thr Leu Phe Val Glu Phe Thr Asp His Leu Phe Asn Ile 
65                  70                  75                  80  


Ala Lys Pro Arg Pro Pro Trp Met Gly Leu Leu Gly Pro Thr Ile Gln 
                85                  90                  95      


Ala Glu Val Tyr Asp Thr Val Val Ile Thr Leu Lys Asn Met Ala Ser 
            100                 105                 110         


His Pro Val Ser Leu His Ala Val Gly Val Ser Tyr Trp Lys Ala Ser 
        115                 120                 125             


Glu Gly Ala Glu Tyr Asp Asp Gln Thr Ser Gln Arg Glu Lys Glu Asp 
    130                 135                 140                 


Asp Lys Val Phe Pro Gly Gly Ser His Thr Tyr Val Trp Gln Val Leu 
145                 150                 155                 160 


Lys Glu Asn Gly Pro Met Ala Ser Asp Pro Leu Cys Leu Thr Tyr Ser 
                165                 170                 175     


Tyr Leu Ser His Val Asp Leu Val Lys Asp Leu Asn Ser Gly Leu Ile 
            180                 185                 190         


Gly Ala Leu Leu Val Cys Arg Glu Gly Ser Leu Ala Lys Glu Lys Thr 
        195                 200                 205             


Gln Thr Leu His Lys Phe Ile Leu Leu Phe Ala Val Phe Asp Glu Gly 
    210                 215                 220                 


Lys Ser Trp His Ser Glu Thr Lys Asn Ser Leu Met Gln Asp Arg Asp 
225                 230                 235                 240 


Ala Ala Ser Ala Arg Ala Trp Pro Lys Met His Thr Val Asn Gly Tyr 
                245                 250                 255     


Val Asn Arg Ser Leu Pro Gly Leu Ile Gly Cys His Arg Lys Ser Val 
            260                 265                 270         


Tyr Trp His Val Ile Gly Met Gly Thr Thr Pro Glu Val His Ser Ile 
        275                 280                 285             


Phe Leu Glu Gly His Thr Phe Leu Val Arg Asn His Arg Gln Ala Ser 
    290                 295                 300                 


Leu Glu Ile Ser Pro Ile Thr Phe Leu Thr Ala Gln Thr Leu Leu Met 
305                 310                 315                 320 


Asp Leu Gly Gln Phe Leu Leu Phe Cys His Ile Ser Ser His Gln His 
                325                 330                 335     


Asp Gly Met Glu Ala Tyr Val Lys Val Asp Ser Cys Pro Glu Glu Pro 
            340                 345                 350         


Gln Leu Arg Met Lys Asn Asn Glu Glu Ala Glu Asp Tyr Asp Asp Asp 
        355                 360                 365             


Leu Thr Asp Ser Glu Met Asp Val Val Arg Phe Asp Asp Asp Asn Ser 
    370                 375                 380                 


Pro Ser Phe Ile Gln Ile Arg Ser Val Ala Lys Lys His Pro Lys Thr 
385                 390                 395                 400 


Trp Val His Tyr Ile Ala Ala Glu Glu Glu Asp Trp Asp Tyr Ala Pro 
                405                 410                 415     


Leu Val Leu Ala Pro Asp Asp Arg Ser Tyr Lys Ser Gln Tyr Leu Asn 
            420                 425                 430         


Asn Gly Pro Gln Arg Ile Gly Arg Lys Tyr Lys Lys Val Arg Phe Met 
        435                 440                 445             


Ala Tyr Thr Asp Glu Thr Phe Lys Thr Arg Glu Ala Ile Gln His Glu 
    450                 455                 460                 


Ser Gly Ile Leu Gly Pro Leu Leu Tyr Gly Glu Val Gly Asp Thr Leu 
465                 470                 475                 480 


Leu Ile Ile Phe Lys Asn Gln Ala Ser Arg Pro Tyr Asn Ile Tyr Pro 
                485                 490                 495     


His Gly Ile Thr Asp Val Arg Pro Leu Tyr Ser Arg Arg Leu Pro Lys 
            500                 505                 510         


Gly Val Lys His Leu Lys Asp Phe Pro Ile Leu Pro Gly Glu Ile Phe 
        515                 520                 525             


Lys Tyr Lys Trp Thr Val Thr Val Glu Asp Gly Pro Thr Lys Ser Asp 
    530                 535                 540                 


Pro Arg Cys Leu Thr Arg Tyr Tyr Ser Ser Phe Val Asn Met Glu Arg 
545                 550                 555                 560 


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


Ser Val Asp Gln Arg Gly Asn Gln Ile Met Ser Asp Lys Arg Asn Val 
            580                 585                 590         


Ile Leu Phe Ser Val Phe Asp Glu Asn Arg Ser Trp Tyr Leu Thr Glu 
        595                 600                 605             


Asn Ile Gln Arg Phe Leu Pro Asn Pro Ala Gly Val Gln Leu Glu Asp 
    610                 615                 620                 


Pro Glu Phe Gln Ala Ser Asn Ile Met His Ser Ile Asn Gly Tyr Val 
625                 630                 635                 640 


Phe Asp Ser Leu Gln Leu Ser Val Cys Leu His Glu Val Ala Tyr Trp 
                645                 650                 655     


Tyr Ile Leu Ser Ile Gly Ala Gln Thr Asp Phe Leu Ser Val Phe Phe 
            660                 665                 670         


Ser Gly Tyr Thr Phe Lys His Lys Met Val Tyr Glu Asp Thr Leu Thr 
        675                 680                 685             


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


Gly Leu Trp Ile Leu Gly Cys His Asn Ser Asp Phe Arg Asn Arg Gly 
705                 710                 715                 720 


Met Thr Ala Leu Leu Lys Val Ser Ser Cys Asp Lys Asn Thr Gly Asp 
                725                 730                 735     


Tyr Tyr Glu Asp Ser Tyr Glu Asp Ile Ser Ala Tyr Leu Leu Ser Lys 
            740                 745                 750         


Asn Asn Ala Ile Glu Pro Arg Ser Phe Ser Gln Asn Ser Arg His Pro 
        755                 760                 765             


Ser Gln Asn Pro Pro Val Leu Lys Arg His Gln Arg Glu Ile Thr Arg 
    770                 775                 780                 


Thr Thr Leu Gln Ser Asp Gln Glu Glu Ile Asp Tyr Asp Asp Thr Ile 
785                 790                 795                 800 


Ser Val Glu Met Lys Lys Glu Asp Phe Asp Ile Tyr Asp Glu Asp Glu 
                805                 810                 815     


Asn Gln Ser Pro Arg Ser Phe Gln Lys Lys Thr Arg His Tyr Phe Ile 
            820                 825                 830         


Ala Ala Val Glu Arg Leu Trp Asp Tyr Gly Met Ser Ser Ser Pro His 
        835                 840                 845             


Val Leu Arg Asn Arg Ala Gln Ser Gly Ser Val Pro Gln Phe Lys Lys 
    850                 855                 860                 


Val Val Phe Gln Glu Phe Thr Asp Gly Ser Phe Thr Gln Pro Leu Tyr 
865                 870                 875                 880 


Arg Gly Glu Leu Asn Glu His Leu Gly Leu Leu Gly Pro Tyr Ile Arg 
                885                 890                 895     


Ala Glu Val Glu Asp Asn Ile Met Val Thr Phe Arg Asn Gln Ala Ser 
            900                 905                 910         


Arg Pro Tyr Ser Phe Tyr Ser Ser Leu Ile Ser Tyr Glu Glu Asp Gln 
        915                 920                 925             


Arg Gln Gly Ala Glu Pro Arg Lys Asn Phe Val Lys Pro Asn Glu Thr 
    930                 935                 940                 


Lys Thr Tyr Phe Trp Lys Val Gln His His Met Ala Pro Thr Lys Asp 
945                 950                 955                 960 


Glu Phe Asp Cys Lys Ala Trp Ala Tyr Phe Ser Asp Val Asp Leu Glu 
                965                 970                 975     


Lys Asp Val His Ser Gly Leu Ile Gly Pro Leu Leu Val Cys His Thr 
            980                 985                 990         


Asn Thr Leu Asn Pro Ala His Gly  Arg Gln Val Thr Val  Gln Glu Phe 
        995                 1000                 1005             


Ala Leu  Phe Phe Thr Ile Phe  Asp Glu Thr Lys Ser  Trp Tyr Phe 
    1010                 1015                 1020             


Thr Glu  Asn Met Glu Arg Asn  Cys Arg Ala Pro Cys  Asn Ile Gln 
    1025                 1030                 1035             


Met Glu  Asp Pro Thr Phe Lys  Glu Asn Tyr Arg Phe  His Ala Ile 
    1040                 1045                 1050             


Asn Gly  Tyr Ile Met Asp Thr  Leu Pro Gly Leu Val  Met Ala Gln 
    1055                 1060                 1065             


Asp Gln  Arg Ile Arg Trp Tyr  Leu Leu Ser Met Gly  Ser Asn Glu 
    1070                 1075                 1080             


Asn Ile  His Ser Ile His Phe  Ser Gly His Val Phe  Thr Val Arg 
    1085                 1090                 1095             


Lys Lys  Glu Glu Tyr Lys Met  Ala Leu Tyr Asn Leu  Tyr Pro Gly 
    1100                 1105                 1110             


Val Phe  Glu Thr Val Glu Met  Leu Pro Ser Lys Ala  Gly Ile Trp 
    1115                 1120                 1125             


Arg Val  Glu Cys Leu Ile Gly  Glu His Leu His Ala  Gly Met Ser 
    1130                 1135                 1140             


Thr Leu  Phe Leu Val Tyr Ser  Asn Lys Cys Gln Thr  Pro Leu Gly 
    1145                 1150                 1155             


Met Ala  Ser Gly His Ile Arg  Asp Phe Gln Ile Thr  Ala Ser Gly 
    1160                 1165                 1170             


Gln Tyr  Gly Gln Trp Ala Pro  Lys Leu Ala Arg Leu  His Tyr Ser 
    1175                 1180                 1185             


Gly Ser  Ile Asn Ala Trp Ser  Thr Lys Glu Pro Phe  Ser Trp Ile 
    1190                 1195                 1200             


Lys Val  Asp Leu Leu Ala Pro  Met Ile Ile His Gly  Ile Lys Thr 
    1205                 1210                 1215             


Gln Gly  Ala Arg Gln Lys Phe  Ser Ser Leu Tyr Ile  Ser Gln Phe 
    1220                 1225                 1230             


Ile Ile  Met Tyr Ser Leu Asp  Gly Lys Lys Trp Gln  Thr Tyr Arg 
    1235                 1240                 1245             


Gly Asn  Ser Thr Gly Thr Leu  Met Val Phe Phe Gly  Asn Val Asp 
    1250                 1255                 1260             


Ser Ser  Gly Ile Lys His Asn  Ile Phe Asn Pro Pro  Ile Ile Ala 
    1265                 1270                 1275             


Arg Tyr  Ile Arg Leu His Pro  Thr His Tyr Ser Ile  Arg Ser Thr 
    1280                 1285                 1290             


Leu Arg  Met Glu Leu Met Gly  Cys Asp Leu Asn Ser  Cys Ser Met 
    1295                 1300                 1305             


Pro Leu  Gly Met Glu Ser Lys  Ala Ile Ser Asp Ala  Gln Ile Thr 
    1310                 1315                 1320             


Ala Ser  Ser Tyr Phe Thr Asn  Met Phe Ala Thr Trp  Ser Pro Ser 
    1325                 1330                 1335             


Lys Ala  Arg Leu His Leu Gln  Gly Arg Ser Asn Ala  Trp Arg Pro 
    1340                 1345                 1350             


Gln Val  Asn Asn Pro Lys Glu  Trp Leu Gln Val Asp  Phe Gln Lys 
    1355                 1360                 1365             


Thr Met  Lys Val Thr Gly Val  Thr Thr Gln Gly Val  Lys Ser Leu 
    1370                 1375                 1380             


Leu Thr  Ser Met Tyr Val Lys  Glu Phe Leu Ile Ser  Ser Ser Gln 
    1385                 1390                 1395             


Asp Gly  His Gln Trp Thr Leu  Phe Phe Gln Asn Gly  Lys Val Lys 
    1400                 1405                 1410             


Val Phe  Gln Gly Asn Gln Asp  Ser Phe Thr Pro Val  Val Asn Ser 
    1415                 1420                 1425             


Leu Asp  Pro Pro Leu Leu Thr  Arg Tyr Leu Arg Ile  His Pro Gln 
    1430                 1435                 1440             


Ser Trp  Val His Gln Ile Ala  Leu Arg Met Glu Val  Leu Gly Cys 
    1445                 1450                 1455             


Glu Ala  Gln Asp Leu Tyr 
    1460                 


<210>  4
<211>  21
<212>  PRT
<213>  homo sapiens

<400>  4

Ser Phe Ser Gln Asn Ser Arg His Pro Ser Gln Asn Pro Pro Val Leu 
1               5                   10                  15      


Lys Arg His Gln Arg 
            20      


<210>  5
<211>  28
<212>  PRT
<213>  artificial

<220>
<223>  HIS tagged FVIII B domain linker

<400>  5

Ser Phe Ser Gln Asn Ser Arg His Pro Ser His His His His His His 
1               5                   10                  15      


Ser Gln Asn Pro Pro Val Leu Lys Arg His Gln Arg 
            20                  25              


<210>  6
<211>  28
<212>  PRT
<213>  artificial

<220>
<223>  HIS tagged FVIII B domain linker

<400>  6

Ser Phe Ser Gln Asn Ser Arg His Pro Ser His His His His His His 
1               5                   10                  15      


Ser Gln Asn Pro Pro Val Leu Lys Arg His Gln Arg 
            20                  25              


<210>  7
<211>  44
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  7
ctaatacgac tcactatagg gcaagcagtg gtatcacgca gagt                        44


<210>  8
<211>  22
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  8
ctaatacgac tcactatagg gc                                                22


<210>  9
<211>  36
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  9
gctctagact aacactcatt cctgttgaag ctcttg                                 36


<210>  10
<211>  44
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  10
ctaatacgac tcactatagg gcaagcagtg gtatcacgca gagt                        44


<210>  11
<211>  22
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  11
ctaatacgac tcactatagg gc                                                22


<210>  12
<211>  21
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  12
gtctaccaca acacacgtga c                                                 21


<210>  13
<211>  33
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  13
gactttttgt atgaattcct caccatgagg tgc                                    33


<210>  14
<211>  28
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  14
caacacttac ttgtcctggt tcctgcag                                          28


<210>  15
<211>  28
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  15
ctgcaggaac caggacaagt aagtgttg                                          28


<210>  16
<211>  444
<212>  PRT
<213>  mus musculus

<400>  16

Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Thr 
1               5                   10                  15      


Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
            20                  25                  30          


Trp Leu Gly Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile 
        35                  40                  45              


Gly Asp Ile Tyr Pro Gly Gly Gly Tyr Asn Lys Tyr Asn Glu Asn Phe 
    50                  55                  60                  


Lys Gly Lys Ala Thr Leu Thr Ala Asp Thr Ser Ser Ser Thr Ala Tyr 
65                  70                  75                  80  


Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys 
                85                  90                  95      


Ala Arg Glu Tyr Gly Asn Tyr Asp Tyr Ala Met Asp Ser Trp Gly Gln 
            100                 105                 110         


Gly Thr Ser Val Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val 
        115                 120                 125             


Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr 
    130                 135                 140                 


Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val Thr 
145                 150                 155                 160 


Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val 
                165                 170                 175     


Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro Ser 
            180                 185                 190         


Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala His Pro Ala 
        195                 200                 205             


Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly Cys 
    210                 215                 220                 


Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile Phe 
225                 230                 235                 240 


Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val 
                245                 250                 255     


Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe 
            260                 265                 270         


Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro 
        275                 280                 285             


Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro 
    290                 295                 300                 


Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val 
305                 310                 315                 320 


Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr 
                325                 330                 335     


Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys 
            340                 345                 350         


Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp 
        355                 360                 365             


Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro 
    370                 375                 380                 


Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser 
385                 390                 395                 400 


Tyr Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala 
                405                 410                 415     


Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His 
            420                 425                 430         


His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys 
        435                 440                 


<210>  17
<211>  219
<212>  PRT
<213>  mus musculus

<400>  17

Asp Ile Val Met Thr Gln Ala Ala Pro Ser Val Pro Val Thr Pro Gly 
1               5                   10                  15      


Glu Ser Val Ser Ile Ser Cys Arg Ser Ser Arg Ser Leu Leu His Ser 
            20                  25                  30          


Asn Gly Asn Thr Tyr Leu Cys Trp Phe Leu Gln Arg Pro Gly Gln Ser 
        35                  40                  45              


Pro Gln Leu Leu Ile Tyr Arg Met Ser Asn Leu Ala Ser Gly Val Pro 
    50                  55                  60                  


Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Ala Phe Thr Leu Arg Ile 
65                  70                  75                  80  


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln His 
                85                  90                  95      


Leu Glu Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


Arg Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu 
        115                 120                 125             


Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe 
    130                 135                 140                 


Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg 
145                 150                 155                 160 


Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser 
                165                 170                 175     


Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu 
            180                 185                 190         


Arg His Asn Asn Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser 
        195                 200                 205             


Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys 
    210                 215                 


<210>  18
<211>  219
<212>  PRT
<213>  mus musculus

<400>  18

Asp Ile Val Met Thr Gln Ala Ala Pro Ser Val Pro Val Thr Pro Gly 
1               5                   10                  15      


Glu Ser Val Ser Ile Ser Cys Arg Ser Ser Arg Ser Leu Leu His Ser 
            20                  25                  30          


Asn Gly Asn Thr Tyr Leu Ser Trp Phe Leu Gln Arg Pro Gly Gln Ser 
        35                  40                  45              


Pro Gln Leu Leu Ile Tyr Arg Met Ser Asn Leu Ala Ser Gly Val Pro 
    50                  55                  60                  


Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Ala Phe Thr Leu Arg Ile 
65                  70                  75                  80  


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln His 
                85                  90                  95      


Leu Glu Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


Arg Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu 
        115                 120                 125             


Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe 
    130                 135                 140                 


Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg 
145                 150                 155                 160 


Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser 
                165                 170                 175     


Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu 
            180                 185                 190         


Arg His Asn Asn Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser 
        195                 200                 205             


Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys 
    210                 215                 


<210>  19
<211>  28
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  19
caacacttac ttgtcctggt tcctgcag                                          28


<210>  20
<211>  28
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  20
ctgcaggaac caggacaagt aagtgttg                                          28


<210>  21
<211>  256
<212>  PRT
<213>  mus musculus

<400>  21

Asp Ile Val Met Thr Gln Ala Ala Pro Ser Val Pro Val Thr Pro Gly 
1               5                   10                  15      


Glu Ser Val Ser Ile Ser Cys Arg Ser Ser Arg Ser Leu Leu His Ser 
            20                  25                  30          


Asn Gly Asn Thr Tyr Leu Cys Trp Phe Leu Gln Arg Pro Gly Gln Ser 
        35                  40                  45              


Pro Gln Leu Leu Ile Tyr Arg Met Ser Asn Leu Ala Ser Gly Val Pro 
    50                  55                  60                  


Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Ala Phe Thr Leu Arg Ile 
65                  70                  75                  80  


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln His 
                85                  90                  95      


Leu Glu Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
        115                 120                 125             


Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Thr 
    130                 135                 140                 


Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
145                 150                 155                 160 


Trp Leu Gly Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile 
                165                 170                 175     


Gly Asp Ile Tyr Pro Gly Gly Gly Tyr Asn Lys Tyr Asn Glu Asn Phe 
            180                 185                 190         


Lys Gly Lys Ala Thr Leu Thr Ala Asp Thr Ser Ser Ser Thr Ala Tyr 
        195                 200                 205             


Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys 
    210                 215                 220                 


Ala Arg Glu Tyr Gly Asn Tyr Asp Tyr Ala Met Asp Ser Trp Gly Gln 
225                 230                 235                 240 


Gly Thr Ser Val Thr Val Ser Ser Asp Tyr Lys Asp Asp Asp Asp Lys 
                245                 250                 255     


<210>  22
<211>  256
<212>  PRT
<213>  mus musculus

<400>  22

Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Thr 
1               5                   10                  15      


Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
            20                  25                  30          


Trp Leu Gly Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile 
        35                  40                  45              


Gly Asp Ile Tyr Pro Gly Gly Gly Tyr Asn Lys Tyr Asn Glu Asn Phe 
    50                  55                  60                  


Lys Gly Lys Ala Thr Leu Thr Ala Asp Thr Ser Ser Ser Thr Ala Tyr 
65                  70                  75                  80  


Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys 
                85                  90                  95      


Ala Arg Glu Tyr Gly Asn Tyr Asp Tyr Ala Met Asp Ser Trp Gly Gln 
            100                 105                 110         


Gly Thr Ser Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly 
        115                 120                 125             


Gly Ser Gly Gly Gly Gly Ser Asp Ile Val Met Thr Gln Ala Ala Pro 
    130                 135                 140                 


Ser Val Pro Val Thr Pro Gly Glu Ser Val Ser Ile Ser Cys Arg Ser 
145                 150                 155                 160 


Ser Arg Ser Leu Leu His Ser Asn Gly Asn Thr Tyr Leu Cys Trp Phe 
                165                 170                 175     


Leu Gln Arg Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr Arg Met Ser 
            180                 185                 190         


Asn Leu Ala Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly 
        195                 200                 205             


Thr Ala Phe Thr Leu Arg Ile Ser Arg Val Glu Ala Glu Asp Val Gly 
    210                 215                 220                 


Val Tyr Tyr Cys Met Gln His Leu Glu Tyr Pro Phe Thr Phe Gly Ser 
225                 230                 235                 240 


Gly Thr Lys Leu Glu Ile Lys Arg Asp Tyr Lys Asp Asp Asp Asp Lys 
                245                 250                 255     


<210>  23
<211>  256
<212>  PRT
<213>  mus musculus

<400>  23

Asp Ile Val Met Thr Gln Ala Ala Pro Ser Val Pro Val Thr Pro Gly 
1               5                   10                  15      


Glu Ser Val Ser Ile Ser Cys Arg Ser Ser Arg Ser Leu Leu His Ser 
            20                  25                  30          


Asn Gly Asn Thr Tyr Leu Ser Trp Phe Leu Gln Arg Pro Gly Gln Ser 
        35                  40                  45              


Pro Gln Leu Leu Ile Tyr Arg Met Ser Asn Leu Ala Ser Gly Val Pro 
    50                  55                  60                  


Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Ala Phe Thr Leu Arg Ile 
65                  70                  75                  80  


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln His 
                85                  90                  95      


Leu Glu Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
        115                 120                 125             


Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Thr 
    130                 135                 140                 


Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
145                 150                 155                 160 


Trp Leu Gly Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile 
                165                 170                 175     


Gly Asp Ile Tyr Pro Gly Gly Gly Tyr Asn Lys Tyr Asn Glu Asn Phe 
            180                 185                 190         


Lys Gly Lys Ala Thr Leu Thr Ala Asp Thr Ser Ser Ser Thr Ala Tyr 
        195                 200                 205             


Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys 
    210                 215                 220                 


Ala Arg Glu Tyr Gly Asn Tyr Asp Tyr Ala Met Asp Ser Trp Gly Gln 
225                 230                 235                 240 


Gly Thr Ser Val Thr Val Ser Ser Asp Tyr Lys Asp Asp Asp Asp Lys 
                245                 250                 255     


<210>  24
<211>  31
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  24
cgacgacgac aagtgctgaa agcttcgtac g                                      31


<210>  25
<211>  31
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  25
cgtacgaagc tttcagcact tgtcgtcgtc g                                      31


<210>  26
<211>  27
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  26
gtgaccgtga gctgcgacta caaggac                                           27


<210>  27
<211>  27
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  27
gtccttgtag tcgcagctca cggtcac                                           27


<210>  28
<211>  28
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  28
caacacttac ttgtcctggt tcctgcag                                          28


<210>  29
<211>  28
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  29
ctgcaggaac caggacaagt aagtgttg                                          28


<210>  30
<211>  257
<212>  PRT
<213>  mus musculus

<400>  30

Asp Ile Val Met Thr Gln Ala Ala Pro Ser Val Pro Val Thr Pro Gly 
1               5                   10                  15      


Glu Ser Val Ser Ile Ser Cys Arg Ser Ser Arg Ser Leu Leu His Ser 
            20                  25                  30          


Asn Gly Asn Thr Tyr Leu Cys Trp Phe Leu Gln Arg Pro Gly Gln Ser 
        35                  40                  45              


Pro Gln Leu Leu Ile Tyr Arg Met Ser Asn Leu Ala Ser Gly Val Pro 
    50                  55                  60                  


Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Ala Phe Thr Leu Arg Ile 
65                  70                  75                  80  


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln His 
                85                  90                  95      


Leu Glu Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
        115                 120                 125             


Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Thr 
    130                 135                 140                 


Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
145                 150                 155                 160 


Trp Leu Gly Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile 
                165                 170                 175     


Gly Asp Ile Tyr Pro Gly Gly Gly Tyr Asn Lys Tyr Asn Glu Asn Phe 
            180                 185                 190         


Lys Gly Lys Ala Thr Leu Thr Ala Asp Thr Ser Ser Ser Thr Ala Tyr 
        195                 200                 205             


Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys 
    210                 215                 220                 


Ala Arg Glu Tyr Gly Asn Tyr Asp Tyr Ala Met Asp Ser Trp Gly Gln 
225                 230                 235                 240 


Gly Thr Ser Val Thr Val Ser Ser Asp Tyr Lys Asp Asp Asp Asp Lys 
                245                 250                 255     


Cys 
    


<210>  31
<211>  256
<212>  PRT
<213>  mus musculus

<400>  31

Asp Ile Val Met Thr Gln Ala Ala Pro Ser Val Pro Val Thr Pro Gly 
1               5                   10                  15      


Glu Ser Val Ser Ile Ser Cys Arg Ser Ser Arg Ser Leu Leu His Ser 
            20                  25                  30          


Asn Gly Asn Thr Tyr Leu Ser Trp Phe Leu Gln Arg Pro Gly Gln Ser 
        35                  40                  45              


Pro Gln Leu Leu Ile Tyr Arg Met Ser Asn Leu Ala Ser Gly Val Pro 
    50                  55                  60                  


Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Ala Phe Thr Leu Arg Ile 
65                  70                  75                  80  


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln His 
                85                  90                  95      


Leu Glu Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
        115                 120                 125             


Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Thr 
    130                 135                 140                 


Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
145                 150                 155                 160 


Trp Leu Gly Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile 
                165                 170                 175     


Gly Asp Ile Tyr Pro Gly Gly Gly Tyr Asn Lys Tyr Asn Glu Asn Phe 
            180                 185                 190         


Lys Gly Lys Ala Thr Leu Thr Ala Asp Thr Ser Ser Ser Thr Ala Tyr 
        195                 200                 205             


Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys 
    210                 215                 220                 


Ala Arg Glu Tyr Gly Asn Tyr Asp Tyr Ala Met Asp Ser Trp Gly Gln 
225                 230                 235                 240 


Gly Thr Ser Val Thr Val Ser Cys Asp Tyr Lys Asp Asp Asp Asp Lys 
                245                 250                 255     


<210>  32
<211>  30
<212>  DNA
<213>  artificial

<220>
<223>  primer

<400>  32
cagggattgt ggttgaaagc cttgcatatg                                        30


<210>  33
<211>  30
<212>  DNA
<213>  artificial

<220>
<223>  primer

<400>  33
catatgcaag gctttcaacc acaatccctg                                        30


<210>  34
<211>  223
<212>  PRT
<213>  mus musculus

<400>  34

Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Thr 
1               5                   10                  15      


Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
            20                  25                  30          


Trp Leu Gly Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile 
        35                  40                  45              


Gly Asp Ile Tyr Pro Gly Gly Gly Tyr Asn Lys Tyr Asn Glu Asn Phe 
    50                  55                  60                  


Lys Gly Lys Ala Thr Leu Thr Ala Asp Thr Ser Ser Ser Thr Ala Tyr 
65                  70                  75                  80  


Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys 
                85                  90                  95      


Ala Arg Glu Tyr Gly Asn Tyr Asp Tyr Ala Met Asp Ser Trp Gly Gln 
            100                 105                 110         


Gly Thr Ser Val Thr Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val 
        115                 120                 125             


Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr 
    130                 135                 140                 


Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val Thr 
145                 150                 155                 160 


Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val 
                165                 170                 175     


Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro Ser 
            180                 185                 190         


Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala His Pro Ala 
        195                 200                 205             


Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly 
    210                 215                 220             


<210>  35
<211>  51
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  35
aacccaccgg tcttgaaacg ccatcaacgg caggtccagc tgcagcagag c                51


<210>  36
<211>  39
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  36
gaaagctccg cgggctctgc cgcttgattt ccagcttgg                              39


<210>  37
<211>  51
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  37
aacccaccgg tcttgaaacg ccatcaacgg gacatcgtga tgacccaggc t                51


<210>  38
<211>  39
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  38
gaaagctccg cgggctctgg ctgctcacgg tcacggagg                              39


<210>  39
<211>  1656
<212>  PRT
<213>  artificial

<220>
<223>  FVIII and AP3 fusion protein

<400>  39

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 Gln Asn 
            740                 745                 750         


Pro Pro Val Leu Lys Arg His Gln Arg Asp Ile Val Met Thr Gln Ala 
        755                 760                 765             


Ala Pro Ser Val Pro Val Thr Pro Gly Glu Ser Val Ser Ile Ser Cys 
    770                 775                 780                 


Arg Ser Ser Arg Ser Leu Leu His Ser Asn Gly Asn Thr Tyr Leu Cys 
785                 790                 795                 800 


Trp Phe Leu Gln Arg Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr Arg 
                805                 810                 815     


Met Ser Asn Leu Ala Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly 
            820                 825                 830         


Ser Gly Thr Ala Phe Thr Leu Arg Ile Ser Arg Val Glu Ala Glu Asp 
        835                 840                 845             


Val Gly Val Tyr Tyr Cys Met Gln His Leu Glu Tyr Pro Phe Thr Phe 
    850                 855                 860                 


Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg Gly Gly Gly Gly Ser Gly 
865                 870                 875                 880 


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Gln Ser 
                885                 890                 895     


Gly Ala Glu Leu Val Arg Pro Gly Thr Ser Val Lys Ile Ser Cys Lys 
            900                 905                 910         


Ala Ser Gly Tyr Thr Phe Thr Asn Tyr Trp Leu Gly Trp Val Lys Gln 
        915                 920                 925             


Arg Pro Gly His Gly Leu Glu Trp Ile Gly Asp Ile Tyr Pro Gly Gly 
    930                 935                 940                 


Gly Tyr Asn Lys Tyr Asn Glu Asn Phe Lys Gly Lys Ala Thr Leu Thr 
945                 950                 955                 960 


Ala Asp Thr Ser Ser Ser Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr 
                965                 970                 975     


Ser Glu Asp Ser Ala Val Tyr Phe Cys Ala Arg Glu Tyr Gly Asn Tyr 
            980                 985                 990         


Asp Tyr Ala Met Asp Ser Trp Gly  Gln Gly Thr Ser Val  Thr Val Ser 
        995                 1000                 1005             


Ser Gln  Ser Pro Arg Ser Phe  Gln Lys Lys Thr Arg  His Tyr Phe 
    1010                 1015                 1020             


Ile Ala  Ala Val Glu Arg Leu  Trp Asp Tyr Gly Met  Ser Ser Ser 
    1025                 1030                 1035             


Pro His  Val Leu Arg Asn Arg  Ala Gln Ser Gly Ser  Val Pro Gln 
    1040                 1045                 1050             


Phe Lys  Lys Val Val Phe Gln  Glu Phe Thr Asp Gly  Ser Phe Thr 
    1055                 1060                 1065             


Gln Pro  Leu Tyr Arg Gly Glu  Leu Asn Glu His Leu  Gly Leu Leu 
    1070                 1075                 1080             


Gly Pro  Tyr Ile Arg Ala Glu  Val Glu Asp Asn Ile  Met Val Thr 
    1085                 1090                 1095             


Phe Arg  Asn Gln Ala Ser Arg  Pro Tyr Ser Phe Tyr  Ser Ser Leu 
    1100                 1105                 1110             


Ile Ser  Tyr Glu Glu Asp Gln  Arg Gln Gly Ala Glu  Pro Arg Lys 
    1115                 1120                 1125             


Asn Phe  Val Lys Pro Asn Glu  Thr Lys Thr Tyr Phe  Trp Lys Val 
    1130                 1135                 1140             


Gln His  His Met Ala Pro Thr  Lys Asp Glu Phe Asp  Cys Lys Ala 
    1145                 1150                 1155             


Trp Ala  Tyr Phe Ser Asp Val  Asp Leu Glu Lys Asp  Val His Ser 
    1160                 1165                 1170             


Gly Leu  Ile Gly Pro Leu Leu  Val Cys His Thr Asn  Thr Leu Asn 
    1175                 1180                 1185             


Pro Ala  His Gly Arg Gln Val  Thr Val Gln Glu Phe  Ala Leu Phe 
    1190                 1195                 1200             


Phe Thr  Ile Phe Asp Glu Thr  Lys Ser Trp Tyr Phe  Thr Glu Asn 
    1205                 1210                 1215             


Met Glu  Arg Asn Cys Arg Ala  Pro Cys Asn Ile Gln  Met Glu Asp 
    1220                 1225                 1230             


Pro Thr  Phe Lys Glu Asn Tyr  Arg Phe His Ala Ile  Asn Gly Tyr 
    1235                 1240                 1245             


Ile Met  Asp Thr Leu Pro Gly  Leu Val Met Ala Gln  Asp Gln Arg 
    1250                 1255                 1260             


Ile Arg  Trp Tyr Leu Leu Ser  Met Gly Ser Asn Glu  Asn Ile His 
    1265                 1270                 1275             


Ser Ile  His Phe Ser Gly His  Val Phe Thr Val Arg  Lys Lys Glu 
    1280                 1285                 1290             


Glu Tyr  Lys Met Ala Leu Tyr  Asn Leu Tyr Pro Gly  Val Phe Glu 
    1295                 1300                 1305             


Thr Val  Glu Met Leu Pro Ser  Lys Ala Gly Ile Trp  Arg Val Glu 
    1310                 1315                 1320             


Cys Leu  Ile Gly Glu His Leu  His Ala Gly Met Ser  Thr Leu Phe 
    1325                 1330                 1335             


Leu Val  Tyr Ser Asn Lys Cys  Gln Thr Pro Leu Gly  Met Ala Ser 
    1340                 1345                 1350             


Gly His  Ile Arg Asp Phe Gln  Ile Thr Ala Ser Gly  Gln Tyr Gly 
    1355                 1360                 1365             


Gln Trp  Ala Pro Lys Leu Ala  Arg Leu His Tyr Ser  Gly Ser Ile 
    1370                 1375                 1380             


Asn Ala  Trp Ser Thr Lys Glu  Pro Phe Ser Trp Ile  Lys Val Asp 
    1385                 1390                 1395             


Leu Leu  Ala Pro Met Ile Ile  His Gly Ile Lys Thr  Gln Gly Ala 
    1400                 1405                 1410             


Arg Gln  Lys Phe Ser Ser Leu  Tyr Ile Ser Gln Phe  Ile Ile Met 
    1415                 1420                 1425             


Tyr Ser  Leu Asp Gly Lys Lys  Trp Gln Thr Tyr Arg  Gly Asn Ser 
    1430                 1435                 1440             


Thr Gly  Thr Leu Met Val Phe  Phe Gly Asn Val Asp  Ser Ser Gly 
    1445                 1450                 1455             


Ile Lys  His Asn Ile Phe Asn  Pro Pro Ile Ile Ala  Arg Tyr Ile 
    1460                 1465                 1470             


Arg Leu  His Pro Thr His Tyr  Ser Ile Arg Ser Thr  Leu Arg Met 
    1475                 1480                 1485             


Glu Leu  Met Gly Cys Asp Leu  Asn Ser Cys Ser Met  Pro Leu Gly 
    1490                 1495                 1500             


Met Glu  Ser Lys Ala Ile Ser  Asp Ala Gln Ile Thr  Ala Ser Ser 
    1505                 1510                 1515             


Tyr Phe  Thr Asn Met Phe Ala  Thr Trp Ser Pro Ser  Lys Ala Arg 
    1520                 1525                 1530             


Leu His  Leu Gln Gly Arg Ser  Asn Ala Trp Arg Pro  Gln Val Asn 
    1535                 1540                 1545             


Asn Pro  Lys Glu Trp Leu Gln  Val Asp Phe Gln Lys  Thr Met Lys 
    1550                 1555                 1560             


Val Thr  Gly Val Thr Thr Gln  Gly Val Lys Ser Leu  Leu Thr Ser 
    1565                 1570                 1575             


Met Tyr  Val Lys Glu Phe Leu  Ile Ser Ser Ser Gln  Asp Gly His 
    1580                 1585                 1590             


Gln Trp  Thr Leu Phe Phe Gln  Asn Gly Lys Val Lys  Val Phe Gln 
    1595                 1600                 1605             


Gly Asn  Gln Asp Ser Phe Thr  Pro Val Val Asn Ser  Leu Asp Pro 
    1610                 1615                 1620             


Pro Leu  Leu Thr Arg Tyr Leu  Arg Ile His Pro Gln  Ser Trp Val 
    1625                 1630                 1635             


His Gln  Ile Ala Leu Arg Met  Glu Val Leu Gly Cys  Glu Ala Gln 
    1640                 1645                 1650             


Asp Leu  Tyr 
    1655     


<210>  40
<211>  1656
<212>  PRT
<213>  artificial

<220>
<223>  FVIII and AP3 fusion protein

<400>  40

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 Gln Asn 
            740                 745                 750         


Pro Pro Val Leu Lys Arg His Gln Arg Gln Val Gln Leu Gln Gln Ser 
        755                 760                 765             


Gly Ala Glu Leu Val Arg Pro Gly Thr Ser Val Lys Ile Ser Cys Lys 
    770                 775                 780                 


Ala Ser Gly Tyr Thr Phe Thr Asn Tyr Trp Leu Gly Trp Val Lys Gln 
785                 790                 795                 800 


Arg Pro Gly His Gly Leu Glu Trp Ile Gly Asp Ile Tyr Pro Gly Gly 
                805                 810                 815     


Gly Tyr Asn Lys Tyr Asn Glu Asn Phe Lys Gly Lys Ala Thr Leu Thr 
            820                 825                 830         


Ala Asp Thr Ser Ser Ser Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr 
        835                 840                 845             


Ser Glu Asp Ser Ala Val Tyr Phe Cys Ala Arg Glu Tyr Gly Asn Tyr 
    850                 855                 860                 


Asp Tyr Ala Met Asp Ser Trp Gly Gln Gly Thr Ser Val Thr Val Ser 
865                 870                 875                 880 


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
                885                 890                 895     


Asp Ile Val Met Thr Gln Ala Ala Pro Ser Val Pro Val Thr Pro Gly 
            900                 905                 910         


Glu Ser Val Ser Ile Ser Cys Arg Ser Ser Arg Ser Leu Leu His Ser 
        915                 920                 925             


Asn Gly Asn Thr Tyr Leu Cys Trp Phe Leu Gln Arg Pro Gly Gln Ser 
    930                 935                 940                 


Pro Gln Leu Leu Ile Tyr Arg Met Ser Asn Leu Ala Ser Gly Val Pro 
945                 950                 955                 960 


Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Ala Phe Thr Leu Arg Ile 
                965                 970                 975     


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln His 
            980                 985                 990         


Leu Glu Tyr Pro Phe Thr Phe Gly  Ser Gly Thr Lys Leu  Glu Ile Lys 
        995                 1000                 1005             


Arg Gln  Ser Pro Arg Ser Phe  Gln Lys Lys Thr Arg  His Tyr Phe 
    1010                 1015                 1020             


Ile Ala  Ala Val Glu Arg Leu  Trp Asp Tyr Gly Met  Ser Ser Ser 
    1025                 1030                 1035             


Pro His  Val Leu Arg Asn Arg  Ala Gln Ser Gly Ser  Val Pro Gln 
    1040                 1045                 1050             


Phe Lys  Lys Val Val Phe Gln  Glu Phe Thr Asp Gly  Ser Phe Thr 
    1055                 1060                 1065             


Gln Pro  Leu Tyr Arg Gly Glu  Leu Asn Glu His Leu  Gly Leu Leu 
    1070                 1075                 1080             


Gly Pro  Tyr Ile Arg Ala Glu  Val Glu Asp Asn Ile  Met Val Thr 
    1085                 1090                 1095             


Phe Arg  Asn Gln Ala Ser Arg  Pro Tyr Ser Phe Tyr  Ser Ser Leu 
    1100                 1105                 1110             


Ile Ser  Tyr Glu Glu Asp Gln  Arg Gln Gly Ala Glu  Pro Arg Lys 
    1115                 1120                 1125             


Asn Phe  Val Lys Pro Asn Glu  Thr Lys Thr Tyr Phe  Trp Lys Val 
    1130                 1135                 1140             


Gln His  His Met Ala Pro Thr  Lys Asp Glu Phe Asp  Cys Lys Ala 
    1145                 1150                 1155             


Trp Ala  Tyr Phe Ser Asp Val  Asp Leu Glu Lys Asp  Val His Ser 
    1160                 1165                 1170             


Gly Leu  Ile Gly Pro Leu Leu  Val Cys His Thr Asn  Thr Leu Asn 
    1175                 1180                 1185             


Pro Ala  His Gly Arg Gln Val  Thr Val Gln Glu Phe  Ala Leu Phe 
    1190                 1195                 1200             


Phe Thr  Ile Phe Asp Glu Thr  Lys Ser Trp Tyr Phe  Thr Glu Asn 
    1205                 1210                 1215             


Met Glu  Arg Asn Cys Arg Ala  Pro Cys Asn Ile Gln  Met Glu Asp 
    1220                 1225                 1230             


Pro Thr  Phe Lys Glu Asn Tyr  Arg Phe His Ala Ile  Asn Gly Tyr 
    1235                 1240                 1245             


Ile Met  Asp Thr Leu Pro Gly  Leu Val Met Ala Gln  Asp Gln Arg 
    1250                 1255                 1260             


Ile Arg  Trp Tyr Leu Leu Ser  Met Gly Ser Asn Glu  Asn Ile His 
    1265                 1270                 1275             


Ser Ile  His Phe Ser Gly His  Val Phe Thr Val Arg  Lys Lys Glu 
    1280                 1285                 1290             


Glu Tyr  Lys Met Ala Leu Tyr  Asn Leu Tyr Pro Gly  Val Phe Glu 
    1295                 1300                 1305             


Thr Val  Glu Met Leu Pro Ser  Lys Ala Gly Ile Trp  Arg Val Glu 
    1310                 1315                 1320             


Cys Leu  Ile Gly Glu His Leu  His Ala Gly Met Ser  Thr Leu Phe 
    1325                 1330                 1335             


Leu Val  Tyr Ser Asn Lys Cys  Gln Thr Pro Leu Gly  Met Ala Ser 
    1340                 1345                 1350             


Gly His  Ile Arg Asp Phe Gln  Ile Thr Ala Ser Gly  Gln Tyr Gly 
    1355                 1360                 1365             


Gln Trp  Ala Pro Lys Leu Ala  Arg Leu His Tyr Ser  Gly Ser Ile 
    1370                 1375                 1380             


Asn Ala  Trp Ser Thr Lys Glu  Pro Phe Ser Trp Ile  Lys Val Asp 
    1385                 1390                 1395             


Leu Leu  Ala Pro Met Ile Ile  His Gly Ile Lys Thr  Gln Gly Ala 
    1400                 1405                 1410             


Arg Gln  Lys Phe Ser Ser Leu  Tyr Ile Ser Gln Phe  Ile Ile Met 
    1415                 1420                 1425             


Tyr Ser  Leu Asp Gly Lys Lys  Trp Gln Thr Tyr Arg  Gly Asn Ser 
    1430                 1435                 1440             


Thr Gly  Thr Leu Met Val Phe  Phe Gly Asn Val Asp  Ser Ser Gly 
    1445                 1450                 1455             


Ile Lys  His Asn Ile Phe Asn  Pro Pro Ile Ile Ala  Arg Tyr Ile 
    1460                 1465                 1470             


Arg Leu  His Pro Thr His Tyr  Ser Ile Arg Ser Thr  Leu Arg Met 
    1475                 1480                 1485             


Glu Leu  Met Gly Cys Asp Leu  Asn Ser Cys Ser Met  Pro Leu Gly 
    1490                 1495                 1500             


Met Glu  Ser Lys Ala Ile Ser  Asp Ala Gln Ile Thr  Ala Ser Ser 
    1505                 1510                 1515             


Tyr Phe  Thr Asn Met Phe Ala  Thr Trp Ser Pro Ser  Lys Ala Arg 
    1520                 1525                 1530             


Leu His  Leu Gln Gly Arg Ser  Asn Ala Trp Arg Pro  Gln Val Asn 
    1535                 1540                 1545             


Asn Pro  Lys Glu Trp Leu Gln  Val Asp Phe Gln Lys  Thr Met Lys 
    1550                 1555                 1560             


Val Thr  Gly Val Thr Thr Gln  Gly Val Lys Ser Leu  Leu Thr Ser 
    1565                 1570                 1575             


Met Tyr  Val Lys Glu Phe Leu  Ile Ser Ser Ser Gln  Asp Gly His 
    1580                 1585                 1590             


Gln Trp  Thr Leu Phe Phe Gln  Asn Gly Lys Val Lys  Val Phe Gln 
    1595                 1600                 1605             


Gly Asn  Gln Asp Ser Phe Thr  Pro Val Val Asn Ser  Leu Asp Pro 
    1610                 1615                 1620             


Pro Leu  Leu Thr Arg Tyr Leu  Arg Ile His Pro Gln  Ser Trp Val 
    1625                 1630                 1635             


His Gln  Ile Ala Leu Arg Met  Glu Val Leu Gly Cys  Glu Ala Gln 
    1640                 1645                 1650             


Asp Leu  Tyr 
    1655     


<210>  41
<211>  1694
<212>  PRT
<213>  artificial

<220>
<223>  FVIII and AP3 fusion protein

<400>  41

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 Gln Val 
            740                 745                 750         


Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Thr Ser Val 
        755                 760                 765             


Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr Trp Leu 
    770                 775                 780                 


Gly Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile Gly Asp 
785                 790                 795                 800 


Ile Tyr Pro Gly Gly Gly Tyr Asn Lys Tyr Asn Glu Asn Phe Lys Gly 
                805                 810                 815     


Lys Ala Thr Leu Thr Ala Asp Thr Ser Ser Ser Thr Ala Tyr Met Gln 
            820                 825                 830         


Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys Ala Arg 
        835                 840                 845             


Glu Tyr Gly Asn Tyr Asp Tyr Ala Met Asp Ser Trp Gly Gln Gly Thr 
    850                 855                 860                 


Ser Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
865                 870                 875                 880 


Gly Gly Gly Gly Ser Asp Ile Val Met Thr Gln Ala Ala Pro Ser Val 
                885                 890                 895     


Pro Val Thr Pro Gly Glu Ser Val Ser Ile Ser Cys Arg Ser Ser Arg 
            900                 905                 910         


Ser Leu Leu His Ser Asn Gly Asn Thr Tyr Leu Cys Trp Phe Leu Gln 
        915                 920                 925             


Arg Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr Arg Met Ser Asn Leu 
    930                 935                 940                 


Ala Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Ala 
945                 950                 955                 960 


Phe Thr Leu Arg Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr 
                965                 970                 975     


Tyr Cys Met Gln His Leu Glu Tyr Pro Phe Thr Phe Gly Ser Gly Thr 
            980                 985                 990         


Lys Leu Glu Ile Lys Arg Ser Gln  Asn Pro Pro Val Leu  Lys Arg His 
        995                 1000                 1005             


Gln Arg  Glu Ile Thr Arg Thr  Thr Leu Gln Ser Asp  Gln Glu Glu 
    1010                 1015                 1020             


Ile Asp  Tyr Asp Asp Thr Ile  Ser Val Glu Met Lys  Lys Glu Asp 
    1025                 1030                 1035             


Phe Asp  Ile Tyr Asp Glu Asp  Glu Asn Gln Ser Pro  Arg Ser Phe 
    1040                 1045                 1050             


Gln Lys  Lys Thr Arg His Tyr  Phe Ile Ala Ala Val  Glu Arg Leu 
    1055                 1060                 1065             


Trp Asp  Tyr Gly Met Ser Ser  Ser Pro His Val Leu  Arg Asn Arg 
    1070                 1075                 1080             


Ala Gln  Ser Gly Ser Val Pro  Gln Phe Lys Lys Val  Val Phe Gln 
    1085                 1090                 1095             


Glu Phe  Thr Asp Gly Ser Phe  Thr Gln Pro Leu Tyr  Arg Gly Glu 
    1100                 1105                 1110             


Leu Asn  Glu His Leu Gly Leu  Leu Gly Pro Tyr Ile  Arg Ala Glu 
    1115                 1120                 1125             


Val Glu  Asp Asn Ile Met Val  Thr Phe Arg Asn Gln  Ala Ser Arg 
    1130                 1135                 1140             


Pro Tyr  Ser Phe Tyr Ser Ser  Leu Ile Ser Tyr Glu  Glu Asp Gln 
    1145                 1150                 1155             


Arg Gln  Gly Ala Glu Pro Arg  Lys Asn Phe Val Lys  Pro Asn Glu 
    1160                 1165                 1170             


Thr Lys  Thr Tyr Phe Trp Lys  Val Gln His His Met  Ala Pro Thr 
    1175                 1180                 1185             


Lys Asp  Glu Phe Asp Cys Lys  Ala Trp Ala Tyr Phe  Ser Asp Val 
    1190                 1195                 1200             


Asp Leu  Glu Lys Asp Val His  Ser Gly Leu Ile Gly  Pro Leu Leu 
    1205                 1210                 1215             


Val Cys  His Thr Asn Thr Leu  Asn Pro Ala His Gly  Arg Gln Val 
    1220                 1225                 1230             


Thr Val  Gln Glu Phe Ala Leu  Phe Phe Thr Ile Phe  Asp Glu Thr 
    1235                 1240                 1245             


Lys Ser  Trp Tyr Phe Thr Glu  Asn Met Glu Arg Asn  Cys Arg Ala 
    1250                 1255                 1260             


Pro Cys  Asn Ile Gln Met Glu  Asp Pro Thr Phe Lys  Glu Asn Tyr 
    1265                 1270                 1275             


Arg Phe  His Ala Ile Asn Gly  Tyr Ile Met Asp Thr  Leu Pro Gly 
    1280                 1285                 1290             


Leu Val  Met Ala Gln Asp Gln  Arg Ile Arg Trp Tyr  Leu Leu Ser 
    1295                 1300                 1305             


Met Gly  Ser Asn Glu Asn Ile  His Ser Ile His Phe  Ser Gly His 
    1310                 1315                 1320             


Val Phe  Thr Val Arg Lys Lys  Glu Glu Tyr Lys Met  Ala Leu Tyr 
    1325                 1330                 1335             


Asn Leu  Tyr Pro Gly Val Phe  Glu Thr Val Glu Met  Leu Pro Ser 
    1340                 1345                 1350             


Lys Ala  Gly Ile Trp Arg Val  Glu Cys Leu Ile Gly  Glu His Leu 
    1355                 1360                 1365             


His Ala  Gly Met Ser Thr Leu  Phe Leu Val Tyr Ser  Asn Lys Cys 
    1370                 1375                 1380             


Gln Thr  Pro Leu Gly Met Ala  Ser Gly His Ile Arg  Asp Phe Gln 
    1385                 1390                 1395             


Ile Thr  Ala Ser Gly Gln Tyr  Gly Gln Trp Ala Pro  Lys Leu Ala 
    1400                 1405                 1410             


Arg Leu  His Tyr Ser Gly Ser  Ile Asn Ala Trp Ser  Thr Lys Glu 
    1415                 1420                 1425             


Pro Phe  Ser Trp Ile Lys Val  Asp Leu Leu Ala Pro  Met Ile Ile 
    1430                 1435                 1440             


His Gly  Ile Lys Thr Gln Gly  Ala Arg Gln Lys Phe  Ser Ser Leu 
    1445                 1450                 1455             


Tyr Ile  Ser Gln Phe Ile Ile  Met Tyr Ser Leu Asp  Gly Lys Lys 
    1460                 1465                 1470             


Trp Gln  Thr Tyr Arg Gly Asn  Ser Thr Gly Thr Leu  Met Val Phe 
    1475                 1480                 1485             


Phe Gly  Asn Val Asp Ser Ser  Gly Ile Lys His Asn  Ile Phe Asn 
    1490                 1495                 1500             


Pro Pro  Ile Ile Ala Arg Tyr  Ile Arg Leu His Pro  Thr His Tyr 
    1505                 1510                 1515             


Ser Ile  Arg Ser Thr Leu Arg  Met Glu Leu Met Gly  Cys Asp Leu 
    1520                 1525                 1530             


Asn Ser  Cys Ser Met Pro Leu  Gly Met Glu Ser Lys  Ala Ile Ser 
    1535                 1540                 1545             


Asp Ala  Gln Ile Thr Ala Ser  Ser Tyr Phe Thr Asn  Met Phe Ala 
    1550                 1555                 1560             


Thr Trp  Ser Pro Ser Lys Ala  Arg Leu His Leu Gln  Gly Arg Ser 
    1565                 1570                 1575             


Asn Ala  Trp Arg Pro Gln Val  Asn Asn Pro Lys Glu  Trp Leu Gln 
    1580                 1585                 1590             


Val Asp  Phe Gln Lys Thr Met  Lys Val Thr Gly Val  Thr Thr Gln 
    1595                 1600                 1605             


Gly Val  Lys Ser Leu Leu Thr  Ser Met Tyr Val Lys  Glu Phe Leu 
    1610                 1615                 1620             


Ile Ser  Ser Ser Gln Asp Gly  His Gln Trp Thr Leu  Phe Phe Gln 
    1625                 1630                 1635             


Asn Gly  Lys Val Lys Val Phe  Gln Gly Asn Gln Asp  Ser Phe Thr 
    1640                 1645                 1650             


Pro Val  Val Asn Ser Leu Asp  Pro Pro Leu Leu Thr  Arg Tyr Leu 
    1655                 1660                 1665             


Arg Ile  His Pro Gln Ser Trp  Val His Gln Ile Ala  Leu Arg Met 
    1670                 1675                 1680             


Glu Val  Leu Gly Cys Glu Ala  Gln Asp Leu Tyr 
    1685                 1690                 


<210>  42
<211>  1694
<212>  PRT
<213>  artificial

<220>
<223>  FVIII and AP3 fusion protein

<400>  42

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 Asp Ile 
            740                 745                 750         


Val Met Thr Gln Ala Ala Pro Ser Val Pro Val Thr Pro Gly Glu Ser 
        755                 760                 765             


Val Ser Ile Ser Cys Arg Ser Ser Arg Ser Leu Leu His Ser Asn Gly 
    770                 775                 780                 


Asn Thr Tyr Leu Cys Trp Phe Leu Gln Arg Pro Gly Gln Ser Pro Gln 
785                 790                 795                 800 


Leu Leu Ile Tyr Arg Met Ser Asn Leu Ala Ser Gly Val Pro Asp Arg 
                805                 810                 815     


Phe Ser Gly Ser Gly Ser Gly Thr Ala Phe Thr Leu Arg Ile Ser Arg 
            820                 825                 830         


Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln His Leu Glu 
        835                 840                 845             


Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg Gly 
    850                 855                 860                 


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val 
865                 870                 875                 880 


Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Thr Ser Val 
                885                 890                 895     


Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr Trp Leu 
            900                 905                 910         


Gly Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile Gly Asp 
        915                 920                 925             


Ile Tyr Pro Gly Gly Gly Tyr Asn Lys Tyr Asn Glu Asn Phe Lys Gly 
    930                 935                 940                 


Lys Ala Thr Leu Thr Ala Asp Thr Ser Ser Ser Thr Ala Tyr Met Gln 
945                 950                 955                 960 


Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys Ala Arg 
                965                 970                 975     


Glu Tyr Gly Asn Tyr Asp Tyr Ala Met Asp Ser Trp Gly Gln Gly Thr 
            980                 985                 990         


Ser Val Thr Val Ser Ser Ser Gln  Asn Pro Pro Val Leu  Lys Arg His 
        995                 1000                 1005             


Gln Arg  Glu Ile Thr Arg Thr  Thr Leu Gln Ser Asp  Gln Glu Glu 
    1010                 1015                 1020             


Ile Asp  Tyr Asp Asp Thr Ile  Ser Val Glu Met Lys  Lys Glu Asp 
    1025                 1030                 1035             


Phe Asp  Ile Tyr Asp Glu Asp  Glu Asn Gln Ser Pro  Arg Ser Phe 
    1040                 1045                 1050             


Gln Lys  Lys Thr Arg His Tyr  Phe Ile Ala Ala Val  Glu Arg Leu 
    1055                 1060                 1065             


Trp Asp  Tyr Gly Met Ser Ser  Ser Pro His Val Leu  Arg Asn Arg 
    1070                 1075                 1080             


Ala Gln  Ser Gly Ser Val Pro  Gln Phe Lys Lys Val  Val Phe Gln 
    1085                 1090                 1095             


Glu Phe  Thr Asp Gly Ser Phe  Thr Gln Pro Leu Tyr  Arg Gly Glu 
    1100                 1105                 1110             


Leu Asn  Glu His Leu Gly Leu  Leu Gly Pro Tyr Ile  Arg Ala Glu 
    1115                 1120                 1125             


Val Glu  Asp Asn Ile Met Val  Thr Phe Arg Asn Gln  Ala Ser Arg 
    1130                 1135                 1140             


Pro Tyr  Ser Phe Tyr Ser Ser  Leu Ile Ser Tyr Glu  Glu Asp Gln 
    1145                 1150                 1155             


Arg Gln  Gly Ala Glu Pro Arg  Lys Asn Phe Val Lys  Pro Asn Glu 
    1160                 1165                 1170             


Thr Lys  Thr Tyr Phe Trp Lys  Val Gln His His Met  Ala Pro Thr 
    1175                 1180                 1185             


Lys Asp  Glu Phe Asp Cys Lys  Ala Trp Ala Tyr Phe  Ser Asp Val 
    1190                 1195                 1200             


Asp Leu  Glu Lys Asp Val His  Ser Gly Leu Ile Gly  Pro Leu Leu 
    1205                 1210                 1215             


Val Cys  His Thr Asn Thr Leu  Asn Pro Ala His Gly  Arg Gln Val 
    1220                 1225                 1230             


Thr Val  Gln Glu Phe Ala Leu  Phe Phe Thr Ile Phe  Asp Glu Thr 
    1235                 1240                 1245             


Lys Ser  Trp Tyr Phe Thr Glu  Asn Met Glu Arg Asn  Cys Arg Ala 
    1250                 1255                 1260             


Pro Cys  Asn Ile Gln Met Glu  Asp Pro Thr Phe Lys  Glu Asn Tyr 
    1265                 1270                 1275             


Arg Phe  His Ala Ile Asn Gly  Tyr Ile Met Asp Thr  Leu Pro Gly 
    1280                 1285                 1290             


Leu Val  Met Ala Gln Asp Gln  Arg Ile Arg Trp Tyr  Leu Leu Ser 
    1295                 1300                 1305             


Met Gly  Ser Asn Glu Asn Ile  His Ser Ile His Phe  Ser Gly His 
    1310                 1315                 1320             


Val Phe  Thr Val Arg Lys Lys  Glu Glu Tyr Lys Met  Ala Leu Tyr 
    1325                 1330                 1335             


Asn Leu  Tyr Pro Gly Val Phe  Glu Thr Val Glu Met  Leu Pro Ser 
    1340                 1345                 1350             


Lys Ala  Gly Ile Trp Arg Val  Glu Cys Leu Ile Gly  Glu His Leu 
    1355                 1360                 1365             


His Ala  Gly Met Ser Thr Leu  Phe Leu Val Tyr Ser  Asn Lys Cys 
    1370                 1375                 1380             


Gln Thr  Pro Leu Gly Met Ala  Ser Gly His Ile Arg  Asp Phe Gln 
    1385                 1390                 1395             


Ile Thr  Ala Ser Gly Gln Tyr  Gly Gln Trp Ala Pro  Lys Leu Ala 
    1400                 1405                 1410             


Arg Leu  His Tyr Ser Gly Ser  Ile Asn Ala Trp Ser  Thr Lys Glu 
    1415                 1420                 1425             


Pro Phe  Ser Trp Ile Lys Val  Asp Leu Leu Ala Pro  Met Ile Ile 
    1430                 1435                 1440             


His Gly  Ile Lys Thr Gln Gly  Ala Arg Gln Lys Phe  Ser Ser Leu 
    1445                 1450                 1455             


Tyr Ile  Ser Gln Phe Ile Ile  Met Tyr Ser Leu Asp  Gly Lys Lys 
    1460                 1465                 1470             


Trp Gln  Thr Tyr Arg Gly Asn  Ser Thr Gly Thr Leu  Met Val Phe 
    1475                 1480                 1485             


Phe Gly  Asn Val Asp Ser Ser  Gly Ile Lys His Asn  Ile Phe Asn 
    1490                 1495                 1500             


Pro Pro  Ile Ile Ala Arg Tyr  Ile Arg Leu His Pro  Thr His Tyr 
    1505                 1510                 1515             


Ser Ile  Arg Ser Thr Leu Arg  Met Glu Leu Met Gly  Cys Asp Leu 
    1520                 1525                 1530             


Asn Ser  Cys Ser Met Pro Leu  Gly Met Glu Ser Lys  Ala Ile Ser 
    1535                 1540                 1545             


Asp Ala  Gln Ile Thr Ala Ser  Ser Tyr Phe Thr Asn  Met Phe Ala 
    1550                 1555                 1560             


Thr Trp  Ser Pro Ser Lys Ala  Arg Leu His Leu Gln  Gly Arg Ser 
    1565                 1570                 1575             


Asn Ala  Trp Arg Pro Gln Val  Asn Asn Pro Lys Glu  Trp Leu Gln 
    1580                 1585                 1590             


Val Asp  Phe Gln Lys Thr Met  Lys Val Thr Gly Val  Thr Thr Gln 
    1595                 1600                 1605             


Gly Val  Lys Ser Leu Leu Thr  Ser Met Tyr Val Lys  Glu Phe Leu 
    1610                 1615                 1620             


Ile Ser  Ser Ser Gln Asp Gly  His Gln Trp Thr Leu  Phe Phe Gln 
    1625                 1630                 1635             


Asn Gly  Lys Val Lys Val Phe  Gln Gly Asn Gln Asp  Ser Phe Thr 
    1640                 1645                 1650             


Pro Val  Val Asn Ser Leu Asp  Pro Pro Leu Leu Thr  Arg Tyr Leu 
    1655                 1660                 1665             


Arg Ile  His Pro Gln Ser Trp  Val His Gln Ile Ala  Leu Arg Met 
    1670                 1675                 1680             


Glu Val  Leu Gly Cys Glu Ala  Gln Asp Leu Tyr 
    1685                 1690                 


