                         SEQUENCE LISTING

<110>  Hadasit Medical Research Services & Development Limited
 
<120>  PLASMINOGEN ACTIVATOR MUTANTS AS ANTI-FIBRINOLYTIC AGENTS

<130>  2231127

<150>  US 61/668,172
<151>  2012-07-05

<160>  17    

<170>  PatentIn version 3.5

<210>  1
<211>  530
<212>  PRT
<213>  Homo sapiens

<400>  1

Gly Ala Arg Ser Tyr Gln Val Ile Cys Arg Asp Glu Lys Thr Gln Met 
1               5                   10                  15      


Ile Tyr Gln Gln His Gln Ser Trp Leu Arg Pro Val Leu Arg Ser Asn 
            20                  25                  30          


Arg Val Glu Tyr Cys Trp Cys Asn Ser Gly Arg Ala Gln Cys His Ser 
        35                  40                  45              


Val Pro Val Lys Ser Cys Ser Glu Pro Arg Cys Phe Asn Gly Gly Thr 
    50                  55                  60                  


Cys Gln Gln Ala Leu Tyr Phe Ser Asp Phe Val Cys Gln Cys Pro Glu 
65                  70                  75                  80  


Gly Phe Ala Gly Lys Cys Cys Glu Ile Asp Thr Arg Ala Thr Cys Tyr 
                85                  90                  95      


Glu Asp Gln Gly Ile Ser Tyr Arg Gly Thr Trp Ser Thr Ala Glu Ser 
            100                 105                 110         


Gly Ala Glu Cys Thr Asn Trp Asn Ser Ser Ala Leu Ala Gln Lys Pro 
        115                 120                 125             


Tyr Ser Gly Arg Arg Pro Asp Ala Ile Arg Leu Gly Leu Gly Asn His 
    130                 135                 140                 


Asn Tyr Cys Arg Asn Pro Asp Arg Asp Ser Lys Pro Trp Cys Tyr Val 
145                 150                 155                 160 


Phe Lys Ala Gly Lys Tyr Ser Ser Glu Phe Cys Ser Thr Pro Ala Cys 
                165                 170                 175     


Ser Glu Gly Asn Ser Asp Cys Tyr Phe Gly Asn Gly Ser Ala Tyr Arg 
            180                 185                 190         


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


Ser Met Ile Leu Ile Gly Lys Val Tyr Thr Ala Gln Asn Pro Ser Ala 
    210                 215                 220                 


Gln Ala Leu Gly Leu Gly Lys His Asn Tyr Cys Arg Asn Pro Asp Gly 
225                 230                 235                 240 


Asp Ala Lys Pro Trp Cys His Val Leu Lys Asn Arg Arg Leu Thr Trp 
                245                 250                 255     


Glu Tyr Cys Asp Val Pro Ser Cys Ser Thr Cys Gly Leu Arg Gln Tyr 
            260                 265                 270         


Ser Gln Pro Gln Phe Arg Ile Lys Gly Gly Leu Phe Ala Asp Ile Ala 
        275                 280                 285             


Ser His Pro Trp Gln Ala Ala Ile Phe Ala Lys His Arg Arg Ser Pro 
    290                 295                 300                 


Gly Glu Arg Phe Leu Cys Gly Gly Ile Leu Ile Ser Ser Cys Trp Ile 
305                 310                 315                 320 


Leu Ser Ala Ala His Cys Phe Gln Glu Arg Phe Pro Pro His His Leu 
                325                 330                 335     


Thr Val Ile Leu Gly Arg Thr Tyr Arg Val Val Pro Gly Glu Glu Glu 
            340                 345                 350         


Gln Lys Phe Glu Val Glu Lys Tyr Ile Val His Lys Glu Phe Asp Asp 
        355                 360                 365             


Asp Thr Tyr Asp Asn Asp Ile Ala Leu Leu Gln Leu Lys Ser Asp Ser 
    370                 375                 380                 


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


Pro Ala Asp Leu Gln Leu Pro Asp Trp Thr Glu Cys Glu Leu Ser Gly 
                405                 410                 415     


Tyr Gly Lys His Glu Ala Leu Ser Pro Phe Tyr Ser Glu Arg Leu Lys 
            420                 425                 430         


Glu Ala His Val Arg Leu Tyr Pro Ser Ser Arg Cys Thr Ser Gln His 
        435                 440                 445             


Leu Leu Asn Arg Thr Val Thr Asp Asn Met Leu Cys Ala Gly Asp Thr 
    450                 455                 460                 


Arg Ser Gly Gly Pro Gln Ala Asn Leu His Asp Ala Cys Gln Gly Asp 
465                 470                 475                 480 


Ala Gly Gly Pro Leu Val Cys Leu Asn Asp Gly Arg Met Thr Leu Val 
                485                 490                 495     


Gly Ile Ile Ser Trp Gly Leu Gly Cys Gly Gln Lys Asp Val Pro Gly 
            500                 505                 510         


Val Tyr Thr Lys Val Thr Asn Tyr Leu Asp Trp Ile Arg Asp Asn Met 
        515                 520                 525             


Arg Pro 
    530 


<210>  2
<211>  530
<212>  PRT
<213>  Homo sapiens

<400>  2

Gly Ala Arg Ser Tyr Gln Val Ile Cys Arg Asp Glu Lys Thr Gln Met 
1               5                   10                  15      


Ile Tyr Gln Gln His Gln Ser Trp Leu Arg Pro Val Leu Arg Ser Asn 
            20                  25                  30          


Arg Val Glu Tyr Cys Trp Cys Asn Ser Gly Arg Ala Gln Cys His Ser 
        35                  40                  45              


Val Pro Val Lys Ser Cys Ser Glu Pro Arg Cys Phe Asn Gly Gly Thr 
    50                  55                  60                  


Cys Gln Gln Ala Leu Tyr Phe Ser Asp Phe Val Cys Gln Cys Pro Glu 
65                  70                  75                  80  


Gly Phe Ala Gly Lys Cys Cys Glu Ile Asp Thr Arg Ala Thr Cys Tyr 
                85                  90                  95      


Glu Asp Gln Gly Ile Ser Tyr Arg Gly Thr Trp Ser Thr Ala Glu Ser 
            100                 105                 110         


Gly Ala Glu Cys Thr Asn Trp Asn Ser Ser Ala Leu Ala Gln Lys Pro 
        115                 120                 125             


Tyr Ser Gly Arg Arg Pro Asp Ala Ile Arg Leu Gly Leu Gly Asn His 
    130                 135                 140                 


Asn Tyr Cys Arg Asn Pro Asp Arg Asp Ser Lys Pro Trp Cys Tyr Val 
145                 150                 155                 160 


Phe Lys Ala Gly Lys Tyr Ser Ser Glu Phe Cys Ser Thr Pro Ala Cys 
                165                 170                 175     


Ser Glu Gly Asn Ser Asp Cys Tyr Phe Gly Asn Gly Ser Ala Tyr Arg 
            180                 185                 190         


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


Ser Met Ile Leu Ile Gly Lys Val Tyr Thr Ala Gln Asn Pro Ser Ala 
    210                 215                 220                 


Gln Ala Leu Gly Leu Gly Lys His Asn Tyr Cys Arg Asn Pro Asp Gly 
225                 230                 235                 240 


Asp Ala Lys Pro Trp Cys His Val Leu Lys Asn Arg Arg Leu Thr Trp 
                245                 250                 255     


Glu Tyr Cys Asp Val Pro Ser Cys Ser Thr Cys Gly Leu Arg Gln Tyr 
            260                 265                 270         


Ser Gln Pro Gln Phe Arg Ile Lys Gly Gly Leu Phe Ala Asp Ile Ala 
        275                 280                 285             


Ser His Pro Trp Gln Ala Ala Ile Phe Ala Ala Ala Ala Ala Ser Pro 
    290                 295                 300                 


Gly Glu Arg Phe Leu Cys Gly Gly Ile Leu Ile Ser Ser Cys Trp Ile 
305                 310                 315                 320 


Leu Ser Ala Ala His Cys Phe Gln Glu Arg Phe Pro Pro His His Leu 
                325                 330                 335     


Thr Val Ile Leu Gly Arg Thr Tyr Arg Val Val Pro Gly Glu Glu Glu 
            340                 345                 350         


Gln Lys Phe Glu Val Glu Lys Tyr Ile Val His Lys Glu Phe Asp Asp 
        355                 360                 365             


Asp Thr Tyr Asp Asn Asp Ile Ala Leu Leu Gln Leu Lys Ser Asp Ser 
    370                 375                 380                 


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


Pro Ala Asp Leu Gln Leu Pro Asp Trp Thr Glu Cys Glu Leu Ser Gly 
                405                 410                 415     


Tyr Gly Lys His Glu Ala Leu Ser Pro Phe Tyr Ser Glu Arg Leu Lys 
            420                 425                 430         


Glu Ala His Val Arg Leu Tyr Pro Ser Ser Arg Cys Thr Ser Gln His 
        435                 440                 445             


Leu Leu Asn Arg Thr Val Thr Asp Asn Met Leu Cys Ala Gly Asp Thr 
    450                 455                 460                 


Arg Ser Gly Gly Pro Gln Ala Asn Leu His Asp Ala Cys Gln Gly Asp 
465                 470                 475                 480 


Ala Gly Gly Pro Leu Val Cys Leu Asn Asp Gly Arg Met Thr Leu Val 
                485                 490                 495     


Gly Ile Ile Ser Trp Gly Leu Gly Cys Gly Gln Lys Asp Val Pro Gly 
            500                 505                 510         


Val Tyr Thr Lys Val Thr Asn Tyr Leu Asp Trp Ile Arg Asp Asn Met 
        515                 520                 525             


Arg Pro 
    530 


<210>  3
<211>  530
<212>  PRT
<213>  Homo sapiens

<400>  3

Gly Ala Arg Ser Tyr Gln Val Ile Cys Arg Asp Glu Lys Thr Gln Met 
1               5                   10                  15      


Ile Tyr Gln Gln His Gln Ser Trp Leu Arg Pro Val Leu Arg Ser Asn 
            20                  25                  30          


Arg Val Glu Tyr Cys Trp Cys Asn Ser Gly Arg Ala Gln Cys His Ser 
        35                  40                  45              


Val Pro Val Lys Ser Cys Ser Glu Pro Arg Cys Phe Asn Gly Gly Thr 
    50                  55                  60                  


Cys Gln Gln Ala Leu Tyr Phe Ser Asp Phe Val Cys Gln Cys Pro Glu 
65                  70                  75                  80  


Gly Phe Ala Gly Lys Cys Cys Glu Ile Asp Thr Arg Ala Thr Cys Tyr 
                85                  90                  95      


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


Gly Ala Glu Cys Thr Asn Trp Gln Ser Ser Ala Leu Ala Gln Lys Pro 
        115                 120                 125             


Tyr Ser Gly Arg Arg Pro Asp Ala Ile Arg Leu Gly Leu Gly Asn His 
    130                 135                 140                 


Asn Tyr Cys Arg Asn Pro Asp Arg Asp Ser Lys Pro Trp Cys Tyr Val 
145                 150                 155                 160 


Phe Lys Ala Gly Lys Tyr Ser Ser Glu Phe Cys Ser Thr Pro Ala Cys 
                165                 170                 175     


Ser Glu Gly Asn Ser Asp Cys Tyr Phe Gly Asn Gly Ser Ala Tyr Arg 
            180                 185                 190         


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


Ser Met Ile Leu Ile Gly Lys Val Tyr Thr Ala Gln Asn Pro Ser Ala 
    210                 215                 220                 


Gln Ala Leu Gly Leu Gly Lys His Asn Tyr Cys Arg Asn Pro Asp Gly 
225                 230                 235                 240 


Asp Ala Lys Pro Trp Cys His Val Leu Lys Asn Arg Arg Leu Thr Trp 
                245                 250                 255     


Glu Tyr Cys Asp Val Pro Ser Cys Ser Thr Cys Gly Leu Arg Gln Tyr 
            260                 265                 270         


Ser Gln Pro Gln Phe Arg Ile Lys Gly Gly Leu Phe Ala Asp Ile Ala 
        275                 280                 285             


Ser His Pro Trp Gln Ala Ala Ile Phe Ala Lys His Arg Arg Ser Pro 
    290                 295                 300                 


Gly Glu Arg Phe Leu Cys Gly Gly Ile Leu Ile Ser Ser Cys Trp Ile 
305                 310                 315                 320 


Leu Ser Ala Ala His Cys Phe Gln Glu Arg Phe Pro Pro His His Leu 
                325                 330                 335     


Thr Val Ile Leu Gly Arg Thr Tyr Arg Val Val Pro Gly Glu Glu Glu 
            340                 345                 350         


Gln Lys Phe Glu Val Glu Lys Tyr Ile Val His Lys Glu Phe Asp Asp 
        355                 360                 365             


Asp Thr Tyr Asp Asn Asp Ile Ala Leu Leu Gln Leu Lys Ser Asp Ser 
    370                 375                 380                 


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


Pro Ala Asp Leu Gln Leu Pro Asp Trp Thr Glu Cys Glu Leu Ser Gly 
                405                 410                 415     


Tyr Gly Lys His Glu Ala Leu Ser Pro Phe Tyr Ser Glu Arg Leu Lys 
            420                 425                 430         


Glu Ala His Val Arg Leu Tyr Pro Ser Ser Arg Cys Thr Ser Gln His 
        435                 440                 445             


Leu Leu Asn Arg Thr Val Thr Asp Asn Met Leu Cys Ala Gly Asp Thr 
    450                 455                 460                 


Arg Ser Gly Gly Pro Gln Ala Asn Leu His Asp Ala Cys Gln Gly Asp 
465                 470                 475                 480 


Ala Gly Gly Pro Leu Val Cys Leu Asn Asp Gly Arg Met Thr Leu Val 
                485                 490                 495     


Gly Ile Ile Ser Trp Gly Leu Gly Cys Gly Gln Lys Asp Val Pro Gly 
            500                 505                 510         


Val Tyr Thr Lys Val Thr Asn Tyr Leu Asp Trp Ile Arg Asp Asn Met 
        515                 520                 525             


Arg Pro 
    530 


<210>  4
<211>  355
<212>  PRT
<213>  Homo sapiens

<400>  4

Ser Tyr Gln Gly Asn Ser Asp Cys Tyr Phe Gly Asn Gly Ser Ala Tyr 
1               5                   10                  15      


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


Asn Ser Met Ile Leu Ile Gly Lys Val Tyr Thr Ala Gln Asn Pro Ser 
        35                  40                  45              


Ala Gln Ala Leu Gly Leu Gly Lys His Asn Tyr Cys Arg Asn Pro Asp 
    50                  55                  60                  


Gly Asp Ala Lys Pro Trp Cys His Val Leu Lys Asn Arg Arg Leu Thr 
65                  70                  75                  80  


Trp Glu Tyr Cys Asp Val Pro Ser Cys Ser Thr Cys Gly Leu Arg Gln 
                85                  90                  95      


Tyr Ser Gln Pro Gln Phe Arg Ile Lys Gly Gly Leu Phe Ala Asp Ile 
            100                 105                 110         


Ala Ser His Pro Trp Gln Ala Ala Ile Phe Ala Lys His Arg Arg Ser 
        115                 120                 125             


Pro Gly Glu Arg Phe Leu Cys Gly Gly Ile Leu Ile Ser Ser Cys Trp 
    130                 135                 140                 


Ile Leu Ser Ala Ala His Cys Phe Gln Glu Arg Phe Pro Pro His His 
145                 150                 155                 160 


Leu Thr Val Ile Leu Gly Arg Thr Tyr Arg Val Val Pro Gly Glu Glu 
                165                 170                 175     


Glu Gln Lys Phe Glu Val Glu Lys Tyr Ile Val His Lys Glu Phe Asp 
            180                 185                 190         


Asp Asp Thr Tyr Asp Asn Asp Ile Ala Leu Leu Gln Leu Lys Ser Asp 
        195                 200                 205             


Ser Ser Arg Cys Ala Gln Glu Ser Ser Val Val Arg Thr Val Cys Leu 
    210                 215                 220                 


Pro Pro Ala Asp Leu Gln Leu Pro Asp Trp Thr Glu Cys Glu Leu Ser 
225                 230                 235                 240 


Gly Tyr Gly Lys His Glu Ala Leu Ser Pro Phe Tyr Ser Glu Arg Leu 
                245                 250                 255     


Lys Glu Ala His Val Arg Leu Tyr Pro Ser Ser Arg Cys Thr Ser Gln 
            260                 265                 270         


His Leu Leu Asn Arg Thr Val Thr Asp Asn Met Leu Cys Ala Gly Asp 
        275                 280                 285             


Thr Arg Ser Gly Gly Pro Gln Ala Asn Leu His Asp Ala Cys Gln Gly 
    290                 295                 300                 


Asp Ala Gly Gly Pro Leu Val Cys Leu Asn Asp Gly Arg Met Thr Leu 
305                 310                 315                 320 


Val Gly Ile Ile Ser Trp Gly Leu Gly Cys Gly Gln Lys Asp Val Pro 
                325                 330                 335     


Gly Val Tyr Thr Lys Val Thr Asn Tyr Leu Asp Trp Ile Arg Asp Asn 
            340                 345                 350         


Met Arg Pro 
        355 


<210>  5
<211>  411
<212>  PRT
<213>  Homo sapiens

<400>  5

Ser Asn Glu Leu His Gln Val Pro Ser Asn Cys Asp Cys Leu Asn Gly 
1               5                   10                  15      


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


Cys Pro Lys Lys Phe Gly Gly Gln His Cys Glu Ile Asp Lys Ser Lys 
        35                  40                  45              


Thr Cys Tyr Glu Gly Asn Gly His Phe Tyr Arg Gly Lys Ala Ser Thr 
    50                  55                  60                  


Asp Thr Met Gly Arg Pro Cys Leu Pro Trp Asn Ser Ala Thr Val Leu 
65                  70                  75                  80  


Gln Gln Thr Tyr His Ala His Arg Ser Asp Ala Leu Gln Leu Gly Leu 
                85                  90                  95      


Gly Lys His Asn Tyr Cys Arg Asn Pro Asp Asn Arg Arg Arg Pro Trp 
            100                 105                 110         


Cys Tyr Val Gln Val Gly Leu Lys Pro Leu Val Gln Glu Cys Met Val 
        115                 120                 125             


His Asp Cys Ala Asp Gly Lys Lys Pro Ser Ser Pro Pro Glu Glu Leu 
    130                 135                 140                 


Lys Phe Gln Cys Gly Gln Lys Thr Leu Arg Pro Arg Phe Lys Ile Ile 
145                 150                 155                 160 


Gly Gly Glu Phe Thr Thr Ile Glu Asn Gln Pro Trp Phe Ala Ala Ile 
                165                 170                 175     


Tyr Arg Arg His Arg Gly Gly Ser Val Thr Tyr Val Cys Gly Gly Ser 
            180                 185                 190         


Leu Ile Ser Pro Cys Trp Val Ile Ser Ala Thr His Cys Phe Ile Asp 
        195                 200                 205             


Tyr Pro Lys Lys Glu Asp Tyr Ile Val Tyr Leu Gly Arg Ser Arg Leu 
    210                 215                 220                 


Asn Ser Asn Thr Gln Gly Glu Met Lys Phe Glu Val Glu Asn Leu Ile 
225                 230                 235                 240 


Leu His Lys Asp Tyr Ser Ala Asp Thr Leu Ala His His Asn Asp Ile 
                245                 250                 255     


Ala Leu Leu Lys Ile Arg Ser Lys Glu Gly Arg Cys Ala Gln Pro Ser 
            260                 265                 270         


Arg Thr Ile Gln Thr Ile Cys Leu Pro Ser Met Tyr Asn Asp Pro Gln 
        275                 280                 285             


Phe Gly Thr Ser Cys Glu Ile Thr Gly Phe Gly Lys Glu Asn Ser Thr 
    290                 295                 300                 


Asp Tyr Leu Tyr Pro Glu Gln Leu Lys Met Thr Val Val Lys Leu Ile 
305                 310                 315                 320 


Ser His Arg Glu Cys Gln Gln Pro His Tyr Tyr Gly Ser Glu Val Thr 
                325                 330                 335     


Thr Lys Met Leu Cys Ala Ala Asp Pro Gln Trp Lys Thr Asp Ser Cys 
            340                 345                 350         


Gln Gly Asp Ala Gly Gly Pro Leu Val Cys Ser Leu Gln Gly Arg Met 
        355                 360                 365             


Thr Leu Thr Gly Ile Val Ser Trp Gly Arg Gly Cys Ala Leu Lys Asp 
    370                 375                 380                 


Lys Pro Gly Val Tyr Thr Arg Val Ser His Phe Leu Pro Trp Ile Arg 
385                 390                 395                 400 


Ser His Thr Lys Glu Glu Asn Gly Leu Ala Leu 
                405                 410     


<210>  6
<211>  411
<212>  PRT
<213>  Homo sapiens

<400>  6

Ser Asn Glu Leu His Gln Val Pro Ser Asn Cys Asp Cys Leu Asn Gly 
1               5                   10                  15      


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


Cys Pro Lys Lys Phe Gly Gly Gln His Cys Glu Ile Asp Lys Ser Lys 
        35                  40                  45              


Thr Cys Tyr Glu Gly Asn Gly His Phe Tyr Arg Gly Lys Ala Ser Thr 
    50                  55                  60                  


Asp Thr Met Gly Arg Pro Cys Leu Pro Trp Asn Ser Ala Thr Val Leu 
65                  70                  75                  80  


Gln Gln Thr Tyr His Ala His Arg Ser Asp Ala Leu Gln Leu Gly Leu 
                85                  90                  95      


Gly Lys His Asn Tyr Cys Arg Asn Pro Asp Asn Arg Arg Arg Pro Trp 
            100                 105                 110         


Cys Tyr Val Gln Val Gly Leu Lys Pro Leu Val Gln Glu Cys Met Val 
        115                 120                 125             


His Asp Cys Ala Asp Gly Lys Lys Pro Ser Ser Pro Pro Glu Glu Leu 
    130                 135                 140                 


Lys Phe Gln Cys Gly Gln Lys Thr Leu Arg Pro Arg Phe Lys Ile Ile 
145                 150                 155                 160 


Gly Gly Glu Phe Thr Thr Ile Glu Asn Gln Pro Trp Phe Ala Ala Ile 
                165                 170                 175     


Tyr Arg Arg His Arg Gly Gly Ser Val Thr Tyr Val Cys Gly Gly Ser 
            180                 185                 190         


Leu Ile Ser Pro Cys Trp Val Ile Ser Ala Thr His Cys Phe Ile Asp 
        195                 200                 205             


Tyr Pro Lys Lys Glu Asp Tyr Ile Val Tyr Leu Gly Arg Ser Arg Leu 
    210                 215                 220                 


Asn Ser Asn Thr Gln Gly Glu Met Lys Phe Glu Val Glu Asn Leu Ile 
225                 230                 235                 240 


Leu His Lys Asp Tyr Ser Ala Asp Thr Leu Ala His His Asn Asp Ile 
                245                 250                 255     


Ala Leu Leu Lys Ile Arg Ser Lys Glu Gly Arg Cys Ala Gln Pro Ser 
            260                 265                 270         


Arg Thr Ile Gln Thr Ile Cys Leu Pro Ser Met Tyr Asn Asp Pro Gln 
        275                 280                 285             


Phe Gly Thr Ser Cys Glu Ile Thr Gly Phe Gly Lys Glu Asn Ser Thr 
    290                 295                 300                 


Asp Tyr Leu Tyr Pro Glu Gln Leu Lys Met Thr Val Val Lys Leu Ile 
305                 310                 315                 320 


Ser His Arg Glu Cys Gln Gln Pro His Tyr Tyr Gly Ser Glu Val Thr 
                325                 330                 335     


Thr Lys Met Leu Cys Ala Ala Asp Pro Gln Trp Lys Thr Asp Ser Cys 
            340                 345                 350         


Gln Gly Asp Ser Gly Gly Pro Leu Val Cys Ser Leu Gln Gly Arg Met 
        355                 360                 365             


Thr Leu Thr Gly Ile Val Ser Trp Gly Arg Gly Cys Ala Leu Lys Asp 
    370                 375                 380                 


Lys Pro Gly Val Tyr Thr Arg Val Ser His Phe Leu Pro Trp Ile Arg 
385                 390                 395                 400 


Ser His Thr Lys Glu Glu Asn Gly Leu Ala Leu 
                405                 410     


<210>  7
<211>  530
<212>  PRT
<213>  Homo sapiens

<400>  7

Gly Ala Arg Ser Tyr Gln Val Ile Cys Arg Asp Glu Lys Thr Gln Met 
1               5                   10                  15      


Ile Tyr Gln Gln His Gln Ser Trp Leu Arg Pro Val Leu Arg Ser Asn 
            20                  25                  30          


Arg Val Glu Tyr Cys Trp Cys Asn Ser Gly Arg Ala Gln Cys His Ser 
        35                  40                  45              


Val Pro Val Lys Ser Cys Ser Glu Pro Arg Cys Phe Asn Gly Gly Thr 
    50                  55                  60                  


Cys Gln Gln Ala Leu Tyr Phe Ser Asp Phe Val Cys Gln Cys Pro Glu 
65                  70                  75                  80  


Gly Phe Ala Gly Lys Cys Cys Glu Ile Asp Thr Arg Ala Thr Cys Tyr 
                85                  90                  95      


Glu Asp Gln Gly Ile Ser Tyr Arg Gly Thr Trp Ser Thr Ala Glu Ser 
            100                 105                 110         


Gly Ala Glu Cys Thr Asn Trp Asn Ser Ser Ala Leu Ala Gln Lys Pro 
        115                 120                 125             


Tyr Ser Gly Arg Arg Pro Asp Ala Ile Arg Leu Gly Leu Gly Asn His 
    130                 135                 140                 


Asn Tyr Cys Arg Asn Pro Asp Arg Asp Ser Lys Pro Trp Cys Tyr Val 
145                 150                 155                 160 


Phe Lys Ala Gly Lys Tyr Ser Ser Glu Phe Cys Ser Thr Pro Ala Cys 
                165                 170                 175     


Ser Glu Gly Asn Ser Asp Cys Tyr Phe Gly Asn Gly Ser Ala Tyr Arg 
            180                 185                 190         


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


Ser Met Ile Leu Ile Gly Lys Val Tyr Thr Ala Gln Asn Pro Ser Ala 
    210                 215                 220                 


Gln Ala Leu Gly Leu Gly Lys His Asn Tyr Cys Arg Asn Pro Asp Gly 
225                 230                 235                 240 


Asp Ala Lys Pro Trp Cys His Val Leu Lys Asn Arg Arg Leu Thr Trp 
                245                 250                 255     


Glu Tyr Cys Asp Val Pro Ser Cys Ser Thr Cys Gly Leu Arg Gln Tyr 
            260                 265                 270         


Ser Gln Pro Gln Phe Arg Ile Lys Gly Gly Leu Phe Ala Asp Ile Ala 
        275                 280                 285             


Ser His Pro Trp Gln Ala Ala Ile Phe Ala Lys His Arg Arg Ser Pro 
    290                 295                 300                 


Gly Glu Arg Phe Leu Cys Gly Gly Ile Leu Ile Ser Ser Cys Trp Ile 
305                 310                 315                 320 


Leu Ser Ala Ala His Cys Phe Gln Glu Arg Phe Pro Pro His His Leu 
                325                 330                 335     


Thr Val Ile Leu Gly Arg Thr Tyr Arg Val Val Pro Gly Glu Glu Glu 
            340                 345                 350         


Gln Lys Phe Glu Val Glu Lys Tyr Ile Val His Lys Glu Phe Asp Asp 
        355                 360                 365             


Asp Thr Tyr Asp Asn Asp Ile Ala Leu Leu Gln Leu Lys Ser Asp Ser 
    370                 375                 380                 


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


Pro Ala Asp Leu Gln Leu Pro Asp Trp Thr Glu Cys Glu Leu Ser Gly 
                405                 410                 415     


Tyr Gly Lys His Glu Ala Leu Ser Pro Phe Tyr Ser Glu Arg Leu Lys 
            420                 425                 430         


Glu Ala His Val Arg Leu Tyr Pro Ser Ser Arg Cys Thr Ser Gln His 
        435                 440                 445             


Leu Leu Asn Arg Thr Val Thr Asp Asn Met Leu Cys Ala Gly Asp Thr 
    450                 455                 460                 


Arg Ser Gly Gly Pro Gln Ala Asn Leu His Asp Ala Cys Gln Gly Asp 
465                 470                 475                 480 


Ser Gly Gly Pro Leu Val Cys Leu Asn Asp Gly Arg Met Thr Leu Val 
                485                 490                 495     


Gly Ile Ile Ser Trp Gly Leu Gly Cys Gly Gln Lys Asp Val Pro Gly 
            500                 505                 510         


Val Tyr Thr Lys Val Thr Asn Tyr Leu Asp Trp Ile Arg Asp Asn Met 
        515                 520                 525             


Arg Pro 
    530 


<210>  8
<211>  39
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer htPA-Bgl II

<400>  8
gcccgattca gatctggagc ccgcagctac caagtgatc                              39


<210>  9
<211>  37
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer htPA-Xho I

<400>  9
ttttgaggac tcgagtgttc cttatcacgg tcgcatg                                37


<210>  10
<211>  33
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Anti-parallel primers for introduction of the S481A mutation - 
       Primer S481A

<400>  10
gcctgccagg gcgatgccgg aggccccctg gtg                                    33


<210>  11
<211>  33
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Anti-parallel primers for introduction of the S481A mutation - 
       Primer S481A reverse

<400>  11
caccaggggg cctccggcat cgccctggca ggc                                    33


<210>  12
<211>  532
<212>  PRT
<213>  Homo sapiens

<400>  12

Arg Ser Gly Ala Arg Ser Tyr Gln Val Ile Cys Arg Asp Glu Lys Thr 
1               5                   10                  15      


Gln Met Ile Tyr Gln Gln His Gln Ser Trp Leu Arg Pro Val Leu Arg 
            20                  25                  30          


Ser Asn Arg Val Glu Tyr Cys Trp Cys Asn Ser Gly Arg Ala Gln Cys 
        35                  40                  45              


His Ser Val Pro Val Lys Ser Cys Ser Glu Pro Arg Cys Phe Asn Gly 
    50                  55                  60                  


Gly Thr Cys Gln Gln Ala Leu Tyr Phe Ser Asp Phe Val Cys Gln Cys 
65                  70                  75                  80  


Pro Glu Gly Phe Ala Gly Lys Cys Cys Glu Ile Asp Thr Arg Ala Thr 
                85                  90                  95      


Cys Tyr Glu Asp Gln Gly Ile Ser Tyr Arg Gly Thr Trp Ser Thr Ala 
            100                 105                 110         


Glu Ser Gly Ala Glu Cys Thr Asn Trp Asn Ser Ser Ala Leu Ala Gln 
        115                 120                 125             


Lys Pro Tyr Ser Gly Arg Arg Pro Asp Ala Ile Arg Leu Gly Leu Gly 
    130                 135                 140                 


Asn His Asn Tyr Cys Arg Asn Pro Asp Arg Asp Ser Lys Pro Trp Cys 
145                 150                 155                 160 


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


Ala Cys Ser Glu Gly Asn Ser Asp Cys Tyr Phe Gly Asn Gly Ser Ala 
            180                 185                 190         


Tyr Arg Gly Thr His Ser Leu Thr Glu Ser Gly Ala Ser Cys Leu Pro 
        195                 200                 205             


Trp Asn Ser Met Ile Leu Ile Gly Lys Val Tyr Thr Ala Gln Asn Pro 
    210                 215                 220                 


Ser Ala Gln Ala Leu Gly Leu Gly Lys His Asn Tyr Cys Arg Asn Pro 
225                 230                 235                 240 


Asp Gly Asp Ala Lys Pro Trp Cys His Val Leu Lys Asn Arg Arg Leu 
                245                 250                 255     


Thr Trp Glu Tyr Cys Asp Val Pro Ser Cys Ser Thr Cys Gly Leu Arg 
            260                 265                 270         


Gln Tyr Ser Gln Pro Gln Phe Arg Ile Lys Gly Gly Leu Phe Ala Asp 
        275                 280                 285             


Ile Ala Ser His Pro Trp Gln Ala Ala Ile Phe Ala Lys His Arg Arg 
    290                 295                 300                 


Ser Pro Gly Glu Arg Phe Leu Cys Gly Gly Ile Leu Ile Ser Ser Cys 
305                 310                 315                 320 


Trp Ile Leu Ser Ala Ala His Cys Phe Gln Glu Arg Phe Pro Pro His 
                325                 330                 335     


His Leu Thr Val Ile Leu Gly Arg Thr Tyr Arg Val Val Pro Gly Glu 
            340                 345                 350         


Glu Glu Gln Lys Phe Glu Val Glu Lys Tyr Ile Val His Lys Glu Phe 
        355                 360                 365             


Asp Asp Asp Thr Tyr Asp Asn Asp Ile Ala Leu Leu Gln Leu Lys Ser 
    370                 375                 380                 


Asp Ser Ser Arg Cys Ala Gln Glu Ser Ser Val Val Arg Thr Val Cys 
385                 390                 395                 400 


Leu Pro Pro Ala Asp Leu Gln Leu Pro Asp Trp Thr Glu Cys Glu Leu 
                405                 410                 415     


Ser Gly Tyr Gly Lys His Glu Ala Leu Ser Pro Phe Tyr Ser Glu Arg 
            420                 425                 430         


Leu Lys Glu Ala His Val Arg Leu Tyr Pro Ser Ser Arg Cys Thr Ser 
        435                 440                 445             


Gln His Leu Leu Asn Arg Thr Val Thr Asp Asn Met Leu Cys Ala Gly 
    450                 455                 460                 


Asp Thr Arg Ser Gly Gly Pro Gln Ala Asn Leu His Asp Ala Cys Gln 
465                 470                 475                 480 


Gly Asp Ala Gly Gly Pro Leu Val Cys Leu Asn Asp Gly Arg Met Thr 
                485                 490                 495     


Leu Val Gly Ile Ile Ser Trp Gly Leu Gly Cys Gly Gln Lys Asp Val 
            500                 505                 510         


Pro Gly Val Tyr Thr Lys Val Thr Asn Tyr Leu Asp Trp Ile Arg Asp 
        515                 520                 525             


Asn Met Arg Pro 
    530         


<210>  13
<211>  532
<212>  PRT
<213>  Homo sapiens

<400>  13

Arg Ser Gly Ala Arg Ser Tyr Gln Val Ile Cys Arg Asp Glu Lys Thr 
1               5                   10                  15      


Gln Met Ile Tyr Gln Gln His Gln Ser Trp Leu Arg Pro Val Leu Arg 
            20                  25                  30          


Ser Asn Arg Val Glu Tyr Cys Trp Cys Asn Ser Gly Arg Ala Gln Cys 
        35                  40                  45              


His Ser Val Pro Val Lys Ser Cys Ser Glu Pro Arg Cys Phe Asn Gly 
    50                  55                  60                  


Gly Thr Cys Gln Gln Ala Leu Tyr Phe Ser Asp Phe Val Cys Gln Cys 
65                  70                  75                  80  


Pro Glu Gly Phe Ala Gly Lys Cys Cys Glu Ile Asp Thr Arg Ala Thr 
                85                  90                  95      


Cys Tyr Glu Asp Gln Gly Ile Ser Tyr Arg Gly Thr Trp Ser Thr Ala 
            100                 105                 110         


Glu Ser Gly Ala Glu Cys Thr Asn Trp Asn Ser Ser Ala Leu Ala Gln 
        115                 120                 125             


Lys Pro Tyr Ser Gly Arg Arg Pro Asp Ala Ile Arg Leu Gly Leu Gly 
    130                 135                 140                 


Asn His Asn Tyr Cys Arg Asn Pro Asp Arg Asp Ser Lys Pro Trp Cys 
145                 150                 155                 160 


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


Ala Cys Ser Glu Gly Asn Ser Asp Cys Tyr Phe Gly Asn Gly Ser Ala 
            180                 185                 190         


Tyr Arg Gly Thr His Ser Leu Thr Glu Ser Gly Ala Ser Cys Leu Pro 
        195                 200                 205             


Trp Asn Ser Met Ile Leu Ile Gly Lys Val Tyr Thr Ala Gln Asn Pro 
    210                 215                 220                 


Ser Ala Gln Ala Leu Gly Leu Gly Lys His Asn Tyr Cys Arg Asn Pro 
225                 230                 235                 240 


Asp Gly Asp Ala Lys Pro Trp Cys His Val Leu Lys Asn Arg Arg Leu 
                245                 250                 255     


Thr Trp Glu Tyr Cys Asp Val Pro Ser Cys Ser Thr Cys Gly Leu Arg 
            260                 265                 270         


Gln Tyr Ser Gln Pro Gln Phe Arg Ile Lys Gly Gly Leu Phe Ala Asp 
        275                 280                 285             


Ile Ala Ser His Pro Trp Gln Ala Ala Ile Phe Ala Ala Ala Ala Ala 
    290                 295                 300                 


Ser Pro Gly Glu Arg Phe Leu Cys Gly Gly Ile Leu Ile Ser Ser Cys 
305                 310                 315                 320 


Trp Ile Leu Ser Ala Ala His Cys Phe Gln Glu Arg Phe Pro Pro His 
                325                 330                 335     


His Leu Thr Val Ile Leu Gly Arg Thr Tyr Arg Val Val Pro Gly Glu 
            340                 345                 350         


Glu Glu Gln Lys Phe Glu Val Glu Lys Tyr Ile Val His Lys Glu Phe 
        355                 360                 365             


Asp Asp Asp Thr Tyr Asp Asn Asp Ile Ala Leu Leu Gln Leu Lys Ser 
    370                 375                 380                 


Asp Ser Ser Arg Cys Ala Gln Glu Ser Ser Val Val Arg Thr Val Cys 
385                 390                 395                 400 


Leu Pro Pro Ala Asp Leu Gln Leu Pro Asp Trp Thr Glu Cys Glu Leu 
                405                 410                 415     


Ser Gly Tyr Gly Lys His Glu Ala Leu Ser Pro Phe Tyr Ser Glu Arg 
            420                 425                 430         


Leu Lys Glu Ala His Val Arg Leu Tyr Pro Ser Ser Arg Cys Thr Ser 
        435                 440                 445             


Gln His Leu Leu Asn Arg Thr Val Thr Asp Asn Met Leu Cys Ala Gly 
    450                 455                 460                 


Asp Thr Arg Ser Gly Gly Pro Gln Ala Asn Leu His Asp Ala Cys Gln 
465                 470                 475                 480 


Gly Asp Ala Gly Gly Pro Leu Val Cys Leu Asn Asp Gly Arg Met Thr 
                485                 490                 495     


Leu Val Gly Ile Ile Ser Trp Gly Leu Gly Cys Gly Gln Lys Asp Val 
            500                 505                 510         


Pro Gly Val Tyr Thr Lys Val Thr Asn Tyr Leu Asp Trp Ile Arg Asp 
        515                 520                 525             


Asn Met Arg Pro 
    530         


<210>  14
<211>  532
<212>  PRT
<213>  Homo sapiens

<400>  14

Arg Ser Gly Ala Arg Ser Tyr Gln Val Ile Cys Arg Asp Glu Lys Thr 
1               5                   10                  15      


Gln Met Ile Tyr Gln Gln His Gln Ser Trp Leu Arg Pro Val Leu Arg 
            20                  25                  30          


Ser Asn Arg Val Glu Tyr Cys Trp Cys Asn Ser Gly Arg Ala Gln Cys 
        35                  40                  45              


His Ser Val Pro Val Lys Ser Cys Ser Glu Pro Arg Cys Phe Asn Gly 
    50                  55                  60                  


Gly Thr Cys Gln Gln Ala Leu Tyr Phe Ser Asp Phe Val Cys Gln Cys 
65                  70                  75                  80  


Pro Glu Gly Phe Ala Gly Lys Cys Cys Glu Ile Asp Thr Arg Ala Thr 
                85                  90                  95      


Cys Tyr Glu Asp Gln Gly Ile Ser Tyr Arg Gly Asn Trp Ser Thr Ala 
            100                 105                 110         


Glu Ser Gly Ala Glu Cys Thr Asn Trp Gln Ser Ser Ala Leu Ala Gln 
        115                 120                 125             


Lys Pro Tyr Ser Gly Arg Arg Pro Asp Ala Ile Arg Leu Gly Leu Gly 
    130                 135                 140                 


Asn His Asn Tyr Cys Arg Asn Pro Asp Arg Asp Ser Lys Pro Trp Cys 
145                 150                 155                 160 


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


Ala Cys Ser Glu Gly Asn Ser Asp Cys Tyr Phe Gly Asn Gly Ser Ala 
            180                 185                 190         


Tyr Arg Gly Thr His Ser Leu Thr Glu Ser Gly Ala Ser Cys Leu Pro 
        195                 200                 205             


Trp Asn Ser Met Ile Leu Ile Gly Lys Val Tyr Thr Ala Gln Asn Pro 
    210                 215                 220                 


Ser Ala Gln Ala Leu Gly Leu Gly Lys His Asn Tyr Cys Arg Asn Pro 
225                 230                 235                 240 


Asp Gly Asp Ala Lys Pro Trp Cys His Val Leu Lys Asn Arg Arg Leu 
                245                 250                 255     


Thr Trp Glu Tyr Cys Asp Val Pro Ser Cys Ser Thr Cys Gly Leu Arg 
            260                 265                 270         


Gln Tyr Ser Gln Pro Gln Phe Arg Ile Lys Gly Gly Leu Phe Ala Asp 
        275                 280                 285             


Ile Ala Ser His Pro Trp Gln Ala Ala Ile Phe Ala Lys His Arg Arg 
    290                 295                 300                 


Ser Pro Gly Glu Arg Phe Leu Cys Gly Gly Ile Leu Ile Ser Ser Cys 
305                 310                 315                 320 


Trp Ile Leu Ser Ala Ala His Cys Phe Gln Glu Arg Phe Pro Pro His 
                325                 330                 335     


His Leu Thr Val Ile Leu Gly Arg Thr Tyr Arg Val Val Pro Gly Glu 
            340                 345                 350         


Glu Glu Gln Lys Phe Glu Val Glu Lys Tyr Ile Val His Lys Glu Phe 
        355                 360                 365             


Asp Asp Asp Thr Tyr Asp Asn Asp Ile Ala Leu Leu Gln Leu Lys Ser 
    370                 375                 380                 


Asp Ser Ser Arg Cys Ala Gln Glu Ser Ser Val Val Arg Thr Val Cys 
385                 390                 395                 400 


Leu Pro Pro Ala Asp Leu Gln Leu Pro Asp Trp Thr Glu Cys Glu Leu 
                405                 410                 415     


Ser Gly Tyr Gly Lys His Glu Ala Leu Ser Pro Phe Tyr Ser Glu Arg 
            420                 425                 430         


Leu Lys Glu Ala His Val Arg Leu Tyr Pro Ser Ser Arg Cys Thr Ser 
        435                 440                 445             


Gln His Leu Leu Asn Arg Thr Val Thr Asp Asn Met Leu Cys Ala Gly 
    450                 455                 460                 


Asp Thr Arg Ser Gly Gly Pro Gln Ala Asn Leu His Asp Ala Cys Gln 
465                 470                 475                 480 


Gly Asp Ala Gly Gly Pro Leu Val Cys Leu Asn Asp Gly Arg Met Thr 
                485                 490                 495     


Leu Val Gly Ile Ile Ser Trp Gly Leu Gly Cys Gly Gln Lys Asp Val 
            500                 505                 510         


Pro Gly Val Tyr Thr Lys Val Thr Asn Tyr Leu Asp Trp Ile Arg Asp 
        515                 520                 525             


Asn Met Arg Pro 
    530         


<210>  15
<211>  530
<212>  PRT
<213>  Homo sapiens

<400>  15

Gly Ala Arg Ser Tyr Gln Val Ile Cys Arg Asp Glu Lys Thr Gln Met 
1               5                   10                  15      


Ile Tyr Gln Gln His Gln Ser Trp Leu Arg Pro Val Leu Arg Ser Asn 
            20                  25                  30          


Arg Val Glu Tyr Cys Trp Cys Asn Ser Gly Arg Ala Gln Cys His Ser 
        35                  40                  45              


Val Pro Val Lys Ser Cys Ser Glu Pro Arg Cys Phe Asn Gly Gly Thr 
    50                  55                  60                  


Cys Gln Gln Ala Leu Tyr Phe Ser Asp Phe Val Cys Gln Cys Pro Glu 
65                  70                  75                  80  


Gly Phe Ala Gly Lys Cys Cys Glu Ile Asp Thr Arg Ala Thr Cys Tyr 
                85                  90                  95      


Glu Asp Gln Gly Ile Ser Tyr Arg Gly Thr Trp Ser Thr Ala Glu Ser 
            100                 105                 110         


Gly Ala Glu Cys Thr Asn Trp Asn Ser Ser Ala Leu Ala Gln Lys Pro 
        115                 120                 125             


Tyr Ser Gly Arg Arg Pro Asp Ala Ile Arg Leu Gly Leu Gly Asn His 
    130                 135                 140                 


Asn Tyr Cys Arg Asn Pro Asp Arg Asp Ser Lys Pro Trp Cys Tyr Val 
145                 150                 155                 160 


Phe Lys Ala Gly Lys Tyr Ser Ser Glu Phe Cys Ser Thr Pro Ala Cys 
                165                 170                 175     


Ser Glu Gly Asn Ser Asp Cys Tyr Phe Gly Asn Gly Ser Ala Tyr Arg 
            180                 185                 190         


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


Ser Met Ile Leu Ile Gly Lys Val Tyr Thr Ala Gln Asn Pro Ser Ala 
    210                 215                 220                 


Gln Ala Leu Gly Leu Gly Lys His Asn Tyr Cys Arg Asn Pro Asp Gly 
225                 230                 235                 240 


Asp Ala Lys Pro Trp Cys His Val Leu Lys Asn Arg Arg Leu Thr Trp 
                245                 250                 255     


Glu Tyr Cys Asp Val Pro Ser Cys Ser Thr Cys Gly Leu Arg Gln Tyr 
            260                 265                 270         


Ser Gln Pro Gln Phe Arg Ile Lys Gly Gly Leu Phe Ala Asp Ile Ala 
        275                 280                 285             


Ser His Pro Trp Gln Ala Ala Ile Phe Ala Ala Ala Ala Ala Ser Pro 
    290                 295                 300                 


Gly Glu Arg Phe Leu Cys Gly Gly Ile Leu Ile Ser Ser Cys Trp Ile 
305                 310                 315                 320 


Leu Ser Ala Ala His Cys Phe Gln Glu Arg Phe Pro Pro His His Leu 
                325                 330                 335     


Thr Val Ile Leu Gly Arg Thr Tyr Arg Val Val Pro Gly Glu Glu Glu 
            340                 345                 350         


Gln Lys Phe Glu Val Glu Lys Tyr Ile Val His Lys Glu Phe Asp Asp 
        355                 360                 365             


Asp Thr Tyr Asp Asn Asp Ile Ala Leu Leu Gln Leu Lys Ser Asp Ser 
    370                 375                 380                 


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


Pro Ala Asp Leu Gln Leu Pro Asp Trp Thr Glu Cys Glu Leu Ser Gly 
                405                 410                 415     


Tyr Gly Lys His Glu Ala Leu Ser Pro Phe Tyr Ser Glu Arg Leu Lys 
            420                 425                 430         


Glu Ala His Val Arg Leu Tyr Pro Ser Ser Arg Cys Thr Ser Gln His 
        435                 440                 445             


Leu Leu Asn Arg Thr Val Thr Asp Asn Met Leu Cys Ala Gly Asp Thr 
    450                 455                 460                 


Arg Ser Gly Gly Pro Gln Ala Asn Leu His Asp Ala Cys Gln Gly Asp 
465                 470                 475                 480 


Ser Gly Gly Pro Leu Val Cys Leu Asn Asp Gly Arg Met Thr Leu Val 
                485                 490                 495     


Gly Ile Ile Ser Trp Gly Leu Gly Cys Gly Gln Lys Asp Val Pro Gly 
            500                 505                 510         


Val Tyr Thr Lys Val Thr Asn Tyr Leu Asp Trp Ile Arg Asp Asn Met 
        515                 520                 525             


Arg Pro 
    530 


<210>  16
<211>  530
<212>  PRT
<213>  Homo sapiens

<400>  16

Gly Ala Arg Ser Tyr Gln Val Ile Cys Arg Asp Glu Lys Thr Gln Met 
1               5                   10                  15      


Ile Tyr Gln Gln His Gln Ser Trp Leu Arg Pro Val Leu Arg Ser Asn 
            20                  25                  30          


Arg Val Glu Tyr Cys Trp Cys Asn Ser Gly Arg Ala Gln Cys His Ser 
        35                  40                  45              


Val Pro Val Lys Ser Cys Ser Glu Pro Arg Cys Phe Asn Gly Gly Thr 
    50                  55                  60                  


Cys Gln Gln Ala Leu Tyr Phe Ser Asp Phe Val Cys Gln Cys Pro Glu 
65                  70                  75                  80  


Gly Phe Ala Gly Lys Cys Cys Glu Ile Asp Thr Arg Ala Thr Cys Tyr 
                85                  90                  95      


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


Gly Ala Glu Cys Thr Asn Trp Gln Ser Ser Ala Leu Ala Gln Lys Pro 
        115                 120                 125             


Tyr Ser Gly Arg Arg Pro Asp Ala Ile Arg Leu Gly Leu Gly Asn His 
    130                 135                 140                 


Asn Tyr Cys Arg Asn Pro Asp Arg Asp Ser Lys Pro Trp Cys Tyr Val 
145                 150                 155                 160 


Phe Lys Ala Gly Lys Tyr Ser Ser Glu Phe Cys Ser Thr Pro Ala Cys 
                165                 170                 175     


Ser Glu Gly Asn Ser Asp Cys Tyr Phe Gly Asn Gly Ser Ala Tyr Arg 
            180                 185                 190         


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


Ser Met Ile Leu Ile Gly Lys Val Tyr Thr Ala Gln Asn Pro Ser Ala 
    210                 215                 220                 


Gln Ala Leu Gly Leu Gly Lys His Asn Tyr Cys Arg Asn Pro Asp Gly 
225                 230                 235                 240 


Asp Ala Lys Pro Trp Cys His Val Leu Lys Asn Arg Arg Leu Thr Trp 
                245                 250                 255     


Glu Tyr Cys Asp Val Pro Ser Cys Ser Thr Cys Gly Leu Arg Gln Tyr 
            260                 265                 270         


Ser Gln Pro Gln Phe Arg Ile Lys Gly Gly Leu Phe Ala Asp Ile Ala 
        275                 280                 285             


Ser His Pro Trp Gln Ala Ala Ile Phe Ala Lys His Arg Arg Ser Pro 
    290                 295                 300                 


Gly Glu Arg Phe Leu Cys Gly Gly Ile Leu Ile Ser Ser Cys Trp Ile 
305                 310                 315                 320 


Leu Ser Ala Ala His Cys Phe Gln Glu Arg Phe Pro Pro His His Leu 
                325                 330                 335     


Thr Val Ile Leu Gly Arg Thr Tyr Arg Val Val Pro Gly Glu Glu Glu 
            340                 345                 350         


Gln Lys Phe Glu Val Glu Lys Tyr Ile Val His Lys Glu Phe Asp Asp 
        355                 360                 365             


Asp Thr Tyr Asp Asn Asp Ile Ala Leu Leu Gln Leu Lys Ser Asp Ser 
    370                 375                 380                 


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


Pro Ala Asp Leu Gln Leu Pro Asp Trp Thr Glu Cys Glu Leu Ser Gly 
                405                 410                 415     


Tyr Gly Lys His Glu Ala Leu Ser Pro Phe Tyr Ser Glu Arg Leu Lys 
            420                 425                 430         


Glu Ala His Val Arg Leu Tyr Pro Ser Ser Arg Cys Thr Ser Gln His 
        435                 440                 445             


Leu Leu Asn Arg Thr Val Thr Asp Asn Met Leu Cys Ala Gly Asp Thr 
    450                 455                 460                 


Arg Ser Gly Gly Pro Gln Ala Asn Leu His Asp Ala Cys Gln Gly Asp 
465                 470                 475                 480 


Ser Gly Gly Pro Leu Val Cys Leu Asn Asp Gly Arg Met Thr Leu Val 
                485                 490                 495     


Gly Ile Ile Ser Trp Gly Leu Gly Cys Gly Gln Lys Asp Val Pro Gly 
            500                 505                 510         


Val Tyr Thr Lys Val Thr Asn Tyr Leu Asp Trp Ile Arg Asp Asn Met 
        515                 520                 525             


Arg Pro 
    530 


<210>  17
<211>  355
<212>  PRT
<213>  Homo sapiens

<400>  17

Ser Tyr Gln Gly Asn Ser Asp Cys Tyr Phe Gly Asn Gly Ser Ala Tyr 
1               5                   10                  15      


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


Asn Ser Met Ile Leu Ile Gly Lys Val Tyr Thr Ala Gln Asn Pro Ser 
        35                  40                  45              


Ala Gln Ala Leu Gly Leu Gly Lys His Asn Tyr Cys Arg Asn Pro Asp 
    50                  55                  60                  


Gly Asp Ala Lys Pro Trp Cys His Val Leu Lys Asn Arg Arg Leu Thr 
65                  70                  75                  80  


Trp Glu Tyr Cys Asp Val Pro Ser Cys Ser Thr Cys Gly Leu Arg Gln 
                85                  90                  95      


Tyr Ser Gln Pro Gln Phe Arg Ile Lys Gly Gly Leu Phe Ala Asp Ile 
            100                 105                 110         


Ala Ser His Pro Trp Gln Ala Ala Ile Phe Ala Lys His Arg Arg Ser 
        115                 120                 125             


Pro Gly Glu Arg Phe Leu Cys Gly Gly Ile Leu Ile Ser Ser Cys Trp 
    130                 135                 140                 


Ile Leu Ser Ala Ala His Cys Phe Gln Glu Arg Phe Pro Pro His His 
145                 150                 155                 160 


Leu Thr Val Ile Leu Gly Arg Thr Tyr Arg Val Val Pro Gly Glu Glu 
                165                 170                 175     


Glu Gln Lys Phe Glu Val Glu Lys Tyr Ile Val His Lys Glu Phe Asp 
            180                 185                 190         


Asp Asp Thr Tyr Asp Asn Asp Ile Ala Leu Leu Gln Leu Lys Ser Asp 
        195                 200                 205             


Ser Ser Arg Cys Ala Gln Glu Ser Ser Val Val Arg Thr Val Cys Leu 
    210                 215                 220                 


Pro Pro Ala Asp Leu Gln Leu Pro Asp Trp Thr Glu Cys Glu Leu Ser 
225                 230                 235                 240 


Gly Tyr Gly Lys His Glu Ala Leu Ser Pro Phe Tyr Ser Glu Arg Leu 
                245                 250                 255     


Lys Glu Ala His Val Arg Leu Tyr Pro Ser Ser Arg Cys Thr Ser Gln 
            260                 265                 270         


His Leu Leu Asn Arg Thr Val Thr Asp Asn Met Leu Cys Ala Gly Asp 
        275                 280                 285             


Thr Arg Ser Gly Gly Pro Gln Ala Asn Leu His Asp Ala Cys Gln Gly 
    290                 295                 300                 


Asp Ser Gly Gly Pro Leu Val Cys Leu Asn Asp Gly Arg Met Thr Leu 
305                 310                 315                 320 


Val Gly Ile Ile Ser Trp Gly Leu Gly Cys Gly Gln Lys Asp Val Pro 
                325                 330                 335     


Gly Val Tyr Thr Lys Val Thr Asn Tyr Leu Asp Trp Ile Arg Asp Asn 
            340                 345                 350         


Met Arg Pro 
        355 


