                         SEQUENCE LISTING

<110>  Shenzhen Genius Biotech Services Co.,Ltd.
 
<120>  A fusion protein as a subunit vaccine immunogen against 
       SARS-CoV-2 and preparation method thereof

<130>  0192-PA-002

<150>  CN2020109830249
<151>  2020-09-17

<150>  PCT/CN2020111907
<151>  2020-08-27

<160>  10    

<170>  PatentIn version 3.5

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

<220>
<223>  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 
    1010                 1015                 1020             


Leu Ala  Ala Thr Lys Met Ser  Glu Cys Val Leu Gly  Gln Ser Lys 
    1025                 1030                 1035             


Arg Val  Asp Phe Cys Gly Lys  Gly Tyr His Leu Met  Ser Phe Pro 
    1040                 1045                 1050             


Gln Ser  Ala Pro His Gly Val  Val Phe Leu His Val  Thr Tyr Val 
    1055                 1060                 1065             


Pro Ala  Gln Glu Lys Asn Phe  Thr Thr Ala Pro Ala  Ile Cys His 
    1070                 1075                 1080             


Asp Gly  Lys Ala His Phe Pro  Arg Glu Gly Val Phe  Val Ser Asn 
    1085                 1090                 1095             


Gly Thr  His Trp Phe Val Thr  Gln Arg Asn Phe Tyr  Glu Pro Gln 
    1100                 1105                 1110             


Ile Ile  Thr Thr Asp Asn Thr  Phe Val Ser Gly Asn  Cys Asp Val 
    1115                 1120                 1125             


Val Ile  Gly Ile Val Asn Asn  Thr Val Tyr Asp Pro  Leu Gln Pro 
    1130                 1135                 1140             


Glu Leu  Asp Ser Phe Lys Glu  Glu Leu Asp Lys Tyr  Phe Lys Asn 
    1145                 1150                 1155             


His Thr  Ser Pro Asp Val Asp  Leu Gly Asp Ile Ser  Gly Ile Asn 
    1160                 1165                 1170             


Ala Ser  Val Val Asn Ile Gln  Lys Glu Ile Asp Arg  Leu Asn Glu 
    1175                 1180                 1185             


Val Ala  Lys Asn Leu Asn Glu  Ser Leu Ile Asp Leu  Gln Glu Leu 
    1190                 1195                 1200             


Gly Lys  Tyr Glu Gln Tyr Ile  Lys Trp Pro Trp Tyr  Ile Trp Leu 
    1205                 1210                 1215             


Gly Phe  Ile Ala Gly Leu Ile  Ala Ile Val Met Val  Thr Ile Met 
    1220                 1225                 1230             


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 
    1250                 1255                 1260             


Val Leu  Lys Gly Val Lys Leu  His Tyr Thr 
    1265                 1270             


<210>  2
<211>  258
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  S1-4

<400>  2

Met Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro 
1               5                   10                  15      


Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe 
            20                  25                  30          


Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn 
        35                  40                  45              


Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn 
    50                  55                  60                  


Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys 
65                  70                  75                  80  


Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile 
                85                  90                  95      


Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile 
            100                 105                 110         


Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile 
        115                 120                 125             


Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn 
    130                 135                 140                 


Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg 
145                 150                 155                 160 


Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly 
                165                 170                 175     


Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln 
            180                 185                 190         


Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser 
        195                 200                 205             


Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser 
    210                 215                 220                 


Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu 
225                 230                 235                 240 


Thr Gly Gly Gly Gln Tyr Ile Lys Ala Asn Ser Lys Phe Ile Gly Ile 
                245                 250                 255     


Phe Glu 
        


<210>  3
<211>  241
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  S1-5

<400>  3

Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr 
1               5                   10                  15      


Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly 
            20                  25                  30          


Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg 
        35                  40                  45              


Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser 
    50                  55                  60                  


Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu 
65                  70                  75                  80  


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


Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala 
            100                 105                 110         


Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala 
        115                 120                 125             


Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr 
    130                 135                 140                 


Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 
145                 150                 155                 160 


Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val 
                165                 170                 175     


Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro 
            180                 185                 190         


Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe 
        195                 200                 205             


Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr 
    210                 215                 220                 


Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr 
225                 230                 235                 240 


Gly 
    


<210>  4
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Gln830CGlu843 of TT peptide

<400>  4

Gln Tyr Ile Lys Ala Asn Ser Lys Phe Ile Gly Ile Phe Glu 
1               5                   10                  


<210>  5
<211>  777
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  S1-4 

<400>  5
atggttgaga aaggtatcta ccagacctct aacttccgtg ttcagccgac cgaatctatc       60

gttcgtttcc cgaacatcac caacctgtgc ccgttcggtg aagtgttcaa cgctacccgt      120

ttcgcttctg tttacgcttg gaaccgtaaa cgtatctcta actgcgttgc tgactactct      180

gttctgtaca actctgctag cttctctacc ttcaaatgct acggtgttag tccgaccaaa      240

ctgaacgacc tgtgcttcac caacgtttac gctgacagct tcgttatccg tggtgacgaa      300

gttcgtcaga tcgctccggg tcagaccggt aagatcgctg actacaacta caaactgccg      360

gacgacttca ccggttgcgt tatcgcttgg aactctaata acctggactc taaagttggt      420

ggtaactaca actacctgta ccgtctgttc cgtaaatcta acctgaaacc gttcgaacgt      480

gacatctcta ccgaaatcta ccaggctggt tctactccgt gcaacggtgt tgaaggtttc      540

aactgctact tcccgctgca gtcttacggt ttccagccga ccaacggtgt tggttaccag      600

ccgtaccgtg ttgtggttct gagctttgaa ctgctgcacg ctccggctac tgtttgcggt      660

ccgaagaaat ctaccaacct ggttaagaac aaatgcgtta acttcaactt caacggtctg      720

actggtggcg gtcagtacat caaagctaac tctaaattca tcggtatctt cgaataa         777


<210>  6
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker

<400>  6

Gly Gly Gly Gly 
1               


<210>  7
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  LINKER

<400>  7

Gly Gly Gly Gly Ser 
1               5   


<210>  8
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker

<400>  8

Gly Gly Ser Ser 
1               


<210>  9
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker

<400>  9

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
1               5                   10                  15  


<210>  10
<211>  1315
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  tetanus toxoid

<400>  10

Met Pro Ile Thr Ile Asn Asn Phe Arg Tyr Ser Asp Pro Val Asn Asn 
1               5                   10                  15      


Asp Thr Ile Ile Met Met Glu Pro Pro Tyr Cys Lys Gly Leu Asp Ile 
            20                  25                  30          


Tyr Tyr Lys Ala Phe Lys Ile Thr Asp Arg Ile Trp Ile Val Pro Glu 
        35                  40                  45              


Arg Tyr Glu Phe Gly Thr Lys Pro Glu Asp Phe Asn Pro Pro Ser Ser 
    50                  55                  60                  


Leu Ile Glu Gly Ala Ser Glu Tyr Tyr Asp Pro Asn Tyr Leu Arg Thr 
65                  70                  75                  80  


Asp Ser Asp Lys Asp Arg Phe Leu Gln Thr Met Val Lys Leu Phe Asn 
                85                  90                  95      


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


Asn Ala Ile Pro Tyr Leu Gly Asn Ser Tyr Ser Leu Leu Asp Lys Phe 
        115                 120                 125             


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


Ser Gly Ala Thr Thr Lys Ser Ala Met Leu Thr Asn Leu Ile Ile Phe 
145                 150                 155                 160 


Gly Pro Gly Pro Val Leu Asn Lys Asn Glu Val Arg Gly Ile Val Leu 
                165                 170                 175     


Arg Val Asp Asn Lys Asn Tyr Phe Pro Cys Arg Asp Gly Phe Gly Ser 
            180                 185                 190         


Ile Met Gln Met Ala Phe Cys Pro Glu Tyr Val Pro Thr Phe Asp Asn 
        195                 200                 205             


Val Ile Glu Asn Ile Thr Ser Leu Thr Ile Gly Lys Ser Lys Tyr Phe 
    210                 215                 220                 


Gln Asp Pro Ala Leu Leu Leu Met His Glu Leu Ile His Val Leu His 
225                 230                 235                 240 


Gly Leu Tyr Gly Met Gln Val Ser Ser His Glu Ile Ile Pro Ser Lys 
                245                 250                 255     


Gln Glu Ile Tyr Met Gln His Thr Tyr Pro Ile Ser Ala Glu Glu Leu 
            260                 265                 270         


Phe Thr Phe Gly Gly Gln Asp Ala Asn Leu Ile Ser Ile Asp Ile Lys 
        275                 280                 285             


Asn Asp Leu Tyr Glu Lys Thr Leu Asn Asp Tyr Lys Ala Ile Ala Asn 
    290                 295                 300                 


Lys Leu Ser Gln Val Thr Ser Cys Asn Asp Pro Asn Ile Asp Ile Asp 
305                 310                 315                 320 


Ser Tyr Lys Gln Ile Tyr Gln Gln Lys Tyr Gln Phe Asp Lys Asp Ser 
                325                 330                 335     


Asn Gly Gln Tyr Ile Val Asn Glu Asp Lys Phe Gln Ile Leu Tyr Asn 
            340                 345                 350         


Ser Ile Met Tyr Gly Phe Thr Glu Ile Glu Leu Gly Lys Lys Phe Asn 
        355                 360                 365             


Ile Lys Thr Arg Leu Ser Tyr Phe Ser Met Asn His Asp Pro Val Lys 
    370                 375                 380                 


Ile Pro Asn Leu Leu Asp Asp Thr Ile Tyr Asn Asp Thr Glu Gly Phe 
385                 390                 395                 400 


Asn Ile Glu Ser Lys Asp Leu Lys Ser Glu Tyr Lys Gly Gln Asn Met 
                405                 410                 415     


Arg Val Asn Thr Asn Ala Phe Arg Asn Val Asp Gly Ser Gly Leu Val 
            420                 425                 430         


Ser Lys Leu Ile Gly Leu Cys Lys Lys Ile Ile Pro Pro Thr Asn Ile 
        435                 440                 445             


Arg Glu Asn Leu Tyr Asn Arg Thr Ala Ser Leu Thr Asp Leu Gly Gly 
    450                 455                 460                 


Glu Leu Cys Ile Lys Ile Lys Asn Glu Asp Leu Thr Phe Ile Ala Glu 
465                 470                 475                 480 


Lys Asn Ser Phe Ser Glu Glu Pro Phe Gln Asp Glu Ile Val Ser Tyr 
                485                 490                 495     


Asn Thr Lys Asn Lys Pro Leu Asn Phe Asn Tyr Ser Leu Asp Lys Ile 
            500                 505                 510         


Ile Val Asp Tyr Asn Leu Gln Ser Lys Ile Thr Leu Pro Asn Asp Arg 
        515                 520                 525             


Thr Thr Pro Val Thr Lys Gly Ile Pro Tyr Ala Pro Glu Tyr Lys Ser 
    530                 535                 540                 


Asn Ala Ala Ser Thr Ile Glu Ile His Asn Ile Asp Asp Asn Thr Ile 
545                 550                 555                 560 


Tyr Gln Tyr Leu Tyr Ala Gln Lys Ser Pro Thr Thr Leu Gln Arg Ile 
                565                 570                 575     


Thr Met Thr Asn Ser Val Asp Asp Ala Leu Ile Asn Ser Thr Lys Ile 
            580                 585                 590         


Tyr Ser Tyr Phe Pro Ser Val Ile Ser Lys Val Asn Gln Gly Ala Gln 
        595                 600                 605             


Gly Ile Leu Phe Leu Gln Trp Val Arg Asp Ile Ile Asp Asp Phe Thr 
    610                 615                 620                 


Asn Glu Ser Ser Gln Lys Thr Thr Ile Asp Lys Ile Ser Asp Val Ser 
625                 630                 635                 640 


Thr Ile Val Pro Tyr Ile Gly Pro Ala Leu Asn Ile Val Lys Gln Gly 
                645                 650                 655     


Tyr Glu Gly Asn Phe Ile Gly Ala Leu Glu Thr Thr Gly Val Val Leu 
            660                 665                 670         


Leu Leu Glu Tyr Ile Pro Glu Ile Thr Leu Pro Val Ile Ala Ala Leu 
        675                 680                 685             


Ser Ile Ala Glu Ser Ser Thr Gln Lys Glu Lys Ile Ile Lys Thr Ile 
    690                 695                 700                 


Asp Asn Phe Leu Glu Lys Arg Tyr Glu Lys Trp Ile Glu Val Tyr Lys 
705                 710                 715                 720 


Leu Val Lys Ala Lys Trp Leu Gly Thr Val Asn Thr Gln Phe Gln Lys 
                725                 730                 735     


Arg Ser Tyr Gln Met Tyr Arg Ser Leu Glu Tyr Gln Val Asp Ala Ile 
            740                 745                 750         


Lys Lys Ile Ile Asp Tyr Glu Tyr Lys Ile Tyr Ser Gly Pro Asp Lys 
        755                 760                 765             


Glu Gln Ile Ala Asp Glu Ile Asn Asn Leu Lys Asn Lys Leu Glu Glu 
    770                 775                 780                 


Lys Ala Asn Lys Ala Met Ile Asn Ile Asn Ile Phe Met Arg Glu Ser 
785                 790                 795                 800 


Ser Arg Ser Phe Leu Val Asn Gln Met Ile Asn Glu Ala Lys Lys Gln 
                805                 810                 815     


Leu Leu Glu Phe Asp Thr Gln Ser Lys Asn Ile Leu Met Gln Tyr Ile 
            820                 825                 830         


Lys Ala Asn Ser Lys Phe Ile Gly Ile Thr Glu Leu Lys Lys Leu Glu 
        835                 840                 845             


Ser Lys Ile Asn Lys Val Phe Ser Thr Pro Ile Pro Phe Ser Tyr Ser 
    850                 855                 860                 


Lys Asn Leu Asp Cys Trp Val Asp Asn Glu Glu Asp Ile Asp Val Ile 
865                 870                 875                 880 


Leu Lys Lys Ser Thr Ile Leu Asn Leu Asp Ile Asn Asn Asp Ile Ile 
                885                 890                 895     


Ser Asp Ile Ser Gly Phe Asn Ser Ser Val Ile Thr Tyr Pro Asp Ala 
            900                 905                 910         


Gln Leu Val Pro Gly Ile Asn Gly Lys Ala Ile His Leu Val Asn Asn 
        915                 920                 925             


Glu Ser Ser Glu Val Ile Val His Lys Ala Met Asp Ile Glu Tyr Asn 
    930                 935                 940                 


Asp Met Phe Asn Asn Phe Thr Val Ser Phe Trp Leu Arg Val Pro Lys 
945                 950                 955                 960 


Val Ser Ala Ser His Leu Glu Gln Tyr Gly Thr Asn Glu Tyr Ser Ile 
                965                 970                 975     


Ile Ser Ser Met Lys Lys His Ser Leu Ser Ile Gly Ser Gly Trp Ser 
            980                 985                 990         


Val Ser Leu Lys Gly Asn Asn Leu  Ile Trp Thr Leu Lys  Asp Ser Ala 
        995                 1000                 1005             


Gly Glu  Val Arg Gln Ile Thr  Phe Arg Asp Leu Pro  Asp Lys Phe 
    1010                 1015                 1020             


Asn Ala  Tyr Leu Ala Asn Lys  Trp Val Phe Ile Thr  Ile Thr Asn 
    1025                 1030                 1035             


Asp Arg  Leu Ser Ser Ala Asn  Leu Tyr Ile Asn Gly  Val Leu Met 
    1040                 1045                 1050             


Gly Ser  Ala Glu Ile Thr Gly  Leu Gly Ala Ile Arg  Glu Asp Asn 
    1055                 1060                 1065             


Asn Ile  Thr Leu Lys Leu Asp  Arg Cys Asn Asn Asn  Asn Gln Tyr 
    1070                 1075                 1080             


Val Ser  Ile Asp Lys Phe Arg  Ile Phe Cys Lys Ala  Leu Asn Pro 
    1085                 1090                 1095             


Lys Glu  Ile Glu Lys Leu Tyr  Thr Ser Tyr Leu Ser  Ile Thr Phe 
    1100                 1105                 1110             


Leu Arg  Asp Phe Trp Gly Asn  Pro Leu Arg Tyr Asp  Thr Glu Tyr 
    1115                 1120                 1125             


Tyr Leu  Ile Pro Val Ala Ser  Ser Ser Lys Asp Val  Gln Leu Lys 
    1130                 1135                 1140             


Asn Ile  Thr Asp Tyr Met Tyr  Leu Thr Asn Ala Pro  Ser Tyr Thr 
    1145                 1150                 1155             


Asn Gly  Lys Leu Asn Ile Tyr  Tyr Arg Arg Leu Tyr  Asn Gly Leu 
    1160                 1165                 1170             


Lys Phe  Ile Ile Lys Arg Tyr  Thr Pro Asn Asn Glu  Ile Asp Ser 
    1175                 1180                 1185             


Phe Val  Lys Ser Gly Asp Phe  Ile Lys Leu Tyr Val  Ser Tyr Asn 
    1190                 1195                 1200             


Asn Asn  Glu His Ile Val Gly  Tyr Pro Lys Asp Gly  Asn Ala Phe 
    1205                 1210                 1215             


Asn Asn  Leu Asp Arg Ile Leu  Arg Val Gly Tyr Asn  Ala Pro Gly 
    1220                 1225                 1230             


Ile Pro  Leu Tyr Lys Lys Met  Glu Ala Val Lys Leu  Arg Asp Leu 
    1235                 1240                 1245             


Lys Thr  Tyr Ser Val Gln Leu  Lys Leu Tyr Asp Asp  Lys Asn Ala 
    1250                 1255                 1260             


Ser Leu  Gly Leu Val Gly Thr  His Asn Gly Gln Ile  Gly Asn Asp 
    1265                 1270                 1275             


Pro Asn  Arg Asp Ile Leu Ile  Ala Ser Asn Trp Tyr  Phe Asn His 
    1280                 1285                 1290             


Leu Lys  Asp Lys Ile Leu Gly  Cys Asp Trp Tyr Phe  Val Pro Thr 
    1295                 1300                 1305             


Asp Glu  Gly Trp Thr Asn Asp  
    1310                 1315 


