                         SEQUENCE LISTING

<110>  RiboxX GmbH
 
<120>  Method for exponential amplification of RNA using thermostable 
       RNA-dependent RNA polymerase

<130>  R 0055 WO

<150>  EP 09173697.5
<151>  2009-10-21

<150>  EP 09175558.7
<151>  2009-11-10

<160>  6     

<170>  PatentIn version 3.3

<210>  1
<211>  517
<212>  PRT
<213>  Sapovirus

<400>  1

Met Lys Asp Glu Phe Gln Trp Lys Gly Leu Pro Val Val Lys Ser Gly 
1               5                   10                  15      


Leu Asp Val Gly Gly Met Pro Thr Gly Thr Arg Tyr His Arg Ser Pro 
            20                  25                  30          


Ala Trp Pro Glu Glu Gln Pro Gly Glu Thr His Ala Pro Ala Pro Phe 
        35                  40                  45              


Gly Ala Gly Asp Lys Arg Tyr Thr Phe Ser Gln Thr Glu Met Leu Val 
    50                  55                  60                  


Asn Gly Leu Lys Pro Tyr Thr Glu Pro Thr Ala Gly Val Pro Pro Gln 
65                  70                  75                  80  


Leu Leu Ser Arg Ala Val Thr His Val Arg Ser Tyr Ile Glu Thr Ile 
                85                  90                  95      


Ile Gly Thr His Arg Ser Pro Val Leu Thr Tyr His Gln Ala Cys Glu 
            100                 105                 110         


Leu Leu Glu Arg Thr Thr Ser Cys Gly Pro Phe Val Gln Gly Leu Lys 
        115                 120                 125             


Gly Asp Tyr Trp Asp Glu Glu Gln Gln Gln Tyr Thr Gly Val Leu Ala 
    130                 135                 140                 


Asn His Leu Glu Gln Ala Trp Asp Lys Ala Asn Lys Gly Ile Ala Pro 
145                 150                 155                 160 


Arg Asn Ala Tyr Lys Leu Ala Leu Lys Asp Glu Leu Arg Pro Ile Glu 
                165                 170                 175     


Lys Asn Lys Ala Gly Lys Arg Arg Leu Leu Trp Gly Cys Asp Ala Ala 
            180                 185                 190         


Thr Thr Leu Ile Ala Thr Ala Ala Phe Lys Ala Val Ala Thr Arg Leu 
        195                 200                 205             


Gln Val Val Thr Pro Met Thr Pro Val Ala Val Gly Ile Asn Met Asp 
    210                 215                 220                 


Ser Val Gln Met Gln Val Met Asn Asp Ser Leu Lys Gly Gly Val Leu 
225                 230                 235                 240 


Tyr Cys Leu Asp Tyr Ser Lys Trp Asp Ser Thr Gln Asn Pro Ala Val 
                245                 250                 255     


Thr Ala Ala Ser Leu Ala Ile Leu Glu Arg Phe Ala Glu Pro His Pro 
            260                 265                 270         


Ile Val Ser Cys Ala Ile Glu Ala Leu Ser Ser Pro Ala Glu Gly Tyr 
        275                 280                 285             


Val Asn Asp Ile Lys Phe Val Thr Arg Gly Gly Leu Pro Ser Gly Met 
    290                 295                 300                 


Pro Phe Thr Ser Val Val Asn Ser Ile Asn His Met Ile Tyr Val Ala 
305                 310                 315                 320 


Ala Ala Ile Leu Gln Ala Tyr Glu Ser His Asn Val Pro Tyr Thr Gly 
                325                 330                 335     


Asn Val Phe Gln Val Glu Thr Val His Thr Tyr Gly Asp Asp Cys Met 
            340                 345                 350         


Tyr Ser Val Cys Pro Ala Thr Ala Ser Ile Phe His Ala Val Leu Ala 
        355                 360                 365             


Asn Leu Thr Ser Tyr Gly Leu Lys Pro Thr Ala Ala Asp Lys Ser Asp 
    370                 375                 380                 


Ala Ile Lys Pro Thr Asn Thr Pro Val Phe Leu Lys Arg Thr Phe Thr 
385                 390                 395                 400 


Gln Thr Pro His Gly Val Arg Ala Leu Leu Asp Ile Thr Ser Ile Thr 
                405                 410                 415     


Arg Gln Phe Tyr Trp Leu Lys Ala Asn Arg Thr Ser Asp Pro Ser Ser 
            420                 425                 430         


Pro Pro Ala Phe Asp Arg Gln Ala Arg Ser Ala Gln Leu Glu Asn Ala 
        435                 440                 445             


Leu Ala Tyr Ala Ser Gln His Gly Pro Val Val Phe Asp Thr Val Arg 
    450                 455                 460                 


Gln Ile Ala Ile Lys Thr Ala Gln Gly Glu Gly Leu Val Leu Val Asn 
465                 470                 475                 480 


Thr Asn Tyr Asp Gln Ala Leu Ala Thr Tyr Asn Ala Trp Phe Ile Gly 
                485                 490                 495     


Gly Thr Val Pro Asp Pro Val Gly His Thr Glu Gly Thr His Lys Ile 
            500                 505                 510         


Val Phe Glu Met Glu 
        515         


<210>  2
<211>  526
<212>  PRT
<213>  Artificial

<220>
<223>  Sapovirus-RdRp having C-terminal His-tag

<400>  2

Met Gly Gly Asp Ser Lys Gly Thr Tyr Cys Gly Ala Pro Ile Leu Gly 
1               5                   10                  15      


Pro Gly Ser Ala Pro Lys Leu Ser Thr Lys Thr Lys Phe Trp Arg Ser 
            20                  25                  30          


Ser Thr Thr Pro Leu Pro Pro Gly Thr Tyr Glu Pro Ala Tyr Leu Gly 
        35                  40                  45              


Gly Lys Asp Pro Arg Val Lys Gly Gly Pro Ser Leu Gln Gln Val Met 
    50                  55                  60                  


Arg Asp Gln Leu Lys Pro Phe Thr Glu Pro Arg Gly Lys Pro Pro Lys 
65                  70                  75                  80  


Pro Ser Val Leu Glu Ala Ala Lys Lys Thr Ile Ile Asn Val Leu Glu 
                85                  90                  95      


Gln Thr Ile Asp Pro Pro Glu Lys Trp Ser Phe Thr Gln Ala Cys Ala 
            100                 105                 110         


Ser Leu Asp Lys Thr Thr Ser Ser Gly His Pro His His Met Arg Lys 
        115                 120                 125             


Asn Asp Cys Trp Asn Gly Glu Ser Phe Thr Gly Lys Leu Ala Asp Gln 
    130                 135                 140                 


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


Val Tyr Thr Gly Ala Leu Lys Asp Glu Leu Val Lys Thr Asp Lys Ile 
                165                 170                 175     


Tyr Gly Lys Ile Lys Lys Arg Leu Leu Trp Gly Ser Asp Leu Ala Thr 
            180                 185                 190         


Met Ile Arg Cys Ala Arg Ala Phe Gly Gly Leu Met Asp Glu Leu Lys 
        195                 200                 205             


Ala His Cys Val Thr Leu Pro Ile Arg Val Gly Met Asn Met Asn Glu 
    210                 215                 220                 


Asp Gly Pro Ile Ile Phe Glu Arg His Ser Arg Tyr Lys Tyr His Tyr 
225                 230                 235                 240 


Asp Ala Asp Tyr Ser Arg Trp Asp Ser Thr Gln Gln Arg Ala Val Leu 
                245                 250                 255     


Ala Ala Ala Leu Glu Ile Met Val Lys Phe Ser Ser Glu Pro His Leu 
            260                 265                 270         


Ala Gln Val Val Ala Glu Asp Leu Leu Ser Pro Ser Val Val Asp Val 
        275                 280                 285             


Gly Asp Phe Lys Ile Ser Ile Asn Glu Gly Leu Pro Ser Gly Val Pro 
    290                 295                 300                 


Cys Thr Ser Gln Trp Asn Ser Ile Ala His Trp Leu Leu Thr Leu Cys 
305                 310                 315                 320 


Ala Leu Ser Glu Val Thr Asn Leu Ser Pro Asp Ile Ile Gln Ala Asn 
                325                 330                 335     


Ser Leu Phe Ser Phe Tyr Gly Asp Asp Glu Ile Val Ser Thr Asp Ile 
            340                 345                 350         


Lys Leu Asp Pro Glu Lys Leu Thr Ala Lys Leu Lys Glu Tyr Gly Leu 
        355                 360                 365             


Lys Pro Thr Arg Pro Asp Lys Thr Glu Gly Pro Leu Val Ile Ser Glu 
    370                 375                 380                 


Asp Leu Asn Gly Leu Thr Phe Leu Arg Arg Thr Val Thr Arg Asp Pro 
385                 390                 395                 400 


Ala Gly Trp Phe Gly Lys Leu Glu Gln Ser Ser Ile Leu Arg Gln Met 
                405                 410                 415     


Tyr Trp Thr Arg Gly Pro Asn His Glu Asp Pro Ser Glu Thr Met Ile 
            420                 425                 430         


Pro His Ser Gln Arg Pro Ile Gln Leu Met Ser Leu Leu Gly Glu Ala 
        435                 440                 445             


Ala Leu His Gly Pro Ala Phe Tyr Ser Lys Ile Ser Lys Leu Val Ile 
    450                 455                 460                 


Ala Glu Leu Lys Glu Gly Gly Met Asp Phe Tyr Val Pro Arg Gln Glu 
465                 470                 475                 480 


Pro Met Phe Arg Trp Met Arg Phe Ser Asp Leu Ser Thr Trp Glu Gly 
                485                 490                 495     


Asp Arg Asn Leu Ala Pro Ser Phe Val Asn Glu Asp Gly Val Glu Val 
            500                 505                 510         


Asp Lys Leu Ala Ala Ala Leu Glu His His His His His His 
        515                 520                 525     


<210>  3
<211>  523
<212>  PRT
<213>  Artificial

<220>
<223>  Sapovirus-RdRp having N-terminal His-tag

<400>  3

Met Lys His His His His His His Asp Glu Phe Gln Trp Lys Gly Leu 
1               5                   10                  15      


Pro Val Val Lys Ser Gly Leu Asp Val Gly Gly Met Pro Thr Gly Thr 
            20                  25                  30          


Arg Tyr His Arg Ser Pro Ala Trp Pro Glu Glu Gln Pro Gly Glu Thr 
        35                  40                  45              


His Ala Pro Ala Pro Phe Gly Ala Gly Asp Lys Arg Tyr Thr Phe Ser 
    50                  55                  60                  


Gln Thr Glu Met Leu Val Asn Gly Leu Lys Pro Tyr Thr Glu Pro Thr 
65                  70                  75                  80  


Ala Gly Val Pro Pro Gln Leu Leu Ser Arg Ala Val Thr His Val Arg 
                85                  90                  95      


Ser Tyr Ile Glu Thr Ile Ile Gly Thr His Arg Ser Pro Val Leu Thr 
            100                 105                 110         


Tyr His Gln Ala Cys Glu Leu Leu Glu Arg Thr Thr Ser Cys Gly Pro 
        115                 120                 125             


Phe Val Gln Gly Leu Lys Gly Asp Tyr Trp Asp Glu Glu Gln Gln Gln 
    130                 135                 140                 


Tyr Thr Gly Val Leu Ala Asn His Leu Glu Gln Ala Trp Asp Lys Ala 
145                 150                 155                 160 


Asn Lys Gly Ile Ala Pro Arg Asn Ala Tyr Lys Leu Ala Leu Lys Asp 
                165                 170                 175     


Glu Leu Arg Pro Ile Glu Lys Asn Lys Ala Gly Lys Arg Arg Leu Leu 
            180                 185                 190         


Trp Gly Cys Asp Ala Ala Thr Thr Leu Ile Ala Thr Ala Ala Phe Lys 
        195                 200                 205             


Ala Val Ala Thr Arg Leu Gln Val Val Thr Pro Met Thr Pro Val Ala 
    210                 215                 220                 


Val Gly Ile Asn Met Asp Ser Val Gln Met Gln Val Met Asn Asp Ser 
225                 230                 235                 240 


Leu Lys Gly Gly Val Leu Tyr Cys Leu Asp Tyr Ser Lys Trp Asp Ser 
                245                 250                 255     


Thr Gln Asn Pro Ala Val Thr Ala Ala Ser Leu Ala Ile Leu Glu Arg 
            260                 265                 270         


Phe Ala Glu Pro His Pro Ile Val Ser Cys Ala Ile Glu Ala Leu Ser 
        275                 280                 285             


Ser Pro Ala Glu Gly Tyr Val Asn Asp Ile Lys Phe Val Thr Arg Gly 
    290                 295                 300                 


Gly Leu Pro Ser Gly Met Pro Phe Thr Ser Val Val Asn Ser Ile Asn 
305                 310                 315                 320 


His Met Ile Tyr Val Ala Ala Ala Ile Leu Gln Ala Tyr Glu Ser His 
                325                 330                 335     


Asn Val Pro Tyr Thr Gly Asn Val Phe Gln Val Glu Thr Val His Thr 
            340                 345                 350         


Tyr Gly Asp Asp Cys Met Tyr Ser Val Cys Pro Ala Thr Ala Ser Ile 
        355                 360                 365             


Phe His Ala Val Leu Ala Asn Leu Thr Ser Tyr Gly Leu Lys Pro Thr 
    370                 375                 380                 


Ala Ala Asp Lys Ser Asp Ala Ile Lys Pro Thr Asn Thr Pro Val Phe 
385                 390                 395                 400 


Leu Lys Arg Thr Phe Thr Gln Thr Pro His Gly Val Arg Ala Leu Leu 
                405                 410                 415     


Asp Ile Thr Ser Ile Thr Arg Gln Phe Tyr Trp Leu Lys Ala Asn Arg 
            420                 425                 430         


Thr Ser Asp Pro Ser Ser Pro Pro Ala Phe Asp Arg Gln Ala Arg Ser 
        435                 440                 445             


Ala Gln Leu Glu Asn Ala Leu Ala Tyr Ala Ser Gln His Gly Pro Val 
    450                 455                 460                 


Val Phe Asp Thr Val Arg Gln Ile Ala Ile Lys Thr Ala Gln Gly Glu 
465                 470                 475                 480 


Gly Leu Val Leu Val Asn Thr Asn Tyr Asp Gln Ala Leu Ala Thr Tyr 
                485                 490                 495     


Asn Ala Trp Phe Ile Gly Gly Thr Val Pro Asp Pro Val Gly His Thr 
            500                 505                 510         


Glu Gly Thr His Lys Ile Val Phe Glu Met Glu 
        515                 520             


<210>  4
<211>  520
<212>  PRT
<213>  Norovirus

<400>  4

Met Gly Gly Asp Ser Lys Gly Thr Tyr Cys Gly Ala Pro Ile Leu Gly 
1               5                   10                  15      


Pro Gly Ser Ala Pro Lys Leu Ser Thr Lys Thr Lys Phe Trp Arg Ser 
            20                  25                  30          


Ser Thr Thr Pro Leu Pro Pro Gly Thr Tyr Glu Pro Ala Tyr Leu Gly 
        35                  40                  45              


Gly Lys Asp Pro Arg Val Lys Gly Gly Pro Ser Leu Gln Gln Val Met 
    50                  55                  60                  


Arg Asp Gln Leu Lys Pro Phe Thr Glu Pro Arg Gly Lys Pro Pro Lys 
65                  70                  75                  80  


Pro Ser Val Leu Glu Ala Ala Lys Lys Thr Ile Ile Asn Val Leu Glu 
                85                  90                  95      


Gln Thr Ile Asp Pro Pro Glu Lys Trp Ser Phe Thr Gln Ala Cys Ala 
            100                 105                 110         


Ser Leu Asp Lys Thr Thr Ser Ser Gly His Pro His His Met Arg Lys 
        115                 120                 125             


Asn Asp Cys Trp Asn Gly Glu Ser Phe Thr Gly Lys Leu Ala Asp Gln 
    130                 135                 140                 


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


Val Tyr Thr Gly Ala Leu Lys Asp Glu Leu Val Lys Thr Asp Lys Ile 
                165                 170                 175     


Tyr Gly Lys Ile Lys Lys Arg Leu Leu Trp Gly Ser Asp Leu Ala Thr 
            180                 185                 190         


Met Ile Arg Cys Ala Arg Ala Phe Gly Gly Leu Met Asp Glu Leu Lys 
        195                 200                 205             


Ala His Cys Val Thr Leu Pro Ile Arg Val Gly Met Asn Met Asn Glu 
    210                 215                 220                 


Asp Gly Pro Ile Ile Phe Glu Arg His Ser Arg Tyr Lys Tyr His Tyr 
225                 230                 235                 240 


Asp Ala Asp Tyr Ser Arg Trp Asp Ser Thr Gln Gln Arg Ala Val Leu 
                245                 250                 255     


Ala Ala Ala Leu Glu Ile Met Val Lys Phe Ser Ser Glu Pro His Leu 
            260                 265                 270         


Ala Gln Val Val Ala Glu Asp Leu Leu Ser Pro Ser Val Val Asp Val 
        275                 280                 285             


Gly Asp Phe Lys Ile Ser Ile Asn Glu Gly Leu Pro Ser Gly Val Pro 
    290                 295                 300                 


Cys Thr Ser Gln Trp Asn Ser Ile Ala His Trp Leu Leu Thr Leu Cys 
305                 310                 315                 320 


Ala Leu Ser Glu Val Thr Asn Leu Ser Pro Asp Ile Ile Gln Ala Asn 
                325                 330                 335     


Ser Leu Phe Ser Phe Tyr Gly Asp Asp Glu Ile Val Ser Thr Asp Ile 
            340                 345                 350         


Lys Leu Asp Pro Glu Lys Leu Thr Ala Lys Leu Lys Glu Tyr Gly Leu 
        355                 360                 365             


Lys Pro Thr Arg Pro Asp Lys Thr Glu Gly Pro Leu Val Ile Ser Glu 
    370                 375                 380                 


Asp Leu Asn Gly Leu Thr Phe Leu Arg Arg Thr Val Thr Arg Asp Pro 
385                 390                 395                 400 


Ala Gly Trp Phe Gly Lys Leu Glu Gln Ser Ser Ile Leu Arg Gln Met 
                405                 410                 415     


Tyr Trp Thr Arg Gly Pro Asn His Glu Asp Pro Ser Glu Thr Met Ile 
            420                 425                 430         


Pro His Ser Gln Arg Pro Ile Gln Leu Met Ser Leu Leu Gly Glu Ala 
        435                 440                 445             


Ala Leu His Gly Pro Ala Phe Tyr Ser Lys Ile Ser Lys Leu Val Ile 
    450                 455                 460                 


Ala Glu Leu Lys Glu Gly Gly Met Asp Phe Tyr Val Pro Arg Gln Glu 
465                 470                 475                 480 


Pro Met Phe Arg Trp Met Arg Phe Ser Asp Leu Ser Thr Trp Glu Gly 
                485                 490                 495     


Asp Arg Asn Leu Ala Pro Ser Phe Val Asn Glu Asp Gly Val Glu Val 
            500                 505                 510         


Asp Lys Leu Ala Ala Ala Leu Glu 
        515                 520 


<210>  5
<211>  526
<212>  PRT
<213>  Artificial

<220>
<223>  Norovirus-RdRp having C-terminal his tag

<400>  5

Met Gly Gly Asp Ser Lys Gly Thr Tyr Cys Gly Ala Pro Ile Leu Gly 
1               5                   10                  15      


Pro Gly Ser Ala Pro Lys Leu Ser Thr Lys Thr Lys Phe Trp Arg Ser 
            20                  25                  30          


Ser Thr Thr Pro Leu Pro Pro Gly Thr Tyr Glu Pro Ala Tyr Leu Gly 
        35                  40                  45              


Gly Lys Asp Pro Arg Val Lys Gly Gly Pro Ser Leu Gln Gln Val Met 
    50                  55                  60                  


Arg Asp Gln Leu Lys Pro Phe Thr Glu Pro Arg Gly Lys Pro Pro Lys 
65                  70                  75                  80  


Pro Ser Val Leu Glu Ala Ala Lys Lys Thr Ile Ile Asn Val Leu Glu 
                85                  90                  95      


Gln Thr Ile Asp Pro Pro Glu Lys Trp Ser Phe Thr Gln Ala Cys Ala 
            100                 105                 110         


Ser Leu Asp Lys Thr Thr Ser Ser Gly His Pro His His Met Arg Lys 
        115                 120                 125             


Asn Asp Cys Trp Asn Gly Glu Ser Phe Thr Gly Lys Leu Ala Asp Gln 
    130                 135                 140                 


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


Val Tyr Thr Gly Ala Leu Lys Asp Glu Leu Val Lys Thr Asp Lys Ile 
                165                 170                 175     


Tyr Gly Lys Ile Lys Lys Arg Leu Leu Trp Gly Ser Asp Leu Ala Thr 
            180                 185                 190         


Met Ile Arg Cys Ala Arg Ala Phe Gly Gly Leu Met Asp Glu Leu Lys 
        195                 200                 205             


Ala His Cys Val Thr Leu Pro Ile Arg Val Gly Met Asn Met Asn Glu 
    210                 215                 220                 


Asp Gly Pro Ile Ile Phe Glu Arg His Ser Arg Tyr Lys Tyr His Tyr 
225                 230                 235                 240 


Asp Ala Asp Tyr Ser Arg Trp Asp Ser Thr Gln Gln Arg Ala Val Leu 
                245                 250                 255     


Ala Ala Ala Leu Glu Ile Met Val Lys Phe Ser Ser Glu Pro His Leu 
            260                 265                 270         


Ala Gln Val Val Ala Glu Asp Leu Leu Ser Pro Ser Val Val Asp Val 
        275                 280                 285             


Gly Asp Phe Lys Ile Ser Ile Asn Glu Gly Leu Pro Ser Gly Val Pro 
    290                 295                 300                 


Cys Thr Ser Gln Trp Asn Ser Ile Ala His Trp Leu Leu Thr Leu Cys 
305                 310                 315                 320 


Ala Leu Ser Glu Val Thr Asn Leu Ser Pro Asp Ile Ile Gln Ala Asn 
                325                 330                 335     


Ser Leu Phe Ser Phe Tyr Gly Asp Asp Glu Ile Val Ser Thr Asp Ile 
            340                 345                 350         


Lys Leu Asp Pro Glu Lys Leu Thr Ala Lys Leu Lys Glu Tyr Gly Leu 
        355                 360                 365             


Lys Pro Thr Arg Pro Asp Lys Thr Glu Gly Pro Leu Val Ile Ser Glu 
    370                 375                 380                 


Asp Leu Asn Gly Leu Thr Phe Leu Arg Arg Thr Val Thr Arg Asp Pro 
385                 390                 395                 400 


Ala Gly Trp Phe Gly Lys Leu Glu Gln Ser Ser Ile Leu Arg Gln Met 
                405                 410                 415     


Tyr Trp Thr Arg Gly Pro Asn His Glu Asp Pro Ser Glu Thr Met Ile 
            420                 425                 430         


Pro His Ser Gln Arg Pro Ile Gln Leu Met Ser Leu Leu Gly Glu Ala 
        435                 440                 445             


Ala Leu His Gly Pro Ala Phe Tyr Ser Lys Ile Ser Lys Leu Val Ile 
    450                 455                 460                 


Ala Glu Leu Lys Glu Gly Gly Met Asp Phe Tyr Val Pro Arg Gln Glu 
465                 470                 475                 480 


Pro Met Phe Arg Trp Met Arg Phe Ser Asp Leu Ser Thr Trp Glu Gly 
                485                 490                 495     


Asp Arg Asn Leu Ala Pro Ser Phe Val Asn Glu Asp Gly Val Glu Val 
            500                 505                 510         


Asp Lys Leu Ala Ala Ala Leu Glu His His His His His His 
        515                 520                 525     


<210>  6
<211>  456
<212>  PRT
<213>  Artificial

<220>
<223>  Norovirus-RdRp having N-terminal His-tag

<400>  6

Met His His His His His His Gly Gly Asp Ser Lys Gly Thr Tyr Cys 
1               5                   10                  15      


Gly Ala Pro Ile Leu Gly Pro Gly Ser Ala Pro Lys Leu Ser Thr Lys 
            20                  25                  30          


Thr Lys Phe Trp Arg Ser Ser Thr Thr Pro Leu Pro Pro Gly Thr Tyr 
        35                  40                  45              


Glu Pro Ala Tyr Leu Gly Gly Lys Asp Pro Arg Val Lys Gly Gly Pro 
    50                  55                  60                  


Ser Leu Gln Gln Val Met Arg Asp Gln Leu Lys Pro Phe Thr Glu Pro 
65                  70                  75                  80  


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


Ile Ile Asn Val Leu Glu Gln Thr Ile Asp Pro Pro Glu Lys Trp Ser 
            100                 105                 110         


Phe Thr Gln Ala Cys Ala Ser Leu Asp Lys Thr Thr Ser Ser Gly His 
        115                 120                 125             


Pro His His Met Arg Lys Asn Asp Cys Trp Asn Gly Glu Ser Phe Thr 
    130                 135                 140                 


Gly Lys Leu Ala Asp Gln Ala Ser Lys Ala Asn Leu Met Phe Glu Gly 
145                 150                 155                 160 


Gly Lys Asn Met Thr Pro Val Tyr Thr Gly Ala Leu Lys Asp Glu Leu 
                165                 170                 175     


Val Lys Thr Asp Lys Ile Tyr Gly Lys Ile Lys Lys Arg Leu Leu Trp 
            180                 185                 190         


Gly Ser Asp Leu Ala Thr Met Ile Arg Cys Ala Arg Ala Phe Gly Gly 
        195                 200                 205             


Leu Met Asp Glu Leu Lys Ala His Cys Val Thr Leu Pro Ile Arg Val 
    210                 215                 220                 


Gly Met Asn Met Asn Glu Asp Gly Pro Ile Ile Phe Glu Arg His Ser 
225                 230                 235                 240 


Arg Tyr Lys Tyr His Tyr Asp Ala Asp Tyr Ser Arg Trp Asp Ser Thr 
                245                 250                 255     


Gln Gln Arg Ala Val Leu Ala Ala Ala Leu Glu Ile Met Val Lys Phe 
            260                 265                 270         


Ser Ser Glu Pro His Leu Ala Gln Val Val Ala Glu Asp Leu Leu Ser 
        275                 280                 285             


Pro Ser Val Val Asp Val Gly Asp Phe Lys Ile Ser Ile Asn Glu Gly 
    290                 295                 300                 


Leu Pro Ser Gly Val Pro Cys Thr Ser Gln Trp Asn Ser Ile Ala His 
305                 310                 315                 320 


Trp Leu Leu Thr Leu Cys Ala Leu Ser Glu Val Thr Asn Leu Ser Pro 
                325                 330                 335     


Asp Ile Ile Gln Ala Asn Ser Leu Phe Ser Phe Tyr Gly Asp Asp Glu 
            340                 345                 350         


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


Leu Lys Glu Tyr Gly Leu Lys Pro Thr Arg Pro Asp Lys Thr Glu Gly 
    370                 375                 380                 


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


Thr Val Thr Arg Asp Pro Ala Gly Trp Phe Gly Lys Leu Glu Gln Ser 
                405                 410                 415     


Ser Ile Leu Arg Gln Met Tyr Trp Thr Arg Gly Pro Asn His Glu Asp 
            420                 425                 430         


Pro Ser Glu Thr Met Ile Pro His Ser Gln Arg Pro Ile Gln Leu Met 
        435                 440                 445             


Ser Leu Leu Gly Glu Ala Ala Leu 
    450                 455     


