                         SEQUENCE LISTING

<110>  EMORY UNIVERSITY
       Lollar, John S.
       Healey, John F.
 
<120>  TARGETED ELIMINATION OF FACTOR VIII IMMUNE CELLS

<130>  09073 PCT

<150>  US 61/778,815
<151>  2013-03-13

<160>  4     

<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>  2332
<212>  PRT
<213>  Homo sapiens

<400>  2

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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Thr Asp Pro Trp Phe Ala His Arg Thr Pro Met Pro Lys Ile Gln Asn 
    770                 775                 780                 


Val Ser Ser Ser Asp Leu Leu Met Leu Leu Arg Gln Ser Pro Thr Pro 
785                 790                 795                 800 


His Gly Leu Ser Leu Ser Asp Leu Gln Glu Ala Lys Tyr Glu Thr Phe 
                805                 810                 815     


Ser Asp Asp Pro Ser Pro Gly Ala Ile Asp Ser Asn Asn Ser Leu Ser 
            820                 825                 830         


Glu Met Thr His Phe Arg Pro Gln Leu His His Ser Gly Asp Met Val 
        835                 840                 845             


Phe Thr Pro Glu Ser Gly Leu Gln Leu Arg Leu Asn Glu Lys Leu Gly 
    850                 855                 860                 


Thr Thr Ala Ala Thr Glu Leu Lys Lys Leu Asp Phe Lys Val Ser Ser 
865                 870                 875                 880 


Thr Ser Asn Asn Leu Ile Ser Thr Ile Pro Ser Asp Asn Leu Ala Ala 
                885                 890                 895     


Gly Thr Asp Asn Thr Ser Ser Leu Gly Pro Pro Ser Met Pro Val His 
            900                 905                 910         


Tyr Asp Ser Gln Leu Asp Thr Thr Leu Phe Gly Lys Lys Ser Ser Pro 
        915                 920                 925             


Leu Thr Glu Ser Gly Gly Pro Leu Ser Leu Ser Glu Glu Asn Asn Asp 
    930                 935                 940                 


Ser Lys Leu Leu Glu Ser Gly Leu Met Asn Ser Gln Glu Ser Ser Trp 
945                 950                 955                 960 


Gly Lys Asn Val Ser Ser Thr Glu Ser Gly Arg Leu Phe Lys Gly Lys 
                965                 970                 975     


Arg Ala His Gly Pro Ala Leu Leu Thr Lys Asp Asn Ala Leu Phe Lys 
            980                 985                 990         


Val Ser Ile Ser Leu Leu Lys Thr  Asn Lys Thr Ser Asn  Asn Ser Ala 
        995                 1000                 1005             


Thr Asn  Arg Lys Thr His Ile  Asp Gly Pro Ser Leu  Leu Ile Glu 
    1010                 1015                 1020             


Asn Ser  Pro Ser Val Trp Gln  Asn Ile Leu Glu Ser  Asp Thr Glu 
    1025                 1030                 1035             


Phe Lys  Lys Val Thr Pro Leu  Ile His Asp Arg Met  Leu Met Asp 
    1040                 1045                 1050             


Lys Asn  Ala Thr Ala Leu Arg  Leu Asn His Met Ser  Asn Lys Thr 
    1055                 1060                 1065             


Thr Ser  Ser Lys Asn Met Glu  Met Val Gln Gln Lys  Lys Glu Gly 
    1070                 1075                 1080             


Pro Ile  Pro Pro Asp Ala Gln  Asn Pro Asp Met Ser  Phe Phe Lys 
    1085                 1090                 1095             


Met Leu  Phe Leu Pro Glu Ser  Ala Arg Trp Ile Gln  Arg Thr His 
    1100                 1105                 1110             


Gly Lys  Asn Ser Leu Asn Ser  Gly Gln Gly Pro Ser  Pro Lys Gln 
    1115                 1120                 1125             


Leu Val  Ser Leu Gly Pro Glu  Lys Ser Val Glu Gly  Gln Asn Phe 
    1130                 1135                 1140             


Leu Ser  Glu Lys Asn Lys Val  Val Val Gly Lys Gly  Glu Phe Thr 
    1145                 1150                 1155             


Lys Asp  Val Gly Leu Lys Glu  Met Val Phe Pro Ser  Ser Arg Asn 
    1160                 1165                 1170             


Leu Phe  Leu Thr Asn Leu Asp  Asn Leu His Glu Asn  Asn Thr His 
    1175                 1180                 1185             


Asn Gln  Glu Lys Lys Ile Gln  Glu Glu Ile Glu Lys  Lys Glu Thr 
    1190                 1195                 1200             


Leu Ile  Gln Glu Asn Val Val  Leu Pro Gln Ile His  Thr Val Thr 
    1205                 1210                 1215             


Gly Thr  Lys Asn Phe Met Lys  Asn Leu Phe Leu Leu  Ser Thr Arg 
    1220                 1225                 1230             


Gln Asn  Val Glu Gly Ser Tyr  Asp Gly Ala Tyr Ala  Pro Val Leu 
    1235                 1240                 1245             


Gln Asp  Phe Arg Ser Leu Asn  Asp Ser Thr Asn Arg  Thr Lys Lys 
    1250                 1255                 1260             


His Thr  Ala His Phe Ser Lys  Lys Gly Glu Glu Glu  Asn Leu Glu 
    1265                 1270                 1275             


Gly Leu  Gly Asn Gln Thr Lys  Gln Ile Val Glu Lys  Tyr Ala Cys 
    1280                 1285                 1290             


Thr Thr  Arg Ile Ser Pro Asn  Thr Ser Gln Gln Asn  Phe Val Thr 
    1295                 1300                 1305             


Gln Arg  Ser Lys Arg Ala Leu  Lys Gln Phe Arg Leu  Pro Leu Glu 
    1310                 1315                 1320             


Glu Thr  Glu Leu Glu Lys Arg  Ile Ile Val Asp Asp  Thr Ser Thr 
    1325                 1330                 1335             


Gln Trp  Ser Lys Asn Met Lys  His Leu Thr Pro Ser  Thr Leu Thr 
    1340                 1345                 1350             


Gln Ile  Asp Tyr Asn Glu Lys  Glu Lys Gly Ala Ile  Thr Gln Ser 
    1355                 1360                 1365             


Pro Leu  Ser Asp Cys Leu Thr  Arg Ser His Ser Ile  Pro Gln Ala 
    1370                 1375                 1380             


Asn Arg  Ser Pro Leu Pro Ile  Ala Lys Val Ser Ser  Phe Pro Ser 
    1385                 1390                 1395             


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


Ser His  Leu Pro Ala Ala Ser  Tyr Arg Lys Lys Asp  Ser Gly Val 
    1415                 1420                 1425             


Gln Glu  Ser Ser His Phe Leu  Gln Gly Ala Lys Lys  Asn Asn Leu 
    1430                 1435                 1440             


Ser Leu  Ala Ile Leu Thr Leu  Glu Met Thr Gly Asp  Gln Arg Glu 
    1445                 1450                 1455             


Val Gly  Ser Leu Gly Thr Ser  Ala Thr Asn Ser Val  Thr Tyr Lys 
    1460                 1465                 1470             


Lys Val  Glu Asn Thr Val Leu  Pro Lys Pro Asp Leu  Pro Lys Thr 
    1475                 1480                 1485             


Ser Gly  Lys Val Glu Leu Leu  Pro Lys Val His Ile  Tyr Gln Lys 
    1490                 1495                 1500             


Asp Leu  Phe Pro Thr Glu Thr  Ser Asn Gly Ser Pro  Gly His Leu 
    1505                 1510                 1515             


Asp Leu  Val Glu Gly Ser Leu  Leu Gln Gly Thr Glu  Gly Ala Ile 
    1520                 1525                 1530             


Lys Trp  Asn Glu Ala Asn Arg  Pro Gly Lys Val Pro  Phe Leu Arg 
    1535                 1540                 1545             


Val Ala  Thr Glu Ser Ser Ala  Lys Thr Pro Ser Lys  Leu Leu Asp 
    1550                 1555                 1560             


Pro Leu  Ala Trp Asp Asn His  Tyr Gly Thr Gln Ile  Pro Lys Glu 
    1565                 1570                 1575             


Glu Trp  Lys Ser Gln Glu Lys  Ser Pro Glu Lys Thr  Ala Phe Lys 
    1580                 1585                 1590             


Lys Lys  Asp Thr Ile Leu Ser  Leu Asn Ala Cys Glu  Ser Asn His 
    1595                 1600                 1605             


Ala Ile  Ala Ala Ile Asn Glu  Gly Gln Asn Lys Pro  Glu Ile Glu 
    1610                 1615                 1620             


Val Thr  Trp Ala Lys Gln Gly  Arg Thr Glu Arg Leu  Cys Ser Gln 
    1625                 1630                 1635             


Asn Pro  Pro Val Leu Lys Arg  His Gln Arg Glu Ile  Thr Arg Thr 
    1640                 1645                 1650             


Thr Leu  Gln Ser Asp Gln Glu  Glu Ile Asp Tyr Asp  Asp Thr Ile 
    1655                 1660                 1665             


Ser Val  Glu Met Lys Lys Glu  Asp Phe Asp Ile Tyr  Asp Glu Asp 
    1670                 1675                 1680             


Glu Asn  Gln Ser Pro Arg Ser  Phe Gln Lys Lys Thr  Arg His Tyr 
    1685                 1690                 1695             


Phe Ile  Ala Ala Val Glu Arg  Leu Trp Asp Tyr Gly  Met Ser Ser 
    1700                 1705                 1710             


Ser Pro  His Val Leu Arg Asn  Arg Ala Gln Ser Gly  Ser Val Pro 
    1715                 1720                 1725             


Gln Phe  Lys Lys Val Val Phe  Gln Glu Phe Thr Asp  Gly Ser Phe 
    1730                 1735                 1740             


Thr Gln  Pro Leu Tyr Arg Gly  Glu Leu Asn Glu His  Leu Gly Leu 
    1745                 1750                 1755             


Leu Gly  Pro Tyr Ile Arg Ala  Glu Val Glu Asp Asn  Ile Met Val 
    1760                 1765                 1770             


Thr Phe  Arg Asn Gln Ala Ser  Arg Pro Tyr Ser Phe  Tyr Ser Ser 
    1775                 1780                 1785             


Leu Ile  Ser Tyr Glu Glu Asp  Gln Arg Gln Gly Ala  Glu Pro Arg 
    1790                 1795                 1800             


Lys Asn  Phe Val Lys Pro Asn  Glu Thr Lys Thr Tyr  Phe Trp Lys 
    1805                 1810                 1815             


Val Gln  His His Met Ala Pro  Thr Lys Asp Glu Phe  Asp Cys Lys 
    1820                 1825                 1830             


Ala Trp  Ala Tyr Phe Ser Asp  Val Asp Leu Glu Lys  Asp Val His 
    1835                 1840                 1845             


Ser Gly  Leu Ile Gly Pro Leu  Leu Val Cys His Thr  Asn Thr Leu 
    1850                 1855                 1860             


Asn Pro  Ala His Gly Arg Gln  Val Thr Val Gln Glu  Phe Ala Leu 
    1865                 1870                 1875             


Phe Phe  Thr Ile Phe Asp Glu  Thr Lys Ser Trp Tyr  Phe Thr Glu 
    1880                 1885                 1890             


Asn Met  Glu Arg Asn Cys Arg  Ala Pro Cys Asn Ile  Gln Met Glu 
    1895                 1900                 1905             


Asp Pro  Thr Phe Lys Glu Asn  Tyr Arg Phe His Ala  Ile Asn Gly 
    1910                 1915                 1920             


Tyr Ile  Met Asp Thr Leu Pro  Gly Leu Val Met Ala  Gln Asp Gln 
    1925                 1930                 1935             


Arg Ile  Arg Trp Tyr Leu Leu  Ser Met Gly Ser Asn  Glu Asn Ile 
    1940                 1945                 1950             


His Ser  Ile His Phe Ser Gly  His Val Phe Thr Val  Arg Lys Lys 
    1955                 1960                 1965             


Glu Glu  Tyr Lys Met Ala Leu  Tyr Asn Leu Tyr Pro  Gly Val Phe 
    1970                 1975                 1980             


Glu Thr  Val Glu Met Leu Pro  Ser Lys Ala Gly Ile  Trp Arg Val 
    1985                 1990                 1995             


Glu Cys  Leu Ile Gly Glu His  Leu His Ala Gly Met  Ser Thr Leu 
    2000                 2005                 2010             


Phe Leu  Val Tyr Ser Asn Lys  Cys Gln Thr Pro Leu  Gly Met Ala 
    2015                 2020                 2025             


Ser Gly  His Ile Arg Asp Phe  Gln Ile Thr Ala Ser  Gly Gln Tyr 
    2030                 2035                 2040             


Gly Gln  Trp Ala Pro Lys Leu  Ala Arg Leu His Tyr  Ser Gly Ser 
    2045                 2050                 2055             


Ile Asn  Ala Trp Ser Thr Lys  Glu Pro Phe Ser Trp  Ile Lys Val 
    2060                 2065                 2070             


Asp Leu  Leu Ala Pro Met Ile  Ile His Gly Ile Lys  Thr Gln Gly 
    2075                 2080                 2085             


Ala Arg  Gln Lys Phe Ser Ser  Leu Tyr Ile Ser Gln  Phe Ile Ile 
    2090                 2095                 2100             


Met Tyr  Ser Leu Asp Gly Lys  Lys Trp Gln Thr Tyr  Arg Gly Asn 
    2105                 2110                 2115             


Ser Thr  Gly Thr Leu Met Val  Phe Phe Gly Asn Val  Asp Ser Ser 
    2120                 2125                 2130             


Gly Ile  Lys His Asn Ile Phe  Asn Pro Pro Ile Ile  Ala Arg Tyr 
    2135                 2140                 2145             


Ile Arg  Leu His Pro Thr His  Tyr Ser Ile Arg Ser  Thr Leu Arg 
    2150                 2155                 2160             


Met Glu  Leu Met Gly Cys Asp  Leu Asn Ser Cys Ser  Met Pro Leu 
    2165                 2170                 2175             


Gly Met  Glu Ser Lys Ala Ile  Ser Asp Ala Gln Ile  Thr Ala Ser 
    2180                 2185                 2190             


Ser Tyr  Phe Thr Asn Met Phe  Ala Thr Trp Ser Pro  Ser Lys Ala 
    2195                 2200                 2205             


Arg Leu  His Leu Gln Gly Arg  Ser Asn Ala Trp Arg  Pro Gln Val 
    2210                 2215                 2220             


Asn Asn  Pro Lys Glu Trp Leu  Gln Val Asp Phe Gln  Lys Thr Met 
    2225                 2230                 2235             


Lys Val  Thr Gly Val Thr Thr  Gln Gly Val Lys Ser  Leu Leu Thr 
    2240                 2245                 2250             


Ser Met  Tyr Val Lys Glu Phe  Leu Ile Ser Ser Ser  Gln Asp Gly 
    2255                 2260                 2265             


His Gln  Trp Thr Leu Phe Phe  Gln Asn Gly Lys Val  Lys Val Phe 
    2270                 2275                 2280             


Gln Gly  Asn Gln Asp Ser Phe  Thr Pro Val Val Asn  Ser Leu Asp 
    2285                 2290                 2295             


Pro Pro  Leu Leu Thr Arg Tyr  Leu Arg Ile His Pro  Gln Ser Trp 
    2300                 2305                 2310             


Val His  Gln Ile Ala Leu Arg  Met Glu Val Leu Gly  Cys Glu Ala 
    2315                 2320                 2325             


Gln Asp  Leu Tyr 
    2330         


<210>  3
<211>  253
<212>  PRT
<213>  Saponaria officinalis

<400>  3

Val Thr Ser Ile Thr Leu Asp Leu Val Asn Pro Thr Ala Gly Gln Tyr 
1               5                   10                  15      


Ser Ser Phe Val Asp Lys Ile Arg Asn Asn Val Lys Asp Pro Asn Leu 
            20                  25                  30          


Lys Tyr Gly Gly Thr Asp Ile Ala Val Ile Gly Pro Pro Ser Lys Glu 
        35                  40                  45              


Lys Phe Leu Arg Ile Asn Phe Gln Ser Ser Arg Gly Thr Val Ser Leu 
    50                  55                  60                  


Gly Leu Lys Arg Asp Asn Leu Tyr Val Val Ala Tyr Leu Ala Met Asp 
65                  70                  75                  80  


Asn Thr Asn Val Asn Arg Ala Tyr Tyr Phe Lys Ser Glu Ile Thr Ser 
                85                  90                  95      


Ala Glu Leu Thr Ala Leu Phe Pro Glu Ala Thr Thr Ala Asn Gln Lys 
            100                 105                 110         


Ala Leu Glu Tyr Thr Glu Asp Tyr Gln Ser Ile Glu Lys Asn Ala Gln 
        115                 120                 125             


Ile Thr Gln Gly Asp Lys Ser Arg Lys Glu Leu Gly Leu Gly Ile Asp 
    130                 135                 140                 


Leu Leu Leu Thr Phe Met Glu Ala Val Asn Lys Lys Ala Arg Val Val 
145                 150                 155                 160 


Lys Asn Glu Ala Arg Phe Leu Leu Ile Ala Ile Gln Met Thr Ala Glu 
                165                 170                 175     


Val Ala Arg Phe Arg Tyr Ile Gln Asn Leu Val Thr Lys Asn Phe Pro 
            180                 185                 190         


Asn Lys Phe Asp Ser Asp Asn Lys Val Ile Gln Phe Glu Val Ser Trp 
        195                 200                 205             


Arg Lys Ile Ser Thr Ala Ile Tyr Gly Asp Ala Lys Asn Gly Val Phe 
    210                 215                 220                 


Asn Lys Asp Tyr Asp Phe Gly Phe Gly Lys Val Arg Gln Val Lys Asp 
225                 230                 235                 240 


Leu Gln Met Gly Leu Leu Met Tyr Leu Gly Lys Pro Lys 
                245                 250             


<210>  4
<211>  2311
<212>  PRT
<213>  Homo sapiens

<400>  4

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


Phe Pro Phe Asn Thr Ser Val Val Tyr Lys Lys Thr Leu Phe Val Glu 
            20                  25                  30          


Phe Thr Asp His Leu Phe Asn Ile Ala Lys Pro Arg Pro Pro Trp Met 
        35                  40                  45              


Gly Leu Leu Gly Pro Thr Ile Gln Ala Glu Val Tyr Asp Thr Val Val 
    50                  55                  60                  


Ile Thr Leu Lys Asn Met Ala Ser His Pro Val Ser Leu His Ala Val 
65                  70                  75                  80  


Gly Val Ser Tyr Trp Lys Ala Ser Glu Gly Ala Glu Tyr Asp Asp Gln 
                85                  90                  95      


Thr Ser Gln Arg Glu Lys Glu Asp Asp Lys Val Phe Pro Gly Gly Ser 
            100                 105                 110         


His Thr Tyr Val Trp Gln Val Leu Lys Glu Asn Gly Pro Met Ala Ser 
        115                 120                 125             


Asp Pro Leu Cys Leu Thr Tyr Ser Tyr Leu Ser His Val Asp Leu Val 
    130                 135                 140                 


Lys Asp Leu Asn Ser Gly Leu Ile Gly Ala Leu Leu Val Cys Arg Glu 
145                 150                 155                 160 


Gly Ser Leu Ala Lys Glu Lys Thr Gln Thr Leu His Lys Phe Ile Leu 
                165                 170                 175     


Leu Phe Ala Val Phe Asp Glu Gly Lys Ser Trp His Ser Glu Thr Lys 
            180                 185                 190         


Asn Ser Leu Met Gln Asp Arg Asp Ala Ala Ser Ala Arg Ala Trp Pro 
        195                 200                 205             


Lys Met His Thr Val Asn Gly Tyr Val Asn Arg Ser Leu Pro Gly Leu 
    210                 215                 220                 


Ile Gly Cys His Arg Lys Ser Val Tyr Trp His Val Ile Gly Met Gly 
225                 230                 235                 240 


Thr Thr Pro Glu Val His Ser Ile Phe Leu Glu Gly His Thr Phe Leu 
                245                 250                 255     


Val Arg Asn His Arg Gln Ala Ser Leu Glu Ile Ser Pro Ile Thr Phe 
            260                 265                 270         


Leu Thr Ala Gln Thr Leu Leu Met Asp Leu Gly Gln Phe Leu Leu Phe 
        275                 280                 285             


Cys His Ile Ser Ser His Gln His Asp Gly Met Glu Ala Tyr Val Lys 
    290                 295                 300                 


Val Asp Ser Cys Pro Glu Glu Pro Gln Leu Arg Met Lys Asn Asn Glu 
305                 310                 315                 320 


Glu Ala Glu Asp Tyr Asp Asp Asp Leu Thr Asp Ser Glu Met Asp Val 
                325                 330                 335     


Val Arg Phe Asp Asp Asp Asn Ser Pro Ser Phe Ile Gln Ile Arg Ser 
            340                 345                 350         


Val Ala Lys Lys His Pro Lys Thr Trp Val His Tyr Ile Ala Ala Glu 
        355                 360                 365             


Glu Glu Asp Trp Asp Tyr Ala Pro Leu Val Leu Ala Pro Asp Asp Arg 
    370                 375                 380                 


Ser Tyr Lys Ser Gln Tyr Leu Asn Asn Gly Pro Gln Arg Ile Gly Arg 
385                 390                 395                 400 


Lys Tyr Lys Lys Val Arg Phe Met Ala Tyr Thr Asp Glu Thr Phe Lys 
                405                 410                 415     


Thr Arg Glu Ala Ile Gln His Glu Ser Gly Ile Leu Gly Pro Leu Leu 
            420                 425                 430         


Tyr Gly Glu Val Gly Asp Thr Leu Leu Ile Ile Phe Lys Asn Gln Ala 
        435                 440                 445             


Ser Arg Pro Tyr Asn Ile Tyr Pro His Gly Ile Thr Asp Val Arg Pro 
    450                 455                 460                 


Leu Tyr Ser Arg Arg Leu Pro Lys Gly Val Lys His Leu Lys Asp Phe 
465                 470                 475                 480 


Pro Ile Leu Pro Gly Glu Ile Phe Lys Tyr Lys Trp Thr Val Thr Val 
                485                 490                 495     


Glu Asp Gly Pro Thr Lys Ser Asp Pro Arg Cys Leu Thr Arg Tyr Tyr 
            500                 505                 510         


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


Pro Leu Leu Ile Cys Tyr Lys Glu Ser Val Asp Gln Arg Gly Asn Gln 
    530                 535                 540                 


Ile Met Ser Asp Lys Arg Asn Val Ile Leu Phe Ser Val Phe Asp Glu 
545                 550                 555                 560 


Asn Arg Ser Trp Tyr Leu Thr Glu Asn Ile Gln Arg Phe Leu Pro Asn 
                565                 570                 575     


Pro Ala Gly Val Gln Leu Glu Asp Pro Glu Phe Gln Ala Ser Asn Ile 
            580                 585                 590         


Met His Ser Ile Asn Gly Tyr Val Phe Asp Ser Leu Gln Leu Ser Val 
        595                 600                 605             


Cys Leu His Glu Val Ala Tyr Trp Tyr Ile Leu Ser Ile Gly Ala Gln 
    610                 615                 620                 


Thr Asp Phe Leu Ser Val Phe Phe Ser Gly Tyr Thr Phe Lys His Lys 
625                 630                 635                 640 


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


Val Phe Met Ser Met Glu Asn Pro Gly Leu Trp Ile Leu Gly Cys His 
            660                 665                 670         


Asn Ser Asp Phe Arg Asn Arg Gly Met Thr Ala Leu Leu Lys Val Ser 
        675                 680                 685             


Ser Cys Asp Lys Asn Thr Gly Asp Tyr Tyr Glu Asp Ser Tyr Glu Asp 
    690                 695                 700                 


Ile Ser Ala Tyr Leu Leu Ser Lys Asn Asn Ala Ile Glu Pro Arg Ser 
705                 710                 715                 720 


Phe Ser Gln Asn Ser Arg His Pro Ser Thr Arg Gln Lys Gln Phe Asn 
                725                 730                 735     


Ala Thr Thr Ile Pro Glu Asn Asp Ile Glu Lys Thr Asp Pro Trp Phe 
            740                 745                 750         


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


Leu Leu Met Leu Leu Arg Gln Ser Pro Thr Pro His Gly Leu Ser Leu 
    770                 775                 780                 


Ser Asp Leu Gln Glu Ala Lys Tyr Glu Thr Phe Ser Asp Asp Pro Ser 
785                 790                 795                 800 


Pro Gly Ala Ile Asp Ser Asn Asn Ser Leu Ser Glu Met Thr His Phe 
                805                 810                 815     


Arg Pro Gln Leu His His Ser Gly Asp Met Val Phe Thr Pro Glu Ser 
            820                 825                 830         


Gly Leu Gln Leu Arg Leu Asn Glu Lys Leu Gly Thr Thr Ala Ala Thr 
        835                 840                 845             


Glu Leu Lys Lys Leu Asp Phe Lys Val Ser Ser Thr Ser Asn Asn Leu 
    850                 855                 860                 


Ile Ser Thr Ile Pro Ser Asp Asn Leu Ala Ala Gly Thr Asp Asn Thr 
865                 870                 875                 880 


Ser Ser Leu Gly Pro Pro Ser Met Pro Val His Tyr Asp Ser Gln Leu 
                885                 890                 895     


Asp Thr Thr Leu Phe Gly Lys Lys Ser Ser Pro Leu Thr Glu Ser Gly 
            900                 905                 910         


Gly Pro Leu Ser Leu Ser Glu Glu Asn Asn Asp Ser Lys Leu Leu Glu 
        915                 920                 925             


Ser Gly Leu Met Asn Ser Gln Glu Ser Ser Trp Gly Lys Asn Val Ser 
    930                 935                 940                 


Ser Thr Glu Ser Gly Arg Leu Phe Lys Gly Lys Arg Ala His Gly Pro 
945                 950                 955                 960 


Ala Leu Leu Thr Lys Asp Asn Ala Leu Phe Lys Val Ser Ile Ser Leu 
                965                 970                 975     


Leu Lys Thr Asn Lys Thr Ser Asn Asn Ser Ala Thr Asn Arg Lys Thr 
            980                 985                 990         


His Ile Asp Gly Pro Ser Leu Leu  Ile Glu Asn Ser Pro  Ser Val Trp 
        995                 1000                 1005             


Gln Asn  Ile Leu Glu Ser Asp  Thr Glu Phe Lys Lys  Val Thr Pro 
    1010                 1015                 1020             


Leu Ile  His Asp Arg Met Leu  Met Asp Lys Asn Ala  Thr Ala Leu 
    1025                 1030                 1035             


Arg Leu  Asn His Met Ser Asn  Lys Thr Thr Ser Ser  Lys Asn Met 
    1040                 1045                 1050             


Glu Met  Val Gln Gln Lys Lys  Glu Gly Pro Ile Pro  Pro Asp Ala 
    1055                 1060                 1065             


Gln Asn  Pro Asp Met Ser Phe  Phe Lys Met Leu Phe  Leu Pro Glu 
    1070                 1075                 1080             


Ser Ala  Arg Trp Ile Gln Arg  Thr His Gly Lys Asn  Ser Leu Asn 
    1085                 1090                 1095             


Ser Gly  Gln Gly Pro Ser Pro  Lys Gln Leu Val Ser  Leu Gly Pro 
    1100                 1105                 1110             


Glu Lys  Ser Val Glu Gly Gln  Asn Phe Leu Ser Glu  Lys Asn Lys 
    1115                 1120                 1125             


Val Val  Val Gly Lys Gly Glu  Phe Thr Lys Asp Val  Gly Leu Lys 
    1130                 1135                 1140             


Glu Met  Val Phe Pro Ser Ser  Arg Asn Leu Phe Leu  Thr Asn Leu 
    1145                 1150                 1155             


Asp Asn  Leu His Glu Asn Asn  Thr His Asn Gln Glu  Lys Lys Ile 
    1160                 1165                 1170             


Gln Glu  Glu Ile Glu Lys Lys  Glu Thr Leu Ile Gln  Glu Asn Val 
    1175                 1180                 1185             


Val Leu  Pro Gln Ile His Thr  Val Thr Gly Thr Lys  Asn Phe Met 
    1190                 1195                 1200             


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


Tyr Asp  Gly Ala Tyr Ala Pro  Val Leu Gln Asp Phe  Arg Ser Leu 
    1220                 1225                 1230             


Asn Asp  Ser Thr Asn Arg Thr  Lys Lys His Thr Ala  His Phe Ser 
    1235                 1240                 1245             


Lys Lys  Gly Glu Glu Glu Asn  Leu Glu Gly Leu Gly  Asn Gln Thr 
    1250                 1255                 1260             


Lys Gln  Ile Val Glu Lys Tyr  Ala Cys Thr Thr Arg  Ile Ser Pro 
    1265                 1270                 1275             


Asn Thr  Ser Gln Gln Asn Phe  Val Thr Gln Arg Ser  Lys Arg Ala 
    1280                 1285                 1290             


Leu Lys  Gln Phe Arg Leu Pro  Leu Glu Glu Thr Glu  Leu Glu Lys 
    1295                 1300                 1305             


Arg Ile  Ile Val Asp Asp Thr  Ser Thr Gln Trp Ser  Lys Asn Met 
    1310                 1315                 1320             


Lys His  Leu Thr Pro Ser Thr  Leu Thr Gln Ile Asp  Tyr Asn Glu 
    1325                 1330                 1335             


Lys Glu  Lys Gly Ala Ile Thr  Gln Ser Pro Leu Ser  Asp Cys Leu 
    1340                 1345                 1350             


Thr Arg  Ser His Ser Ile Pro  Gln Ala Asn Arg Ser  Pro Leu Pro 
    1355                 1360                 1365             


Ile Ala  Lys Val Ser Ser Phe  Pro Ser Ile Arg Pro  Ile Tyr Leu 
    1370                 1375                 1380             


Thr Arg  Val Leu Phe Gln Asp  Asn Ser Ser His Leu  Pro Ala Ala 
    1385                 1390                 1395             


Ser Tyr  Arg Lys Lys Asp Ser  Gly Val Gln Glu Ser  Ser His Phe 
    1400                 1405                 1410             


Leu Gln  Gly Ala Lys Lys Asn  Asn Leu Ser Leu Ala  Ile Leu Thr 
    1415                 1420                 1425             


Leu Glu  Met Thr Gly Asp Gln  Arg Glu Val Gly Ser  Leu Gly Thr 
    1430                 1435                 1440             


Ser Ala  Thr Asn Ser Val Thr  Tyr Lys Lys Val Glu  Asn Thr Val 
    1445                 1450                 1455             


Leu Pro  Lys Pro Asp Leu Pro  Lys Thr Ser Gly Lys  Val Glu Leu 
    1460                 1465                 1470             


Leu Pro  Lys Val His Ile Tyr  Gln Lys Asp Leu Phe  Pro Thr Glu 
    1475                 1480                 1485             


Thr Ser  Asn Gly Ser Pro Gly  His Leu Asp Leu Val  Glu Gly Ser 
    1490                 1495                 1500             


Leu Leu  Gln Gly Thr Glu Gly  Ala Ile Lys Trp Asn  Glu Ala Asn 
    1505                 1510                 1515             


Arg Pro  Gly Lys Val Pro Phe  Leu Arg Val Ala Thr  Glu Ser Ser 
    1520                 1525                 1530             


Ala Lys  Thr Pro Ser Lys Leu  Leu Asp Pro Leu Ala  Trp Asp Asn 
    1535                 1540                 1545             


His Tyr  Gly Thr Gln Ile Pro  Lys Glu Glu Trp Lys  Ser Gln Glu 
    1550                 1555                 1560             


Lys Ser  Pro Glu Lys Thr Ala  Phe Lys Lys Lys Asp  Thr Ile Leu 
    1565                 1570                 1575             


Ser Leu  Asn Ala Cys Glu Ser  Asn His Ala Ile Ala  Ala Ile Asn 
    1580                 1585                 1590             


Glu Gly  Gln Asn Lys Pro Glu  Ile Glu Val Thr Trp  Ala Lys Gln 
    1595                 1600                 1605             


Gly Arg  Thr Glu Arg Leu Cys  Ser Gln Asn Pro Pro  Val Leu Lys 
    1610                 1615                 1620             


Arg His  Gln Arg Glu Ile Thr  Arg Thr Thr Leu Gln  Ser Asp Gln 
    1625                 1630                 1635             


Glu Glu  Ile Asp Tyr Asp Asp  Thr Ile Ser Val Glu  Met Lys Lys 
    1640                 1645                 1650             


Glu Asp  Phe Asp Ile Tyr Asp  Glu Asp Glu Asn Gln  Ser Pro Arg 
    1655                 1660                 1665             


Ser Phe  Gln Lys Lys Thr Arg  His Tyr Phe Ile Ala  Ala Val Glu 
    1670                 1675                 1680             


Arg Leu  Trp Asp Tyr Gly Met  Ser Ser Ser Pro His  Val Leu Arg 
    1685                 1690                 1695             


Asn Arg  Ala Gln Ser Gly Ser  Val Pro Gln Phe Lys  Lys Val Val 
    1700                 1705                 1710             


Phe Gln  Glu Phe Thr Asp Gly  Ser Phe Thr Gln Pro  Leu Tyr Arg 
    1715                 1720                 1725             


Gly Glu  Leu Asn Glu His Leu  Gly Leu Leu Gly Pro  Tyr Ile Arg 
    1730                 1735                 1740             


Ala Glu  Val Glu Asp Asn Ile  Met Val Thr Phe Arg  Asn Gln Ala 
    1745                 1750                 1755             


Ser Arg  Pro Tyr Ser Phe Tyr  Ser Ser Leu Ile Ser  Tyr Glu Glu 
    1760                 1765                 1770             


Asp Gln  Arg Gln Gly Ala Glu  Pro Arg Lys Asn Phe  Val Lys Pro 
    1775                 1780                 1785             


Asn Glu  Thr Lys Thr Tyr Phe  Trp Lys Val Gln His  His Met Ala 
    1790                 1795                 1800             


Pro Thr  Lys Asp Glu Phe Asp  Cys Lys Ala Trp Ala  Tyr Phe Ser 
    1805                 1810                 1815             


Asp Val  Asp Leu Glu Lys Asp  Val His Ser Gly Leu  Ile Gly Pro 
    1820                 1825                 1830             


Leu Leu  Val Cys His Thr Asn  Thr Leu Asn Pro Ala  His Gly Arg 
    1835                 1840                 1845             


Gln Val  Thr Val Gln Glu Phe  Ala Leu Phe Phe Thr  Ile Phe Asp 
    1850                 1855                 1860             


Glu Thr  Lys Ser Trp Tyr Phe  Thr Glu Asn Met Glu  Arg Asn Cys 
    1865                 1870                 1875             


Arg Ala  Pro Cys Asn Ile Gln  Met Glu Asp Pro Thr  Phe Lys Glu 
    1880                 1885                 1890             


Asn Tyr  Arg Phe His Ala Ile  Asn Gly Tyr Ile Met  Asp Thr Leu 
    1895                 1900                 1905             


Pro Gly  Leu Val Met Ala Gln  Asp Gln Arg Ile Arg  Trp Tyr Leu 
    1910                 1915                 1920             


Leu Ser  Met Gly Ser Asn Glu  Asn Ile His Ser Ile  His Phe Ser 
    1925                 1930                 1935             


Gly His  Val Phe Thr Val Arg  Lys Lys Glu Glu Tyr  Lys Met Ala 
    1940                 1945                 1950             


Leu Tyr  Asn Leu Tyr Pro Gly  Val Phe Glu Thr Val  Glu Met Leu 
    1955                 1960                 1965             


Pro Ser  Lys Ala Gly Ile Trp  Arg Val Glu Cys Leu  Ile Gly Glu 
    1970                 1975                 1980             


His Leu  His Ala Gly Met Ser  Thr Leu Phe Leu Val  Tyr Ser Asn 
    1985                 1990                 1995             


Lys Cys  Gln Thr Pro Leu Gly  Met Ala Ser Gly His  Ile Arg Asp 
    2000                 2005                 2010             


Phe Gln  Ile Thr Ala Ser Gly  Gln Tyr Gly Gln Trp  Ala Pro Lys 
    2015                 2020                 2025             


Leu Ala  Arg Leu His Tyr Ser  Gly Ser Ile Asn Ala  Trp Ser Thr 
    2030                 2035                 2040             


Lys Glu  Pro Phe Ser Trp Ile  Lys Val Asp Leu Leu  Ala Pro Met 
    2045                 2050                 2055             


Ile Ile  His Gly Ile Lys Thr  Gln Gly Ala Arg Gln  Lys Phe Ser 
    2060                 2065                 2070             


Ser Leu  Tyr Ile Ser Gln Phe  Ile Ile Met Tyr Ser  Leu Asp Gly 
    2075                 2080                 2085             


Lys Lys  Trp Gln Thr Tyr Arg  Gly Asn Ser Thr Gly  Thr Leu Met 
    2090                 2095                 2100             


Val Phe  Phe Gly Asn Val Asp  Ser Ser Gly Ile Lys  His Asn Ile 
    2105                 2110                 2115             


Phe Asn  Pro Pro Ile Ile Ala  Arg Tyr Ile Arg Leu  His Pro Thr 
    2120                 2125                 2130             


His Tyr  Ser Ile Arg Ser Thr  Leu Arg Met Glu Leu  Met Gly Cys 
    2135                 2140                 2145             


Asp Leu  Asn Ser Cys Ser Met  Pro Leu Gly Met Glu  Ser Lys Ala 
    2150                 2155                 2160             


Ile Ser  Asp Ala Gln Ile Thr  Ala Ser Ser Tyr Phe  Thr Asn Met 
    2165                 2170                 2175             


Phe Ala  Thr Trp Ser Pro Ser  Lys Ala Arg Leu His  Leu Gln Gly 
    2180                 2185                 2190             


Arg Ser  Asn Ala Trp Arg Pro  Gln Val Asn Asn Pro  Lys Glu Trp 
    2195                 2200                 2205             


Leu Gln  Val Asp Phe Gln Lys  Thr Met Lys Val Thr  Gly Val Thr 
    2210                 2215                 2220             


Thr Gln  Gly Val Lys Ser Leu  Leu Thr Ser Met Tyr  Val Lys Glu 
    2225                 2230                 2235             


Phe Leu  Ile Ser Ser Ser Gln  Asp Gly His Gln Trp  Thr Leu Phe 
    2240                 2245                 2250             


Phe Gln  Asn Gly Lys Val Lys  Val Phe Gln Gly Asn  Gln Asp Ser 
    2255                 2260                 2265             


Phe Thr  Pro Val Val Asn Ser  Leu Asp Pro Pro Leu  Leu Thr Arg 
    2270                 2275                 2280             


Tyr Leu  Arg Ile His Pro Gln  Ser Trp Val His Gln  Ile Ala Leu 
    2285                 2290                 2295             


Arg Met  Glu Val Leu Gly Cys  Glu Ala Gln Asp Leu  Tyr 
    2300                 2305                 2310     


