                               SEQUENCE LISTING

<110> INSIDEOUTBIO, INC.
 
<120> GENETICALLY ENGINEERED ARGONAUTE PROTEINS WITH ENHANCED GENE 
      SILENCING ACTIVITY AND METHODS OF USE THEREOF

<130> 0371.0004WO1

<140>
<141>

<150> 62/673,485
<151> 2018-05-18

<160> 14    

<170> PatentIn version 3.5

<210> 1
<211> 859
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      polypeptide"

<400> 1
Met Tyr Ser Gly Ala Gly Pro Ala Leu Ala Pro Pro Ala Pro Pro Pro 
1               5                   10                  15      


Pro Ile Gln Gly Tyr Ala Phe Lys Pro Pro Pro Arg Pro Asp Phe Gly 
            20                  25                  30          


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


Ile Pro Lys Ile Asp Ile Tyr His Tyr Glu Leu Asp Ile Lys Pro Glu 
    50                  55                  60                  


Lys Cys Pro Arg Arg Val Asn Arg Glu Ile Val Glu His Met Val Gln 
65                  70                  75                  80  


His Phe Lys Thr Gln Ile Phe Gly Asp Arg Lys Pro Val Phe Asp Gly 
                85                  90                  95      


Arg Lys Asn Leu Tyr Thr Ala Met Pro Leu Pro Ile Gly Arg Asp Ala 
            100                 105                 110         


Val Ala Leu Glu Val Thr Leu Pro Gly Glu Gly Lys Asp Arg Ile Phe 
        115                 120                 125             


Lys Val Ser Ile Lys Trp Val Ser Cys Val Ser Leu Gln Ala Leu His 
    130                 135                 140                 


Asp Ala Leu Ser Gly Arg Leu Pro Ser Val Pro Phe Glu Thr Ile Gln 
145                 150                 155                 160 


Ala Leu Asp Val Val Met Arg His Leu Pro Ser Met Arg Tyr Thr Pro 
                165                 170                 175     


Val Gly Arg Ser Phe Phe Thr Ala Ser Glu Gly Cys Ser Asn Pro Leu 
            180                 185                 190         


Gly Gly Gly Arg Glu Val Trp Phe Gly Phe His Gln Ser Val Arg Pro 
        195                 200                 205             


Ser Leu Trp Lys Met Met Leu Asn Ile Asp Val Ser Ala Thr Ala Phe 
    210                 215                 220                 


Tyr Lys Ala Gln Pro Val Ile Glu Phe Val Cys Glu Val Leu Asp Phe 
225                 230                 235                 240 


Lys Ser Ile Glu Glu Gln Gln Lys Pro Leu Thr Asp Ser Gln Arg Val 
                245                 250                 255     


Lys Phe Thr Lys Glu Ile Lys Gly Leu Lys Val Glu Ile Thr His Cys 
            260                 265                 270         


Gly Gln Met Lys Arg Lys Tyr Arg Val Cys Asn Val Thr Arg Arg Pro 
        275                 280                 285             


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


Glu Cys Thr Val Ala Gln Tyr Phe Lys Asp Arg His Lys Leu Val Leu 
305                 310                 315                 320 


Arg Tyr Pro His Leu Pro Cys Leu Gln Val Gly Gln Glu Gln Lys His 
                325                 330                 335     


Thr Tyr Leu Pro Leu Glu Val Cys Asn Ile Val Ala Gly Gln Arg Cys 
            340                 345                 350         


Ile Lys Lys Leu Thr Asp Asn Gln Thr Ser Thr Met Ile Arg Ala Thr 
        355                 360                 365             


Ala Arg Ser Ala Pro Asp Arg Gln Glu Glu Ile Ser Lys Leu Met Arg 
    370                 375                 380                 


Ser Ala Ala Phe Asn Thr Asp Pro Phe Val Arg Glu Phe Gly Ile Met 
385                 390                 395                 400 


Val Lys Asp Glu Met Thr Asp Val Thr Gly Arg Val Leu Gln Pro Pro 
                405                 410                 415     


Ser Ile Leu Tyr Gly Gly Arg Asn Lys Ala Ile Ala Thr Pro Val Gln 
            420                 425                 430         


Gly Val Trp Asp Met Arg Asn Lys Gln Phe His Thr Gly Ile Glu Ile 
        435                 440                 445             


Lys Val Trp Ala Ile Ala Cys Phe Ala Pro Gln Arg Gln Cys Thr Glu 
    450                 455                 460                 


Val His Leu Lys Ser Phe Thr Glu Gln Leu Arg Lys Ile Ser Arg Asp 
465                 470                 475                 480 


Ala Gly Met Pro Ile Gln Gly Gln Pro Cys Phe Cys Lys Tyr Ala Gln 
                485                 490                 495     


Gly Ala Asp Ser Val Glu Pro Met Phe Arg His Leu Lys Asn Thr Tyr 
            500                 505                 510         


Ala Gly Leu Gln Leu Val Val Val Ile Leu Pro Gly Lys Thr Pro Val 
        515                 520                 525             


Phe Ala Glu Val Lys Arg Val Gly Asp Thr Val Leu Gly Met Ala Thr 
    530                 535                 540                 


Gln Cys Val Gln Met Lys Asn Val Gln Arg Thr Thr Pro Gln Thr Leu 
545                 550                 555                 560 


Ser Asn Leu Cys Leu Lys Ile Asn Val Lys Leu Gly Gly Val Asn Asn 
                565                 570                 575     


Ile Leu Leu Pro Gln Gly Arg Pro Pro Val Phe Gln Gln Pro Val Ile 
            580                 585                 590         


Phe Leu Gly Ala Asp Val Thr His Pro Pro Ala Gly Asp Gly Lys Lys 
        595                 600                 605             


Pro Ser Ile Ala Ala Val Val Gly Ser Met Asp Ala His Pro Asn Arg 
    610                 615                 620                 


Tyr Cys Ala Thr Val Arg Val Gln Gln His Arg Gln Glu Ile Ile Gln 
625                 630                 635                 640 


Asp Leu Ala Ala Met Val Arg Glu Leu Leu Ile Gln Phe Tyr Lys Ser 
                645                 650                 655     


Thr Arg Phe Lys Pro Thr Arg Ile Ile Phe Tyr Arg Asp Gly Val Ser 
            660                 665                 670         


Glu Gly Gln Phe Gln Gln Val Leu His His Glu Leu Leu Ala Ile Arg 
        675                 680                 685             


Glu Ala Cys Ile Lys Leu Glu Lys Asp Tyr Gln Pro Gly Ile Thr Phe 
    690                 695                 700                 


Ile Val Val Gln Lys Arg His His Thr Arg Leu Phe Cys Thr Asp Lys 
705                 710                 715                 720 


Asn Glu Arg Val Gly Lys Ser Gly Asn Ile Pro Ala Gly Thr Thr Val 
                725                 730                 735     


Asp Thr Lys Ile Thr His Pro Thr Glu Phe Asp Phe Tyr Leu Cys Ser 
            740                 745                 750         


His Ala Gly Ile Gln Gly Thr Ser Arg Pro Ser His Tyr His Val Leu 
        755                 760                 765             


Trp Asp Asp Asn Arg Phe Ser Ser Asp Glu Leu Gln Ile Leu Thr Tyr 
    770                 775                 780                 


Gln Leu Cys His Thr Tyr Val Arg Cys Thr Arg Ser Val Ala Ile Pro 
785                 790                 795                 800 


Ala Pro Ala Tyr Tyr Ala His Leu Val Ala Phe Arg Ala Arg Tyr His 
                805                 810                 815     


Leu Val Asp Lys Glu His Asp Ser Ala Glu Gly Ser His Thr Ser Gly 
            820                 825                 830         


Gln Ser Asn Gly Arg Asp His Gln Ala Leu Ala Lys Ala Val Gln Val 
        835                 840                 845             


His Gln Asp Thr Leu Arg Thr Met Tyr Phe Ala 
    850                 855                 


<210> 2
<211> 21
<212> DNA
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      oligonucleotide"

<400> 2
atgaaatgat ggtagacagc a                                                 21


<210> 3
<211> 22
<212> DNA
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      oligonucleotide"

<400> 3
agtgtaggat ctctgtaggt tc                                                22


<210> 4
<211> 21
<212> DNA
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      oligonucleotide"

<400> 4
agtggatacg gtgggtgatc t                                                 21


<210> 5
<211> 852
<212> PRT
<213> Homo sapiens

<400> 5
Met Ser Gly Arg Ala Arg Val Lys Ala Arg Gly Ile Ala Arg Ser Pro 
1               5                   10                  15      


Ser Ala Thr Glu Val Gly Arg Ile Gln Ala Ser Pro Leu Pro Arg Ser 
            20                  25                  30          


Val Asp Leu Ser Asn Asn Glu Ala Ser Ser Ser Asn Gly Phe Leu Gly 
        35                  40                  45              


Thr Ser Arg Ile Ser Thr Asn Asp Lys Tyr Gly Ile Ser Ser Gly Asp 
    50                  55                  60                  


Ala Gly Ser Thr Phe Met Glu Arg Gly Val Lys Asn Lys Gln Asp Phe 
65                  70                  75                  80  


Met Asp Leu Ser Ile Cys Thr Arg Glu Lys Leu Ala His Val Arg Asn 
                85                  90                  95      


Cys Lys Thr Gly Ser Ser Gly Ile Pro Val Lys Leu Val Thr Asn Leu 
            100                 105                 110         


Phe Asn Leu Asp Phe Pro Gln Asp Trp Gln Leu Tyr Gln Tyr His Val 
        115                 120                 125             


Thr Tyr Ile Pro Asp Leu Ala Ser Arg Arg Leu Arg Ile Ala Leu Leu 
    130                 135                 140                 


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


Ile Leu Phe Leu Ser Gln Lys Leu Glu Glu Lys Val Thr Glu Leu Ser 
                165                 170                 175     


Ser Glu Thr Gln Arg Gly Glu Thr Ile Lys Met Thr Ile Thr Leu Lys 
            180                 185                 190         


Arg Glu Leu Pro Ser Ser Ser Pro Val Cys Ile Gln Val Phe Asn Ile 
        195                 200                 205             


Ile Phe Arg Lys Ile Leu Lys Lys Leu Ser Met Tyr Gln Ile Gly Arg 
    210                 215                 220                 


Asn Phe Tyr Asn Pro Ser Glu Pro Met Glu Ile Pro Gln His Lys Leu 
225                 230                 235                 240 


Ser Leu Trp Pro Gly Phe Ala Ile Ser Val Ser Tyr Phe Glu Arg Lys 
                245                 250                 255     


Leu Leu Phe Ser Ala Asp Val Ser Tyr Lys Val Leu Arg Asn Glu Thr 
            260                 265                 270         


Val Leu Glu Phe Met Thr Ala Leu Cys Gln Arg Thr Gly Leu Ser Cys 
        275                 280                 285             


Phe Thr Gln Thr Cys Glu Lys Gln Leu Ile Gly Leu Ile Val Leu Thr 
    290                 295                 300                 


Arg Tyr Asn Asn Arg Thr Tyr Ser Ile Asp Asp Ile Asp Trp Ser Val 
305                 310                 315                 320 


Lys Pro Thr His Thr Phe Gln Lys Arg Asp Gly Thr Glu Ile Thr Tyr 
                325                 330                 335     


Val Asp Tyr Tyr Lys Gln Gln Tyr Asp Ile Thr Val Ser Asp Leu Asn 
            340                 345                 350         


Gln Pro Met Leu Val Ser Leu Leu Lys Lys Lys Arg Asn Asp Asn Ser 
        355                 360                 365             


Glu Ala Gln Leu Ala His Leu Ile Pro Glu Leu Cys Phe Leu Thr Gly 
    370                 375                 380                 


Leu Thr Asp Gln Ala Thr Ser Asp Phe Gln Leu Met Lys Ala Val Ala 
385                 390                 395                 400 


Glu Lys Thr Arg Leu Ser Pro Ser Gly Arg Gln Gln Arg Leu Ala Arg 
                405                 410                 415     


Leu Val Asp Asn Ile Gln Arg Asn Thr Asn Ala Arg Phe Glu Leu Glu 
            420                 425                 430         


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


Val Pro Ser Glu Lys Ile Leu Met Gln Asp His Ile Cys Gln Pro Val 
    450                 455                 460                 


Ser Ala Ala Asp Trp Ser Lys Asp Ile Arg Thr Cys Lys Ile Leu Asn 
465                 470                 475                 480 


Ala Gln Ser Leu Asn Thr Trp Leu Ile Leu Cys Ser Asp Arg Thr Glu 
                485                 490                 495     


Tyr Val Ala Glu Ser Phe Leu Asn Cys Leu Arg Arg Val Ala Gly Ser 
            500                 505                 510         


Met Gly Phe Asn Val Asp Tyr Pro Lys Ile Ile Lys Val Gln Glu Asn 
        515                 520                 525             


Pro Ala Ala Phe Val Arg Ala Ile Gln Gln Tyr Val Asp Pro Asp Val 
    530                 535                 540                 


Gln Leu Val Met Cys Ile Leu Pro Ser Asn Gln Lys Thr Tyr Tyr Asp 
545                 550                 555                 560 


Ser Ile Lys Lys Tyr Leu Ser Ser Asp Cys Pro Val Pro Ser Gln Cys 
                565                 570                 575     


Val Leu Ala Arg Thr Leu Asn Lys Gln Gly Met Met Met Ser Ile Ala 
            580                 585                 590         


Thr Lys Ile Ala Met Gln Met Thr Cys Lys Leu Gly Gly Glu Leu Trp 
        595                 600                 605             


Ala Val Glu Ile Pro Leu Lys Ser Leu Met Val Val Gly Ile Asp Val 
    610                 615                 620                 


Cys Lys Asp Ala Leu Ser Lys Asp Val Met Val Val Gly Cys Val Ala 
625                 630                 635                 640 


Ser Val Asn Pro Arg Ile Thr Arg Trp Phe Ser Arg Cys Ile Leu Gln 
                645                 650                 655     


Arg Thr Met Thr Asp Val Ala Asp Cys Leu Lys Val Phe Met Thr Gly 
            660                 665                 670         


Ala Leu Asn Lys Trp Tyr Lys Tyr Asn His Asp Leu Pro Ala Arg Ile 
        675                 680                 685             


Ile Val Tyr Arg Ala Gly Val Gly Asp Gly Gln Leu Lys Thr Leu Ile 
    690                 695                 700                 


Glu Tyr Glu Val Pro Gln Leu Leu Ser Ser Val Ala Glu Ser Ser Ser 
705                 710                 715                 720 


Asn Thr Ser Ser Arg Leu Ser Val Ile Val Val Arg Lys Lys Cys Met 
                725                 730                 735     


Pro Arg Phe Phe Thr Glu Met Asn Arg Thr Val Gln Asn Pro Pro Leu 
            740                 745                 750         


Gly Thr Val Val Asp Ser Glu Ala Thr Arg Asn Glu Trp Tyr Asp Phe 
        755                 760                 765             


Tyr Leu Ile Ser Gln Val Ala Cys Arg Gly Thr Val Ser Pro Thr Tyr 
    770                 775                 780                 


Tyr Asn Val Ile Tyr Asp Asp Asn Gly Leu Lys Pro Asp His Met Gln 
785                 790                 795                 800 


Arg Leu Thr Phe Lys Leu Cys His Leu Tyr Tyr Asn Trp Pro Gly Ile 
                805                 810                 815     


Val Ser Val Pro Ala Pro Cys Gln Tyr Ala His Lys Leu Thr Phe Leu 
            820                 825                 830         


Val Ala Gln Ser Ile His Lys Glu Pro Ser Leu Glu Leu Ala Asn His 
        835                 840                 845             


Leu Phe Tyr Leu 
    850         


<210> 6
<211> 861
<212> PRT
<213> Homo sapiens

<400> 6
Met Thr Gly Arg Ala Arg Ala Arg Ala Arg Gly Arg Ala Arg Gly Gln 
1               5                   10                  15      


Glu Thr Ala Gln Leu Val Gly Ser Thr Ala Ser Gln Gln Pro Gly Tyr 
            20                  25                  30          


Ile Gln Pro Arg Pro Gln Pro Pro Pro Ala Glu Gly Glu Leu Phe Gly 
        35                  40                  45              


Arg Gly Arg Gln Arg Gly Thr Ala Gly Gly Thr Ala Lys Ser Gln Gly 
    50                  55                  60                  


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


Gly Arg Arg Arg Asp Phe His Asp Leu Gly Val Asn Thr Arg Gln Asn 
                85                  90                  95      


Leu Asp His Val Lys Glu Ser Lys Thr Gly Ser Ser Gly Ile Ile Val 
            100                 105                 110         


Arg Leu Ser Thr Asn His Phe Arg Leu Thr Ser Arg Pro Gln Trp Ala 
        115                 120                 125             


Leu Tyr Gln Tyr His Ile Asp Tyr Asn Pro Leu Met Glu Ala Arg Arg 
    130                 135                 140                 


Leu Arg Ser Ala Leu Leu Phe Gln His Glu Asp Leu Ile Gly Lys Cys 
145                 150                 155                 160 


His Ala Phe Asp Gly Thr Ile Leu Phe Leu Pro Lys Arg Leu Gln Gln 
                165                 170                 175     


Lys Val Thr Glu Val Phe Ser Lys Thr Arg Asn Gly Glu Asp Val Arg 
            180                 185                 190         


Ile Thr Ile Thr Leu Thr Asn Glu Leu Pro Pro Thr Ser Pro Thr Cys 
        195                 200                 205             


Leu Gln Phe Tyr Asn Ile Ile Phe Arg Arg Leu Leu Lys Ile Met Asn 
    210                 215                 220                 


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


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


Leu Gln Tyr Glu Asn Ser Ile Met Leu Cys Thr Asp Val Ser His Lys 
            260                 265                 270         


Val Leu Arg Ser Glu Thr Val Leu Asp Phe Met Phe Asn Phe Tyr His 
        275                 280                 285             


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


Gly Leu Val Val Leu Thr Lys Tyr Asn Asn Lys Thr Tyr Arg Val Asp 
305                 310                 315                 320 


Asp Ile Asp Trp Asp Gln Asn Pro Lys Ser Thr Phe Lys Lys Ala Asp 
                325                 330                 335     


Gly Ser Glu Val Ser Phe Leu Glu Tyr Tyr Arg Lys Gln Tyr Asn Gln 
            340                 345                 350         


Glu Ile Thr Asp Leu Lys Gln Pro Val Leu Val Ser Gln Pro Lys Arg 
        355                 360                 365             


Arg Arg Gly Pro Gly Gly Thr Leu Pro Gly Pro Ala Met Leu Ile Pro 
    370                 375                 380                 


Glu Leu Cys Tyr Leu Thr Gly Leu Thr Asp Lys Met Arg Asn Asp Phe 
385                 390                 395                 400 


Asn Val Met Lys Asp Leu Ala Val His Thr Arg Leu Thr Pro Glu Gln 
                405                 410                 415     


Arg Gln Arg Glu Val Gly Arg Leu Ile Asp Tyr Ile His Lys Asn Asp 
            420                 425                 430         


Asn Val Gln Arg Glu Leu Arg Asp Trp Gly Leu Ser Phe Asp Ser Asn 
        435                 440                 445             


Leu Leu Ser Phe Ser Gly Arg Ile Leu Gln Thr Glu Lys Ile His Gln 
    450                 455                 460                 


Gly Gly Lys Thr Phe Asp Tyr Asn Pro Gln Phe Ala Asp Trp Ser Lys 
465                 470                 475                 480 


Glu Thr Arg Gly Ala Pro Leu Ile Ser Val Lys Pro Leu Asp Asn Trp 
                485                 490                 495     


Leu Leu Ile Tyr Thr Arg Arg Asn Tyr Glu Ala Ala Asn Ser Leu Ile 
            500                 505                 510         


Gln Asn Leu Phe Lys Val Thr Pro Ala Met Gly Met Gln Met Arg Lys 
        515                 520                 525             


Ala Ile Met Ile Glu Val Asp Asp Arg Thr Glu Ala Tyr Leu Arg Val 
    530                 535                 540                 


Leu Gln Gln Lys Val Thr Ala Asp Thr Gln Ile Val Val Cys Leu Leu 
545                 550                 555                 560 


Ser Ser Asn Arg Lys Asp Lys Tyr Asp Ala Ile Lys Lys Tyr Leu Cys 
                565                 570                 575     


Thr Asp Cys Pro Thr Pro Ser Gln Cys Val Val Ala Arg Thr Leu Gly 
            580                 585                 590         


Lys Gln Gln Thr Val Met Ala Ile Ala Thr Lys Ile Ala Leu Gln Met 
        595                 600                 605             


Asn Cys Lys Met Gly Gly Glu Leu Trp Arg Val Asp Ile Pro Leu Lys 
    610                 615                 620                 


Leu Val Met Ile Val Gly Ile Asp Cys Tyr His Asp Met Thr Ala Gly 
625                 630                 635                 640 


Arg Arg Ser Ile Ala Gly Phe Val Ala Ser Ile Asn Glu Gly Met Thr 
                645                 650                 655     


Arg Trp Phe Ser Arg Cys Ile Phe Gln Asp Arg Gly Gln Glu Leu Val 
            660                 665                 670         


Asp Gly Leu Lys Val Cys Leu Gln Ala Ala Leu Arg Ala Trp Asn Ser 
        675                 680                 685             


Cys Asn Glu Tyr Met Pro Ser Arg Ile Ile Val Tyr Arg Asp Gly Val 
    690                 695                 700                 


Gly Asp Gly Gln Leu Lys Thr Leu Val Asn Tyr Glu Val Pro Gln Phe 
705                 710                 715                 720 


Leu Asp Cys Leu Lys Ser Ile Gly Arg Gly Tyr Asn Pro Arg Leu Thr 
                725                 730                 735     


Val Ile Val Val Lys Lys Arg Val Asn Thr Arg Phe Phe Ala Gln Ser 
            740                 745                 750         


Gly Gly Arg Leu Gln Asn Pro Leu Pro Gly Thr Val Ile Asp Val Glu 
        755                 760                 765             


Val Thr Arg Pro Glu Trp Tyr Asp Phe Phe Ile Val Ser Gln Ala Val 
    770                 775                 780                 


Arg Ser Gly Ser Val Ser Pro Thr His Tyr Asn Val Ile Tyr Asp Asn 
785                 790                 795                 800 


Ser Gly Leu Lys Pro Asp His Ile Gln Arg Leu Thr Tyr Lys Leu Cys 
                805                 810                 815     


His Ile Tyr Tyr Asn Trp Pro Gly Val Ile Arg Val Pro Ala Pro Cys 
            820                 825                 830         


Gln Tyr Ala His Lys Leu Ala Phe Leu Val Gly Gln Ser Ile His Arg 
        835                 840                 845             


Glu Pro Asn Leu Ser Leu Ser Asn Arg Leu Tyr Tyr Leu 
    850                 855                 860     


<210> 7
<211> 859
<212> PRT
<213> Homo sapiens

<400> 7
Met Tyr Ser Gly Ala Gly Pro Ala Leu Ala Pro Pro Ala Pro Pro Pro 
1               5                   10                  15      


Pro Ile Gln Gly Tyr Ala Phe Lys Pro Pro Pro Arg Pro Asp Phe Gly 
            20                  25                  30          


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


Ile Pro Lys Ile Asp Ile Tyr His Tyr Glu Leu Asp Ile Lys Pro Glu 
    50                  55                  60                  


Lys Cys Pro Arg Arg Val Asn Arg Glu Ile Val Glu His Met Val Gln 
65                  70                  75                  80  


His Phe Lys Thr Gln Ile Phe Gly Asp Arg Lys Pro Val Phe Asp Gly 
                85                  90                  95      


Arg Lys Asn Leu Tyr Thr Ala Met Pro Leu Pro Ile Gly Arg Asp Lys 
            100                 105                 110         


Val Glu Leu Glu Val Thr Leu Pro Gly Glu Gly Lys Asp Arg Ile Phe 
        115                 120                 125             


Lys Val Ser Ile Lys Trp Val Ser Cys Val Ser Leu Gln Ala Leu His 
    130                 135                 140                 


Asp Ala Leu Ser Gly Arg Leu Pro Ser Val Pro Phe Glu Thr Ile Gln 
145                 150                 155                 160 


Ala Leu Asp Val Val Met Arg His Leu Pro Ser Met Arg Tyr Thr Pro 
                165                 170                 175     


Val Gly Arg Ser Phe Phe Thr Ala Ser Glu Gly Cys Ser Asn Pro Leu 
            180                 185                 190         


Gly Gly Gly Arg Glu Val Trp Phe Gly Phe His Gln Ser Val Arg Pro 
        195                 200                 205             


Ser Leu Trp Lys Met Met Leu Asn Ile Asp Val Ser Ala Thr Ala Phe 
    210                 215                 220                 


Tyr Lys Ala Gln Pro Val Ile Glu Phe Val Cys Glu Val Leu Asp Phe 
225                 230                 235                 240 


Lys Ser Ile Glu Glu Gln Gln Lys Pro Leu Thr Asp Ser Gln Arg Val 
                245                 250                 255     


Lys Phe Thr Lys Glu Ile Lys Gly Leu Lys Val Glu Ile Thr His Cys 
            260                 265                 270         


Gly Gln Met Lys Arg Lys Tyr Arg Val Cys Asn Val Thr Arg Arg Pro 
        275                 280                 285             


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


Glu Cys Thr Val Ala Gln Tyr Phe Lys Asp Arg His Lys Leu Val Leu 
305                 310                 315                 320 


Arg Tyr Pro His Leu Pro Cys Leu Gln Val Gly Gln Glu Gln Lys His 
                325                 330                 335     


Thr Tyr Leu Pro Leu Glu Val Cys Asn Ile Val Ala Gly Gln Arg Cys 
            340                 345                 350         


Ile Lys Lys Leu Thr Asp Asn Gln Thr Ser Thr Met Ile Arg Ala Thr 
        355                 360                 365             


Ala Arg Ser Ala Pro Asp Arg Gln Glu Glu Ile Ser Lys Leu Met Arg 
    370                 375                 380                 


Ser Ala Ser Phe Asn Thr Asp Pro Tyr Val Arg Glu Phe Gly Ile Met 
385                 390                 395                 400 


Val Lys Asp Glu Met Thr Asp Val Thr Gly Arg Val Leu Gln Pro Pro 
                405                 410                 415     


Ser Ile Leu Tyr Gly Gly Arg Asn Lys Ala Ile Ala Thr Pro Val Gln 
            420                 425                 430         


Gly Val Trp Asp Met Arg Asn Lys Gln Phe His Thr Gly Ile Glu Ile 
        435                 440                 445             


Lys Val Trp Ala Ile Ala Cys Phe Ala Pro Gln Arg Gln Cys Thr Glu 
    450                 455                 460                 


Val His Leu Lys Ser Phe Thr Glu Gln Leu Arg Lys Ile Ser Arg Asp 
465                 470                 475                 480 


Ala Gly Met Pro Ile Gln Gly Gln Pro Cys Phe Cys Lys Tyr Ala Gln 
                485                 490                 495     


Gly Ala Asp Ser Val Glu Pro Met Phe Arg His Leu Lys Asn Thr Tyr 
            500                 505                 510         


Ala Gly Leu Gln Leu Val Val Val Ile Leu Pro Gly Lys Thr Pro Val 
        515                 520                 525             


Tyr Ala Glu Val Lys Arg Val Gly Asp Thr Val Leu Gly Met Ala Thr 
    530                 535                 540                 


Gln Cys Val Gln Met Lys Asn Val Gln Arg Thr Thr Pro Gln Thr Leu 
545                 550                 555                 560 


Ser Asn Leu Cys Leu Lys Ile Asn Val Lys Leu Gly Gly Val Asn Asn 
                565                 570                 575     


Ile Leu Leu Pro Gln Gly Arg Pro Pro Val Phe Gln Gln Pro Val Ile 
            580                 585                 590         


Phe Leu Gly Ala Asp Val Thr His Pro Pro Ala Gly Asp Gly Lys Lys 
        595                 600                 605             


Pro Ser Ile Ala Ala Val Val Gly Ser Met Asp Ala His Pro Asn Arg 
    610                 615                 620                 


Tyr Cys Ala Thr Val Arg Val Gln Gln His Arg Gln Glu Ile Ile Gln 
625                 630                 635                 640 


Asp Leu Ala Ala Met Val Arg Glu Leu Leu Ile Gln Phe Tyr Lys Ser 
                645                 650                 655     


Thr Arg Phe Lys Pro Thr Arg Ile Ile Phe Tyr Arg Asp Gly Val Ser 
            660                 665                 670         


Glu Gly Gln Phe Gln Gln Val Leu His His Glu Leu Leu Ala Ile Arg 
        675                 680                 685             


Glu Ala Cys Ile Lys Leu Glu Lys Asp Tyr Gln Pro Gly Ile Thr Phe 
    690                 695                 700                 


Ile Val Val Gln Lys Arg His His Thr Arg Leu Phe Cys Thr Asp Lys 
705                 710                 715                 720 


Asn Glu Arg Val Gly Lys Ser Gly Asn Ile Pro Ala Gly Thr Thr Val 
                725                 730                 735     


Asp Thr Lys Ile Thr His Pro Thr Glu Phe Asp Phe Tyr Leu Cys Ser 
            740                 745                 750         


His Ala Gly Ile Gln Gly Thr Ser Arg Pro Ser His Tyr His Val Leu 
        755                 760                 765             


Trp Asp Asp Asn Arg Phe Ser Ser Asp Glu Leu Gln Ile Leu Thr Tyr 
    770                 775                 780                 


Gln Leu Cys His Thr Tyr Val Arg Cys Thr Arg Ser Val Ser Ile Pro 
785                 790                 795                 800 


Ala Pro Ala Tyr Tyr Ala His Leu Val Ala Phe Arg Ala Arg Tyr His 
                805                 810                 815     


Leu Val Asp Lys Glu His Asp Ser Ala Glu Gly Ser His Thr Ser Gly 
            820                 825                 830         


Gln Ser Asn Gly Arg Asp His Gln Ala Leu Ala Lys Ala Val Gln Val 
        835                 840                 845             


His Gln Asp Thr Leu Arg Thr Met Tyr Phe Ala 
    850                 855                 


<210> 8
<211> 973
<212> PRT
<213> Homo sapiens

<400> 8
Met Asp Pro Phe Arg Pro Ser Phe Arg Gly Gln Ser Pro Ile His Pro 
1               5                   10                  15      


Ser Gln Cys Gln Ala Val Arg Met Pro Gly Cys Trp Pro Gln Ala Ser 
            20                  25                  30          


Lys Pro Leu Asp Pro Ala Leu Gly Arg Gly Ala Pro Ala Gly Arg Gly 
        35                  40                  45              


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


Gln Arg Glu Ser Val Gly Leu Val Ser Met Phe Arg Gly Leu Gly Ile 
65                  70                  75                  80  


Glu Thr Val Ser Lys Thr Pro Leu Lys Arg Glu Met Leu Pro Ser Gly 
                85                  90                  95      


Arg Gly Ile Leu Gly Arg Gly Leu Ser Ala Asn Leu Val Arg Lys Asp 
            100                 105                 110         


Arg Glu Glu Leu Ser Pro Thr Phe Trp Asp Pro Lys Val Leu Ala Ala 
        115                 120                 125             


Gly Asp Ser Lys Met Ala Glu Thr Ser Val Gly Trp Ser Arg Thr Leu 
    130                 135                 140                 


Gly Arg Gly Ser Ser Asp Ala Ser Leu Leu Pro Leu Gly Arg Ala Ala 
145                 150                 155                 160 


Gly Gly Ile Ser Arg Glu Val Asp Lys Pro Pro Cys Thr Phe Ser Thr 
                165                 170                 175     


Pro Ser Arg Gly Pro Pro Gln Leu Ser Ser Pro Pro Ala Leu Pro Gln 
            180                 185                 190         


Ser Pro Leu His Ser Pro Asp Arg Pro Leu Val Leu Thr Val Glu His 
        195                 200                 205             


Lys Glu Lys Glu Leu Ile Val Lys Gln Gly Ser Lys Gly Thr Pro Gln 
    210                 215                 220                 


Ser Leu Gly Leu Asn Leu Val Lys Ile Gln Cys His Asn Glu Ala Val 
225                 230                 235                 240 


Tyr Gln Tyr His Val Thr Phe Ser Pro Asn Val Glu Cys Lys Ser Met 
                245                 250                 255     


Arg Phe Gly Met Leu Lys Asp His Gln Ala Val Thr Gly Asn Val Thr 
            260                 265                 270         


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


Leu Glu Leu Lys Ser Gln Arg Lys Thr Asp Ser Ala Glu Ile Ser Ile 
    290                 295                 300                 


Lys Ile Gln Met Thr Lys Ile Leu Glu Pro Cys Ser Asp Leu Cys Ile 
305                 310                 315                 320 


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


Lys Leu Val Gly Arg Asn Phe Tyr Asp Pro Thr Ser Ala Met Val Leu 
            340                 345                 350         


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


Arg Thr Asp Gly Gly Leu Phe Leu Leu Ala Asp Val Ser His Lys Val 
    370                 375                 380                 


Ile Arg Asn Asp Cys Val Leu Asp Val Met His Ala Ile Tyr Gln Gln 
385                 390                 395                 400 


Asn Lys Glu His Phe Gln Asp Glu Cys Thr Lys Leu Leu Val Gly Asn 
                405                 410                 415     


Ile Val Ile Thr Arg Tyr Asn Asn Arg Thr Tyr Arg Ile Asp Asp Val 
            420                 425                 430         


Asp Trp Asn Lys Thr Pro Lys Asp Ser Phe Thr Met Ser Asp Gly Lys 
        435                 440                 445             


Glu Ile Thr Phe Leu Glu Tyr Tyr Ser Lys Asn Tyr Gly Ile Thr Val 
    450                 455                 460                 


Lys Glu Glu Asp Gln Pro Leu Leu Ile His Arg Pro Ser Glu Arg Gln 
465                 470                 475                 480 


Asp Asn His Gly Met Leu Leu Lys Gly Glu Ile Leu Leu Leu Pro Glu 
                485                 490                 495     


Leu Ser Phe Met Thr Gly Ile Pro Glu Lys Met Lys Lys Asp Phe Arg 
            500                 505                 510         


Ala Met Lys Asp Leu Ala Gln Gln Ile Asn Leu Ser Pro Lys Gln His 
        515                 520                 525             


His Ser Ala Leu Glu Cys Leu Leu Gln Arg Ile Ala Lys Asn Glu Ala 
    530                 535                 540                 


Ala Thr Asn Glu Leu Met Arg Trp Gly Leu Arg Leu Gln Lys Asp Val 
545                 550                 555                 560 


His Lys Ile Glu Gly Arg Val Leu Pro Met Glu Arg Ile Asn Leu Lys 
                565                 570                 575     


Asn Thr Ser Phe Ile Thr Ser Gln Glu Leu Asn Trp Val Lys Glu Val 
            580                 585                 590         


Thr Arg Asp Pro Ser Ile Leu Thr Ile Pro Met His Phe Trp Ala Leu 
        595                 600                 605             


Phe Tyr Pro Lys Arg Ala Met Asp Gln Ala Arg Glu Leu Val Asn Met 
    610                 615                 620                 


Leu Glu Lys Ile Ala Gly Pro Ile Gly Met Arg Met Ser Pro Pro Ala 
625                 630                 635                 640 


Trp Val Glu Leu Lys Asp Asp Arg Ile Glu Thr Tyr Val Arg Thr Ile 
                645                 650                 655     


Gln Ser Thr Leu Gly Ala Glu Gly Lys Ile Gln Met Val Val Cys Ile 
            660                 665                 670         


Ile Met Gly Pro Arg Asp Asp Leu Tyr Gly Ala Ile Lys Lys Leu Cys 
        675                 680                 685             


Cys Val Gln Ser Pro Val Pro Ser Gln Val Val Asn Val Arg Thr Ile 
    690                 695                 700                 


Gly Gln Pro Thr Arg Leu Arg Ser Val Ala Gln Lys Ile Leu Leu Gln 
705                 710                 715                 720 


Ile Asn Cys Lys Leu Gly Gly Glu Leu Trp Gly Val Asp Ile Pro Leu 
                725                 730                 735     


Lys Gln Leu Met Val Ile Gly Met Asp Val Tyr His Asp Pro Ser Arg 
            740                 745                 750         


Gly Met Arg Ser Val Val Gly Phe Val Ala Ser Ile Asn Leu Thr Leu 
        755                 760                 765             


Thr Lys Trp Tyr Ser Arg Val Val Phe Gln Met Pro His Gln Glu Ile 
    770                 775                 780                 


Val Asp Ser Leu Lys Leu Cys Leu Val Gly Ser Leu Lys Lys Phe Tyr 
785                 790                 795                 800 


Glu Val Asn His Cys Leu Pro Glu Lys Ile Val Val Tyr Arg Asp Gly 
                805                 810                 815     


Val Ser Asp Gly Gln Leu Lys Thr Val Ala Asn Tyr Glu Ile Pro Gln 
            820                 825                 830         


Leu Gln Lys Cys Phe Glu Ala Phe Glu Asn Tyr Gln Pro Lys Met Val 
        835                 840                 845             


Val Phe Val Val Gln Lys Lys Ile Ser Thr Asn Leu Tyr Leu Ala Ala 
    850                 855                 860                 


Pro Gln Asn Phe Val Thr Pro Thr Pro Gly Thr Val Val Asp His Thr 
865                 870                 875                 880 


Ile Thr Ser Cys Glu Trp Val Asp Phe Tyr Leu Leu Ala His His Val 
                885                 890                 895     


Arg Gln Gly Cys Gly Ile Pro Thr His Tyr Val Cys Val Leu Asn Thr 
            900                 905                 910         


Ala Asn Leu Ser Pro Asp His Met Gln Arg Leu Thr Phe Lys Leu Cys 
        915                 920                 925             


His Met Tyr Trp Asn Trp Pro Gly Thr Ile Arg Val Pro Ala Pro Cys 
    930                 935                 940                 


Lys Tyr Ala His Lys Leu Ala Phe Leu Ser Gly His Ile Leu His His 
945                 950                 955                 960 


Glu Pro Ala Ile Gln Leu Cys Glu Asn Leu Phe Phe Leu 
                965                 970             


<210> 9
<211> 857
<212> PRT
<213> Homo sapiens

<400> 9
Met Glu Ala Gly Pro Ser Gly Ala Ala Ala Gly Ala Tyr Leu Pro Pro 
1               5                   10                  15      


Leu Gln Gln Val Phe Gln Ala Pro Arg Arg Pro Gly Ile Gly Thr Val 
            20                  25                  30          


Gly Lys Pro Ile Lys Leu Leu Ala Asn Tyr Phe Glu Val Asp Ile Pro 
        35                  40                  45              


Lys Ile Asp Val Tyr His Tyr Glu Val Asp Ile Lys Pro Asp Lys Cys 
    50                  55                  60                  


Pro Arg Arg Val Asn Arg Glu Val Val Glu Tyr Met Val Gln His Phe 
65                  70                  75                  80  


Lys Pro Gln Ile Phe Gly Asp Arg Lys Pro Val Tyr Asp Gly Lys Lys 
                85                  90                  95      


Asn Ile Tyr Thr Val Thr Ala Leu Pro Ile Gly Asn Glu Arg Val Asp 
            100                 105                 110         


Phe Glu Val Thr Ile Pro Gly Glu Gly Lys Asp Arg Ile Phe Lys Val 
        115                 120                 125             


Ser Ile Lys Trp Leu Ala Ile Val Ser Trp Arg Met Leu His Glu Ala 
    130                 135                 140                 


Leu Val Ser Gly Gln Ile Pro Val Pro Leu Glu Ser Val Gln Ala Leu 
145                 150                 155                 160 


Asp Val Ala Met Arg His Leu Ala Ser Met Arg Tyr Thr Pro Val Gly 
                165                 170                 175     


Arg Ser Phe Phe Ser Pro Pro Glu Gly Tyr Tyr His Pro Leu Gly Gly 
            180                 185                 190         


Gly Arg Glu Val Trp Phe Gly Phe His Gln Ser Val Arg Pro Ala Met 
        195                 200                 205             


Trp Lys Met Met Leu Asn Ile Asp Val Ser Ala Thr Ala Phe Tyr Lys 
    210                 215                 220                 


Ala Gln Pro Val Ile Glu Phe Met Cys Glu Val Leu Asp Ile Arg Asn 
225                 230                 235                 240 


Ile Asp Glu Gln Pro Lys Pro Leu Thr Asp Ser Gln Arg Val Arg Phe 
                245                 250                 255     


Thr Lys Glu Ile Lys Gly Leu Lys Val Glu Val Thr His Cys Gly Gln 
            260                 265                 270         


Met Lys Arg Lys Tyr Arg Val Cys Asn Val Thr Arg Arg Pro Ala Ser 
        275                 280                 285             


His Gln Thr Phe Pro Leu Gln Leu Glu Ser Gly Gln Thr Val Glu Cys 
    290                 295                 300                 


Thr Val Ala Gln Tyr Phe Lys Gln Lys Tyr Asn Leu Gln Leu Lys Tyr 
305                 310                 315                 320 


Pro His Leu Pro Cys Leu Gln Val Gly Gln Glu Gln Lys His Thr Tyr 
                325                 330                 335     


Leu Pro Leu Glu Val Cys Asn Ile Val Ala Gly Gln Arg Cys Ile Lys 
            340                 345                 350         


Lys Leu Thr Asp Asn Gln Thr Ser Thr Met Ile Lys Ala Thr Ala Arg 
        355                 360                 365             


Ser Ala Pro Asp Arg Gln Glu Glu Ile Ser Arg Leu Met Lys Asn Ala 
    370                 375                 380                 


Ser Tyr Asn Leu Asp Pro Tyr Ile Gln Glu Phe Gly Ile Lys Val Lys 
385                 390                 395                 400 


Asp Asp Met Thr Glu Val Thr Gly Arg Val Leu Pro Ala Pro Ile Leu 
                405                 410                 415     


Gln Tyr Gly Gly Arg Asn Arg Ala Ile Ala Thr Pro Asn Gln Gly Val 
            420                 425                 430         


Trp Asp Met Arg Gly Lys Gln Phe Tyr Asn Gly Ile Glu Ile Lys Val 
        435                 440                 445             


Trp Ala Ile Ala Cys Phe Ala Pro Gln Lys Gln Cys Arg Glu Glu Val 
    450                 455                 460                 


Leu Lys Asn Phe Thr Asp Gln Leu Arg Lys Ile Ser Lys Asp Ala Gly 
465                 470                 475                 480 


Met Pro Ile Gln Gly Gln Pro Cys Phe Cys Lys Tyr Ala Gln Gly Ala 
                485                 490                 495     


Asp Ser Val Glu Pro Met Phe Arg His Leu Lys Asn Thr Tyr Ser Gly 
            500                 505                 510         


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


Glu Val Lys Arg Val Gly Asp Thr Leu Leu Gly Met Ala Thr Gln Cys 
    530                 535                 540                 


Val Gln Val Lys Asn Val Val Lys Thr Ser Pro Gln Thr Leu Ser Asn 
545                 550                 555                 560 


Leu Cys Leu Lys Ile Asn Val Lys Leu Gly Gly Ile Asn Asn Ile Leu 
                565                 570                 575     


Val Pro His Gln Arg Ser Ala Val Phe Gln Gln Pro Val Ile Phe Leu 
            580                 585                 590         


Gly Ala Asp Val Thr His Pro Pro Ala Gly Asp Gly Lys Lys Pro Ser 
        595                 600                 605             


Ile Thr Ala Val Val Gly Ser Met Asp Ala His Pro Ser Arg Tyr Cys 
    610                 615                 620                 


Ala Thr Val Arg Val Gln Arg Pro Arg Gln Glu Ile Ile Glu Asp Leu 
625                 630                 635                 640 


Ser Tyr Met Val Arg Glu Leu Leu Ile Gln Phe Tyr Lys Ser Thr Arg 
                645                 650                 655     


Phe Lys Pro Thr Arg Ile Ile Phe Tyr Arg Asp Gly Val Pro Glu Gly 
            660                 665                 670         


Gln Leu Pro Gln Ile Leu His Tyr Glu Leu Leu Ala Ile Arg Asp Ala 
        675                 680                 685             


Cys Ile Lys Leu Glu Lys Asp Tyr Gln Pro Gly Ile Thr Tyr Ile Val 
    690                 695                 700                 


Val Gln Lys Arg His His Thr Arg Leu Phe Cys Ala Asp Lys Asn Glu 
705                 710                 715                 720 


Arg Ile Gly Lys Ser Gly Asn Ile Pro Ala Gly Thr Thr Val Asp Thr 
                725                 730                 735     


Asn Ile Thr His Pro Phe Glu Phe Asp Phe Tyr Leu Cys Ser His Ala 
            740                 745                 750         


Gly Ile Gln Gly Thr Ser Arg Pro Ser His Tyr Tyr Val Leu Trp Asp 
        755                 760                 765             


Asp Asn Arg Phe Thr Ala Asp Glu Leu Gln Ile Leu Thr Tyr Gln Leu 
    770                 775                 780                 


Cys His Thr Tyr Val Arg Cys Thr Arg Ser Val Ser Ile Pro Ala Pro 
785                 790                 795                 800 


Ala Tyr Tyr Ala Arg Leu Val Ala Phe Arg Ala Arg Tyr His Leu Val 
                805                 810                 815     


Asp Lys Glu His Asp Ser Gly Glu Gly Ser His Ile Ser Gly Gln Ser 
            820                 825                 830         


Asn Gly Arg Asp Pro Gln Ala Leu Ala Lys Ala Val Gln Val His Gln 
        835                 840                 845             


Asp Thr Leu Arg Thr Met Tyr Phe Ala 
    850                 855         


<210> 10
<211> 861
<212> PRT
<213> Homo sapiens

<400> 10
Met Glu Ala Leu Gly Pro Gly Pro Pro Ala Ser Leu Phe Gln Pro Pro 
1               5                   10                  15      


Arg Arg Pro Gly Leu Gly Thr Val Gly Lys Pro Ile Arg Leu Leu Ala 
            20                  25                  30          


Asn His Phe Gln Val Gln Ile Pro Lys Ile Asp Val Tyr His Tyr Asp 
        35                  40                  45              


Val Asp Ile Lys Pro Glu Lys Arg Pro Arg Arg Val Asn Arg Glu Val 
    50                  55                  60                  


Val Asp Thr Met Val Arg His Phe Lys Met Gln Ile Phe Gly Asp Arg 
65                  70                  75                  80  


Gln Pro Gly Tyr Asp Gly Lys Arg Asn Met Tyr Thr Ala His Pro Leu 
                85                  90                  95      


Pro Ile Gly Arg Asp Arg Val Asp Met Glu Val Thr Leu Pro Gly Glu 
            100                 105                 110         


Gly Lys Asp Gln Thr Phe Lys Val Ser Val Gln Trp Val Ser Val Val 
        115                 120                 125             


Ser Leu Gln Leu Leu Leu Glu Ala Leu Ala Gly His Leu Asn Glu Val 
    130                 135                 140                 


Pro Asp Asp Ser Val Gln Ala Leu Asp Val Ile Thr Arg His Leu Pro 
145                 150                 155                 160 


Ser Met Arg Tyr Thr Pro Val Gly Arg Ser Phe Phe Ser Pro Pro Glu 
                165                 170                 175     


Gly Tyr Tyr His Pro Leu Gly Gly Gly Arg Glu Val Trp Phe Gly Phe 
            180                 185                 190         


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


Val Ser Ala Thr Ala Phe Tyr Arg Ala Gln Pro Ile Ile Glu Phe Met 
    210                 215                 220                 


Cys Glu Val Leu Asp Ile Gln Asn Ile Asn Glu Gln Thr Lys Pro Leu 
225                 230                 235                 240 


Thr Asp Ser Gln Arg Val Lys Phe Thr Lys Glu Ile Arg Gly Leu Lys 
                245                 250                 255     


Val Glu Val Thr His Cys Gly Gln Met Lys Arg Lys Tyr Arg Val Cys 
            260                 265                 270         


Asn Val Thr Arg Arg Pro Ala Ser His Gln Thr Phe Pro Leu Gln Leu 
        275                 280                 285             


Glu Asn Gly Gln Ala Met Glu Cys Thr Val Ala Gln Tyr Phe Lys Gln 
    290                 295                 300                 


Lys Tyr Ser Leu Gln Leu Lys Tyr Pro His Leu Pro Cys Leu Gln Val 
305                 310                 315                 320 


Gly Gln Glu Gln Lys His Thr Tyr Leu Pro Leu Glu Val Cys Asn Ile 
                325                 330                 335     


Val Ala Gly Gln Arg Cys Ile Lys Lys Leu Thr Asp Asn Gln Thr Ser 
            340                 345                 350         


Thr Met Ile Lys Ala Thr Ala Arg Ser Ala Pro Asp Arg Gln Glu Glu 
        355                 360                 365             


Ile Ser Arg Leu Val Lys Ser Asn Ser Met Val Gly Gly Pro Asp Pro 
    370                 375                 380                 


Tyr Leu Lys Glu Phe Gly Ile Val Val His Asn Glu Met Thr Glu Leu 
385                 390                 395                 400 


Thr Gly Arg Val Leu Pro Ala Pro Met Leu Gln Tyr Gly Gly Arg Asn 
                405                 410                 415     


Lys Thr Val Ala Thr Pro Asn Gln Gly Val Trp Asp Met Arg Gly Lys 
            420                 425                 430         


Gln Phe Tyr Ala Gly Ile Glu Ile Lys Val Trp Ala Val Ala Cys Phe 
        435                 440                 445             


Ala Pro Gln Lys Gln Cys Arg Glu Asp Leu Leu Lys Ser Phe Thr Asp 
    450                 455                 460                 


Gln Leu Arg Lys Ile Ser Lys Asp Ala Gly Met Pro Ile Gln Gly Gln 
465                 470                 475                 480 


Pro Cys Phe Cys Lys Tyr Ala Gln Gly Ala Asp Ser Val Glu Pro Met 
                485                 490                 495     


Phe Lys His Leu Lys Met Thr Tyr Val Gly Leu Gln Leu Ile Val Val 
            500                 505                 510         


Ile Leu Pro Gly Lys Thr Pro Val Tyr Ala Glu Val Lys Arg Val Gly 
        515                 520                 525             


Asp Thr Leu Leu Gly Met Ala Thr Gln Cys Val Gln Val Lys Asn Val 
    530                 535                 540                 


Val Lys Thr Ser Pro Gln Thr Leu Ser Asn Leu Cys Leu Lys Ile Asn 
545                 550                 555                 560 


Ala Lys Leu Gly Gly Ile Asn Asn Val Leu Val Pro His Gln Arg Pro 
                565                 570                 575     


Ser Val Phe Gln Gln Pro Val Ile Phe Leu Gly Ala Asp Val Thr His 
            580                 585                 590         


Pro Pro Ala Gly Asp Gly Lys Lys Pro Ser Ile Ala Ala Val Val Gly 
        595                 600                 605             


Ser Met Asp Gly His Pro Ser Arg Tyr Cys Ala Thr Val Arg Val Gln 
    610                 615                 620                 


Thr Ser Arg Gln Glu Ile Ser Gln Glu Leu Leu Tyr Ser Gln Glu Val 
625                 630                 635                 640 


Ile Gln Asp Leu Thr Asn Met Val Arg Glu Leu Leu Ile Gln Phe Tyr 
                645                 650                 655     


Lys Ser Thr Arg Phe Lys Pro Thr Arg Ile Ile Tyr Tyr Arg Gly Gly 
            660                 665                 670         


Val Ser Glu Gly Gln Met Lys Gln Val Ala Trp Pro Glu Leu Ile Ala 
        675                 680                 685             


Ile Arg Lys Ala Cys Ile Ser Leu Glu Glu Asp Tyr Arg Pro Gly Ile 
    690                 695                 700                 


Thr Tyr Ile Val Val Gln Lys Arg His His Thr Arg Leu Phe Cys Ala 
705                 710                 715                 720 


Asp Lys Thr Glu Arg Val Gly Lys Ser Gly Asn Val Pro Ala Gly Thr 
                725                 730                 735     


Thr Val Asp Ser Thr Ile Thr His Pro Ser Glu Phe Asp Phe Tyr Leu 
            740                 745                 750         


Cys Ser His Ala Gly Ile Gln Gly Thr Ser Arg Pro Ser His Tyr Gln 
        755                 760                 765             


Val Leu Trp Asp Asp Asn Cys Phe Thr Ala Asp Glu Leu Gln Leu Leu 
    770                 775                 780                 


Thr Tyr Gln Leu Cys His Thr Tyr Val Arg Cys Thr Arg Ser Val Ser 
785                 790                 795                 800 


Ile Pro Ala Pro Ala Tyr Tyr Ala Arg Leu Val Ala Phe Arg Ala Arg 
                805                 810                 815     


Tyr His Leu Val Asp Lys Asp His Asp Ser Ala Glu Gly Ser His Val 
            820                 825                 830         


Ser Gly Gln Ser Asn Gly Arg Asp Pro Gln Ala Leu Ala Lys Ala Val 
        835                 840                 845             


Gln Ile His His Asp Thr Gln His Thr Met Tyr Phe Ala 
    850                 855                 860     


<210> 11
<211> 860
<212> PRT
<213> Homo sapiens

<400> 11
Met Glu Ile Gly Ser Ala Gly Pro Ala Gly Ala Gln Pro Leu Leu Met 
1               5                   10                  15      


Val Pro Arg Arg Pro Gly Tyr Gly Thr Met Gly Lys Pro Ile Lys Leu 
            20                  25                  30          


Leu Ala Asn Cys Phe Gln Val Glu Ile Pro Lys Ile Asp Val Tyr Leu 
        35                  40                  45              


Tyr Glu Val Asp Ile Lys Pro Asp Lys Cys Pro Arg Arg Val Asn Arg 
    50                  55                  60                  


Glu Val Val Asp Ser Met Val Gln His Phe Lys Val Thr Ile Phe Gly 
65                  70                  75                  80  


Asp Arg Arg Pro Val Tyr Asp Gly Lys Arg Ser Leu Tyr Thr Ala Asn 
                85                  90                  95      


Pro Leu Pro Val Ala Thr Thr Gly Val Asp Leu Asp Val Thr Leu Pro 
            100                 105                 110         


Gly Glu Gly Gly Lys Asp Arg Pro Phe Lys Val Ser Ile Lys Phe Val 
        115                 120                 125             


Ser Arg Val Ser Trp His Leu Leu His Glu Val Leu Thr Gly Arg Thr 
    130                 135                 140                 


Leu Pro Glu Pro Leu Glu Leu Asp Lys Pro Ile Ser Thr Asn Pro Val 
145                 150                 155                 160 


His Ala Val Asp Val Val Leu Arg His Leu Pro Ser Met Lys Tyr Thr 
                165                 170                 175     


Pro Val Gly Arg Ser Phe Phe Ser Ala Pro Glu Gly Tyr Asp His Pro 
            180                 185                 190         


Leu Gly Gly Gly Arg Glu Val Trp Phe Gly Phe His Gln Ser Val Arg 
        195                 200                 205             


Pro Ala Met Trp Lys Met Met Leu Asn Ile Asp Val Ser Ala Thr Ala 
    210                 215                 220                 


Phe Tyr Lys Ala Gln Pro Val Ile Gln Phe Met Cys Glu Val Leu Asp 
225                 230                 235                 240 


Ile His Asn Ile Asp Glu Gln Pro Arg Pro Leu Thr Asp Ser His Arg 
                245                 250                 255     


Val Lys Phe Thr Lys Glu Ile Lys Gly Leu Lys Val Glu Val Thr His 
            260                 265                 270         


Cys Gly Thr Met Arg Arg Lys Tyr Arg Val Cys Asn Val Thr Arg Arg 
        275                 280                 285             


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


Val Glu Arg Thr Val Ala Gln Tyr Phe Arg Glu Lys Tyr Thr Leu Gln 
305                 310                 315                 320 


Leu Lys Tyr Pro His Leu Pro Cys Leu Gln Val Gly Gln Glu Gln Lys 
                325                 330                 335     


His Thr Tyr Leu Pro Leu Glu Val Cys Asn Ile Val Ala Gly Gln Arg 
            340                 345                 350         


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


Thr Ala Arg Ser Ala Pro Asp Arg Gln Glu Glu Ile Ser Arg Leu Val 
    370                 375                 380                 


Arg Ser Ala Asn Tyr Glu Thr Asp Pro Phe Val Gln Glu Phe Gln Phe 
385                 390                 395                 400 


Lys Val Arg Asp Glu Met Ala His Val Thr Gly Arg Val Leu Pro Ala 
                405                 410                 415     


Pro Met Leu Gln Tyr Gly Gly Arg Asn Arg Thr Val Ala Thr Pro Ser 
            420                 425                 430         


His Gly Val Trp Asp Met Arg Gly Lys Gln Phe His Thr Gly Val Glu 
        435                 440                 445             


Ile Lys Met Trp Ala Ile Ala Cys Phe Ala Thr Gln Arg Gln Cys Arg 
    450                 455                 460                 


Glu Glu Ile Leu Lys Gly Phe Thr Asp Gln Leu Arg Lys Ile Ser Lys 
465                 470                 475                 480 


Asp Ala Gly Met Pro Ile Gln Gly Gln Pro Cys Phe Cys Lys Tyr Ala 
                485                 490                 495     


Gln Gly Ala Asp Ser Val Glu Pro Met Phe Arg His Leu Lys Asn Thr 
            500                 505                 510         


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


Val Tyr Ala Glu Val Lys Arg Val Gly Asp Thr Leu Leu Gly Met Ala 
    530                 535                 540                 


Thr Gln Cys Val Gln Val Lys Asn Val Ile Lys Thr Ser Pro Gln Thr 
545                 550                 555                 560 


Leu Ser Asn Leu Cys Leu Lys Ile Asn Val Lys Leu Gly Gly Ile Asn 
                565                 570                 575     


Asn Ile Leu Val Pro His Gln Arg Pro Ser Val Phe Gln Gln Pro Val 
            580                 585                 590         


Ile Phe Leu Gly Ala Asp Val Thr His Pro Pro Ala Gly Asp Gly Lys 
        595                 600                 605             


Lys Pro Ser Ile Ala Ala Val Val Gly Ser Met Asp Ala His Pro Ser 
    610                 615                 620                 


Arg Tyr Cys Ala Thr Val Arg Val Gln Arg Pro Arg Gln Glu Ile Ile 
625                 630                 635                 640 


Gln Asp Leu Ala Ser Met Val Arg Glu Leu Leu Ile Gln Phe Tyr Lys 
                645                 650                 655     


Ser Thr Arg Phe Lys Pro Thr Arg Ile Ile Phe Tyr Arg Asp Gly Val 
            660                 665                 670         


Ser Glu Gly Gln Phe Arg Gln Val Leu Tyr Tyr Glu Leu Leu Ala Ile 
        675                 680                 685             


Arg Glu Ala Cys Ile Ser Leu Glu Lys Asp Tyr Gln Pro Gly Ile Thr 
    690                 695                 700                 


Tyr Ile Val Val Gln Lys Arg His His Thr Arg Leu Phe Cys Ala Asp 
705                 710                 715                 720 


Arg Thr Glu Arg Val Gly Arg Ser Gly Asn Ile Pro Ala Gly Thr Thr 
                725                 730                 735     


Val Asp Thr Asp Ile Thr His Pro Tyr Glu Phe Asp Phe Tyr Leu Cys 
            740                 745                 750         


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


Leu Trp Asp Asp Asn Cys Phe Thr Ala Asp Glu Leu Gln Leu Leu Thr 
    770                 775                 780                 


Tyr Gln Leu Cys His Thr Tyr Val Arg Cys Thr Arg Ser Val Ser Ile 
785                 790                 795                 800 


Pro Ala Pro Ala Tyr Tyr Ala His Leu Val Ala Phe Arg Ala Arg Tyr 
                805                 810                 815     


His Leu Val Asp Lys Glu His Asp Ser Ala Glu Gly Ser His Val Ser 
            820                 825                 830         


Gly Gln Ser Asn Gly Arg Asp Pro Gln Ala Leu Ala Lys Ala Val Gln 
        835                 840                 845             


Ile His Gln Asp Thr Leu Arg Thr Met Tyr Phe Ala 
    850                 855                 860 


<210> 12
<211> 882
<212> PRT
<213> Homo sapiens

<400> 12
Met Pro Gly Arg Ala Arg Thr Arg Ala Arg Gly Arg Ala Arg Arg Arg 
1               5                   10                  15      


Glu Ser Tyr Gln Gln Glu Ala Pro Gly Gly Pro Arg Ala Pro Gly Ser 
            20                  25                  30          


Ala Thr Thr Gln Glu Pro Pro Gln Leu Gln Ser Thr Pro Arg Pro Leu 
        35                  40                  45              


Gln Glu Glu Val Pro Val Val Arg Pro Leu Gln Pro Arg Ala Ala Arg 
    50                  55                  60                  


Gly Gly Ala Gly Gly Gly Ala Gln Ser Gln Gly Val Lys Glu Pro Gly 
65                  70                  75                  80  


Pro Glu Ala Gly Leu His Thr Ala Pro Leu Gln Glu Arg Arg Ile Gly 
                85                  90                  95      


Gly Val Phe Gln Asp Leu Val Val Asn Thr Arg Gln Asp Met Lys His 
            100                 105                 110         


Val Lys Asp Ser Lys Thr Gly Ser Glu Gly Thr Val Val Gln Leu Leu 
        115                 120                 125             


Ala Asn His Phe Arg Val Ile Ser Arg Pro Gln Trp Val Ala Tyr Lys 
    130                 135                 140                 


Tyr Asn Val Asp Tyr Lys Pro Asp Ile Glu Asp Gly Asn Leu Arg Thr 
145                 150                 155                 160 


Ile Leu Leu Asp Gln His Arg Arg Lys Phe Gly Glu Arg His Ile Phe 
                165                 170                 175     


Asp Gly Asn Ser Leu Leu Leu Ser Arg Pro Leu Lys Glu Arg Arg Val 
            180                 185                 190         


Glu Trp Leu Ser Thr Thr Lys Asp Lys Asn Ile Val Lys Ile Thr Val 
        195                 200                 205             


Glu Phe Ser Lys Glu Leu Thr Pro Thr Ser Pro Asp Cys Leu Arg Tyr 
    210                 215                 220                 


Tyr Asn Ile Leu Phe Arg Arg Thr Phe Lys Leu Leu Asp Phe Glu Gln 
225                 230                 235                 240 


Val Gly Arg Asn Tyr Tyr Thr Lys Lys Lys Ala Ile Gln Leu Tyr Arg 
                245                 250                 255     


His Gly Thr Ser Leu Glu Ile Trp Leu Gly Tyr Val Thr Ser Val Leu 
            260                 265                 270         


Gln Tyr Glu Asn Ser Ile Thr Leu Cys Ala Asp Val Ser His Lys Leu 
        275                 280                 285             


Leu Arg Ile Glu Thr Ala Tyr Asp Phe Ile Lys Arg Thr Ser Ala Gln 
    290                 295                 300                 


Ala Gln Thr Gly Asn Ile Arg Glu Glu Val Thr Asn Lys Leu Ile Gly 
305                 310                 315                 320 


Ser Ile Val Leu Thr Lys Tyr Asn Asn Lys Thr Tyr Arg Val Asp Asp 
                325                 330                 335     


Ile Asp Trp Lys Gln Asn Pro Glu Asp Thr Phe Asn Lys Ser Asp Gly 
            340                 345                 350         


Ser Lys Ile Thr Tyr Ile Asp Tyr Tyr Arg Gln Gln His Lys Glu Ile 
        355                 360                 365             


Val Thr Val Lys Lys Gln Pro Leu Leu Val Ser Gln Gly Arg Trp Lys 
    370                 375                 380                 


Lys Gly Leu Thr Gly Thr Gln Arg Glu Pro Ile Leu Leu Ile Pro Gln 
385                 390                 395                 400 


Leu Cys His Met Thr Gly Leu Thr Asp Glu Ile Cys Lys Asp Tyr Ser 
                405                 410                 415     


Ile Val Lys Glu Leu Ala Lys His Thr Arg Leu Ser Pro Arg Arg Arg 
            420                 425                 430         


His His Thr Leu Lys Glu Phe Ile Asn Thr Leu Gln Asp Asn Lys Lys 
        435                 440                 445             


Val Arg Glu Leu Leu Gln Leu Trp Asp Leu Lys Phe Asp Thr Asn Phe 
    450                 455                 460                 


Leu Ser Val Pro Gly Arg Val Leu Lys Asn Ala Asn Ile Val Gln Gly 
465                 470                 475                 480 


Arg Arg Met Val Lys Ala Asn Ser Gln Gly Asp Trp Ser Arg Glu Ile 
                485                 490                 495     


Arg Glu Leu Pro Leu Leu Asn Ala Met Pro Leu His Ser Trp Leu Ile 
            500                 505                 510         


Leu Tyr Ser Arg Ser Ser His Arg Glu Ala Met Ser Leu Lys Gly His 
        515                 520                 525             


Leu Gln Ser Val Thr Ala Pro Met Gly Ile Thr Met Lys Pro Ala Glu 
    530                 535                 540                 


Met Ile Glu Val Asp Gly Asp Ala Asn Ser Tyr Ile Asp Thr Leu Arg 
545                 550                 555                 560 


Lys Tyr Thr Arg Pro Thr Leu Gln Met Gly Met Ser Cys Leu Leu Val 
                565                 570                 575     


Phe Lys Val Ile Cys Ile Leu Pro Asn Asp Asp Lys Arg Arg Tyr Asp 
            580                 585                 590         


Ser Ile Lys Arg Tyr Leu Cys Thr Lys Cys Pro Ile Pro Ser Gln Cys 
        595                 600                 605             


Val Val Lys Lys Thr Leu Glu Lys Val Gln Ala Arg Thr Ile Val Thr 
    610                 615                 620                 


Lys Ile Ala Gln Gln Met Asn Cys Lys Met Gly Gly Ala Leu Trp Lys 
625                 630                 635                 640 


Val Glu Thr Asp Val Gln Arg Thr Met Phe Val Gly Ile Asp Cys Phe 
                645                 650                 655     


His Asp Ile Val Asn Arg Gln Lys Ser Ile Ala Gly Phe Val Ala Ser 
            660                 665                 670         


Thr Asn Ala Glu Leu Thr Lys Trp Tyr Ser Gln Cys Val Ile Gln Lys 
        675                 680                 685             


Thr Gly Glu Glu Leu Val Lys Glu Leu Glu Ile Cys Leu Lys Ala Ala 
    690                 695                 700                 


Leu Asp Val Trp Cys Lys Asn Glu Ser Ser Met Pro His Ser Val Ile 
705                 710                 715                 720 


Val Tyr Arg Asp Gly Val Gly Asp Gly Gln Leu Gln Ala Leu Leu Asp 
                725                 730                 735     


His Glu Ala Lys Lys Met Ser Thr Tyr Leu Lys Thr Ile Ser Pro Asn 
            740                 745                 750         


Asn Phe Thr Leu Ala Phe Ile Val Val Lys Lys Arg Ile Asn Thr Arg 
        755                 760                 765             


Phe Phe Leu Lys His Gly Ser Asn Phe Gln Asn Pro Pro Pro Gly Thr 
    770                 775                 780                 


Val Ile Asp Val Glu Leu Thr Arg Asn Glu Trp Tyr Asp Phe Phe Ile 
785                 790                 795                 800 


Val Ser Gln Ser Val Gln Asp Gly Thr Val Thr Pro Thr His Tyr Asn 
                805                 810                 815     


Val Ile Tyr Asp Thr Ile Gly Leu Ser Pro Asp Thr Val Gln Arg Leu 
            820                 825                 830         


Thr Tyr Cys Leu Cys His Met Tyr Tyr Asn Leu Pro Gly Ile Ile Arg 
        835                 840                 845             


Val Pro Ala Pro Cys His Tyr Ala His Lys Leu Ala Tyr Leu Val Gly 
    850                 855                 860                 


Gln Ser Ile His Gln Glu Pro Asn Arg Ser Leu Ser Thr Arg Leu Phe 
865                 870                 875                 880 


Tyr Leu 
        


<210> 13
<211> 108
<212> DNA
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      polynucleotide"

<400> 13
ccttaaggtt aagtcgatcc tgcaaggcga gggcgactta accttcattt tttgagctca       60

aaaaatgatg gacagaatac tggacacttt gtccagtatt ctgtccat                   108


<210> 14
<211> 108
<212> DNA
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      polynucleotide"

<400> 14
ccttatgatc atgcgtttgc gttaagaacg caaacgcatg atcaccattt tttgagctca       60

aaaaatggtt gatgaaggag tccagccttg ctggactcct tcatcaat                   108


