                         SEQUENCE LISTING

<110>  THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
       THE SCRIPPS RESEARCH INSTITUTE
       GRIFFIN, JOHN H.
       MOSNIER, LAURENT
 
<120>  THERAPY FOR TREATMENT OR PREVENTION OF CONDITIONS ASSOCIATED WITH
        BLEEDING OR HYPOCOAGULATION

<130>  41112.1013

<140>  PCT/US2014/063898
<141>  2014-11-04

<150>  US 61/899,544
<151>  2013-11-04

<150>  US 61/944,915
<151>  2014-02-26

<160>  4     

<170>  PatentIn version 3.5

<210>  1
<211>  1516
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  superFVa

<400>  1

Ala Gln Leu Arg Gln Phe Tyr Val Ala Ala Gln Gly Ile Ser Trp Ser 
1               5                   10                  15      


Tyr Arg Pro Glu Pro Thr Asn Ser Ser Leu Asn Leu Ser Val Thr Ser 
            20                  25                  30          


Phe Lys Lys Ile Val Tyr Arg Glu Tyr Glu Pro Tyr Phe Lys Lys Glu 
        35                  40                  45              


Lys Pro Gln Ser Thr Ile Ser Gly Leu Leu Gly Pro Thr Leu Tyr Ala 
    50                  55                  60                  


Glu Val Gly Asp Ile Ile Lys Val His Phe Lys Asn Lys Ala Asp Lys 
65                  70                  75                  80  


Pro Leu Ser Ile His Pro Gln Gly Ile Arg Tyr Ser Lys Leu Ser Glu 
                85                  90                  95      


Gly Ala Ser Tyr Leu Asp His Thr Phe Pro Ala Glu Lys Met Asp Asp 
            100                 105                 110         


Ala Val Ala Pro Gly Arg Glu Tyr Thr Tyr Glu Trp Ser Ile Ser Glu 
        115                 120                 125             


Asp Ser Gly Pro Thr His Asp Asp Pro Pro Cys Leu Thr His Ile Tyr 
    130                 135                 140                 


Tyr Ser His Glu Asn Leu Ile Glu Asp Phe Asn Ser Gly Leu Ile Gly 
145                 150                 155                 160 


Pro Leu Leu Ile Cys Lys Lys Gly Thr Leu Thr Glu Gly Gly Thr Gln 
                165                 170                 175     


Lys Thr Phe Asp Lys Gln Ile Val Leu Leu Phe Ala Val Phe Asp Glu 
            180                 185                 190         


Ser Lys Ser Trp Ser Gln Ser Ser Ser Leu Met Tyr Thr Val Asn Gly 
        195                 200                 205             


Tyr Val Asn Gly Thr Met Pro Asp Ile Thr Val Cys Ala His Asp His 
    210                 215                 220                 


Ile Ser Trp His Leu Leu Gly Met Ser Ser Gly Pro Glu Leu Phe Ser 
225                 230                 235                 240 


Ile His Phe Asn Gly Gln Val Leu Glu Gln Asn His His Lys Val Ser 
                245                 250                 255     


Ala Ile Thr Leu Val Ser Ala Thr Ser Thr Thr Ala Asn Met Thr Val 
            260                 265                 270         


Gly Pro Glu Gly Lys Trp Ile Ile Ser Ser Leu Thr Pro Lys His Leu 
        275                 280                 285             


Gln Ala Gly Met Gln Ala Tyr Ile Asp Ile Lys Asn Cys Pro Lys Lys 
    290                 295                 300                 


Thr Gln Asn Leu Lys Lys Ile Thr Arg Glu Gln Arg Arg His Met Lys 
305                 310                 315                 320 


Arg Trp Glu Tyr Phe Ile Ala Ala Glu Glu Val Ile Trp Asp Tyr Ala 
                325                 330                 335     


Pro Val Ile Pro Ala Asn Met Asp Lys Lys Tyr Arg Ser Gln His Leu 
            340                 345                 350         


Asp Asn Phe Ser Asn Gln Ile Gly Lys His Tyr Lys Lys Val Met Tyr 
        355                 360                 365             


Thr Gln Tyr Glu Asp Glu Ser Phe Thr Lys His Thr Val Asn Pro Asn 
    370                 375                 380                 


Met Lys Glu Asp Gly Ile Leu Gly Pro Ile Ile Arg Ala Gln Val Arg 
385                 390                 395                 400 


Asp Thr Leu Lys Ile Val Phe Lys Asn Met Ala Ser Arg Pro Tyr Ser 
                405                 410                 415     


Ile Tyr Pro His Gly Val Thr Phe Ser Pro Tyr Glu Asp Glu Val Asn 
            420                 425                 430         


Ser Ser Phe Thr Ser Gly Arg Asn Asn Thr Met Ile Arg Ala Val Gln 
        435                 440                 445             


Pro Gly Glu Thr Tyr Thr Tyr Lys Trp Asn Ile Leu Glu Phe Asp Glu 
    450                 455                 460                 


Pro Thr Glu Asn Asp Ala Gln Cys Leu Thr Arg Pro Tyr Tyr Ser Asp 
465                 470                 475                 480 


Val Asp Ile Met Arg Asp Ile Ala Ser Gly Leu Ile Gly Leu Leu Leu 
                485                 490                 495     


Ile Cys Lys Ser Arg Ser Leu Asp Arg Gln Gly Ile Gln Arg Ala Ala 
            500                 505                 510         


Asp Ile Glu Gln Gln Ala Val Phe Ala Val Phe Asp Glu Asn Lys Ser 
        515                 520                 525             


Trp Tyr Leu Glu Asp Asn Ile Asn Lys Phe Cys Glu Asn Pro Asp Glu 
    530                 535                 540                 


Val Lys Arg Asp Asp Pro Lys Phe Tyr Glu Ser Asn Ile Met Ser Thr 
545                 550                 555                 560 


Ile Asn Gly Tyr Val Pro Glu Ser Ile Thr Thr Leu Gly Phe Cys Phe 
                565                 570                 575     


Asp Asp Thr Val Gln Trp His Phe Cys Ser Val Gly Thr Gln Asn Glu 
            580                 585                 590         


Ile Leu Thr Ile His Phe Thr Gly His Ser Phe Ile Tyr Gly Lys Arg 
        595                 600                 605             


Cys Glu Asp Thr Leu Thr Leu Phe Pro Met Arg Gly Glu Ser Val Thr 
    610                 615                 620                 


Val Thr Met Asp Asn Val Gly Thr Trp Met Leu Thr Ser Met Asn Ser 
625                 630                 635                 640 


Ser Pro Arg Ser Lys Lys Leu Arg Leu Lys Phe Arg Asp Val Lys Cys 
                645                 650                 655     


Ile Pro Asp Asp Asp Glu Asp Ser Tyr Glu Ile Phe Glu Pro Pro Glu 
            660                 665                 670         


Ser Thr Val Met Ala Thr Gln Lys Met His Asp Arg Leu Glu Pro Glu 
        675                 680                 685             


Asp Glu Glu Ser Asp Ala Asp Tyr Asp Tyr Gln Asn Arg Leu Ala Ala 
    690                 695                 700                 


Ala Leu Gly Ile Arg Ser Phe Arg Asn Ser Ser Leu Asn Gln Glu Glu 
705                 710                 715                 720 


Glu Glu Phe Asn Leu Thr Ala Leu Ala Leu Glu Asn Gly Thr Glu Phe 
                725                 730                 735     


Val Ser Ser Asn Thr Asp Ile Ile Val Gly Ser Asn Tyr Ser Ser Pro 
            740                 745                 750         


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


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


Leu Ile Gly Lys Asn Ser Val Leu Asn Ser Ser Thr Ala Glu His Ser 
785                 790                 795                 800 


Ser Pro Tyr Ser Glu Asp Pro Ile Glu Asp Pro Thr Asp Tyr Ile Glu 
                805                 810                 815     


Ile Ile Pro Lys Glu Glu Val Gln Ser Ser Glu Asp Asp Tyr Ala Glu 
            820                 825                 830         


Ile Asp Tyr Val Pro Tyr Asp Asp Pro Tyr Lys Thr Asp Val Arg Thr 
        835                 840                 845             


Asn Ile Asn Ser Ser Arg Asp Pro Asp Asn Ile Ala Ala Trp Tyr Leu 
    850                 855                 860                 


Arg Ser Asn Asn Gly Asn Arg Arg Asn Tyr Tyr Ile Ala Ala Glu Glu 
865                 870                 875                 880 


Ile Ser Trp Asp Tyr Ser Glu Phe Val Gln Arg Glu Thr Asp Ile Glu 
                885                 890                 895     


Asp Ser Asp Asp Ile Pro Glu Asp Thr Thr Tyr Lys Lys Val Val Phe 
            900                 905                 910         


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


Tyr Glu Glu His Leu Gly Ile Leu Gly Pro Ile Ile Arg Ala Glu Val 
    930                 935                 940                 


Asp Asp Val Ile Gln Val Arg Phe Lys Asn Leu Ala Ser Arg Pro Tyr 
945                 950                 955                 960 


Ser Leu His Ala His Gly Leu Ser Tyr Glu Lys Ser Ser Glu Gly Lys 
                965                 970                 975     


Thr Tyr Glu Asp Asp Ser Pro Glu Trp Phe Lys Glu Asp Asn Ala Val 
            980                 985                 990         


Gln Pro Asn Ser Ser Tyr Thr Tyr  Val Trp His Ala Thr  Glu Arg Ser 
        995                 1000                 1005             


Gly Pro  Cys Ser Pro Gly Ser  Ala Cys Arg Ala Trp  Ala Tyr Tyr 
    1010                 1015                 1020             


Ser Ala  Val Asn Pro Glu Lys  Asp Ile His Ser Gly  Leu Ile Gly 
    1025                 1030                 1035             


Pro Leu  Leu Ile Cys Gln Lys  Gly Ile Leu His Lys  Asp Ser Asn 
    1040                 1045                 1050             


Met Pro  Val Asp Met Arg Glu  Phe Val Leu Leu Phe  Met Thr Phe 
    1055                 1060                 1065             


Asp Glu  Lys Lys Ser Trp Tyr  Tyr Glu Lys Lys Ser  Arg Ser Ser 
    1070                 1075                 1080             


Trp Arg  Leu Thr Ser Ser Glu  Met Lys Lys Ser His  Glu Phe His 
    1085                 1090                 1095             


Ala Ile  Asn Gly Met Ile Tyr  Ser Leu Pro Gly Leu  Lys Met Tyr 
    1100                 1105                 1110             


Glu Gln  Glu Trp Val Arg Leu  His Leu Leu Asn Ile  Gly Gly Ser 
    1115                 1120                 1125             


Gln Asp  Ile His Val Val His  Phe His Gly Gln Thr  Leu Leu Glu 
    1130                 1135                 1140             


Asn Gly  Asn Lys Gln His Gln  Leu Gly Val Trp Pro  Leu Leu Pro 
    1145                 1150                 1155             


Gly Ser  Phe Lys Thr Leu Glu  Met Lys Ala Ser Lys  Pro Gly Trp 
    1160                 1165                 1170             


Trp Leu  Leu Asn Thr Glu Val  Gly Glu Asn Gln Arg  Ala Gly Met 
    1175                 1180                 1185             


Gln Thr  Pro Phe Leu Ile Met  Asp Arg Asp Cys Arg  Met Pro Met 
    1190                 1195                 1200             


Gly Leu  Ser Thr Gly Ile Ile  Ser Asp Ser Gln Ile  Lys Ala Ser 
    1205                 1210                 1215             


Glu Phe  Leu Gly Tyr Trp Glu  Pro Arg Leu Ala Arg  Leu Asn Asn 
    1220                 1225                 1230             


Gly Gly  Ser Tyr Asn Ala Trp  Ser Val Glu Lys Leu  Ala Ala Glu 
    1235                 1240                 1245             


Phe Ala  Ser Lys Pro Trp Ile  Gln Val Asp Met Gln  Lys Glu Val 
    1250                 1255                 1260             


Ile Ile  Thr Gly Ile Gln Thr  Gln Gly Ala Lys His  Tyr Leu Lys 
    1265                 1270                 1275             


Ser Cys  Tyr Thr Thr Glu Phe  Tyr Val Ala Tyr Ser  Ser Asn Gln 
    1280                 1285                 1290             


Ile Asn  Trp Gln Ile Phe Lys  Gly Asn Ser Thr Arg  Asn Val Met 
    1295                 1300                 1305             


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


Phe Asp  Pro Pro Ile Val Ala  Arg Tyr Ile Arg Ile  Ser Pro Thr 
    1325                 1330                 1335             


Arg Ala  Tyr Asn Arg Pro Thr  Leu Arg Leu Glu Leu  Gln Gly Cys 
    1340                 1345                 1350             


Glu Val  Asn Gly Cys Ser Thr  Pro Leu Gly Met Glu  Asn Gly Lys 
    1355                 1360                 1365             


Ile Glu  Asn Lys Gln Ile Thr  Ala Ser Ser Phe Lys  Lys Ser Trp 
    1370                 1375                 1380             


Trp Gly  Asp Tyr Trp Glu Pro  Phe Arg Ala Arg Leu  Asn Ala Gln 
    1385                 1390                 1395             


Gly Arg  Val Asn Ala Trp Gln  Ala Lys Ala Asn Asn  Asn Lys Gln 
    1400                 1405                 1410             


Trp Leu  Glu Ile Asp Leu Leu  Lys Ile Lys Lys Ile  Thr Ala Ile 
    1415                 1420                 1425             


Ile Thr  Gln Gly Cys Lys Ser  Leu Ser Ser Glu Met  Tyr Val Lys 
    1430                 1435                 1440             


Ser Tyr  Thr Ile His Tyr Ser  Glu Gln Gly Val Glu  Trp Lys Pro 
    1445                 1450                 1455             


Tyr Arg  Leu Lys Ser Ser Met  Val Asp Lys Ile Phe  Glu Gly Asn 
    1460                 1465                 1470             


Thr Asn  Thr Lys Gly His Val  Lys Asn Phe Phe Asn  Pro Pro Ile 
    1475                 1480                 1485             


Ile Ser  Arg Phe Ile Arg Val  Ile Pro Lys Thr Trp  Asn Gln Ala 
    1490                 1495                 1500             


Ile Thr  Leu Arg Leu Glu Leu  Phe Gly Cys Asp Ile  Tyr 
    1505                 1510                 1515     


<210>  2
<211>  406
<212>  PRT
<213>  Homo sapiens

<400>  2

Ala Asn Ala Phe Leu Glu Glu Leu Arg Pro Gly Ser Leu Glu Arg Glu 
1               5                   10                  15      


Cys Lys Glu Glu Gln Cys Ser Phe Glu Glu Ala Arg Glu Ile Phe Lys 
            20                  25                  30          


Asp Ala Glu Arg Thr Lys Leu Phe Trp Ile Ser Tyr Ser Asp Gly Asp 
        35                  40                  45              


Gln Cys Ala Ser Ser Pro Cys Gln Asn Gly Gly Ser Cys Lys Asp Gln 
    50                  55                  60                  


Leu Gln Ser Tyr Ile Cys Phe Cys Leu Pro Ala Phe Glu Gly Arg Asn 
65                  70                  75                  80  


Cys Glu Thr His Lys Asp Asp Gln Leu Ile Cys Val Asn Glu Asn Gly 
                85                  90                  95      


Gly Cys Glu Gln Tyr Cys Ser Asp His Thr Gly Thr Lys Arg Ser Cys 
            100                 105                 110         


Arg Cys His Glu Gly Tyr Ser Leu Leu Ala Asp Gly Val Ser Cys Thr 
        115                 120                 125             


Pro Thr Val Glu Tyr Pro Cys Gly Lys Ile Pro Ile Leu Glu Lys Arg 
    130                 135                 140                 


Asn Ala Ser Lys Pro Gln Gly Arg Ile Val Gly Gly Lys Val Cys Pro 
145                 150                 155                 160 


Lys Gly Glu Cys Pro Trp Gln Val Leu Leu Leu Val Asn Gly Ala Gln 
                165                 170                 175     


Leu Cys Gly Gly Thr Leu Ile Asn Thr Ile Trp Val Val Ser Ala Ala 
            180                 185                 190         


His Cys Phe Asp Lys Ile Lys Asn Trp Arg Asn Leu Ile Ala Val Leu 
        195                 200                 205             


Gly Glu His Asp Leu Ser Glu His Asp Gly Asp Glu Gln Ser Arg Arg 
    210                 215                 220                 


Val Ala Gln Val Ile Ile Pro Ser Thr Tyr Val Pro Gly Thr Thr Asn 
225                 230                 235                 240 


His Asp Ile Ala Leu Leu Arg Leu His Gln Pro Val Val Leu Thr Asp 
                245                 250                 255     


His Val Val Pro Leu Cys Leu Pro Glu Arg Thr Phe Ser Glu Arg Thr 
            260                 265                 270         


Leu Ala Phe Val Arg Phe Ser Leu Val Ser Gly Trp Gly Gln Leu Leu 
        275                 280                 285             


Asp Arg Gly Ala Thr Ala Leu Glu Leu Met Val Leu Asn Val Pro Arg 
    290                 295                 300                 


Leu Met Thr Gln Asp Cys Leu Gln Gln Ser Arg Lys Val Gly Asp Ser 
305                 310                 315                 320 


Pro Asn Ile Thr Glu Tyr Met Phe Cys Ala Gly Tyr Ser Asp Gly Ser 
                325                 330                 335     


Lys Asp Ser Cys Lys Gly Asp Ser Gly Gly Pro His Ala Thr His Tyr 
            340                 345                 350         


Arg Gly Thr Trp Tyr Leu Thr Gly Ile Val Ser Trp Gly Gln Gly Cys 
        355                 360                 365             


Ala Thr Val Gly His Phe Gly Val Tyr Thr Arg Val Ser Gln Tyr Ile 
    370                 375                 380                 


Glu Trp Leu Gln Lys Leu Met Arg Ser Glu Pro Arg Pro Gly Val Leu 
385                 390                 395                 400 


Leu Arg Ala Pro Phe Pro 
                405     


<210>  3
<211>  466
<212>  PRT
<213>  Homo sapiens

<400>  3

Met Val Ser Gln Ala Leu Arg Leu Leu Cys Leu Leu Leu Gly Leu Gln 
1               5                   10                  15      


Gly Cys Leu Ala Ala Gly Gly Val Ala Lys Ala Ser Gly Gly Glu Thr 
            20                  25                  30          


Arg Asp Met Pro Trp Lys Pro Gly Pro His Arg Val Phe Val Thr Gln 
        35                  40                  45              


Glu Glu Ala His Gly Val Leu His Arg Arg Arg Arg Ala Asn Ala Phe 
    50                  55                  60                  


Leu Glu Glu Leu Arg Pro Gly Ser Leu Glu Arg Glu Cys Lys Glu Glu 
65                  70                  75                  80  


Gln Cys Ser Phe Glu Glu Ala Arg Glu Ile Phe Lys Asp Ala Glu Arg 
                85                  90                  95      


Thr Lys Leu Phe Trp Ile Ser Tyr Ser Asp Gly Asp Gln Cys Ala Ser 
            100                 105                 110         


Ser Pro Cys Gln Asn Gly Gly Ser Cys Lys Asp Gln Leu Gln Ser Tyr 
        115                 120                 125             


Ile Cys Phe Cys Leu Pro Ala Phe Glu Gly Arg Asn Cys Glu Thr His 
    130                 135                 140                 


Lys Asp Asp Gln Leu Ile Cys Val Asn Glu Asn Gly Gly Cys Glu Gln 
145                 150                 155                 160 


Tyr Cys Ser Asp His Thr Gly Thr Lys Arg Ser Cys Arg Cys His Glu 
                165                 170                 175     


Gly Tyr Ser Leu Leu Ala Asp Gly Val Ser Cys Thr Pro Thr Val Glu 
            180                 185                 190         


Tyr Pro Cys Gly Lys Ile Pro Ile Leu Glu Lys Arg Asn Ala Ser Lys 
        195                 200                 205             


Pro Gln Gly Arg Ile Val Gly Gly Lys Val Cys Pro Lys Gly Glu Cys 
    210                 215                 220                 


Pro Trp Gln Val Leu Leu Leu Val Asn Gly Ala Gln Leu Cys Gly Gly 
225                 230                 235                 240 


Thr Leu Ile Asn Thr Ile Trp Val Val Ser Ala Ala His Cys Phe Asp 
                245                 250                 255     


Lys Ile Lys Asn Trp Arg Asn Leu Ile Ala Val Leu Gly Glu His Asp 
            260                 265                 270         


Leu Ser Glu His Asp Gly Asp Glu Gln Ser Arg Arg Val Ala Gln Val 
        275                 280                 285             


Ile Ile Pro Ser Thr Tyr Val Pro Gly Thr Thr Asn His Asp Ile Ala 
    290                 295                 300                 


Leu Leu Arg Leu His Gln Pro Val Val Leu Thr Asp His Val Val Pro 
305                 310                 315                 320 


Leu Cys Leu Pro Glu Arg Thr Phe Ser Glu Arg Thr Leu Ala Phe Val 
                325                 330                 335     


Arg Phe Ser Leu Val Ser Gly Trp Gly Gln Leu Leu Asp Arg Gly Ala 
            340                 345                 350         


Thr Ala Leu Glu Leu Met Val Leu Asn Val Pro Arg Leu Met Thr Gln 
        355                 360                 365             


Asp Cys Leu Gln Gln Ser Arg Lys Val Gly Asp Ser Pro Asn Ile Thr 
    370                 375                 380                 


Glu Tyr Met Phe Cys Ala Gly Tyr Ser Asp Gly Ser Lys Asp Ser Cys 
385                 390                 395                 400 


Lys Gly Asp Ser Gly Gly Pro His Ala Thr His Tyr Arg Gly Thr Trp 
                405                 410                 415     


Tyr Leu Thr Gly Ile Val Ser Trp Gly Gln Gly Cys Ala Thr Val Gly 
            420                 425                 430         


His Phe Gly Val Tyr Thr Arg Val Ser Gln Tyr Ile Glu Trp Leu Gln 
        435                 440                 445             


Lys Leu Met Arg Ser Glu Pro Arg Pro Gly Val Leu Leu Arg Ala Pro 
    450                 455                 460                 


Phe Pro 
465     


<210>  4
<211>  1516
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  super FVa

<400>  4

Ala Gln Leu Arg Gln Phe Tyr Val Ala Ala Gln Gly Ile Ser Trp Ser 
1               5                   10                  15      


Tyr Arg Pro Glu Pro Thr Asn Ser Ser Leu Asn Leu Ser Val Thr Ser 
            20                  25                  30          


Phe Lys Lys Ile Val Tyr Arg Glu Tyr Glu Pro Tyr Phe Lys Lys Glu 
        35                  40                  45              


Lys Pro Gln Ser Thr Ile Ser Gly Leu Leu Gly Pro Thr Leu Tyr Ala 
    50                  55                  60                  


Glu Val Gly Asp Ile Ile Lys Val His Phe Lys Asn Lys Ala Asp Lys 
65                  70                  75                  80  


Pro Leu Ser Ile His Pro Gln Gly Ile Arg Tyr Ser Lys Leu Ser Glu 
                85                  90                  95      


Gly Ala Ser Tyr Leu Asp His Thr Phe Pro Ala Glu Lys Met Asp Asp 
            100                 105                 110         


Ala Val Ala Pro Gly Arg Glu Tyr Thr Tyr Glu Trp Ser Ile Ser Glu 
        115                 120                 125             


Asp Ser Gly Pro Thr His Asp Asp Pro Pro Cys Leu Thr His Ile Tyr 
    130                 135                 140                 


Tyr Ser His Glu Asn Leu Ile Glu Asp Phe Asn Ser Gly Leu Ile Gly 
145                 150                 155                 160 


Pro Leu Leu Ile Cys Lys Lys Gly Thr Leu Thr Glu Gly Gly Thr Gln 
                165                 170                 175     


Lys Thr Phe Asp Lys Gln Ile Val Leu Leu Phe Ala Val Phe Asp Glu 
            180                 185                 190         


Ser Lys Ser Trp Ser Gln Ser Ser Ser Leu Met Tyr Thr Val Asn Gly 
        195                 200                 205             


Tyr Val Asn Gly Thr Met Pro Asp Ile Thr Val Cys Ala His Asp His 
    210                 215                 220                 


Ile Ser Trp His Leu Leu Gly Met Ser Ser Gly Pro Glu Leu Phe Ser 
225                 230                 235                 240 


Ile His Phe Asn Gly Gln Val Leu Glu Gln Asn His His Lys Val Ser 
                245                 250                 255     


Ala Ile Thr Leu Val Ser Ala Thr Ser Thr Thr Ala Asn Met Thr Val 
            260                 265                 270         


Gly Pro Glu Gly Lys Trp Ile Ile Ser Ser Leu Thr Pro Lys His Leu 
        275                 280                 285             


Gln Ala Gly Met Gln Ala Tyr Ile Asp Ile Lys Asn Cys Pro Lys Lys 
    290                 295                 300                 


Thr Gln Asn Leu Lys Lys Ile Thr Arg Glu Gln Arg Arg His Met Lys 
305                 310                 315                 320 


Arg Trp Glu Tyr Phe Ile Ala Ala Glu Glu Val Ile Trp Asp Tyr Ala 
                325                 330                 335     


Pro Val Ile Pro Ala Asn Met Asp Lys Lys Tyr Arg Ser Gln His Leu 
            340                 345                 350         


Asp Asn Phe Ser Asn Gln Ile Gly Lys His Tyr Lys Lys Val Met Tyr 
        355                 360                 365             


Thr Gln Tyr Glu Asp Glu Ser Phe Thr Lys His Thr Val Asn Pro Asn 
    370                 375                 380                 


Met Lys Glu Asp Gly Ile Leu Gly Pro Ile Ile Arg Ala Gln Val Arg 
385                 390                 395                 400 


Asp Thr Leu Lys Ile Val Phe Lys Asn Met Ala Ser Arg Pro Tyr Ser 
                405                 410                 415     


Ile Tyr Pro His Gly Val Thr Phe Ser Pro Tyr Glu Asp Glu Val Asn 
            420                 425                 430         


Ser Ser Phe Thr Ser Gly Arg Asn Asn Thr Met Ile Arg Ala Val Gln 
        435                 440                 445             


Pro Gly Glu Thr Tyr Thr Tyr Lys Trp Asn Ile Leu Glu Phe Asp Glu 
    450                 455                 460                 


Pro Thr Glu Asn Asp Ala Gln Cys Leu Thr Arg Pro Tyr Tyr Ser Asp 
465                 470                 475                 480 


Val Asp Ile Met Arg Asp Ile Ala Ser Gly Leu Ile Gly Leu Leu Leu 
                485                 490                 495     


Ile Cys Lys Ser Arg Ser Leu Asp Arg Gln Gly Ile Gln Arg Ala Ala 
            500                 505                 510         


Asp Ile Glu Gln Gln Ala Val Phe Ala Val Phe Asp Glu Asn Lys Ser 
        515                 520                 525             


Trp Tyr Leu Glu Asp Asn Ile Asn Lys Phe Cys Glu Asn Pro Asp Glu 
    530                 535                 540                 


Val Lys Arg Asp Asp Pro Lys Phe Tyr Glu Ser Asn Ile Met Ser Thr 
545                 550                 555                 560 


Ile Asn Gly Tyr Val Pro Glu Ser Ile Thr Thr Leu Gly Phe Cys Phe 
                565                 570                 575     


Asp Asp Thr Val Gln Trp His Phe Cys Ser Val Gly Thr Gln Asn Glu 
            580                 585                 590         


Ile Leu Thr Ile His Phe Thr Gly His Ser Phe Ile Tyr Gly Lys Arg 
        595                 600                 605             


Cys Glu Asp Thr Leu Thr Leu Phe Pro Met Arg Gly Glu Ser Val Thr 
    610                 615                 620                 


Val Thr Met Asp Asn Val Gly Thr Trp Met Leu Thr Ser Met Asn Ser 
625                 630                 635                 640 


Ser Pro Arg Ser Lys Lys Leu Arg Leu Lys Phe Arg Asp Val Lys Cys 
                645                 650                 655     


Ile Pro Asp Asp Asp Glu Asp Ser Tyr Glu Ile Phe Glu Pro Pro Glu 
            660                 665                 670         


Ser Thr Val Met Ala Thr Gln Lys Met His Asp Arg Leu Glu Pro Glu 
        675                 680                 685             


Asp Glu Glu Ser Asp Ala Asp Tyr Asp Tyr Gln Asn Arg Leu Ala Ala 
    690                 695                 700                 


Ala Leu Gly Ile Arg Ser Phe Arg Asn Ser Ser Leu Asn Gln Glu Glu 
705                 710                 715                 720 


Glu Glu Phe Asn Leu Thr Ala Leu Ala Leu Glu Asn Gly Thr Glu Phe 
                725                 730                 735     


Val Ser Ser Asn Thr Asp Ile Ile Val Gly Ser Asn Tyr Ser Ser Pro 
            740                 745                 750         


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


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


Leu Ile Gly Lys Asn Ser Val Leu Asn Ser Ser Thr Ala Glu His Ser 
785                 790                 795                 800 


Ser Pro Tyr Ser Glu Asp Pro Ile Glu Asp Pro Thr Asp Tyr Ile Glu 
                805                 810                 815     


Ile Ile Pro Lys Glu Glu Val Gln Ser Ser Glu Asp Asp Tyr Ala Glu 
            820                 825                 830         


Ile Asp Tyr Val Pro Tyr Asp Asp Pro Tyr Lys Thr Asp Val Arg Thr 
        835                 840                 845             


Asn Ile Asn Ser Ser Arg Asp Pro Asp Asn Ile Ala Ala Trp Tyr Leu 
    850                 855                 860                 


Arg Ser Asn Asn Gly Asn Arg Arg Asn Tyr Tyr Ile Ala Ala Glu Glu 
865                 870                 875                 880 


Ile Ser Trp Asp Tyr Ser Glu Phe Val Gln Arg Glu Thr Asp Ile Glu 
                885                 890                 895     


Asp Ser Asp Asp Ile Pro Glu Asp Thr Thr Tyr Lys Lys Val Val Phe 
            900                 905                 910         


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


Tyr Glu Glu His Leu Gly Ile Leu Gly Pro Ile Ile Arg Ala Glu Val 
    930                 935                 940                 


Asp Asp Val Ile Gln Val Arg Phe Lys Asn Leu Ala Ser Arg Pro Tyr 
945                 950                 955                 960 


Ser Leu His Ala His Gly Leu Ser Tyr Glu Lys Ser Ser Glu Gly Lys 
                965                 970                 975     


Thr Tyr Glu Asp Asp Ser Pro Glu Trp Phe Lys Glu Asp Asn Ala Val 
            980                 985                 990         


Gln Pro Asn Ser Ser Tyr Thr Tyr  Val Trp His Ala Thr  Glu Arg Ser 
        995                 1000                 1005             


Gly Pro  Cys Ser Pro Gly Ser  Ala Cys Arg Ala Trp  Ala Tyr Tyr 
    1010                 1015                 1020             


Ser Ala  Val Asn Pro Glu Lys  Asp Ile His Ser Gly  Leu Ile Gly 
    1025                 1030                 1035             


Pro Leu  Leu Ile Cys Gln Lys  Gly Ile Leu His Lys  Asp Ser Asn 
    1040                 1045                 1050             


Met Pro  Val Asp Met Arg Glu  Phe Val Leu Leu Phe  Met Thr Phe 
    1055                 1060                 1065             


Asp Glu  Lys Lys Ser Trp Tyr  Tyr Glu Lys Lys Ser  Arg Ser Ser 
    1070                 1075                 1080             


Trp Arg  Leu Thr Ser Ser Glu  Met Lys Lys Ser His  Glu Phe His 
    1085                 1090                 1095             


Ala Ile  Asn Gly Met Ile Tyr  Ser Leu Pro Gly Leu  Lys Met Tyr 
    1100                 1105                 1110             


Glu Gln  Glu Trp Val Arg Leu  His Leu Leu Asn Ile  Gly Gly Ser 
    1115                 1120                 1125             


Gln Asp  Ile His Val Val His  Phe His Gly Gln Thr  Leu Leu Glu 
    1130                 1135                 1140             


Asn Gly  Asn Lys Gln His Gln  Leu Gly Val Trp Pro  Leu Leu Pro 
    1145                 1150                 1155             


Gly Ser  Phe Lys Thr Leu Glu  Met Lys Ala Ser Lys  Pro Gly Trp 
    1160                 1165                 1170             


Trp Leu  Leu Asn Thr Glu Val  Gly Glu Asn Gln Arg  Ala Gly Met 
    1175                 1180                 1185             


Gln Thr  Pro Phe Leu Ile Met  Asp Arg Asp Cys Arg  Met Pro Met 
    1190                 1195                 1200             


Gly Leu  Ser Thr Gly Ile Ile  Ser Asp Ser Gln Ile  Lys Ala Ser 
    1205                 1210                 1215             


Glu Phe  Leu Gly Tyr Trp Glu  Pro Arg Leu Ala Arg  Leu Asn Asn 
    1220                 1225                 1230             


Gly Gly  Ser Tyr Asn Ala Trp  Ser Val Glu Lys Leu  Ala Ala Glu 
    1235                 1240                 1245             


Phe Ala  Ser Lys Pro Trp Ile  Gln Val Asp Met Gln  Lys Glu Val 
    1250                 1255                 1260             


Ile Ile  Thr Gly Ile Gln Thr  Gln Gly Ala Lys His  Tyr Leu Lys 
    1265                 1270                 1275             


Ser Cys  Tyr Thr Thr Glu Phe  Tyr Val Ala Tyr Ser  Ser Asn Gln 
    1280                 1285                 1290             


Ile Asn  Trp Gln Ile Phe Lys  Gly Asn Ser Thr Arg  Asn Val Met 
    1295                 1300                 1305             


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


Phe Asp  Pro Pro Ile Val Ala  Arg Tyr Ile Arg Ile  Ser Pro Thr 
    1325                 1330                 1335             


Arg Ala  Tyr Asn Arg Pro Thr  Leu Arg Leu Glu Leu  Gln Gly Cys 
    1340                 1345                 1350             


Glu Val  Asn Gly Cys Ser Thr  Pro Leu Gly Met Glu  Asn Gly Lys 
    1355                 1360                 1365             


Ile Glu  Asn Lys Gln Ile Thr  Ala Ser Ser Phe Lys  Lys Ser Trp 
    1370                 1375                 1380             


Trp Gly  Asp Tyr Trp Glu Pro  Phe Arg Ala Arg Leu  Asn Ala Gln 
    1385                 1390                 1395             


Gly Arg  Val Asn Ala Trp Gln  Ala Lys Ala Asn Asn  Asn Lys Gln 
    1400                 1405                 1410             


Trp Leu  Glu Ile Asp Leu Leu  Lys Ile Lys Lys Ile  Thr Ala Ile 
    1415                 1420                 1425             


Ile Thr  Gln Gly Cys Lys Ser  Leu Ser Ser Glu Met  Tyr Val Lys 
    1430                 1435                 1440             


Ser Tyr  Thr Ile His Tyr Ser  Glu Gln Gly Val Glu  Trp Lys Pro 
    1445                 1450                 1455             


Tyr Arg  Leu Lys Ser Ser Met  Val Asp Lys Ile Phe  Glu Gly Asn 
    1460                 1465                 1470             


Thr Asn  Thr Lys Gly His Val  Lys Asn Phe Phe Asn  Pro Pro Ile 
    1475                 1480                 1485             


Ile Ser  Arg Phe Ile Arg Val  Ile Pro Lys Thr Trp  Asn Gln Ala 
    1490                 1495                 1500             


Ile Ala  Leu Arg Leu Glu Leu  Phe Gly Cys Asp Ile  Tyr 
    1505                 1510                 1515     


