                         SEQUENCE LISTING

<110>  Stichting Het Nederlands Kanker Instituut
 
<120>  Combined PDK and MAPK inhibition

<130>  P31041PC00

<160>  12    

<170>  PatentIn version 3.5

<210>  1
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  primer

<400>  1
ccaagacctc gtgttgagac c                                                 21


<210>  2
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  primer

<400>  2
aatacagctt caggtctcct tgg                                               23


<210>  3
<211>  436
<212>  PRT
<213>  Homo sapiens

<400>  3

Met Arg Leu Ala Arg Leu Leu Arg Gly Ala Ala Leu Ala Gly Pro Gly 
1               5                   10                  15      


Pro Gly Leu Arg Ala Ala Gly Phe Ser Arg Ser Phe Ser Ser Asp Ser 
            20                  25                  30          


Gly Ser Ser Pro Ala Ser Glu Arg Gly Val Pro Gly Gln Val Asp Phe 
        35                  40                  45              


Tyr Ala Arg Phe Ser Pro Ser Pro Leu Ser Met Lys Gln Phe Leu Asp 
    50                  55                  60                  


Phe Gly Ser Val Asn Ala Cys Glu Lys Thr Ser Phe Met Phe Leu Arg 
65                  70                  75                  80  


Gln Glu Leu Pro Val Arg Leu Ala Asn Ile Met Lys Glu Ile Ser Leu 
                85                  90                  95      


Leu Pro Asp Asn Leu Leu Arg Thr Pro Ser Val Gln Leu Val Gln Ser 
            100                 105                 110         


Trp Tyr Ile Gln Ser Leu Gln Glu Leu Leu Asp Phe Lys Asp Lys Ser 
        115                 120                 125             


Ala Glu Asp Ala Lys Ala Ile Tyr Asp Phe Thr Asp Thr Val Ile Arg 
    130                 135                 140                 


Ile Arg Asn Arg His Asn Asp Val Ile Pro Thr Met Ala Gln Gly Val 
145                 150                 155                 160 


Ile Glu Tyr Lys Glu Ser Phe Gly Val Asp Pro Val Thr Ser Gln Asn 
                165                 170                 175     


Val Gln Tyr Phe Leu Asp Arg Phe Tyr Met Ser Arg Ile Ser Ile Arg 
            180                 185                 190         


Met Leu Leu Asn Gln His Ser Leu Leu Phe Gly Gly Lys Gly Lys Gly 
        195                 200                 205             


Ser Pro Ser His Arg Lys His Ile Gly Ser Ile Asn Pro Asn Cys Asn 
    210                 215                 220                 


Val Leu Glu Val Ile Lys Asp Gly Tyr Glu Asn Ala Arg Arg Leu Cys 
225                 230                 235                 240 


Asp Leu Tyr Tyr Ile Asn Ser Pro Glu Leu Glu Leu Glu Glu Leu Asn 
                245                 250                 255     


Ala Lys Ser Pro Gly Gln Pro Ile Gln Val Val Tyr Val Pro Ser His 
            260                 265                 270         


Leu Tyr His Met Val Phe Glu Leu Phe Lys Asn Ala Met Arg Ala Thr 
        275                 280                 285             


Met Glu His His Ala Asn Arg Gly Val Tyr Pro Pro Ile Gln Val His 
    290                 295                 300                 


Val Thr Leu Gly Asn Glu Asp Leu Thr Val Lys Met Ser Asp Arg Gly 
305                 310                 315                 320 


Gly Gly Val Pro Leu Arg Lys Ile Asp Arg Leu Phe Asn Tyr Met Tyr 
                325                 330                 335     


Ser Thr Ala Pro Arg Pro Arg Val Glu Thr Ser Arg Ala Val Pro Leu 
            340                 345                 350         


Ala Gly Phe Gly Tyr Gly Leu Pro Ile Ser Arg Leu Tyr Ala Gln Tyr 
        355                 360                 365             


Phe Gln Gly Asp Leu Lys Leu Tyr Ser Leu Glu Gly Tyr Gly Thr Asp 
    370                 375                 380                 


Ala Val Ile Tyr Ile Lys Ala Leu Ser Thr Asp Ser Ile Glu Arg Leu 
385                 390                 395                 400 


Pro Val Tyr Asn Lys Ala Ala Trp Lys His Tyr Asn Thr Asn His Glu 
                405                 410                 415     


Ala Asp Asp Trp Cys Val Pro Ser Arg Glu Pro Lys Asp Met Thr Thr 
            420                 425                 430         


Phe Arg Ser Ala 
        435     


<210>  4
<211>  407
<212>  PRT
<213>  Homo sapiens

<400>  4

Met Arg Trp Val Trp Ala Leu Leu Lys Asn Ala Ser Leu Ala Gly Ala 
1               5                   10                  15      


Pro Lys Tyr Ile Glu His Phe Ser Lys Phe Ser Pro Ser Pro Leu Ser 
            20                  25                  30          


Met Lys Gln Phe Leu Asp Phe Gly Ser Ser Asn Ala Cys Glu Lys Thr 
        35                  40                  45              


Ser Phe Thr Phe Leu Arg Gln Glu Leu Pro Val Arg Leu Ala Asn Ile 
    50                  55                  60                  


Met Lys Glu Ile Asn Leu Leu Pro Asp Arg Val Leu Ser Thr Pro Ser 
65                  70                  75                  80  


Val Gln Leu Val Gln Ser Trp Tyr Val Gln Ser Leu Leu Asp Ile Met 
                85                  90                  95      


Glu Phe Leu Asp Lys Asp Pro Glu Asp His Arg Thr Leu Ser Gln Phe 
            100                 105                 110         


Thr Asp Ala Leu Val Thr Ile Arg Asn Arg His Asn Asp Val Val Pro 
        115                 120                 125             


Thr Met Ala Gln Gly Val Leu Glu Tyr Lys Asp Thr Tyr Gly Asp Asp 
    130                 135                 140                 


Pro Val Ser Asn Gln Asn Ile Gln Tyr Phe Leu Asp Arg Phe Tyr Leu 
145                 150                 155                 160 


Ser Arg Ile Ser Ile Arg Met Leu Ile Asn Gln His Thr Leu Ile Phe 
                165                 170                 175     


Asp Gly Ser Thr Asn Pro Ala His Pro Lys His Ile Gly Ser Ile Asp 
            180                 185                 190         


Pro Asn Cys Asn Val Ser Glu Val Val Lys Asp Ala Tyr Asp Met Ala 
        195                 200                 205             


Lys Leu Leu Cys Asp Lys Tyr Tyr Met Ala Ser Pro Asp Leu Glu Ile 
    210                 215                 220                 


Gln Glu Ile Asn Ala Ala Asn Ser Lys Gln Pro Ile His Met Val Tyr 
225                 230                 235                 240 


Val Pro Ser His Leu Tyr His Met Leu Phe Glu Leu Phe Lys Asn Ala 
                245                 250                 255     


Met Arg Ala Thr Val Glu Ser His Glu Ser Ser Leu Ile Leu Pro Pro 
            260                 265                 270         


Ile Lys Val Met Val Ala Leu Gly Glu Glu Asp Leu Ser Ile Lys Met 
        275                 280                 285             


Ser Asp Arg Gly Gly Gly Val Pro Leu Arg Lys Ile Glu Arg Leu Phe 
    290                 295                 300                 


Ser Tyr Met Tyr Ser Thr Ala Pro Thr Pro Gln Pro Gly Thr Gly Gly 
305                 310                 315                 320 


Thr Pro Leu Ala Gly Phe Gly Tyr Gly Leu Pro Ile Ser Arg Leu Tyr 
                325                 330                 335     


Ala Lys Tyr Phe Gln Gly Asp Leu Gln Leu Phe Ser Met Glu Gly Phe 
            340                 345                 350         


Gly Thr Asp Ala Val Ile Tyr Leu Lys Ala Leu Ser Thr Asp Ser Val 
        355                 360                 365             


Glu Arg Leu Pro Val Tyr Asn Lys Ser Ala Trp Arg His Tyr Gln Thr 
    370                 375                 380                 


Ile Gln Glu Ala Gly Asp Trp Cys Val Pro Ser Thr Glu Pro Lys Asn 
385                 390                 395                 400 


Thr Ser Thr Tyr Arg Val Ser 
                405         


<210>  5
<211>  406
<212>  PRT
<213>  Homo sapiens

<400>  5

Met Arg Leu Phe Arg Trp Leu Leu Lys Gln Pro Val Pro Lys Gln Ile 
1               5                   10                  15      


Glu Arg Tyr Ser Arg Phe Ser Pro Ser Pro Leu Ser Ile Lys Gln Phe 
            20                  25                  30          


Leu Asp Phe Gly Arg Asp Asn Ala Cys Glu Lys Thr Ser Tyr Met Phe 
        35                  40                  45              


Leu Arg Lys Glu Leu Pro Val Arg Leu Ala Asn Thr Met Arg Glu Val 
    50                  55                  60                  


Asn Leu Leu Pro Asp Asn Leu Leu Asn Arg Pro Ser Val Gly Leu Val 
65                  70                  75                  80  


Gln Ser Trp Tyr Met Gln Ser Phe Leu Glu Leu Leu Glu Tyr Glu Asn 
                85                  90                  95      


Lys Ser Pro Glu Asp Pro Gln Val Leu Asp Asn Phe Leu Gln Val Leu 
            100                 105                 110         


Ile Lys Val Arg Asn Arg His Asn Asp Val Val Pro Thr Met Ala Gln 
        115                 120                 125             


Gly Val Ile Glu Tyr Lys Glu Lys Phe Gly Phe Asp Pro Phe Ile Ser 
    130                 135                 140                 


Thr Asn Ile Gln Tyr Phe Leu Asp Arg Phe Tyr Thr Asn Arg Ile Ser 
145                 150                 155                 160 


Phe Arg Met Leu Ile Asn Gln His Thr Leu Leu Phe Gly Gly Asp Thr 
                165                 170                 175     


Asn Pro Val His Pro Lys His Ile Gly Ser Ile Asp Pro Thr Cys Asn 
            180                 185                 190         


Val Ala Asp Val Val Lys Asp Ala Tyr Glu Thr Ala Lys Met Leu Cys 
        195                 200                 205             


Glu Gln Tyr Tyr Leu Val Ala Pro Glu Leu Glu Val Glu Glu Phe Asn 
    210                 215                 220                 


Ala Lys Ala Pro Asp Lys Pro Ile Gln Val Val Tyr Val Pro Ser His 
225                 230                 235                 240 


Leu Phe His Met Leu Phe Glu Leu Phe Lys Asn Ser Met Arg Ala Thr 
                245                 250                 255     


Val Glu Leu Tyr Glu Asp Arg Lys Glu Gly Tyr Pro Ala Val Lys Thr 
            260                 265                 270         


Leu Val Thr Leu Gly Lys Glu Asp Leu Ser Ile Lys Ile Ser Asp Leu 
        275                 280                 285             


Gly Gly Gly Val Pro Leu Arg Lys Ile Asp Arg Leu Phe Asn Tyr Met 
    290                 295                 300                 


Tyr Ser Thr Ala Pro Arg Pro Ser Leu Glu Pro Thr Arg Ala Ala Pro 
305                 310                 315                 320 


Leu Ala Gly Phe Gly Tyr Gly Leu Pro Ile Ser Arg Leu Tyr Ala Arg 
                325                 330                 335     


Tyr Phe Gln Gly Asp Leu Lys Leu Tyr Ser Met Glu Gly Val Gly Thr 
            340                 345                 350         


Asp Ala Val Ile Tyr Leu Lys Ala Leu Ser Ser Glu Ser Phe Glu Arg 
        355                 360                 365             


Leu Pro Val Phe Asn Lys Ser Ala Trp Arg His Tyr Lys Thr Thr Pro 
    370                 375                 380                 


Glu Ala Asp Asp Trp Ser Asn Pro Ser Ser Glu Pro Arg Asp Ala Ser 
385                 390                 395                 400 


Lys Tyr Lys Ala Lys Gln 
                405     


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

<400>  6

Met Lys Ala Ala Arg Phe Val Leu Arg Ser Ala Gly Ser Leu Asn Gly 
1               5                   10                  15      


Ala Gly Leu Val Pro Arg Glu Val Glu His Phe Ser Arg Tyr Ser Pro 
            20                  25                  30          


Ser Pro Leu Ser Met Lys Gln Leu Leu Asp Phe Gly Ser Glu Asn Ala 
        35                  40                  45              


Cys Glu Arg Thr Ser Phe Ala Phe Leu Arg Gln Glu Leu Pro Val Arg 
    50                  55                  60                  


Leu Ala Asn Ile Leu Lys Glu Ile Asp Ile Leu Pro Thr Gln Leu Val 
65                  70                  75                  80  


Asn Thr Ser Ser Val Gln Leu Val Lys Ser Trp Tyr Ile Gln Ser Leu 
                85                  90                  95      


Met Asp Leu Val Glu Phe His Glu Lys Ser Pro Asp Asp Gln Lys Ala 
            100                 105                 110         


Leu Ser Asp Phe Val Asp Thr Leu Ile Lys Val Arg Asn Arg His His 
        115                 120                 125             


Asn Val Val Pro Thr Met Ala Gln Gly Ile Ile Glu Tyr Lys Asp Ala 
    130                 135                 140                 


Cys Thr Val Asp Pro Val Thr Asn Gln Asn Leu Gln Tyr Phe Leu Asp 
145                 150                 155                 160 


Arg Phe Tyr Met Asn Arg Ile Ser Thr Arg Met Leu Met Asn Gln His 
                165                 170                 175     


Ile Leu Ile Phe Ser Asp Ser Gln Thr Gly Asn Pro Ser His Ile Gly 
            180                 185                 190         


Ser Ile Asp Pro Asn Cys Asp Val Val Ala Val Val Gln Asp Ala Phe 
        195                 200                 205             


Glu Cys Ser Arg Met Leu Cys Asp Gln Tyr Tyr Leu Ser Ser Pro Glu 
    210                 215                 220                 


Leu Lys Leu Thr Gln Val Asn Gly Lys Phe Pro Asp Gln Pro Ile His 
225                 230                 235                 240 


Ile Val Tyr Val Pro Ser His Leu His His Met Leu Phe Glu Leu Phe 
                245                 250                 255     


Lys Asn Ala Met Arg Ala Thr Val Glu His Gln Glu Asn Gln Pro Ser 
            260                 265                 270         


Leu Thr Pro Ile Glu Val Ile Val Val Leu Gly Lys Glu Asp Leu Thr 
        275                 280                 285             


Ile Lys Ile Ser Asp Arg Gly Gly Gly Val Pro Leu Arg Ile Ile Asp 
    290                 295                 300                 


Arg Leu Phe Ser Tyr Thr Tyr Ser Thr Ala Pro Thr Pro Val Met Asp 
305                 310                 315                 320 


Asn Ser Arg Asn Ala Pro Leu Ala Gly Phe Gly Tyr Gly Leu Pro Ile 
                325                 330                 335     


Ser Arg Leu Tyr Ala Lys Tyr Phe Gln Gly Asp Leu Asn Leu Tyr Ser 
            340                 345                 350         


Leu Ser Gly Tyr Gly Thr Asp Ala Ile Ile Tyr Leu Lys Ala Leu Ser 
        355                 360                 365             


Ser Glu Ser Ile Glu Lys Leu Pro Val Phe Asn Lys Ser Ala Phe Lys 
    370                 375                 380                 


His Tyr Gln Met Ser Ser Glu Ala Asp Asp Trp Cys Ile Pro Ser Arg 
385                 390                 395                 400 


Glu Pro Lys Asn Leu Ala Lys Glu Val Ala Met 
                405                 410     


<210>  7
<211>  766
<212>  PRT
<213>  Homo sapiens

<400>  7

Met Ala Ala Leu Ser Gly Gly Gly Gly Gly Gly Ala Glu Pro Gly Gln 
1               5                   10                  15      


Ala Leu Phe Asn Gly Asp Met Glu Pro Glu Ala Gly Ala Gly Ala Gly 
            20                  25                  30          


Ala Ala Ala Ser Ser Ala Ala Asp Pro Ala Ile Pro Glu Glu Val Trp 
        35                  40                  45              


Asn Ile Lys Gln Met Ile Lys Leu Thr Gln Glu His Ile Glu Ala Leu 
    50                  55                  60                  


Leu Asp Lys Phe Gly Gly Glu His Asn Pro Pro Ser Ile Tyr Leu Glu 
65                  70                  75                  80  


Ala Tyr Glu Glu Tyr Thr Ser Lys Leu Asp Ala Leu Gln Gln Arg Glu 
                85                  90                  95      


Gln Gln Leu Leu Glu Ser Leu Gly Asn Gly Thr Asp Phe Ser Val Ser 
            100                 105                 110         


Ser Ser Ala Ser Met Asp Thr Val Thr Ser Ser Ser Ser Ser Ser Leu 
        115                 120                 125             


Ser Val Leu Pro Ser Ser Leu Ser Val Phe Gln Asn Pro Thr Asp Val 
    130                 135                 140                 


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


Leu Pro Asn Lys Gln Arg Thr Val Val Pro Ala Arg Cys Gly Val Thr 
                165                 170                 175     


Val Arg Asp Ser Leu Lys Lys Ala Leu Met Met Arg Gly Leu Ile Pro 
            180                 185                 190         


Glu Cys Cys Ala Val Tyr Arg Ile Gln Asp Gly Glu Lys Lys Pro Ile 
        195                 200                 205             


Gly Trp Asp Thr Asp Ile Ser Trp Leu Thr Gly Glu Glu Leu His Val 
    210                 215                 220                 


Glu Val Leu Glu Asn Val Pro Leu Thr Thr His Asn Phe Val Arg Lys 
225                 230                 235                 240 


Thr Phe Phe Thr Leu Ala Phe Cys Asp Phe Cys Arg Lys Leu Leu Phe 
                245                 250                 255     


Gln Gly Phe Arg Cys Gln Thr Cys Gly Tyr Lys Phe His Gln Arg Cys 
            260                 265                 270         


Ser Thr Glu Val Pro Leu Met Cys Val Asn Tyr Asp Gln Leu Asp Leu 
        275                 280                 285             


Leu Phe Val Ser Lys Phe Phe Glu His His Pro Ile Pro Gln Glu Glu 
    290                 295                 300                 


Ala Ser Leu Ala Glu Thr Ala Leu Thr Ser Gly Ser Ser Pro Ser Ala 
305                 310                 315                 320 


Pro Ala Ser Asp Ser Ile Gly Pro Gln Ile Leu Thr Ser Pro Ser Pro 
                325                 330                 335     


Ser Lys Ser Ile Pro Ile Pro Gln Pro Phe Arg Pro Ala Asp Glu Asp 
            340                 345                 350         


His Arg Asn Gln Phe Gly Gln Arg Asp Arg Ser Ser Ser Ala Pro Asn 
        355                 360                 365             


Val His Ile Asn Thr Ile Glu Pro Val Asn Ile Asp Asp Leu Ile Arg 
    370                 375                 380                 


Asp Gln Gly Phe Arg Gly Asp Gly Gly Ser Thr Thr Gly Leu Ser Ala 
385                 390                 395                 400 


Thr Pro Pro Ala Ser Leu Pro Gly Ser Leu Thr Asn Val Lys Ala Leu 
                405                 410                 415     


Gln Lys Ser Pro Gly Pro Gln Arg Glu Arg Lys Ser Ser Ser Ser Ser 
            420                 425                 430         


Glu Asp Arg Asn Arg Met Lys Thr Leu Gly Arg Arg Asp Ser Ser Asp 
        435                 440                 445             


Asp Trp Glu Ile Pro Asp Gly Gln Ile Thr Val Gly Gln Arg Ile Gly 
    450                 455                 460                 


Ser Gly Ser Phe Gly Thr Val Tyr Lys Gly Lys Trp His Gly Asp Val 
465                 470                 475                 480 


Ala Val Lys Met Leu Asn Val Thr Ala Pro Thr Pro Gln Gln Leu Gln 
                485                 490                 495     


Ala Phe Lys Asn Glu Val Gly Val Leu Arg Lys Thr Arg His Val Asn 
            500                 505                 510         


Ile Leu Leu Phe Met Gly Tyr Ser Thr Lys Pro Gln Leu Ala Ile Val 
        515                 520                 525             


Thr Gln Trp Cys Glu Gly Ser Ser Leu Tyr His His Leu His Ile Ile 
    530                 535                 540                 


Glu Thr Lys Phe Glu Met Ile Lys Leu Ile Asp Ile Ala Arg Gln Thr 
545                 550                 555                 560 


Ala Gln Gly Met Asp Tyr Leu His Ala Lys Ser Ile Ile His Arg Asp 
                565                 570                 575     


Leu Lys Ser Asn Asn Ile Phe Leu His Glu Asp Leu Thr Val Lys Ile 
            580                 585                 590         


Gly Asp Phe Gly Leu Ala Thr Val Lys Ser Arg Trp Ser Gly Ser His 
        595                 600                 605             


Gln Phe Glu Gln Leu Ser Gly Ser Ile Leu Trp Met Ala Pro Glu Val 
    610                 615                 620                 


Ile Arg Met Gln Asp Lys Asn Pro Tyr Ser Phe Gln Ser Asp Val Tyr 
625                 630                 635                 640 


Ala Phe Gly Ile Val Leu Tyr Glu Leu Met Thr Gly Gln Leu Pro Tyr 
                645                 650                 655     


Ser Asn Ile Asn Asn Arg Asp Gln Ile Ile Phe Met Val Gly Arg Gly 
            660                 665                 670         


Tyr Leu Ser Pro Asp Leu Ser Lys Val Arg Ser Asn Cys Pro Lys Ala 
        675                 680                 685             


Met Lys Arg Leu Met Ala Glu Cys Leu Lys Lys Lys Arg Asp Glu Arg 
    690                 695                 700                 


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


Leu Pro Lys Ile His Arg Ser Ala Ser Glu Pro Ser Leu Asn Arg Ala 
                725                 730                 735     


Gly Phe Gln Thr Glu Asp Phe Ser Leu Tyr Ala Cys Ala Ser Pro Lys 
            740                 745                 750         


Thr Pro Ile Gln Ala Gly Gly Tyr Gly Ala Phe Pro Val His 
        755                 760                 765     


<210>  8
<211>  393
<212>  PRT
<213>  Homo sapiens

<400>  8

Met Pro Lys Lys Lys Pro Thr Pro Ile Gln Leu Asn Pro Ala Pro Asp 
1               5                   10                  15      


Gly Ser Ala Val Asn Gly Thr Ser Ser Ala Glu Thr Asn Leu Glu Ala 
            20                  25                  30          


Leu Gln Lys Lys Leu Glu Glu Leu Glu Leu Asp Glu Gln Gln Arg Lys 
        35                  40                  45              


Arg Leu Glu Ala Phe Leu Thr Gln Lys Gln Lys Val Gly Glu Leu Lys 
    50                  55                  60                  


Asp Asp Asp Phe Glu Lys Ile Ser Glu Leu Gly Ala Gly Asn Gly Gly 
65                  70                  75                  80  


Val Val Phe Lys Val Ser His Lys Pro Ser Gly Leu Val Met Ala Arg 
                85                  90                  95      


Lys Leu Ile His Leu Glu Ile Lys Pro Ala Ile Arg Asn Gln Ile Ile 
            100                 105                 110         


Arg Glu Leu Gln Val Leu His Glu Cys Asn Ser Pro Tyr Ile Val Gly 
        115                 120                 125             


Phe Tyr Gly Ala Phe Tyr Ser Asp Gly Glu Ile Ser Ile Cys Met Glu 
    130                 135                 140                 


His Met Asp Gly Gly Ser Leu Asp Gln Val Leu Lys Lys Ala Gly Arg 
145                 150                 155                 160 


Ile Pro Glu Gln Ile Leu Gly Lys Val Ser Ile Ala Val Ile Lys Gly 
                165                 170                 175     


Leu Thr Tyr Leu Arg Glu Lys His Lys Ile Met His Arg Asp Val Lys 
            180                 185                 190         


Pro Ser Asn Ile Leu Val Asn Ser Arg Gly Glu Ile Lys Leu Cys Asp 
        195                 200                 205             


Phe Gly Val Ser Gly Gln Leu Ile Asp Ser Met Ala Asn Ser Phe Val 
    210                 215                 220                 


Gly Thr Arg Ser Tyr Met Ser Pro Glu Arg Leu Gln Gly Thr His Tyr 
225                 230                 235                 240 


Ser Val Gln Ser Asp Ile Trp Ser Met Gly Leu Ser Leu Val Glu Met 
                245                 250                 255     


Ala Val Gly Arg Tyr Pro Ile Pro Pro Pro Asp Ala Lys Glu Leu Glu 
            260                 265                 270         


Leu Met Phe Gly Cys Gln Val Glu Gly Asp Ala Ala Glu Thr Pro Pro 
        275                 280                 285             


Arg Pro Arg Thr Pro Gly Arg Pro Leu Ser Ser Tyr Gly Met Asp Ser 
    290                 295                 300                 


Arg Pro Pro Met Ala Ile Phe Glu Leu Leu Asp Tyr Ile Val Asn Glu 
305                 310                 315                 320 


Pro Pro Pro Lys Leu Pro Ser Gly Val Phe Ser Leu Glu Phe Gln Asp 
                325                 330                 335     


Phe Val Asn Lys Cys Leu Ile Lys Asn Pro Ala Glu Arg Ala Asp Leu 
            340                 345                 350         


Lys Gln Leu Met Val His Ala Phe Ile Lys Arg Ser Asp Ala Glu Glu 
        355                 360                 365             


Val Asp Phe Ala Gly Trp Leu Cys Ser Thr Ile Gly Leu Asn Gln Pro 
    370                 375                 380                 


Ser Thr Pro Thr His Ala Ala Gly Val 
385                 390             


<210>  9
<211>  400
<212>  PRT
<213>  Homo sapiens

<400>  9

Met Leu Ala Arg Arg Lys Pro Val Leu Pro Ala Leu Thr Ile Asn Pro 
1               5                   10                  15      


Thr Ile Ala Glu Gly Pro Ser Pro Thr Ser Glu Gly Ala Ser Glu Ala 
            20                  25                  30          


Asn Leu Val Asp Leu Gln Lys Lys Leu Glu Glu Leu Glu Leu Asp Glu 
        35                  40                  45              


Gln Gln Lys Lys Arg Leu Glu Ala Phe Leu Thr Gln Lys Ala Lys Val 
    50                  55                  60                  


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


Gly Asn Gly Gly Val Val Thr Lys Val Gln His Arg Pro Ser Gly Leu 
                85                  90                  95      


Ile Met Ala Arg Lys Leu Ile His Leu Glu Ile Lys Pro Ala Ile Arg 
            100                 105                 110         


Asn Gln Ile Ile Arg Glu Leu Gln Val Leu His Glu Cys Asn Ser Pro 
        115                 120                 125             


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


Ile Cys Met Glu His Met Asp Gly Gly Ser Leu Asp Gln Val Leu Lys 
145                 150                 155                 160 


Glu Ala Lys Arg Ile Pro Glu Glu Ile Leu Gly Lys Val Ser Ile Ala 
                165                 170                 175     


Val Leu Arg Gly Leu Ala Tyr Leu Arg Glu Lys His Gln Ile Met His 
            180                 185                 190         


Arg Asp Val Lys Pro Ser Asn Ile Leu Val Asn Ser Arg Gly Glu Ile 
        195                 200                 205             


Lys Leu Cys Asp Phe Gly Val Ser Gly Gln Leu Ile Asp Ser Met Ala 
    210                 215                 220                 


Asn Ser Phe Val Gly Thr Arg Ser Tyr Met Ala Pro Glu Arg Leu Gln 
225                 230                 235                 240 


Gly Thr His Tyr Ser Val Gln Ser Asp Ile Trp Ser Met Gly Leu Ser 
                245                 250                 255     


Leu Val Glu Leu Ala Val Gly Arg Tyr Pro Ile Pro Pro Pro Asp Ala 
            260                 265                 270         


Lys Glu Leu Glu Ala Ile Phe Gly Arg Pro Val Val Asp Gly Glu Glu 
        275                 280                 285             


Gly Glu Pro His Ser Ile Ser Pro Arg Pro Arg Pro Pro Gly Arg Pro 
    290                 295                 300                 


Val Ser Gly His Gly Met Asp Ser Arg Pro Ala Met Ala Ile Phe Glu 
305                 310                 315                 320 


Leu Leu Asp Tyr Ile Val Asn Glu Pro Pro Pro Lys Leu Pro Asn Gly 
                325                 330                 335     


Val Phe Thr Pro Asp Phe Gln Glu Phe Val Asn Lys Cys Leu Ile Lys 
            340                 345                 350         


Asn Pro Ala Glu Arg Ala Asp Leu Lys Met Leu Thr Asn His Thr Phe 
        355                 360                 365             


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


Lys Thr Leu Arg Leu Asn Gln Pro Gly Thr Pro Thr Arg Thr Ala Val 
385                 390                 395                 400 


<210>  10
<211>  318
<212>  PRT
<213>  Homo sapiens

<400>  10

Met Ser Lys Pro Pro Ala Pro Asn Pro Thr Pro Pro Arg Asn Leu Asp 
1               5                   10                  15      


Ser Arg Thr Phe Ile Thr Ile Gly Asp Arg Asn Phe Glu Val Glu Ala 
            20                  25                  30          


Asp Asp Leu Val Thr Ile Ser Glu Leu Gly Arg Gly Ala Tyr Gly Val 
        35                  40                  45              


Val Glu Lys Val Arg His Ala Gln Ser Gly Thr Ile Met Ala Val Lys 
    50                  55                  60                  


Arg Ile Arg Ala Thr Val Asn Ser Gln Glu Gln Lys Arg Leu Leu Met 
65                  70                  75                  80  


Asp Leu Asp Ile Asn Met Arg Thr Val Asp Cys Phe Tyr Thr Val Thr 
                85                  90                  95      


Phe Tyr Gly Ala Leu Phe Arg Glu Gly Asp Val Trp Ile Cys Met Glu 
            100                 105                 110         


Leu Met Asp Thr Ser Leu Asp Lys Phe Tyr Arg Lys Val Leu Asp Lys 
        115                 120                 125             


Asn Met Thr Ile Pro Glu Asp Ile Leu Gly Glu Ile Ala Val Ser Ile 
    130                 135                 140                 


Val Arg Ala Leu Glu His Leu His Ser Lys Leu Ser Val Ile His Arg 
145                 150                 155                 160 


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


Met Cys Asp Phe Gly Ile Ser Gly Tyr Leu Val Asp Ser Val Ala Lys 
            180                 185                 190         


Thr Met Asp Ala Gly Cys Lys Pro Tyr Met Ala Pro Glu Arg Ile Asn 
        195                 200                 205             


Pro Glu Leu Asn Gln Lys Gly Tyr Asn Val Lys Ser Asp Val Trp Ser 
    210                 215                 220                 


Leu Gly Ile Thr Met Ile Glu Met Ala Ile Leu Arg Phe Pro Tyr Glu 
225                 230                 235                 240 


Ser Trp Gly Thr Pro Phe Gln Gln Leu Lys Gln Val Val Glu Glu Pro 
                245                 250                 255     


Ser Pro Gln Leu Pro Ala Asp Arg Phe Ser Pro Glu Phe Val Asp Phe 
            260                 265                 270         


Thr Ala Gln Cys Leu Arg Lys Asn Pro Ala Glu Arg Met Ser Tyr Leu 
        275                 280                 285             


Glu Leu Met Glu His Pro Phe Phe Thr Leu His Lys Thr Lys Lys Thr 
    290                 295                 300                 


Asp Ile Ala Ala Phe Val Lys Glu Ile Leu Gly Glu Asp Ser 
305                 310                 315             


<210>  11
<211>  357
<212>  PRT
<213>  Homo sapiens

<400>  11

Met Ala Ala Ala Ala Ala Gln Gly Gly Gly Gly Gly Glu Pro Arg Arg 
1               5                   10                  15      


Thr Glu Gly Val Gly Pro Gly Val Pro Gly Glu Val Glu Met Val Lys 
            20                  25                  30          


Gly Gln Pro Phe Asp Val Gly Pro Arg Tyr Thr Gln Leu Gln Tyr Ile 
        35                  40                  45              


Gly Glu Gly Ala Tyr Gly Met Val Ser Ser Ala Tyr Asp His Val Arg 
    50                  55                  60                  


Lys Thr Arg Val Ala Ile Lys Lys Ile Ser Pro Phe Glu His Gln Thr 
65                  70                  75                  80  


Tyr Cys Gln Arg Thr Leu Arg Glu Ile Gln Ile Leu Leu Arg Phe Arg 
                85                  90                  95      


His Glu Asn Val Ile Gly Ile Arg Asp Ile Leu Arg Ala Ser Thr Leu 
            100                 105                 110         


Glu Ala Met Arg Asp Val Tyr Ile Val Gln Asp Leu Met Glu Thr Asp 
        115                 120                 125             


Leu Tyr Lys Leu Leu Lys Ser Gln Gln Leu Ser Asn Asp His Ile Cys 
    130                 135                 140                 


Tyr Phe Leu Tyr Gln Ile Leu Arg Gly Leu Lys Tyr Ile His Ser Ala 
145                 150                 155                 160 


Asn Val Leu His Arg Asp Leu Lys Pro Ser Asn Leu Leu Ile Asn Thr 
                165                 170                 175     


Thr Cys Asp Leu Lys Ile Cys Asp Phe Gly Leu Ala Arg Ile Ala Asp 
            180                 185                 190         


Pro Glu His Asp His Thr Gly Phe Leu Thr Glu Tyr Val Ala Thr Arg 
        195                 200                 205             


Trp Tyr Arg Ala Pro Glu Ile Met Leu Asn Ser Lys Gly Tyr Thr Lys 
    210                 215                 220                 


Ser Ile Asp Ile Trp Ser Val Gly Cys Ile Leu Ala Glu Met Leu Ser 
225                 230                 235                 240 


Asn Arg Pro Ile Phe Pro Gly Lys His Tyr Leu Asp Gln Leu Asn His 
                245                 250                 255     


Ile Leu Gly Ile Leu Gly Ser Pro Ser Gln Glu Asp Leu Asn Cys Ile 
            260                 265                 270         


Ile Asn Met Lys Ala Arg Asn Tyr Leu Gln Ser Leu Pro Ser Lys Thr 
        275                 280                 285             


Lys Val Ala Trp Ala Lys Leu Phe Pro Lys Ser Asp Ser Lys Ala Leu 
    290                 295                 300                 


Asp Leu Leu Asp Arg Met Leu Thr Phe Asn Pro Asn Lys Arg Ile Thr 
305                 310                 315                 320 


Val Glu Glu Ala Leu Ala His Pro Tyr Leu Glu Gln Tyr Tyr Asp Pro 
                325                 330                 335     


Thr Asp Glu Val Gly Gln Ser Pro Ala Ala Val Gly Leu Gly Ala Gly 
            340                 345                 350         


Glu Gln Gly Gly Thr 
        355         


<210>  12
<211>  360
<212>  PRT
<213>  Homo sapiens

<400>  12

Met Ala Ala Ala Ala Ala Ala Gly Ala Gly Pro Glu Met Val Arg Gly 
1               5                   10                  15      


Gln Val Phe Asp Val Gly Pro Arg Tyr Thr Asn Leu Ser Tyr Ile Gly 
            20                  25                  30          


Glu Gly Ala Tyr Gly Met Val Cys Ser Ala Tyr Asp Asn Val Asn Lys 
        35                  40                  45              


Val Arg Val Ala Ile Lys Lys Ile Ser Pro Phe Glu His Gln Thr Tyr 
    50                  55                  60                  


Cys Gln Arg Thr Leu Arg Glu Ile Lys Ile Leu Leu Arg Phe Arg His 
65                  70                  75                  80  


Glu Asn Ile Ile Gly Ile Asn Asp Ile Ile Arg Ala Pro Thr Ile Glu 
                85                  90                  95      


Gln Met Lys Asp Val Tyr Ile Val Gln Asp Leu Met Glu Thr Asp Leu 
            100                 105                 110         


Tyr Lys Leu Leu Lys Thr Gln His Leu Ser Asn Asp His Ile Cys Tyr 
        115                 120                 125             


Phe Leu Tyr Gln Ile Leu Arg Gly Leu Lys Tyr Ile His Ser Ala Asn 
    130                 135                 140                 


Val Leu His Arg Asp Leu Lys Pro Ser Asn Leu Leu Leu Asn Thr Thr 
145                 150                 155                 160 


Cys Asp Leu Lys Ile Cys Asp Phe Gly Leu Ala Arg Val Ala Asp Pro 
                165                 170                 175     


Asp His Asp His Thr Gly Phe Leu Thr Glu Tyr Val Ala Thr Arg Trp 
            180                 185                 190         


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


Ile Asp Ile Trp Ser Val Gly Cys Ile Leu Ala Glu Met Leu Ser Asn 
    210                 215                 220                 


Arg Pro Ile Phe Pro Gly Lys His Tyr Leu Asp Gln Leu Asn His Ile 
225                 230                 235                 240 


Leu Gly Ile Leu Gly Ser Pro Ser Gln Glu Asp Leu Asn Cys Ile Ile 
                245                 250                 255     


Asn Leu Lys Ala Arg Asn Tyr Leu Leu Ser Leu Pro His Lys Asn Lys 
            260                 265                 270         


Val Pro Trp Asn Arg Leu Phe Pro Asn Ala Asp Ser Lys Ala Leu Asp 
        275                 280                 285             


Leu Leu Asp Lys Met Leu Thr Phe Asn Pro His Lys Arg Ile Glu Val 
    290                 295                 300                 


Glu Gln Ala Leu Ala His Pro Tyr Leu Glu Gln Tyr Tyr Asp Pro Ser 
305                 310                 315                 320 


Asp Glu Pro Ile Ala Glu Ala Pro Phe Lys Phe Asp Met Glu Leu Asp 
                325                 330                 335     


Asp Leu Pro Lys Glu Lys Leu Lys Glu Leu Ile Phe Glu Glu Thr Ala 
            340                 345                 350         


Arg Phe Gln Pro Gly Tyr Arg Ser 
        355                 360 


