                         SEQUENCE LISTING - Rule 13ter

<110>  RUSH UNIVERSITY MEDICAL CENTER
       GUPTA, Vineet
       LI, Xiaobo
 
<120>  IDENTIFICATION OF NOVEL SMALL MOLECULE BETA2 INTEGRIN AGONISTS

<130>  14904-185

<140>  PCT/US2017/014222
<141>  2017-01-20

<150>  US 62/286190
<151>  2016-01-22

<160>  4     

<170>  PatentIn version 3.5

<210>  1
<211>  1152
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Ala Leu Arg Val Leu Leu Leu Thr Ala Leu Thr Leu Cys His Gly 
1               5                   10                  15      


Phe Asn Leu Asp Thr Glu Asn Ala Met Thr Phe Gln Glu Asn Ala Arg 
            20                  25                  30          


Gly Phe Gly Gln Ser Val Val Gln Leu Gln Gly Ser Arg Val Val Val 
        35                  40                  45              


Gly Ala Pro Gln Glu Ile Val Ala Ala Asn Gln Arg Gly Ser Leu Tyr 
    50                  55                  60                  


Gln Cys Asp Tyr Ser Thr Gly Ser Cys Glu Pro Ile Arg Leu Gln Val 
65                  70                  75                  80  


Pro Val Glu Ala Val Asn Met Ser Leu Gly Leu Ser Leu Ala Ala Thr 
                85                  90                  95      


Thr Ser Pro Pro Gln Leu Leu Ala Cys Gly Pro Thr Val His Gln Thr 
            100                 105                 110         


Cys Ser Glu Asn Thr Tyr Val Lys Gly Leu Cys Phe Leu Phe Gly Ser 
        115                 120                 125             


Asn Leu Arg Gln Gln Pro Gln Lys Phe Pro Glu Ala Leu Arg Gly Cys 
    130                 135                 140                 


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


Ile Ile Pro His Asp Phe Arg Arg Met Lys Glu Phe Val Ser Thr Val 
                165                 170                 175     


Met Glu Gln Leu Lys Lys Ser Lys Thr Leu Phe Ser Leu Met Gln Tyr 
            180                 185                 190         


Ser Glu Glu Phe Arg Ile His Phe Thr Phe Lys Glu Phe Gln Asn Asn 
        195                 200                 205             


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


Thr His Thr Ala Thr Gly Ile Arg Lys Val Val Arg Glu Leu Phe Asn 
225                 230                 235                 240 


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


Thr Asp Gly Glu Lys Phe Gly Asp Pro Leu Gly Tyr Glu Asp Val Ile 
            260                 265                 270         


Pro Glu Ala Asp Arg Glu Gly Val Ile Arg Tyr Val Ile Gly Val Gly 
        275                 280                 285             


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


Ser Lys Pro Pro Arg Asp His Val Phe Gln Val Asn Asn Phe Glu Ala 
305                 310                 315                 320 


Leu Lys Thr Ile Gln Asn Gln Leu Arg Glu Lys Ile Phe Ala Ile Glu 
                325                 330                 335     


Gly Thr Gln Thr Gly Ser Ser Ser Ser Phe Glu His Glu Met Ser Gln 
            340                 345                 350         


Glu Gly Phe Ser Ala Ala Ile Thr Ser Asn Gly Pro Leu Leu Ser Thr 
        355                 360                 365             


Val Gly Ser Tyr Asp Trp Ala Gly Gly Val Phe Leu Tyr Thr Ser Lys 
    370                 375                 380                 


Glu Lys Ser Thr Phe Ile Asn Met Thr Arg Val Asp Ser Asp Met Asn 
385                 390                 395                 400 


Asp Ala Tyr Leu Gly Tyr Ala Ala Ala Ile Ile Leu Arg Asn Arg Val 
                405                 410                 415     


Gln Ser Leu Val Leu Gly Ala Pro Arg Tyr Gln His Ile Gly Leu Val 
            420                 425                 430         


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


Lys Gly Thr Gln Ile Gly Ala Tyr Phe Gly Ala Ser Leu Cys Ser Val 
    450                 455                 460                 


Asp Val Asp Ser Asn Gly Ser Thr Asp Leu Val Leu Ile Gly Ala Pro 
465                 470                 475                 480 


His Tyr Tyr Glu Gln Thr Arg Gly Gly Gln Val Ser Val Cys Pro Leu 
                485                 490                 495     


Pro Arg Gly Arg Ala Arg Trp Gln Cys Asp Ala Val Leu Tyr Gly Glu 
            500                 505                 510         


Gln Gly Gln Pro Trp Gly Arg Phe Gly Ala Ala Leu Thr Val Leu Gly 
        515                 520                 525             


Asp Val Asn Gly Asp Lys Leu Thr Asp Val Ala Ile Gly Ala Pro Gly 
    530                 535                 540                 


Glu Glu Asp Asn Arg Gly Ala Val Tyr Leu Phe His Gly Thr Ser Gly 
545                 550                 555                 560 


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


Ser Pro Arg Leu Gln Tyr Phe Gly Gln Ser Leu Ser Gly Gly Gln Asp 
            580                 585                 590         


Leu Thr Met Asp Gly Leu Val Asp Leu Thr Val Gly Ala Gln Gly His 
        595                 600                 605             


Val Leu Leu Leu Arg Ser Gln Pro Val Leu Arg Val Lys Ala Ile Met 
    610                 615                 620                 


Glu Phe Asn Pro Arg Glu Val Ala Arg Asn Val Phe Glu Cys Asn Asp 
625                 630                 635                 640 


Gln Val Val Lys Gly Lys Glu Ala Gly Glu Val Arg Val Cys Leu His 
                645                 650                 655     


Val Gln Lys Ser Thr Arg Asp Arg Leu Arg Glu Gly Gln Ile Gln Ser 
            660                 665                 670         


Val Val Thr Tyr Asp Leu Ala Leu Asp Ser Gly Arg Pro His Ser Arg 
        675                 680                 685             


Ala Val Phe Asn Glu Thr Lys Asn Ser Thr Arg Arg Gln Thr Gln Val 
    690                 695                 700                 


Leu Gly Leu Thr Gln Thr Cys Glu Thr Leu Lys Leu Gln Leu Pro Asn 
705                 710                 715                 720 


Cys Ile Glu Asp Pro Val Ser Pro Ile Val Leu Arg Leu Asn Phe Ser 
                725                 730                 735     


Leu Val Gly Thr Pro Leu Ser Ala Phe Gly Asn Leu Arg Pro Val Leu 
            740                 745                 750         


Ala Glu Asp Ala Gln Arg Leu Phe Thr Ala Leu Phe Pro Phe Glu Lys 
        755                 760                 765             


Asn Cys Gly Asn Asp Asn Ile Cys Gln Asp Asp Leu Ser Ile Thr Phe 
    770                 775                 780                 


Ser Phe Met Ser Leu Asp Cys Leu Val Val Gly Gly Pro Arg Glu Phe 
785                 790                 795                 800 


Asn Val Thr Val Thr Val Arg Asn Asp Gly Glu Asp Ser Tyr Arg Thr 
                805                 810                 815     


Gln Val Thr Phe Phe Phe Pro Leu Asp Leu Ser Tyr Arg Lys Val Ser 
            820                 825                 830         


Thr Leu Gln Asn Gln Arg Ser Gln Arg Ser Trp Arg Leu Ala Cys Glu 
        835                 840                 845             


Ser Ala Ser Ser Thr Glu Val Ser Gly Ala Leu Lys Ser Thr Ser Cys 
    850                 855                 860                 


Ser Ile Asn His Pro Ile Phe Pro Glu Asn Ser Glu Val Thr Phe Asn 
865                 870                 875                 880 


Ile Thr Phe Asp Val Asp Ser Lys Ala Ser Leu Gly Asn Lys Leu Leu 
                885                 890                 895     


Leu Lys Ala Asn Val Thr Ser Glu Asn Asn Met Pro Arg Thr Asn Lys 
            900                 905                 910         


Thr Glu Phe Gln Leu Glu Leu Pro Val Lys Tyr Ala Val Tyr Met Val 
        915                 920                 925             


Val Thr Ser His Gly Val Ser Thr Lys Tyr Leu Asn Phe Thr Ala Ser 
    930                 935                 940                 


Glu Asn Thr Ser Arg Val Met Gln His Gln Tyr Gln Val Ser Asn Leu 
945                 950                 955                 960 


Gly Gln Arg Ser Leu Pro Ile Ser Leu Val Phe Leu Val Pro Val Arg 
                965                 970                 975     


Leu Asn Gln Thr Val Ile Trp Asp Arg Pro Gln Val Thr Phe Ser Glu 
            980                 985                 990         


Asn Leu Ser Ser Thr Cys His Thr  Lys Glu Arg Leu Pro  Ser His Ser 
        995                 1000                 1005             


Asp Phe  Leu Ala Glu Leu Arg  Lys Ala Pro Val Val  Asn Cys Ser 
    1010                 1015                 1020             


Ile Ala  Val Cys Gln Arg Ile  Gln Cys Asp Ile Pro  Phe Phe Gly 
    1025                 1030                 1035             


Ile Gln  Glu Glu Phe Asn Ala  Thr Leu Lys Gly Asn  Leu Ser Phe 
    1040                 1045                 1050             


Asp Trp  Tyr Ile Lys Thr Ser  His Asn His Leu Leu  Ile Val Ser 
    1055                 1060                 1065             


Thr Ala  Glu Ile Leu Phe Asn  Asp Ser Val Phe Thr  Leu Leu Pro 
    1070                 1075                 1080             


Gly Gln  Gly Ala Phe Val Arg  Ser Gln Thr Glu Thr  Lys Val Glu 
    1085                 1090                 1095             


Pro Phe  Glu Val Pro Asn Pro  Leu Pro Leu Ile Val  Gly Ser Ser 
    1100                 1105                 1110             


Val Gly  Gly Leu Leu Leu Leu  Ala Leu Ile Thr Ala  Ala Leu Tyr 
    1115                 1120                 1125             


Lys Leu  Gly Phe Phe Lys Arg  Gln Tyr Lys Asp Met  Met Ser Glu 
    1130                 1135                 1140             


Gly Gly  Pro Pro Gly Ala Glu  Pro Gln 
    1145                 1150         


<210>  2
<211>  1152
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Site Directed Mutation E320A


<220>
<221>  MISC_FEATURE
<223>  E320A

<400>  2

Met Ala Leu Arg Val Leu Leu Leu Thr Ala Leu Thr Leu Cys His Gly 
1               5                   10                  15      


Phe Asn Leu Asp Thr Glu Asn Ala Met Thr Phe Gln Glu Asn Ala Arg 
            20                  25                  30          


Gly Phe Gly Gln Ser Val Val Gln Leu Gln Gly Ser Arg Val Val Val 
        35                  40                  45              


Gly Ala Pro Gln Glu Ile Val Ala Ala Asn Gln Arg Gly Ser Leu Tyr 
    50                  55                  60                  


Gln Cys Asp Tyr Ser Thr Gly Ser Cys Glu Pro Ile Arg Leu Gln Val 
65                  70                  75                  80  


Pro Val Glu Ala Val Asn Met Ser Leu Gly Leu Ser Leu Ala Ala Thr 
                85                  90                  95      


Thr Ser Pro Pro Gln Leu Leu Ala Cys Gly Pro Thr Val His Gln Thr 
            100                 105                 110         


Cys Ser Glu Asn Thr Tyr Val Lys Gly Leu Cys Phe Leu Phe Gly Ser 
        115                 120                 125             


Asn Leu Arg Gln Gln Pro Gln Lys Phe Pro Glu Ala Leu Arg Gly Cys 
    130                 135                 140                 


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


Ile Ile Pro His Asp Phe Arg Arg Met Lys Glu Phe Val Ser Thr Val 
                165                 170                 175     


Met Glu Gln Leu Lys Lys Ser Lys Thr Leu Phe Ser Leu Met Gln Tyr 
            180                 185                 190         


Ser Glu Glu Phe Arg Ile His Phe Thr Phe Lys Glu Phe Gln Asn Asn 
        195                 200                 205             


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


Thr His Thr Ala Thr Gly Ile Arg Lys Val Val Arg Glu Leu Phe Asn 
225                 230                 235                 240 


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


Thr Asp Gly Glu Lys Phe Gly Asp Pro Leu Gly Tyr Glu Asp Val Ile 
            260                 265                 270         


Pro Glu Ala Asp Arg Glu Gly Val Ile Arg Tyr Val Ile Gly Val Gly 
        275                 280                 285             


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


Ser Lys Pro Pro Arg Asp His Val Phe Gln Val Asn Asn Phe Glu Ala 
305                 310                 315                 320 


Leu Lys Thr Ile Gln Asn Gln Leu Arg Ala Lys Ile Phe Ala Ile Glu 
                325                 330                 335     


Gly Thr Gln Thr Gly Ser Ser Ser Ser Phe Glu His Glu Met Ser Gln 
            340                 345                 350         


Glu Gly Phe Ser Ala Ala Ile Thr Ser Asn Gly Pro Leu Leu Ser Thr 
        355                 360                 365             


Val Gly Ser Tyr Asp Trp Ala Gly Gly Val Phe Leu Tyr Thr Ser Lys 
    370                 375                 380                 


Glu Lys Ser Thr Phe Ile Asn Met Thr Arg Val Asp Ser Asp Met Asn 
385                 390                 395                 400 


Asp Ala Tyr Leu Gly Tyr Ala Ala Ala Ile Ile Leu Arg Asn Arg Val 
                405                 410                 415     


Gln Ser Leu Val Leu Gly Ala Pro Arg Tyr Gln His Ile Gly Leu Val 
            420                 425                 430         


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


Lys Gly Thr Gln Ile Gly Ala Tyr Phe Gly Ala Ser Leu Cys Ser Val 
    450                 455                 460                 


Asp Val Asp Ser Asn Gly Ser Thr Asp Leu Val Leu Ile Gly Ala Pro 
465                 470                 475                 480 


His Tyr Tyr Glu Gln Thr Arg Gly Gly Gln Val Ser Val Cys Pro Leu 
                485                 490                 495     


Pro Arg Gly Arg Ala Arg Trp Gln Cys Asp Ala Val Leu Tyr Gly Glu 
            500                 505                 510         


Gln Gly Gln Pro Trp Gly Arg Phe Gly Ala Ala Leu Thr Val Leu Gly 
        515                 520                 525             


Asp Val Asn Gly Asp Lys Leu Thr Asp Val Ala Ile Gly Ala Pro Gly 
    530                 535                 540                 


Glu Glu Asp Asn Arg Gly Ala Val Tyr Leu Phe His Gly Thr Ser Gly 
545                 550                 555                 560 


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


Ser Pro Arg Leu Gln Tyr Phe Gly Gln Ser Leu Ser Gly Gly Gln Asp 
            580                 585                 590         


Leu Thr Met Asp Gly Leu Val Asp Leu Thr Val Gly Ala Gln Gly His 
        595                 600                 605             


Val Leu Leu Leu Arg Ser Gln Pro Val Leu Arg Val Lys Ala Ile Met 
    610                 615                 620                 


Glu Phe Asn Pro Arg Glu Val Ala Arg Asn Val Phe Glu Cys Asn Asp 
625                 630                 635                 640 


Gln Val Val Lys Gly Lys Glu Ala Gly Glu Val Arg Val Cys Leu His 
                645                 650                 655     


Val Gln Lys Ser Thr Arg Asp Arg Leu Arg Glu Gly Gln Ile Gln Ser 
            660                 665                 670         


Val Val Thr Tyr Asp Leu Ala Leu Asp Ser Gly Arg Pro His Ser Arg 
        675                 680                 685             


Ala Val Phe Asn Glu Thr Lys Asn Ser Thr Arg Arg Gln Thr Gln Val 
    690                 695                 700                 


Leu Gly Leu Thr Gln Thr Cys Glu Thr Leu Lys Leu Gln Leu Pro Asn 
705                 710                 715                 720 


Cys Ile Glu Asp Pro Val Ser Pro Ile Val Leu Arg Leu Asn Phe Ser 
                725                 730                 735     


Leu Val Gly Thr Pro Leu Ser Ala Phe Gly Asn Leu Arg Pro Val Leu 
            740                 745                 750         


Ala Glu Asp Ala Gln Arg Leu Phe Thr Ala Leu Phe Pro Phe Glu Lys 
        755                 760                 765             


Asn Cys Gly Asn Asp Asn Ile Cys Gln Asp Asp Leu Ser Ile Thr Phe 
    770                 775                 780                 


Ser Phe Met Ser Leu Asp Cys Leu Val Val Gly Gly Pro Arg Glu Phe 
785                 790                 795                 800 


Asn Val Thr Val Thr Val Arg Asn Asp Gly Glu Asp Ser Tyr Arg Thr 
                805                 810                 815     


Gln Val Thr Phe Phe Phe Pro Leu Asp Leu Ser Tyr Arg Lys Val Ser 
            820                 825                 830         


Thr Leu Gln Asn Gln Arg Ser Gln Arg Ser Trp Arg Leu Ala Cys Glu 
        835                 840                 845             


Ser Ala Ser Ser Thr Glu Val Ser Gly Ala Leu Lys Ser Thr Ser Cys 
    850                 855                 860                 


Ser Ile Asn His Pro Ile Phe Pro Glu Asn Ser Glu Val Thr Phe Asn 
865                 870                 875                 880 


Ile Thr Phe Asp Val Asp Ser Lys Ala Ser Leu Gly Asn Lys Leu Leu 
                885                 890                 895     


Leu Lys Ala Asn Val Thr Ser Glu Asn Asn Met Pro Arg Thr Asn Lys 
            900                 905                 910         


Thr Glu Phe Gln Leu Glu Leu Pro Val Lys Tyr Ala Val Tyr Met Val 
        915                 920                 925             


Val Thr Ser His Gly Val Ser Thr Lys Tyr Leu Asn Phe Thr Ala Ser 
    930                 935                 940                 


Glu Asn Thr Ser Arg Val Met Gln His Gln Tyr Gln Val Ser Asn Leu 
945                 950                 955                 960 


Gly Gln Arg Ser Leu Pro Ile Ser Leu Val Phe Leu Val Pro Val Arg 
                965                 970                 975     


Leu Asn Gln Thr Val Ile Trp Asp Arg Pro Gln Val Thr Phe Ser Glu 
            980                 985                 990         


Asn Leu Ser Ser Thr Cys His Thr  Lys Glu Arg Leu Pro  Ser His Ser 
        995                 1000                 1005             


Asp Phe  Leu Ala Glu Leu Arg  Lys Ala Pro Val Val  Asn Cys Ser 
    1010                 1015                 1020             


Ile Ala  Val Cys Gln Arg Ile  Gln Cys Asp Ile Pro  Phe Phe Gly 
    1025                 1030                 1035             


Ile Gln  Glu Glu Phe Asn Ala  Thr Leu Lys Gly Asn  Leu Ser Phe 
    1040                 1045                 1050             


Asp Trp  Tyr Ile Lys Thr Ser  His Asn His Leu Leu  Ile Val Ser 
    1055                 1060                 1065             


Thr Ala  Glu Ile Leu Phe Asn  Asp Ser Val Phe Thr  Leu Leu Pro 
    1070                 1075                 1080             


Gly Gln  Gly Ala Phe Val Arg  Ser Gln Thr Glu Thr  Lys Val Glu 
    1085                 1090                 1095             


Pro Phe  Glu Val Pro Asn Pro  Leu Pro Leu Ile Val  Gly Ser Ser 
    1100                 1105                 1110             


Val Gly  Gly Leu Leu Leu Leu  Ala Leu Ile Thr Ala  Ala Leu Tyr 
    1115                 1120                 1125             


Lys Leu  Gly Phe Phe Lys Arg  Gln Tyr Lys Asp Met  Met Ser Glu 
    1130                 1135                 1140             


Gly Gly  Pro Pro Gly Ala Glu  Pro Gln 
    1145                 1150         


<210>  3
<211>  1169
<212>  PRT
<213>  Homo sapiens

<400>  3

Met Thr Arg Thr Arg Ala Ala Leu Leu Leu Phe Thr Ala Leu Ala Thr 
1               5                   10                  15      


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


Asp Ser Ala Gly Phe Gly Asp Ser Val Val Gln Tyr Ala Asn Ser Trp 
        35                  40                  45              


Val Val Val Gly Ala Pro Gln Lys Ile Thr Ala Ala Asn Gln Thr Gly 
    50                  55                  60                  


Gly Leu Tyr Gln Cys Gly Tyr Ser Thr Gly Ala Cys Glu Pro Ile Gly 
65                  70                  75                  80  


Leu Gln Val Pro Pro Glu Ala Val Asn Met Ser Leu Gly Leu Ser Leu 
                85                  90                  95      


Ala Ser Thr Thr Ser Pro Ser Gln Leu Leu Ala Cys Gly Pro Thr Val 
            100                 105                 110         


His His Glu Cys Gly Arg Asn Met Tyr Leu Thr Gly Leu Cys Phe Leu 
        115                 120                 125             


Leu Gly Pro Thr Gln Leu Thr Gln Arg Leu Pro Val Ser Arg Gln Glu 
    130                 135                 140                 


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


Ser Ile Ser Ser Arg Asn Phe Ala Thr Met Met Asn Phe Val Arg Ala 
                165                 170                 175     


Val Ile Ser Gln Phe Gln Arg Pro Ser Thr Gln Phe Ser Leu Met Gln 
            180                 185                 190         


Phe Ser Asn Lys Phe Gln Thr His Phe Thr Phe Glu Glu Phe Arg Arg 
        195                 200                 205             


Ser Ser Asn Pro Leu Ser Leu Leu Ala Ser Val His Gln Leu Gln Gly 
    210                 215                 220                 


Phe Thr Tyr Thr Ala Thr Ala Ile Gln Asn Val Val His Arg Leu Phe 
225                 230                 235                 240 


His Ala Ser Tyr Gly Ala Arg Arg Asp Ala Ala Lys Ile Leu Ile Val 
                245                 250                 255     


Ile Thr Asp Gly Lys Lys Glu Gly Asp Ser Leu Asp Tyr Lys Asp Val 
            260                 265                 270         


Ile Pro Met Ala Asp Ala Ala Gly Ile Ile Arg Tyr Ala Ile Gly Val 
        275                 280                 285             


Gly Leu Ala Phe Gln Asn Arg Asn Ser Trp Lys Glu Leu Asn Asp Ile 
    290                 295                 300                 


Ala Ser Lys Pro Ser Gln Glu His Ile Phe Lys Val Glu Asp Phe Asp 
305                 310                 315                 320 


Ala Leu Lys Asp Ile Gln Asn Gln Leu Lys Glu Lys Ile Phe Ala Ile 
                325                 330                 335     


Glu Gly Thr Glu Thr Thr Ser Ser Ser Ser Phe Glu Leu Glu Met Ala 
            340                 345                 350         


Gln Glu Gly Phe Ser Ala Val Phe Thr Pro Asp Gly Pro Val Leu Gly 
        355                 360                 365             


Ala Val Gly Ser Phe Thr Trp Ser Gly Gly Ala Phe Leu Tyr Pro Pro 
    370                 375                 380                 


Asn Met Ser Pro Thr Phe Ile Asn Met Ser Gln Glu Asn Val Asp Met 
385                 390                 395                 400 


Arg Asp Ser Tyr Leu Gly Tyr Ser Thr Glu Leu Ala Leu Trp Lys Gly 
                405                 410                 415     


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


Ala Val Ile Phe Thr Gln Val Ser Arg Gln Trp Arg Met Lys Ala Glu 
        435                 440                 445             


Val Thr Gly Thr Gln Ile Gly Ser Tyr Phe Gly Ala Ser Leu Cys Ser 
    450                 455                 460                 


Val Asp Val Asp Ser Asp Gly Ser Thr Asp Leu Val Leu Ile Gly Ala 
465                 470                 475                 480 


Pro His Tyr Tyr Glu Gln Thr Arg Gly Gly Gln Val Ser Val Cys Pro 
                485                 490                 495     


Leu Pro Arg Gly Trp Arg Arg Trp Trp Cys Asp Ala Val Leu Tyr Gly 
            500                 505                 510         


Glu Gln Gly His Pro Trp Gly Arg Phe Gly Ala Ala Leu Thr Val Leu 
        515                 520                 525             


Gly Asp Val Asn Gly Asp Lys Leu Thr Asp Val Val Ile Gly Ala Pro 
    530                 535                 540                 


Gly Glu Glu Glu Asn Arg Gly Ala Val Tyr Leu Phe His Gly Val Leu 
545                 550                 555                 560 


Gly Pro Ser Ile Ser Pro Ser His Ser Gln Arg Ile Ala Gly Ser Gln 
                565                 570                 575     


Leu Ser Ser Arg Leu Gln Tyr Phe Gly Gln Ala Leu Ser Gly Gly Gln 
            580                 585                 590         


Asp Leu Thr Gln Asp Gly Leu Val Asp Leu Ala Val Gly Ala Arg Gly 
        595                 600                 605             


Gln Val Leu Leu Leu Arg Thr Arg Pro Val Leu Trp Val Gly Val Ser 
    610                 615                 620                 


Met Gln Phe Ile Pro Ala Glu Ile Pro Arg Ser Ala Phe Glu Cys Arg 
625                 630                 635                 640 


Glu Gln Val Val Ser Glu Gln Thr Leu Val Gln Ser Asn Ile Cys Leu 
                645                 650                 655     


Tyr Ile Asp Lys Arg Ser Lys Asn Leu Leu Gly Ser Arg Asp Leu Gln 
            660                 665                 670         


Ser Ser Val Thr Leu Asp Leu Ala Leu Asp Pro Gly Arg Leu Ser Pro 
        675                 680                 685             


Arg Ala Thr Phe Gln Glu Thr Lys Asn Arg Ser Leu Ser Arg Val Arg 
    690                 695                 700                 


Val Leu Gly Leu Lys Ala His Cys Glu Asn Phe Asn Leu Leu Leu Pro 
705                 710                 715                 720 


Ser Cys Val Glu Asp Ser Val Thr Pro Ile Thr Leu Arg Leu Asn Phe 
                725                 730                 735     


Thr Leu Val Gly Lys Pro Leu Leu Ala Phe Arg Asn Leu Arg Pro Met 
            740                 745                 750         


Leu Ala Ala Asp Ala Gln Arg Tyr Phe Thr Ala Ser Leu Pro Phe Glu 
        755                 760                 765             


Lys Asn Cys Gly Ala Asp His Ile Cys Gln Asp Asn Leu Gly Ile Ser 
    770                 775                 780                 


Phe Ser Phe Pro Gly Leu Lys Ser Leu Leu Val Gly Ser Asn Leu Glu 
785                 790                 795                 800 


Leu Asn Ala Glu Val Met Val Trp Asn Asp Gly Glu Asp Ser Tyr Gly 
                805                 810                 815     


Thr Thr Ile Thr Phe Ser His Pro Ala Gly Leu Ser Tyr Arg Tyr Val 
            820                 825                 830         


Ala Glu Gly Gln Lys Gln Gly Gln Leu Arg Ser Leu His Leu Thr Cys 
        835                 840                 845             


Asp Ser Ala Pro Val Gly Ser Gln Gly Thr Trp Ser Thr Ser Cys Arg 
    850                 855                 860                 


Ile Asn His Leu Ile Phe Arg Gly Gly Ala Gln Ile Thr Phe Leu Ala 
865                 870                 875                 880 


Thr Phe Asp Val Ser Pro Lys Ala Val Leu Gly Asp Arg Leu Leu Leu 
                885                 890                 895     


Thr Ala Asn Val Ser Ser Glu Asn Asn Thr Pro Arg Thr Ser Lys Thr 
            900                 905                 910         


Thr Phe Gln Leu Glu Leu Pro Val Lys Tyr Ala Val Tyr Thr Val Val 
        915                 920                 925             


Ser Ser His Glu Gln Phe Thr Lys Tyr Leu Asn Phe Ser Glu Ser Glu 
    930                 935                 940                 


Glu Lys Glu Ser His Val Ala Met His Arg Tyr Gln Val Asn Asn Leu 
945                 950                 955                 960 


Gly Gln Arg Asp Leu Pro Val Ser Ile Asn Phe Trp Val Pro Val Glu 
                965                 970                 975     


Leu Asn Gln Glu Ala Val Trp Met Asp Val Glu Val Ser His Pro Gln 
            980                 985                 990         


Asn Pro Ser Leu Arg Cys Ser Ser  Glu Lys Ile Ala Pro  Pro Ala Ser 
        995                 1000                 1005             


Asp Phe  Leu Ala His Ile Gln  Lys Asn Pro Val Leu  Asp Cys Ser 
    1010                 1015                 1020             


Ile Ala  Gly Cys Leu Arg Phe  Arg Cys Asp Val Pro  Ser Phe Ser 
    1025                 1030                 1035             


Val Gln  Glu Glu Leu Asp Phe  Thr Leu Lys Gly Asn  Leu Ser Phe 
    1040                 1045                 1050             


Gly Trp  Val Arg Gln Ile Leu  Gln Lys Lys Val Ser  Val Val Ser 
    1055                 1060                 1065             


Val Ala  Glu Ile Thr Phe Asp  Thr Ser Val Tyr Ser  Gln Leu Pro 
    1070                 1075                 1080             


Gly Gln  Glu Ala Phe Met Arg  Ala Gln Thr Thr Thr  Val Leu Glu 
    1085                 1090                 1095             


Lys Tyr  Lys Val His Asn Pro  Thr Pro Leu Ile Val  Gly Ser Ser 
    1100                 1105                 1110             


Ile Gly  Gly Leu Leu Leu Leu  Ala Leu Ile Thr Ala  Val Leu Tyr 
    1115                 1120                 1125             


Lys Val  Gly Phe Phe Lys Arg  Gln Tyr Lys Glu Met  Met Glu Glu 
    1130                 1135                 1140             


Ala Asn  Gly Gln Ile Ala Pro  Glu Asn Gly Thr Gln  Thr Pro Ser 
    1145                 1150                 1155             


Pro Pro  Thr Pro His Tyr Pro  Gln Asp Asn Val 
    1160                 1165                 


<210>  4
<211>  1162
<212>  PRT
<213>  Homo sapiens

<400>  4

Met Thr Phe Gly Thr Val Leu Leu Leu Ser Val Leu Ala Ser Tyr His 
1               5                   10                  15      


Gly Phe Asn Leu Asp Val Glu Glu Pro Thr Ile Phe Gln Glu Asp Ala 
            20                  25                  30          


Gly Gly Phe Gly Gln Ser Val Val Gln Phe Gly Gly Ser Arg Leu Val 
        35                  40                  45              


Val Gly Ala Pro Leu Glu Val Val Ala Ala Asn Gln Thr Gly Arg Leu 
    50                  55                  60                  


Tyr Asp Cys Ala Ala Ala Thr Gly Met Cys Gln Pro Ile Pro Leu His 
65                  70                  75                  80  


Ile Arg Pro Glu Ala Val Asn Met Ser Leu Gly Leu Thr Leu Ala Ala 
                85                  90                  95      


Ser Thr Asn Gly Ser Arg Leu Leu Ala Cys Gly Pro Thr Leu His Arg 
            100                 105                 110         


Val Cys Gly Glu Asn Ser Tyr Ser Lys Gly Ser Cys Leu Leu Leu Gly 
        115                 120                 125             


Ser Arg Trp Glu Ile Ile Gln Thr Val Pro Asp Ala Thr Pro Glu Cys 
    130                 135                 140                 


Pro His Gln Glu Met Asp Ile Val Phe Leu Ile Asp Gly Ser Gly Ser 
145                 150                 155                 160 


Ile Asp Gln Asn Asp Phe Asn Gln Met Lys Gly Phe Val Gln Ala Val 
                165                 170                 175     


Met Gly Gln Phe Glu Gly Thr Asp Thr Leu Phe Ala Leu Met Gln Tyr 
            180                 185                 190         


Ser Asn Leu Leu Lys Ile His Phe Thr Phe Thr Gln Phe Arg Thr Ser 
        195                 200                 205             


Pro Ser Gln Gln Ser Leu Val Asp Pro Ile Val Gln Leu Lys Gly Leu 
    210                 215                 220                 


Thr Phe Thr Ala Thr Gly Ile Leu Thr Val Val Thr Gln Leu Phe His 
225                 230                 235                 240 


His Lys Asn Gly Ala Arg Lys Ser Ala Lys Lys Ile Leu Ile Val Ile 
                245                 250                 255     


Thr Asp Gly Gln Lys Tyr Lys Asp Pro Leu Glu Tyr Ser Asp Val Ile 
            260                 265                 270         


Pro Gln Ala Glu Lys Ala Gly Ile Ile Arg Tyr Ala Ile Gly Val Gly 
        275                 280                 285             


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


Ser Ala Pro Pro Gln Asp His Val Phe Lys Val Asp Asn Phe Ala Ala 
305                 310                 315                 320 


Leu Gly Ser Ile Gln Lys Gln Leu Gln Glu Lys Ile Tyr Ala Val Glu 
                325                 330                 335     


Gly Thr Gln Ser Arg Ala Ser Ser Ser Phe Gln His Glu Met Ser Gln 
            340                 345                 350         


Glu Gly Phe Ser Thr Ala Leu Thr Met Asp Gly Leu Phe Leu Gly Ala 
        355                 360                 365             


Val Gly Ser Phe Ser Trp Ser Gly Gly Ala Phe Leu Tyr Pro Pro Asn 
    370                 375                 380                 


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


Asp Ser Tyr Leu Gly Tyr Ser Thr Glu Leu Ala Leu Trp Lys Gly Val 
                405                 410                 415     


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


Val Ile Phe Thr Gln Val Ser Arg Gln Trp Arg Lys Lys Ala Glu Val 
        435                 440                 445             


Thr Gly Thr Gln Ile Gly Ser Tyr Phe Gly Ala Ser Leu Cys Ser Val 
    450                 455                 460                 


Asp Val Asp Ser Asp Gly Ser Thr Asp Leu Ile Leu Ile Gly Ala Pro 
465                 470                 475                 480 


His Tyr Tyr Glu Gln Thr Arg Gly Gly Gln Val Ser Val Cys Pro Leu 
                485                 490                 495     


Pro Arg Gly Gln Arg Val Gln Trp Gln Cys Asp Ala Val Leu Arg Gly 
            500                 505                 510         


Glu Gln Gly His Pro Trp Gly Arg Phe Gly Ala Ala Leu Thr Val Leu 
        515                 520                 525             


Gly Asp Val Asn Glu Asp Lys Leu Ile Asp Val Ala Ile Gly Ala Pro 
    530                 535                 540                 


Gly Glu Gln Glu Asn Arg Gly Ala Val Tyr Leu Phe His Gly Ala Ser 
545                 550                 555                 560 


Glu Ser Gly Ile Ser Pro Ser His Ser Gln Arg Ile Ala Ser Ser Gln 
                565                 570                 575     


Leu Ser Pro Arg Leu Gln Tyr Phe Gly Gln Ala Leu Ser Gly Gly Gln 
            580                 585                 590         


Asp Leu Thr Gln Asp Gly Leu Met Asp Leu Ala Val Gly Ala Arg Gly 
        595                 600                 605             


Gln Val Leu Leu Leu Arg Ser Leu Pro Val Leu Lys Val Gly Val Ala 
    610                 615                 620                 


Met Arg Phe Ser Pro Val Glu Val Ala Lys Ala Val Tyr Arg Cys Trp 
625                 630                 635                 640 


Glu Glu Lys Pro Ser Ala Leu Glu Ala Gly Asp Ala Thr Val Cys Leu 
                645                 650                 655     


Thr Ile Gln Lys Ser Ser Leu Asp Gln Leu Gly Asp Ile Gln Ser Ser 
            660                 665                 670         


Val Arg Phe Asp Leu Ala Leu Asp Pro Gly Arg Leu Thr Ser Arg Ala 
        675                 680                 685             


Ile Phe Asn Glu Thr Lys Asn Pro Thr Leu Thr Arg Arg Lys Thr Leu 
    690                 695                 700                 


Gly Leu Gly Ile His Cys Glu Thr Leu Lys Leu Leu Leu Pro Asp Cys 
705                 710                 715                 720 


Val Glu Asp Val Val Ser Pro Ile Ile Leu His Leu Asn Phe Ser Leu 
                725                 730                 735     


Val Arg Glu Pro Ile Pro Ser Pro Gln Asn Leu Arg Pro Val Leu Ala 
            740                 745                 750         


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


Cys Gly Gln Asp Gly Leu Cys Glu Gly Asp Leu Gly Val Thr Leu Ser 
    770                 775                 780                 


Phe Ser Gly Leu Gln Thr Leu Thr Val Gly Ser Ser Leu Glu Leu Asn 
785                 790                 795                 800 


Val Ile Val Thr Val Trp Asn Ala Gly Glu Asp Ser Tyr Gly Thr Val 
                805                 810                 815     


Val Ser Leu Tyr Tyr Pro Ala Gly Leu Ser His Arg Arg Val Ser Gly 
            820                 825                 830         


Ala Gln Lys Gln Pro His Gln Ser Ala Leu Arg Leu Ala Cys Glu Thr 
        835                 840                 845             


Val Pro Thr Glu Asp Glu Gly Leu Arg Ser Ser Arg Cys Ser Val Asn 
    850                 855                 860                 


His Pro Ile Phe His Glu Gly Ser Asn Gly Thr Phe Ile Val Thr Phe 
865                 870                 875                 880 


Asp Val Ser Tyr Lys Ala Thr Leu Gly Asp Arg Met Leu Met Arg Ala 
                885                 890                 895     


Ser Ala Ser Ser Glu Asn Asn Lys Ala Ser Ser Ser Lys Ala Thr Phe 
            900                 905                 910         


Gln Leu Glu Leu Pro Val Lys Tyr Ala Val Tyr Thr Met Ile Ser Arg 
        915                 920                 925             


Gln Glu Glu Ser Thr Lys Tyr Phe Asn Phe Ala Thr Ser Asp Glu Lys 
    930                 935                 940                 


Lys Met Lys Glu Ala Glu His Arg Tyr Arg Val Asn Asn Leu Ser Gln 
945                 950                 955                 960 


Arg Asp Leu Ala Ile Ser Ile Asn Phe Trp Val Pro Val Leu Leu Asn 
                965                 970                 975     


Gly Val Ala Val Trp Asp Val Val Met Glu Ala Pro Ser Gln Ser Leu 
            980                 985                 990         


Pro Cys Val Ser Glu Arg Lys Pro  Pro Gln His Ser Asp  Phe Leu Thr 
        995                 1000                 1005             


Gln Ile  Ser Arg Ser Pro Met  Leu Asp Cys Ser Ile  Ala Asp Cys 
    1010                 1015                 1020             


Leu Gln  Phe Arg Cys Asp Val  Pro Ser Phe Ser Val  Gln Glu Glu 
    1025                 1030                 1035             


Leu Asp  Phe Thr Leu Lys Gly  Asn Leu Ser Phe Gly  Trp Val Arg 
    1040                 1045                 1050             


Glu Thr  Leu Gln Lys Lys Val  Leu Val Val Ser Val  Ala Glu Ile 
    1055                 1060                 1065             


Thr Phe  Asp Thr Ser Val Tyr  Ser Gln Leu Pro Gly  Gln Glu Ala 
    1070                 1075                 1080             


Phe Met  Arg Ala Gln Met Glu  Met Val Leu Glu Glu  Asp Glu Val 
    1085                 1090                 1095             


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


Leu Leu  Leu Ala Leu Ile Thr  Ala Thr Leu Tyr Lys  Leu Gly Phe 
    1115                 1120                 1125             


Phe Lys  Arg His Tyr Lys Glu  Met Leu Glu Asp Lys  Pro Glu Asp 
    1130                 1135                 1140             


Thr Ala  Thr Phe Ser Gly Asp  Asp Phe Ser Cys Val  Ala Pro Asn 
    1145                 1150                 1155             


Val Pro  Leu Ser 
    1160         


