                         SEQUENCE LISTING

<110>  The University of Hong Kong
       Lee, Chi-Ho
       Lam, Siu-Ling Karen
       Xu, Aimin
 
<120>  FIBROSIS BIOMARKERS FOR NON-ALCOHOLIC FATTY LIVER DISEASE

<130>  UHK 01033 PCT

<160>  5     

<170>  PatentIn version 3.5

<210>  1
<211>  1172
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Val Trp Arg Leu Val Leu Leu Ala Leu Trp Val Trp Pro Ser Thr 
1               5                   10                  15      


Gln Ala Gly His Gln Asp Lys Asp Thr Thr Phe Asp Leu Phe Ser Ile 
            20                  25                  30          


Ser Asn Ile Asn Arg Lys Thr Ile Gly Ala Lys Gln Phe Arg Gly Pro 
        35                  40                  45              


Asp Pro Gly Val Pro Ala Tyr Arg Phe Val Arg Phe Asp Tyr Ile Pro 
    50                  55                  60                  


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


Lys Glu Gly Phe Phe Leu Thr Ala Gln Leu Lys Gln Asp Gly Lys Ser 
                85                  90                  95      


Arg Gly Thr Leu Leu Ala Leu Glu Gly Pro Gly Leu Ser Gln Arg Gln 
            100                 105                 110         


Phe Glu Ile Val Ser Asn Gly Pro Ala Asp Thr Leu Asp Leu Thr Tyr 
        115                 120                 125             


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


Ala Asp Ser Gln Trp Lys Asn Val Thr Val Gln Val Ala Gly Glu Thr 
145                 150                 155                 160 


Tyr Ser Leu His Val Gly Cys Asp Leu Ile Asp Ser Phe Ala Leu Asp 
                165                 170                 175     


Glu Pro Phe Tyr Glu His Leu Gln Ala Glu Lys Ser Arg Met Tyr Val 
            180                 185                 190         


Ala Lys Gly Ser Ala Arg Glu Ser His Phe Arg Gly Leu Leu Gln Asn 
        195                 200                 205             


Val His Leu Val Phe Glu Asn Ser Val Glu Asp Ile Leu Ser Lys Lys 
    210                 215                 220                 


Gly Cys Gln Gln Gly Gln Gly Ala Glu Ile Asn Ala Ile Ser Glu Asn 
225                 230                 235                 240 


Thr Glu Thr Leu Arg Leu Gly Pro His Val Thr Thr Glu Tyr Val Gly 
                245                 250                 255     


Pro Ser Ser Glu Arg Arg Pro Glu Val Cys Glu Arg Ser Cys Glu Glu 
            260                 265                 270         


Leu Gly Asn Met Val Gln Glu Leu Ser Gly Leu His Val Leu Val Asn 
        275                 280                 285             


Gln Leu Ser Glu Asn Leu Lys Arg Val Ser Asn Asp Asn Gln Phe Leu 
    290                 295                 300                 


Trp Glu Leu Ile Gly Gly Pro Pro Lys Thr Arg Asn Met Ser Ala Cys 
305                 310                 315                 320 


Trp Gln Asp Gly Arg Phe Phe Ala Glu Asn Glu Thr Trp Val Val Asp 
                325                 330                 335     


Ser Cys Thr Thr Cys Thr Cys Lys Lys Phe Lys Thr Ile Cys His Gln 
            340                 345                 350         


Ile Thr Cys Pro Pro Ala Thr Cys Ala Ser Pro Ser Phe Val Glu Gly 
        355                 360                 365             


Glu Cys Cys Pro Ser Cys Leu His Ser Val Asp Gly Glu Glu Gly Trp 
    370                 375                 380                 


Ser Pro Trp Ala Glu Trp Thr Gln Cys Ser Val Thr Cys Gly Ser Gly 
385                 390                 395                 400 


Thr Gln Gln Arg Gly Arg Ser Cys Asp Val Thr Ser Asn Thr Cys Leu 
                405                 410                 415     


Gly Pro Ser Ile Gln Thr Arg Ala Cys Ser Leu Ser Lys Cys Asp Thr 
            420                 425                 430         


Arg Ile Arg Gln Asp Gly Gly Trp Ser His Trp Ser Pro Trp Ser Ser 
        435                 440                 445             


Cys Ser Val Thr Cys Gly Val Gly Asn Ile Thr Arg Ile Arg Leu Cys 
    450                 455                 460                 


Asn Ser Pro Val Pro Gln Met Gly Gly Lys Asn Cys Lys Gly Ser Gly 
465                 470                 475                 480 


Arg Glu Thr Lys Ala Cys Gln Gly Ala Pro Cys Pro Ile Asp Gly Arg 
                485                 490                 495     


Trp Ser Pro Trp Ser Pro Trp Ser Ala Cys Thr Val Thr Cys Ala Gly 
            500                 505                 510         


Gly Ile Arg Glu Arg Thr Arg Val Cys Asn Ser Pro Glu Pro Gln Tyr 
        515                 520                 525             


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


Lys Arg Ser Cys Pro Val Asp Gly Cys Leu Ser Asn Pro Cys Phe Pro 
545                 550                 555                 560 


Gly Ala Gln Cys Ser Ser Phe Pro Asp Gly Ser Trp Ser Cys Gly Ser 
                565                 570                 575     


Cys Pro Val Gly Phe Leu Gly Asn Gly Thr His Cys Glu Asp Leu Asp 
            580                 585                 590         


Glu Cys Ala Leu Val Pro Asp Ile Cys Phe Ser Thr Ser Lys Val Pro 
        595                 600                 605             


Arg Cys Val Asn Thr Gln Pro Gly Phe His Cys Leu Pro Cys Pro Pro 
    610                 615                 620                 


Arg Tyr Arg Gly Asn Gln Pro Val Gly Val Gly Leu Glu Ala Ala Lys 
625                 630                 635                 640 


Thr Glu Lys Gln Val Cys Glu Pro Glu Asn Pro Cys Lys Asp Lys Thr 
                645                 650                 655     


His Asn Cys His Lys His Ala Glu Cys Ile Tyr Leu Gly His Phe Ser 
            660                 665                 670         


Asp Pro Met Tyr Lys Cys Glu Cys Gln Thr Gly Tyr Ala Gly Asp Gly 
        675                 680                 685             


Leu Ile Cys Gly Glu Asp Ser Asp Leu Asp Gly Trp Pro Asn Leu Asn 
    690                 695                 700                 


Leu Val Cys Ala Thr Asn Ala Thr Tyr His Cys Ile Lys Asp Asn Cys 
705                 710                 715                 720 


Pro His Leu Pro Asn Ser Gly Gln Glu Asp Phe Asp Lys Asp Gly Ile 
                725                 730                 735     


Gly Asp Ala Cys Asp Asp Asp Asp Asp Asn Asp Gly Val Thr Asp Glu 
            740                 745                 750         


Lys Asp Asn Cys Gln Leu Leu Phe Asn Pro Arg Gln Ala Asp Tyr Asp 
        755                 760                 765             


Lys Asp Glu Val Gly Asp Arg Cys Asp Asn Cys Pro Tyr Val His Asn 
    770                 775                 780                 


Pro Ala Gln Ile Asp Thr Asp Asn Asn Gly Glu Gly Asp Ala Cys Ser 
785                 790                 795                 800 


Val Asp Ile Asp Gly Asp Asp Val Phe Asn Glu Arg Asp Asn Cys Pro 
                805                 810                 815     


Tyr Val Tyr Asn Thr Asp Gln Arg Asp Thr Asp Gly Asp Gly Val Gly 
            820                 825                 830         


Asp His Cys Asp Asn Cys Pro Leu Val His Asn Pro Asp Gln Thr Asp 
        835                 840                 845             


Val Asp Asn Asp Leu Val Gly Asp Gln Cys Asp Asn Asn Glu Asp Ile 
    850                 855                 860                 


Asp Asp Asp Gly His Gln Asn Asn Gln Asp Asn Cys Pro Tyr Ile Ser 
865                 870                 875                 880 


Asn Ala Asn Gln Ala Asp His Asp Arg Asp Gly Gln Gly Asp Ala Cys 
                885                 890                 895     


Asp Pro Asp Asp Asp Asn Asp Gly Val Pro Asp Asp Arg Asp Asn Cys 
            900                 905                 910         


Arg Leu Val Phe Asn Pro Asp Gln Glu Asp Leu Asp Gly Asp Gly Arg 
        915                 920                 925             


Gly Asp Ile Cys Lys Asp Asp Phe Asp Asn Asp Asn Ile Pro Asp Ile 
    930                 935                 940                 


Asp Asp Val Cys Pro Glu Asn Asn Ala Ile Ser Glu Thr Asp Phe Arg 
945                 950                 955                 960 


Asn Phe Gln Met Val Pro Leu Asp Pro Lys Gly Thr Thr Gln Ile Asp 
                965                 970                 975     


Pro Asn Trp Val Ile Arg His Gln Gly Lys Glu Leu Val Gln Thr Ala 
            980                 985                 990         


Asn Ser Asp Pro Gly Ile Ala Val  Gly Phe Asp Glu Phe  Gly Ser Val 
        995                 1000                 1005             


Asp Phe  Ser Gly Thr Phe Tyr  Val Asn Thr Asp Arg  Asp Asp Asp 
    1010                 1015                 1020             


Tyr Ala  Gly Phe Val Phe Gly  Tyr Gln Ser Ser Ser  Arg Phe Tyr 
    1025                 1030                 1035             


Val Val  Met Trp Lys Gln Val  Thr Gln Thr Tyr Trp  Glu Asp Gln 
    1040                 1045                 1050             


Pro Thr  Arg Ala Tyr Gly Tyr  Ser Gly Val Ser Leu  Lys Val Val 
    1055                 1060                 1065             


Asn Ser  Thr Thr Gly Thr Gly  Glu His Leu Arg Asn  Ala Leu Trp 
    1070                 1075                 1080             


His Thr  Gly Asn Thr Pro Gly  Gln Val Arg Thr Leu  Trp His Asp 
    1085                 1090                 1095             


Pro Arg  Asn Ile Gly Trp Lys  Asp Tyr Thr Ala Tyr  Arg Trp His 
    1100                 1105                 1110             


Leu Thr  His Arg Pro Lys Thr  Gly Tyr Ile Arg Val  Leu Val His 
    1115                 1120                 1125             


Glu Gly  Lys Gln Val Met Ala  Asp Ser Gly Pro Ile  Tyr Asp Gln 
    1130                 1135                 1140             


Thr Tyr  Ala Gly Gly Arg Leu  Gly Leu Phe Val Phe  Ser Gln Glu 
    1145                 1150                 1155             


Met Val  Tyr Phe Ser Asp Leu  Lys Tyr Glu Cys Arg  Asp Ile 
    1160                 1165                 1170         


<210>  2
<211>  1114
<212>  PRT
<213>  Homo sapiens

<400>  2

Met Val Trp Arg Leu Val Leu Leu Ala Leu Trp Val Trp Pro Ser Thr 
1               5                   10                  15      


Gln Ala Gly His Gln Asp Lys Asp Thr Thr Phe Asp Leu Phe Ser Ile 
            20                  25                  30          


Ser Asn Ile Asn Arg Lys Thr Ile Gly Ala Lys Gln Phe Arg Gly Pro 
        35                  40                  45              


Asp Pro Gly Val Pro Ala Tyr Arg Phe Val Arg Phe Asp Tyr Ile Pro 
    50                  55                  60                  


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


Lys Glu Gly Phe Phe Leu Thr Ala Gln Leu Lys Gln Asp Gly Lys Ser 
                85                  90                  95      


Arg Gly Thr Leu Leu Ala Leu Glu Gly Pro Gly Leu Ser Gln Arg Gln 
            100                 105                 110         


Phe Glu Ile Val Ser Asn Gly Pro Ala Asp Thr Leu Asp Leu Thr Tyr 
        115                 120                 125             


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


Ala Asp Ser Gln Trp Lys Asn Val Thr Val Gln Val Ala Gly Glu Thr 
145                 150                 155                 160 


Tyr Ser Leu His Val Gly Cys Asp Leu Ile Asp Ser Phe Ala Leu Asp 
                165                 170                 175     


Glu Pro Phe Tyr Glu His Leu Gln Ala Glu Lys Ser Arg Met Tyr Val 
            180                 185                 190         


Ala Lys Gly Ser Ala Arg Glu Ser His Phe Arg Gly Leu Leu Gln Asn 
        195                 200                 205             


Val His Leu Val Phe Glu Asn Ser Val Glu Asp Ile Leu Ser Lys Lys 
    210                 215                 220                 


Gly Cys Gln Gln Gly Gln Gly Ala Glu Ile Asn Ala Ile Ser Glu Asn 
225                 230                 235                 240 


Thr Glu Thr Leu Arg Leu Gly Pro His Val Thr Thr Glu Tyr Val Gly 
                245                 250                 255     


Pro Ser Ser Glu Arg Arg Pro Glu Val Cys Glu Arg Ser Cys Glu Glu 
            260                 265                 270         


Leu Gly Asn Met Val Gln Glu Leu Ser Gly Leu His Val Leu Val Asn 
        275                 280                 285             


Gln Leu Ser Glu Asn Leu Lys Arg Val Ser Asn Asp Asn Gln Phe Leu 
    290                 295                 300                 


Trp Glu Leu Ile Gly Gly Pro Pro Lys Thr Arg Asn Met Ser Ala Cys 
305                 310                 315                 320 


Trp Gln Asp Gly Arg Phe Phe Ala Glu Asn Glu Thr Trp Val Val Asp 
                325                 330                 335     


Ser Cys Thr Thr Cys Thr Cys Lys Lys Phe Lys Thr Ile Cys His Gln 
            340                 345                 350         


Ile Thr Cys Pro Pro Ala Thr Cys Ala Ser Pro Ser Phe Val Glu Gly 
        355                 360                 365             


Glu Cys Cys Pro Ser Cys Leu His Ser Val Asp Gly Glu Glu Gly Trp 
    370                 375                 380                 


Ser Pro Trp Ala Glu Trp Thr Gln Cys Ser Val Thr Cys Gly Ser Gly 
385                 390                 395                 400 


Thr Gln Gln Arg Gly Arg Ser Cys Asp Val Thr Ser Asn Thr Cys Leu 
                405                 410                 415     


Gly Pro Ser Ile Gln Thr Arg Ala Cys Ser Leu Ser Lys Cys Asp Thr 
            420                 425                 430         


Arg Ile Arg Gln Asp Gly Gly Trp Ser His Trp Ser Pro Trp Ser Ser 
        435                 440                 445             


Cys Ser Val Thr Cys Gly Val Gly Asn Ile Thr Arg Ile Arg Leu Cys 
    450                 455                 460                 


Asn Ser Pro Val Pro Gln Met Gly Gly Lys Asn Cys Lys Gly Ser Gly 
465                 470                 475                 480 


Arg Glu Thr Lys Ala Cys Gln Gly Ala Pro Cys Pro Asn Gly Cys Leu 
                485                 490                 495     


Ser Asn Pro Cys Phe Pro Gly Ala Gln Cys Ser Ser Phe Pro Asp Gly 
            500                 505                 510         


Ser Trp Ser Cys Gly Ser Cys Pro Val Gly Phe Leu Gly Asn Gly Thr 
        515                 520                 525             


His Cys Glu Asp Leu Asp Glu Cys Ala Leu Val Pro Asp Ile Cys Phe 
    530                 535                 540                 


Ser Thr Ser Lys Val Pro Arg Cys Val Asn Thr Gln Pro Gly Phe His 
545                 550                 555                 560 


Cys Leu Pro Cys Pro Pro Arg Tyr Arg Gly Asn Gln Pro Val Gly Val 
                565                 570                 575     


Gly Leu Glu Ala Ala Lys Thr Glu Lys Gln Val Cys Glu Pro Glu Asn 
            580                 585                 590         


Pro Cys Lys Asp Lys Thr His Asn Cys His Lys His Ala Glu Cys Ile 
        595                 600                 605             


Tyr Leu Gly His Phe Ser Asp Pro Met Tyr Lys Cys Glu Cys Gln Thr 
    610                 615                 620                 


Gly Tyr Ala Gly Asp Gly Leu Ile Cys Gly Glu Asp Ser Asp Leu Asp 
625                 630                 635                 640 


Gly Trp Pro Asn Leu Asn Leu Val Cys Ala Thr Asn Ala Thr Tyr His 
                645                 650                 655     


Cys Ile Lys Asp Asn Cys Pro His Leu Pro Asn Ser Gly Gln Glu Asp 
            660                 665                 670         


Phe Asp Lys Asp Gly Ile Gly Asp Ala Cys Asp Asp Asp Asp Asp Asn 
        675                 680                 685             


Asp Gly Val Thr Asp Glu Lys Asp Asn Cys Gln Leu Leu Phe Asn Pro 
    690                 695                 700                 


Arg Gln Ala Asp Tyr Asp Lys Asp Glu Val Gly Asp Arg Cys Asp Asn 
705                 710                 715                 720 


Cys Pro Tyr Val His Asn Pro Ala Gln Ile Asp Thr Asp Asn Asn Gly 
                725                 730                 735     


Glu Gly Asp Ala Cys Ser Val Asp Ile Asp Gly Asp Asp Val Phe Asn 
            740                 745                 750         


Glu Arg Asp Asn Cys Pro Tyr Val Tyr Asn Thr Asp Gln Arg Asp Thr 
        755                 760                 765             


Asp Gly Asp Gly Val Gly Asp His Cys Asp Asn Cys Pro Leu Val His 
    770                 775                 780                 


Asn Pro Asp Gln Thr Asp Val Asp Asn Asp Leu Val Gly Asp Gln Cys 
785                 790                 795                 800 


Asp Asn Asn Glu Asp Ile Asp Asp Asp Gly His Gln Asn Asn Gln Asp 
                805                 810                 815     


Asn Cys Pro Tyr Ile Ser Asn Ala Asn Gln Ala Asp His Asp Arg Asp 
            820                 825                 830         


Gly Gln Gly Asp Ala Cys Asp Pro Asp Asp Asp Asn Asp Gly Val Pro 
        835                 840                 845             


Asp Asp Arg Asp Asn Cys Arg Leu Val Phe Asn Pro Asp Gln Glu Asp 
    850                 855                 860                 


Leu Asp Gly Asp Gly Arg Gly Asp Ile Cys Lys Asp Asp Phe Asp Asn 
865                 870                 875                 880 


Asp Asn Ile Pro Asp Ile Asp Asp Val Cys Pro Glu Asn Asn Ala Ile 
                885                 890                 895     


Ser Glu Thr Asp Phe Arg Asn Phe Gln Met Val Pro Leu Asp Pro Lys 
            900                 905                 910         


Gly Thr Thr Gln Ile Asp Pro Asn Trp Val Ile Arg His Gln Gly Lys 
        915                 920                 925             


Glu Leu Val Gln Thr Ala Asn Ser Asp Pro Gly Ile Ala Val Gly Phe 
    930                 935                 940                 


Asp Glu Phe Gly Ser Val Asp Phe Ser Gly Thr Phe Tyr Val Asn Thr 
945                 950                 955                 960 


Asp Arg Asp Asp Asp Tyr Ala Gly Phe Val Phe Gly Tyr Gln Ser Ser 
                965                 970                 975     


Ser Arg Phe Tyr Val Val Met Trp Lys Gln Val Thr Gln Thr Tyr Trp 
            980                 985                 990         


Glu Asp Gln Pro Thr Arg Ala Tyr  Gly Tyr Ser Gly Val  Ser Leu Lys 
        995                 1000                 1005             


Val Val  Asn Ser Thr Thr Gly  Thr Gly Glu His Leu  Arg Asn Ala 
    1010                 1015                 1020             


Leu Trp  His Thr Gly Asn Thr  Pro Gly Gln Val Arg  Thr Leu Trp 
    1025                 1030                 1035             


His Asp  Pro Arg Asn Ile Gly  Trp Lys Asp Tyr Thr  Ala Tyr Arg 
    1040                 1045                 1050             


Trp His  Leu Thr His Arg Pro  Lys Thr Gly Tyr Ile  Arg Val Leu 
    1055                 1060                 1065             


Val His  Glu Gly Lys Gln Val  Met Ala Asp Ser Gly  Pro Ile Tyr 
    1070                 1075                 1080             


Asp Gln  Thr Tyr Ala Gly Gly  Arg Leu Gly Leu Phe  Val Phe Ser 
    1085                 1090                 1095             


Gln Glu  Met Val Tyr Phe Ser  Asp Leu Lys Tyr Glu  Cys Arg Asp 
    1100                 1105                 1110             


Ile 
    


<210>  3
<211>  787
<212>  PRT
<213>  Homo sapiens

<400>  3

Met Val Trp Arg Leu Val Leu Leu Ala Leu Trp Val Trp Pro Ser Thr 
1               5                   10                  15      


Gln Ala Gly His Gln Asp Lys Asp Thr Thr Phe Asp Leu Phe Ser Ile 
            20                  25                  30          


Ser Asn Ile Asn Arg Lys Thr Ile Gly Ala Lys Gln Phe Arg Gly Pro 
        35                  40                  45              


Asp Pro Gly Val Pro Ala Tyr Arg Phe Val Arg Phe Asp Tyr Ile Pro 
    50                  55                  60                  


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


Lys Glu Gly Phe Phe Leu Thr Ala Gln Leu Lys Gln Asp Gly Lys Ser 
                85                  90                  95      


Arg Gly Thr Leu Leu Ala Leu Glu Gly Pro Gly Leu Ser Gln Arg Gln 
            100                 105                 110         


Phe Glu Ile Val Ser Asn Gly Pro Ala Asp Thr Leu Asp Leu Thr Tyr 
        115                 120                 125             


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


Ala Asp Ser Gln Trp Lys Asn Val Thr Val Gln Val Ala Gly Glu Thr 
145                 150                 155                 160 


Tyr Ser Leu His Val Gly Cys Asp Leu Ile Asp Ser Phe Ala Leu Asp 
                165                 170                 175     


Glu Pro Phe Tyr Glu His Leu Gln Ala Glu Lys Ser Arg Met Tyr Val 
            180                 185                 190         


Ala Lys Gly Ser Ala Arg Glu Ser His Phe Arg Gly Leu Leu Gln Asn 
        195                 200                 205             


Val His Leu Val Phe Glu Asn Ser Val Glu Asp Ile Leu Ser Lys Lys 
    210                 215                 220                 


Gly Cys Gln Gln Gly Gln Gly Ala Glu Ile Asn Ala Ile Ser Glu Asn 
225                 230                 235                 240 


Thr Glu Thr Leu Arg Leu Gly Pro His Val Thr Thr Glu Tyr Val Gly 
                245                 250                 255     


Pro Ser Ser Glu Arg Arg Pro Glu Val Cys Glu Arg Ser Cys Glu Glu 
            260                 265                 270         


Leu Gly Asn Met Val Gln Glu Leu Ser Gly Leu His Val Leu Val Asn 
        275                 280                 285             


Gln Leu Ser Glu Asn Leu Lys Arg Val Ser Asn Asp Asn Gln Phe Leu 
    290                 295                 300                 


Trp Glu Leu Ile Gly Gly Pro Pro Lys Thr Arg Asn Met Ser Ala Cys 
305                 310                 315                 320 


Trp Gln Asp Gly Arg Phe Phe Ala Glu Asn Glu Thr Trp Val Val Asp 
                325                 330                 335     


Ser Cys Thr Thr Cys Thr Cys Lys Lys Phe Lys Thr Ile Cys His Gln 
            340                 345                 350         


Ile Thr Cys Pro Pro Ala Thr Cys Ala Ser Pro Ser Phe Val Glu Gly 
        355                 360                 365             


Glu Cys Cys Pro Ser Cys Leu His Ser Val Asp Gly Glu Glu Gly Trp 
    370                 375                 380                 


Ser Pro Trp Ala Glu Trp Thr Gln Cys Ser Val Thr Cys Gly Ser Gly 
385                 390                 395                 400 


Thr Gln Gln Arg Gly Arg Ser Cys Asp Val Thr Ser Asn Thr Cys Leu 
                405                 410                 415     


Gly Pro Ser Ile Gln Thr Arg Ala Cys Ser Leu Ser Lys Cys Asp Thr 
            420                 425                 430         


Arg Ile Arg Gln Asp Gly Gly Trp Ser His Trp Ser Pro Trp Ser Ser 
        435                 440                 445             


Cys Ser Val Thr Cys Gly Val Gly Asn Ile Thr Arg Ile Arg Leu Cys 
    450                 455                 460                 


Asn Ser Pro Val Pro Gln Met Gly Gly Lys Asn Cys Lys Gly Ser Gly 
465                 470                 475                 480 


Arg Glu Thr Lys Ala Cys Gln Gly Ala Pro Cys Pro Ile Asp Gly Arg 
                485                 490                 495     


Trp Ser Pro Trp Ser Pro Trp Ser Ala Cys Thr Val Thr Cys Ala Gly 
            500                 505                 510         


Gly Ile Arg Glu Arg Thr Arg Val Cys Asn Ser Pro Glu Pro Gln Tyr 
        515                 520                 525             


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


Lys Arg Ser Cys Pro Val Asp Gly Cys Leu Ser Asn Pro Cys Phe Pro 
545                 550                 555                 560 


Gly Ala Gln Cys Ser Ser Phe Pro Asp Gly Ser Trp Ser Cys Gly Ser 
                565                 570                 575     


Cys Pro Val Gly Phe Leu Gly Asn Gly Thr His Cys Glu Asp Leu Asp 
            580                 585                 590         


Glu Cys Ala Leu Val Pro Asp Ile Cys Phe Ser Thr Ser Lys Val Pro 
        595                 600                 605             


Arg Cys Val Asn Thr Gln Pro Gly Phe His Cys Leu Pro Cys Pro Pro 
    610                 615                 620                 


Arg Tyr Arg Gly Asn Gln Pro Val Gly Val Gly Leu Glu Ala Ala Lys 
625                 630                 635                 640 


Thr Glu Lys Gln Val Cys Glu Pro Glu Asn Pro Cys Lys Asp Lys Thr 
                645                 650                 655     


His Asn Cys His Lys His Ala Glu Cys Ile Tyr Leu Gly His Phe Ser 
            660                 665                 670         


Asp Pro Met Tyr Lys Cys Glu Cys Gln Thr Gly Tyr Ala Gly Asp Gly 
        675                 680                 685             


Leu Ile Cys Gly Glu Asp Ser Asp Leu Asp Gly Trp Pro Asn Leu Asn 
    690                 695                 700                 


Leu Val Cys Ala Thr Asn Ala Thr Tyr His Cys Ile Lys Leu Trp Arg 
705                 710                 715                 720 


Pro Glu Thr Gln Arg Gln Gly Ala Ser Gly Ala Val Leu Pro Leu Leu 
                725                 730                 735     


Leu Pro Ala Ser Leu Ala Gln Ala Ser Leu Gly Phe Trp Arg Trp Trp 
            740                 745                 750         


Leu His Gly Pro Asp Leu Trp Ser Ala Ser His His Phe Leu Gln Cys 
        755                 760                 765             


Leu Ser Leu Arg Lys Leu Pro Leu Pro Leu Phe Asp Lys Asn Thr Cys 
    770                 775                 780                 


Gly Cys Ile 
785         


<210>  4
<211>  334
<212>  PRT
<213>  Homo sapiens

<400>  4

Met Val Trp Arg Leu Val Leu Leu Ala Leu Trp Val Trp Pro Ser Thr 
1               5                   10                  15      


Gln Ala Gly His Gln Asp Lys Asp Thr Thr Phe Asp Leu Phe Ser Ile 
            20                  25                  30          


Ser Asn Ile Asn Arg Lys Thr Ile Gly Ala Lys Gln Phe Arg Gly Pro 
        35                  40                  45              


Asp Pro Gly Val Pro Ala Tyr Arg Phe Val Arg Phe Asp Tyr Ile Pro 
    50                  55                  60                  


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


Lys Glu Gly Phe Phe Leu Thr Ala Gln Leu Lys Gln Asp Gly Lys Ser 
                85                  90                  95      


Arg Gly Thr Leu Leu Ala Leu Glu Gly Pro Gly Leu Ser Gln Arg Gln 
            100                 105                 110         


Phe Glu Ile Val Ser Asn Gly Pro Ala Asp Thr Leu Asp Leu Thr Tyr 
        115                 120                 125             


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


Ala Asp Ser Gln Trp Lys Asn Val Thr Val Gln Val Ala Gly Glu Thr 
145                 150                 155                 160 


Tyr Ser Leu His Val Gly Cys Asp Leu Ile Asp Ser Phe Ala Leu Asp 
                165                 170                 175     


Glu Pro Phe Tyr Glu His Leu Gln Ala Glu Lys Ser Arg Met Tyr Val 
            180                 185                 190         


Ala Lys Gly Ser Ala Arg Glu Ser His Phe Arg Gly Leu Leu Gln Asn 
        195                 200                 205             


Val His Leu Val Phe Glu Asn Ser Val Glu Asp Ile Leu Ser Lys Lys 
    210                 215                 220                 


Gly Cys Gln Gln Gly Gln Gly Ala Glu Ile Asn Ala Ile Ser Glu Asn 
225                 230                 235                 240 


Thr Glu Thr Leu Arg Leu Gly Pro His Val Thr Thr Glu Tyr Val Gly 
                245                 250                 255     


Pro Ser Ser Glu Arg Arg Pro Glu Val Cys Glu Arg Ser Cys Glu Glu 
            260                 265                 270         


Leu Gly Asn Met Val Gln Glu Leu Ser Gly Leu His Val Leu Val Asn 
        275                 280                 285             


Gln Leu Ser Glu Asn Leu Lys Arg Val Val Gly Thr His Ala Gly Ala 
    290                 295                 300                 


Ala Gly Val Ile Gly His Gly Gln Leu Arg Arg Trp Pro Ile Ser Ala 
305                 310                 315                 320 


Gly Ile Asn Ile Pro Trp Leu Gly Ser Ala Ser Cys Ser Met 
                325                 330                 


<210>  5
<211>  1095
<212>  PRT
<213>  Homo sapiens

<400>  5

Met Arg Gln Lys Glu Gly Phe Phe Leu Thr Ala Gln Leu Lys Gln Asp 
1               5                   10                  15      


Gly Lys Ser Arg Gly Thr Leu Leu Ala Leu Glu Gly Pro Gly Leu Ser 
            20                  25                  30          


Gln Arg Gln Phe Glu Ile Val Ser Asn Gly Pro Ala Asp Thr Leu Asp 
        35                  40                  45              


Leu Thr Tyr Trp Ile Asp Gly Thr Arg His Val Val Ser Leu Glu Asp 
    50                  55                  60                  


Val Gly Leu Ala Asp Ser Gln Trp Lys Asn Val Thr Val Gln Val Ala 
65                  70                  75                  80  


Gly Glu Thr Tyr Ser Leu His Val Gly Cys Asp Leu Ile Asp Ser Phe 
                85                  90                  95      


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


Met Tyr Val Ala Lys Gly Ser Ala Arg Glu Ser His Phe Arg Gly Leu 
        115                 120                 125             


Leu Gln Asn Val His Leu Val Phe Glu Asn Ser Val Glu Asp Ile Leu 
    130                 135                 140                 


Ser Lys Lys Gly Cys Gln Gln Gly Gln Gly Ala Glu Ile Asn Ala Ile 
145                 150                 155                 160 


Ser Glu Asn Thr Glu Thr Leu Arg Leu Gly Pro His Val Thr Thr Glu 
                165                 170                 175     


Tyr Val Gly Pro Ser Ser Glu Arg Arg Pro Glu Val Cys Glu Arg Ser 
            180                 185                 190         


Cys Glu Glu Leu Gly Asn Met Val Gln Glu Leu Ser Gly Leu His Val 
        195                 200                 205             


Leu Val Asn Gln Leu Ser Glu Asn Leu Lys Arg Val Ser Asn Asp Asn 
    210                 215                 220                 


Gln Phe Leu Trp Glu Leu Ile Gly Gly Pro Pro Lys Thr Arg Asn Met 
225                 230                 235                 240 


Ser Ala Cys Trp Gln Asp Gly Arg Phe Phe Ala Glu Asn Glu Thr Trp 
                245                 250                 255     


Val Val Asp Ser Cys Thr Thr Cys Thr Cys Lys Lys Phe Lys Thr Ile 
            260                 265                 270         


Cys His Gln Ile Thr Cys Pro Pro Ala Thr Cys Ala Ser Pro Ser Phe 
        275                 280                 285             


Val Glu Gly Glu Cys Cys Pro Ser Cys Leu His Ser Val Asp Gly Glu 
    290                 295                 300                 


Glu Gly Trp Ser Pro Trp Ala Glu Trp Thr Gln Cys Ser Val Thr Cys 
305                 310                 315                 320 


Gly Ser Gly Thr Gln Gln Arg Gly Arg Ser Cys Asp Val Thr Ser Asn 
                325                 330                 335     


Thr Cys Leu Gly Pro Ser Ile Gln Thr Arg Ala Cys Ser Leu Ser Lys 
            340                 345                 350         


Cys Asp Thr Arg Ile Arg Gln Asp Gly Gly Trp Ser His Trp Ser Pro 
        355                 360                 365             


Trp Ser Ser Cys Ser Val Thr Cys Gly Val Gly Asn Ile Thr Arg Ile 
    370                 375                 380                 


Arg Leu Cys Asn Ser Pro Val Pro Gln Met Gly Gly Lys Asn Cys Lys 
385                 390                 395                 400 


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


Asp Gly Arg Trp Ser Pro Trp Ser Pro Trp Ser Ala Cys Thr Val Thr 
            420                 425                 430         


Cys Ala Gly Gly Ile Arg Glu Arg Thr Arg Val Cys Asn Ser Pro Glu 
        435                 440                 445             


Pro Gln Tyr Gly Gly Lys Ala Cys Val Gly Asp Val Gln Glu Arg Gln 
    450                 455                 460                 


Met Cys Asn Lys Arg Ser Cys Pro Val Asp Gly Cys Leu Ser Asn Pro 
465                 470                 475                 480 


Cys Phe Pro Gly Ala Gln Cys Ser Ser Phe Pro Asp Gly Ser Trp Ser 
                485                 490                 495     


Cys Gly Ser Cys Pro Val Gly Phe Leu Gly Asn Gly Thr His Cys Glu 
            500                 505                 510         


Asp Leu Asp Glu Cys Ala Leu Val Pro Asp Ile Cys Phe Ser Thr Ser 
        515                 520                 525             


Lys Val Pro Arg Cys Val Asn Thr Gln Pro Gly Phe His Cys Leu Pro 
    530                 535                 540                 


Cys Pro Pro Arg Tyr Arg Gly Asn Gln Pro Val Gly Val Gly Leu Glu 
545                 550                 555                 560 


Ala Ala Lys Thr Glu Lys Gln Val Cys Glu Pro Glu Asn Pro Cys Lys 
                565                 570                 575     


Asp Lys Thr His Asn Cys His Lys His Ala Glu Cys Ile Tyr Leu Gly 
            580                 585                 590         


His Phe Ser Asp Pro Met Tyr Lys Cys Glu Cys Gln Thr Gly Tyr Ala 
        595                 600                 605             


Gly Asp Gly Leu Ile Cys Gly Glu Asp Ser Asp Leu Asp Gly Trp Pro 
    610                 615                 620                 


Asn Leu Asn Leu Val Cys Ala Thr Asn Ala Thr Tyr His Cys Ile Lys 
625                 630                 635                 640 


Asp Asn Cys Pro His Leu Pro Asn Ser Gly Gln Glu Asp Phe Asp Lys 
                645                 650                 655     


Asp Gly Ile Gly Asp Ala Cys Asp Asp Asp Asp Asp Asn Asp Gly Val 
            660                 665                 670         


Thr Asp Glu Lys Asp Asn Cys Gln Leu Leu Phe Asn Pro Arg Gln Ala 
        675                 680                 685             


Asp Tyr Asp Lys Asp Glu Val Gly Asp Arg Cys Asp Asn Cys Pro Tyr 
    690                 695                 700                 


Val His Asn Pro Ala Gln Ile Asp Thr Asp Asn Asn Gly Glu Gly Asp 
705                 710                 715                 720 


Ala Cys Ser Val Asp Ile Asp Gly Asp Asp Val Phe Asn Glu Arg Asp 
                725                 730                 735     


Asn Cys Pro Tyr Val Tyr Asn Thr Asp Gln Arg Asp Thr Asp Gly Asp 
            740                 745                 750         


Gly Val Gly Asp His Cys Asp Asn Cys Pro Leu Val His Asn Pro Asp 
        755                 760                 765             


Gln Thr Asp Val Asp Asn Asp Leu Val Gly Asp Gln Cys Asp Asn Asn 
    770                 775                 780                 


Glu Asp Ile Asp Asp Asp Gly His Gln Asn Asn Gln Asp Asn Cys Pro 
785                 790                 795                 800 


Tyr Ile Ser Asn Ala Asn Gln Ala Asp His Asp Arg Asp Gly Gln Gly 
                805                 810                 815     


Asp Ala Cys Asp Pro Asp Asp Asp Asn Asp Gly Val Pro Asp Asp Arg 
            820                 825                 830         


Asp Asn Cys Arg Leu Val Phe Asn Pro Asp Gln Glu Asp Leu Asp Gly 
        835                 840                 845             


Asp Gly Arg Gly Asp Ile Cys Lys Asp Asp Phe Asp Asn Asp Asn Ile 
    850                 855                 860                 


Pro Asp Ile Asp Asp Val Cys Pro Glu Asn Asn Ala Ile Ser Glu Thr 
865                 870                 875                 880 


Asp Phe Arg Asn Phe Gln Met Val Pro Leu Asp Pro Lys Gly Thr Thr 
                885                 890                 895     


Gln Ile Asp Pro Asn Trp Val Ile Arg His Gln Gly Lys Glu Leu Val 
            900                 905                 910         


Gln Thr Ala Asn Ser Asp Pro Gly Ile Ala Val Gly Phe Asp Glu Phe 
        915                 920                 925             


Gly Ser Val Asp Phe Ser Gly Thr Phe Tyr Val Asn Thr Asp Arg Asp 
    930                 935                 940                 


Asp Asp Tyr Ala Gly Phe Val Phe Gly Tyr Gln Ser Ser Ser Arg Phe 
945                 950                 955                 960 


Tyr Val Val Met Trp Lys Gln Val Thr Gln Thr Tyr Trp Glu Asp Gln 
                965                 970                 975     


Pro Thr Arg Ala Tyr Gly Tyr Ser Gly Val Ser Leu Lys Val Val Asn 
            980                 985                 990         


Ser Thr Thr Gly Thr Gly Glu His  Leu Arg Asn Ala Leu  Trp His Thr 
        995                 1000                 1005             


Gly Asn  Thr Pro Gly Gln Val  Arg Thr Leu Trp His  Asp Pro Arg 
    1010                 1015                 1020             


Asn Ile  Gly Trp Lys Asp Tyr  Thr Ala Tyr Arg Trp  His Leu Thr 
    1025                 1030                 1035             


His Arg  Pro Lys Thr Gly Tyr  Ile Arg Val Leu Val  His Glu Gly 
    1040                 1045                 1050             


Lys Gln  Val Met Ala Asp Ser  Gly Pro Ile Tyr Asp  Gln Thr Tyr 
    1055                 1060                 1065             


Ala Gly  Gly Arg Leu Gly Leu  Phe Val Phe Ser Gln  Glu Met Val 
    1070                 1075                 1080             


Tyr Phe  Ser Asp Leu Lys Tyr  Glu Cys Arg Asp Ile  
    1085                 1090                 1095 


