﻿               SEQUENCE LISTING

<110> Friedrich-Alexander-Universität Erlangen-Nürnberg
      Graduiertenkolleg GK 1660

<120> A surrogate cell-based SARS-CoV-2 spike blocking assay (SUBA)

<130> PCT134653-FZGS

<140> PCT-not yet assigned
<141> herewith

<150> EP21188288.1
<151> 2021-07-28

<160> 5

<170> BiSSAP 1.3.6

<210> 1
<211> 1273
<212> PRT
<213> Artificial Sequence


<220> 
<223> Complete spike protein

<400> 1
Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 
1               5                   10                  15      
Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe 
            20                  25                  30          
Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 
        35                  40                  45              
His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 
    50                  55                  60                  
Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp 
65                  70                  75                  80  
Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 
                85                  90                  95      
Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 
            100                 105                 110         
Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 
        115                 120                 125             
Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr 
    130                 135                 140                 
Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr 
145                 150                 155                 160 
Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 
                165                 170                 175     
Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe 
            180                 185                 190         
Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 
        195                 200                 205             
Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu 
    210                 215                 220                 
Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 
225                 230                 235                 240 
Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 
                245                 250                 255     
Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 
            260                 265                 270         
Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 
        275                 280                 285             
Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 
    290                 295                 300                 
Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 
305                 310                 315                 320 
Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 
                325                 330                 335     
Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 
            340                 345                 350         
Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 
        355                 360                 365             
Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 
    370                 375                 380                 
Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 
385                 390                 395                 400 
Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 
                405                 410                 415     
Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 
            420                 425                 430         
Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 
        435                 440                 445             
Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 
    450                 455                 460                 
Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys 
465                 470                 475                 480 
Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 
                485                 490                 495     
Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 
            500                 505                 510         
Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 
        515                 520                 525             
Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 
    530                 535                 540                 
Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 
545                 550                 555                 560 
Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val 
                565                 570                 575     
Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 
            580                 585                 590         
Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 
        595                 600                 605             
Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile 
    610                 615                 620                 
His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 
625                 630                 635                 640 
Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val 
                645                 650                 655     
Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 
            660                 665                 670         
Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala 
        675                 680                 685             
Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser 
    690                 695                 700                 
Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile 
705                 710                 715                 720 
Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 
                725                 730                 735     
Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 
            740                 745                 750         
Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 
        755                 760                 765             
Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 
    770                 775                 780                 
Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 
785                 790                 795                 800 
Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 
                805                 810                 815     
Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 
            820                 825                 830         
Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 
        835                 840                 845             
Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 
    850                 855                 860                 
Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 
865                 870                 875                 880 
Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 
                885                 890                 895     
Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 
            900                 905                 910         
Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 
        915                 920                 925             
Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 
    930                 935                 940                 
Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn 
945                 950                 955                 960 
Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 
                965                 970                 975     
Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln 
            980                 985                 990         
Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 
        995                 1000                1005            
Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu 
    1010                1015                1020                
Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val 
1025                1030                1035                1040
Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala 
                1045                1050                1055    
Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu 
            1060                1065                1070        
Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His 
        1075                1080                1085            
Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val 
    1090                1095                1100                
Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr 
1105                1110                1115                1120
Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr 
                1125                1130                1135    
Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu 
            1140                1145                1150        
Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp 
        1155                1160                1165            
Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp 
    1170                1175                1180                
Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu 
1185                1190                1195                1200
Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile 
                1205                1210                1215    
Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile 
            1220                1225                1230        
Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 
        1235                1240                1245            
Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val 
    1250                1255                1260                
Leu Lys Gly Val Lys Leu His Tyr Thr 
1265                1270            

<210> 2
<211> 673
<212> PRT
<213> Artificial Sequence


<220> 
<223> Spike S1

<400> 2
Ser Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr 
1               5                   10                  15      
Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg 
            20                  25                  30          
Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser 
        35                  40                  45              
Asn Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr 
    50                  55                  60                  
Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe 
65                  70                  75                  80  
Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr 
                85                  90                  95      
Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr 
            100                 105                 110         
Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe 
        115                 120                 125             
Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu 
    130                 135                 140                 
Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser 
145                 150                 155                 160 
Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn 
                165                 170                 175     
Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr 
            180                 185                 190         
Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe 
        195                 200                 205             
Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr 
    210                 215                 220                 
Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly 
225                 230                 235                 240 
Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly 
                245                 250                 255     
Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr 
            260                 265                 270         
Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys 
        275                 280                 285             
Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser 
    290                 295                 300                 
Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile 
305                 310                 315                 320 
Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala 
                325                 330                 335     
Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp 
            340                 345                 350         
Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr 
        355                 360                 365             
Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr 
    370                 375                 380                 
Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro 
385                 390                 395                 400 
Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp 
                405                 410                 415     
Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys 
            420                 425                 430         
Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn 
        435                 440                 445             
Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly 
    450                 455                 460                 
Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu 
465                 470                 475                 480 
Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr 
                485                 490                 495     
Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val 
            500                 505                 510         
Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn 
        515                 520                 525             
Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn 
    530                 535                 540                 
Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr 
545                 550                 555                 560 
Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr 
                565                 570                 575     
Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr 
            580                 585                 590         
Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val 
        595                 600                 605             
Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr 
    610                 615                 620                 
Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly 
625                 630                 635                 640 
Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala 
                645                 650                 655     
Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala 
            660                 665                 670         
Arg 
    

<210> 3
<211> 588
<212> PRT
<213> Artificial Sequence


<220> 
<223> Spike S2

<400> 3
Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala 
1               5                   10                  15      
Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn 
            20                  25                  30          
Phe Thr Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys 
        35                  40                  45              
Thr Ser Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys 
    50                  55                  60                  
Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg 
65                  70                  75                  80  
Ala Leu Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val 
                85                  90                  95      
Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe 
            100                 105                 110         
Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser 
        115                 120                 125             
Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala 
    130                 135                 140                 
Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala 
145                 150                 155                 160 
Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu 
                165                 170                 175     
Pro Pro Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu 
            180                 185                 190         
Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala 
        195                 200                 205             
Leu Gln Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile 
    210                 215                 220                 
Gly Val Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn 
225                 230                 235                 240 
Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr 
                245                 250                 255     
Ala Ser Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln 
            260                 265                 270         
Ala Leu Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile 
        275                 280                 285             
Ser Ser Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala 
    290                 295                 300                 
Glu Val Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln 
305                 310                 315                 320 
Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser 
                325                 330                 335     
Ala Asn Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser 
            340                 345                 350         
Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro 
        355                 360                 365             
Gln Ser Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro 
    370                 375                 380                 
Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly 
385                 390                 395                 400 
Lys Ala His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His 
                405                 410                 415     
Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr 
            420                 425                 430         
Asp Asn Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val 
        435                 440                 445             
Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys 
    450                 455                 460                 
Glu Glu Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp 
465                 470                 475                 480 
Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys 
                485                 490                 495     
Glu Ile Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu 
            500                 505                 510         
Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro 
        515                 520                 525             
Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met 
    530                 535                 540                 
Val Thr Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys 
545                 550                 555                 560 
Gly Cys Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser 
                565                 570                 575     
Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr 
            580                 585             

<210> 4
<211> 231
<212> PRT
<213> Artificial Sequence


<220> 
<223> Spike S1 receptor binding domain (RBD)

<400> 4
Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu 
1               5                   10                  15      
Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr 
            20                  25                  30          
Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val 
        35                  40                  45              
Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser 
    50                  55                  60                  
Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser 
65                  70                  75                  80  
Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr 
                85                  90                  95      
Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly 
            100                 105                 110         
Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly 
        115                 120                 125             
Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro 
    130                 135                 140                 
Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro 
145                 150                 155                 160 
Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr 
                165                 170                 175     
Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val 
            180                 185                 190         
Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro 
        195                 200                 205             
Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe 
    210                 215                 220                 
Asn Gly Leu Thr Gly Thr Gly 
225                 230     

<210> 5
<211> 1273
<212> PRT
<213> Artificial Sequence


<220> 
<223> 100 % Consensus

<220> 
<221> VARIANT
<222> 18..18
<223> Xaa is histidine, leucine, phenylalanine or isoleucine

<220> 
<221> VARIANT
<222> 19..19
<223> Xaa is proline, threonine or arginine

<220> 
<221> VARIANT
<222> 20..20
<223> Xaa is serine, threonine or asparagine

<220> 
<221> VARIANT
<222> 26..26
<223> Xaa is serine or proline

<220> 
<221> VARIANT
<222> 69..69
<223> Xaa is histine or absent

<220> 
<221> VARIANT
<222> 70..70
<223> Xaa is valine or absent

<220> 
<221> VARIANT
<222> 80..80
<223> Xaa is serine, aspartate or alanine

<220> 
<221> VARIANT
<222> 138..138
<223> Xaa is aspartate or tyrosine

<220> 
<221> VARIANT
<222> 142..142
<223> Xaa is serine, glycine or aspartate

<220> 
<221> VARIANT
<222> 145..145
<223> Xaa is absent or tyrosine

<220> 
<221> VARIANT
<222> 156..156
<223> Xaa is absent or glutamate

<220> 
<221> VARIANT
<222> 157..157
<223> Xaa is absent or phenylalanine

<220> 
<221> VARIANT
<222> 158..158
<223> Xaa is threonine, arginine or glycine

<220> 
<221> VARIANT
<222> 190..190
<223> Xaa is proline, arginine or serine

<220> 
<221> VARIANT
<222> 215..215
<223> Xaa is serine, aspartate or glycine

<220> 
<221> VARIANT
<222> 241..241
<223> Xaa is absent, leucine or isoleucine

<220> 
<221> VARIANT
<222> 242..242
<223> Xaa is absent, leucine or isoleucine

<220> 
<221> VARIANT
<222> 243..243
<223> Xaa is absent or alanine

<220> 
<221> VARIANT
<222> 417..417
<223> Xaa is proline, lysine, threonine or asparagine

<220> 
<221> VARIANT
<222> 452..452
<223> Xaa is histidine, leucine, arginine or isoleucine

<220> 
<221> VARIANT
<222> 478..478
<223> Xaa is proline, threonine or lysine

<220> 
<221> VARIANT
<222> 484..484
<223> Xaa is cysteine, glutamate or lysine

<220> 
<221> VARIANT
<222> 501..501
<223> Xaa is absent, tyrosine or asparagine

<220> 
<221> VARIANT
<222> 570..570
<223> Xaa is serine, aspartate or alanine

<220> 
<221> VARIANT
<222> 614..614
<223> Xaa is serine, glycine or aspartate

<220> 
<221> VARIANT
<222> 655..655
<223> Xaa is alanine, histidine or tyrosine

<220> 
<221> VARIANT
<222> 681..681
<223> Xaa is absent, histidine, proline or arginine

<220> 
<221> VARIANT
<222> 701..701
<223> Xaa is serine, alanine or valine

<220> 
<221> VARIANT
<222> 716..716
<223> Xaa is histidine, isoleucine or threonine

<220> 
<221> VARIANT
<222> 950..950
<223> Xaa is serine, aspartate or asparagine

<220> 
<221> VARIANT
<222> 982..982
<223> Xaa is selenocysteine, alanine or serine

<220> 
<221> VARIANT
<222> 1027..1027
<223> Xaa is histidine, threonine or isoleucine

<220> 
<221> VARIANT
<222> 1118..1118
<223> Xaa is cysteine, histidine or aspartate

<220> 
<221> VARIANT
<222> 1176..1176
<223> Xaa is histidine, valine or phenylalanine

<400> 5
Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val 
1               5                   10                  15      
Asn Xaa Xaa Xaa Arg Thr Gln Leu Pro Xaa Ala Tyr Thr Asn Ser Phe 
            20                  25                  30          
Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu 
        35                  40                  45              
His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp 
    50                  55                  60                  
Phe His Ala Ile Xaa Xaa Ser Gly Thr Asn Gly Thr Lys Arg Phe Xaa 
65                  70                  75                  80  
Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu 
                85                  90                  95      
Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser 
            100                 105                 110         
Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile 
        115                 120                 125             
Lys Val Cys Glu Phe Gln Phe Cys Asn Xaa Pro Phe Leu Xaa Val Tyr 
    130                 135                 140                 
Xaa His Lys Asn Asn Lys Ser Trp Met Glu Ser Xaa Xaa Xaa Val Tyr 
145                 150                 155                 160 
Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu 
                165                 170                 175     
Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Xaa Glu Phe 
            180                 185                 190         
Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr 
        195                 200                 205             
Pro Ile Asn Leu Val Arg Xaa Leu Pro Gln Gly Phe Ser Ala Leu Glu 
    210                 215                 220                 
Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr 
225                 230                 235                 240 
Xaa Xaa Xaa Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser 
                245                 250                 255     
Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro 
            260                 265                 270         
Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala 
        275                 280                 285             
Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys 
    290                 295                 300                 
Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val 
305                 310                 315                 320 
Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys 
                325                 330                 335     
Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala 
            340                 345                 350         
Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu 
        355                 360                 365             
Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro 
    370                 375                 380                 
Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe 
385                 390                 395                 400 
Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly 
                405                 410                 415     
Xaa Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys 
            420                 425                 430         
Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn 
        435                 440                 445             
Tyr Asn Tyr Xaa Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe 
    450                 455                 460                 
Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Xaa Pro Cys 
465                 470                 475                 480 
Asn Gly Val Xaa Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly 
                485                 490                 495     
Phe Gln Pro Thr Xaa Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val 
            500                 505                 510         
Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys 
        515                 520                 525             
Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn 
    530                 535                 540                 
Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu 
545                 550                 555                 560 
Pro Phe Gln Gln Phe Gly Arg Asp Ile Xaa Asp Thr Thr Asp Ala Val 
                565                 570                 575     
Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe 
            580                 585                 590         
Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val 
        595                 600                 605             
Ala Val Leu Tyr Gln Xaa Val Asn Cys Thr Glu Val Pro Val Ala Ile 
    610                 615                 620                 
His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser 
625                 630                 635                 640 
Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu Xaa Val 
                645                 650                 655     
Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala 
            660                 665                 670         
Ser Tyr Gln Thr Gln Thr Asn Ser Xaa Arg Arg Ala Arg Ser Val Ala 
        675                 680                 685             
Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Xaa Glu Asn Ser 
    690                 695                 700                 
Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Xaa Asn Phe Thr Ile 
705                 710                 715                 720 
Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val 
                725                 730                 735     
Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu 
            740                 745                 750         
Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr 
        755                 760                 765             
Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln 
    770                 775                 780                 
Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe 
785                 790                 795                 800 
Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser 
                805                 810                 815     
Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly 
            820                 825                 830         
Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp 
        835                 840                 845             
Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu 
    850                 855                 860                 
Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly 
865                 870                 875                 880 
Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile 
                885                 890                 895     
Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr 
            900                 905                 910         
Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn 
        915                 920                 925             
Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala 
    930                 935                 940                 
Leu Gly Lys Leu Gln Xaa Val Val Asn Gln Asn Ala Gln Ala Leu Asn 
945                 950                 955                 960 
Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val 
                965                 970                 975     
Leu Asn Asp Ile Leu Xaa Arg Leu Asp Lys Val Glu Ala Glu Val Gln 
            980                 985                 990         
Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val 
        995                 1000                1005            
Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu 
    1010                1015                1020                
Ala Ala Xaa Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val 
1025                1030                1035                1040
Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala 
                1045                1050                1055    
Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu 
            1060                1065                1070        
Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His 
        1075                1080                1085            
Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val 
    1090                1095                1100                
Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Xaa Asn Thr 
1105                1110                1115                1120
Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr 
                1125                1130                1135    
Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu 
            1140                1145                1150        
Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp 
        1155                1160                1165            
Ile Ser Gly Ile Asn Ala Ser Xaa Val Asn Ile Gln Lys Glu Ile Asp 
    1170                1175                1180                
Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu 
1185                1190                1195                1200
Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile 
                1205                1210                1215    
Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile 
            1220                1225                1230        
Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys 
        1235                1240                1245            
Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val 
    1250                1255                1260                
Leu Lys Gly Val Lys Leu His Tyr Thr 
1265                1270            

