                         SEQUENCE LISTING

<110>  THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
       WEINER, David
       SCOTT, Veronica
       HUTNICK, Natalie
 
<120>  MONO OR MULTIVALENT BOTULINUM NEUROTOXIN BASED VACCINE USING THE 
       HEAVY CHAIN FROM SEROTYPES OF CLOSTRIDIUM BOTULINUM

<130>  UPV60045 WO

<150>  61799094
<151>  2013-03-15

<160>  11    

<170>  PatentIn version 3.5

<210>  1
<211>  1328
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Neurotoxin A (BoNT/A)

<400>  1
ggatccgtcg acgccaccat ggactggacc tggattctgt tcctggtcgc cgccgcaaca       60

agagtgcatt cctcaaacca cctgattgac ctgtctagat acgcatcaaa gatcaatatt      120

ggcagcaaag tgaactttga cccaattgat aagaatcaga tccagctgtt caacctggag      180

agctccaaga tcgaagtgat tctgaaaaac gctatcgtct acaattctat gtatgagaac      240

ttttccacct ctttctggat caggattccc aagtacttta atagtatctc actgaacaac      300

gagtacacaa tcattaactg catggaaaac aactctggat ggaaagtgag tctgaactac      360

ggcgagatca tttggacact gcaggacact caggaaatca agcagcgggt ggtctttaaa      420

tactcccaga tgatcaacat ctctgattac atcaaccgct ggattttcgt gactatcacc      480

aacaatcgac tgaacaatag caagatctat attaacggca gactgattga ccagaaaccc      540

atcagcaacc tggggaatat tcacgcctcc aacaatatca tgtttaagct ggacggctgt      600

agggataccc atcgctacat ctggattaag tatttcaatc tgttcgacaa ggagctgaac      660

gagaaggaga tcaaggacct gtacgataac cagagcaatt ccggcatcct gaaggacttc      720

tggggcgact acctgcagta tgataaaccc tactatatgc tgaatctgta cgaccctaac      780

aagtatgtgg atgtcaacaa tgtgggcatt agagggtaca tgtatctgaa aggacctagg      840

ggcagcgtga tgaccacaaa catctacctg aattctagtc tgtatagggg gactaagttc      900

atcattaaga aatacgcatc cggaaacaaa gacaatattg tgcgaaacaa tgatcgggtc      960

tacatcaatg tggtcgtgaa gaacaaagag tatcgcctgg ccaccaatgc ttctcaggca     1020

ggagtggaga agattctgag tgccctggaa atcccagacg tgggcaatct gagtcaggtc     1080

gtggtcatga agtcaaaaaa cgatcagggg atcacaaata agtgcaaaat gaacctgcag     1140

gacaacaatg gcaacgatat cgggttcatt ggatttcacc agttcaacaa tattgccaag     1200

ctggtggctt ccaactggta caatcggcag atcgaacggt caagcagaac actgggatgt     1260

agttgggagt tcattcctgt ggacgatgga tggggagaga gaccactgtg ataaacgcgt     1320

gcggccgc                                                              1328


<210>  2
<211>  430
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Neurotoxin A (BoNT/A)

<400>  2

Met Asp Trp Thr Trp Ile Leu Phe Leu Val Ala Ala Ala Thr Arg Val 
1               5                   10                  15      


His Ser Ser Asn His Leu Ile Asp Leu Ser Arg Tyr Ala Ser Lys Ile 
            20                  25                  30          


Asn Ile Gly Ser Lys Val Asn Phe Asp Pro Ile Asp Lys Asn Gln Ile 
        35                  40                  45              


Gln Leu Phe Asn Leu Glu Ser Ser Lys Ile Glu Val Ile Leu Lys Asn 
    50                  55                  60                  


Ala Ile Val Tyr Asn Ser Met Tyr Glu Asn Phe Ser Thr Ser Phe Trp 
65                  70                  75                  80  


Ile Arg Ile Pro Lys Tyr Phe Asn Ser Ile Ser Leu Asn Asn Glu Tyr 
                85                  90                  95      


Thr Ile Ile Asn Cys Met Glu Asn Asn Ser Gly Trp Lys Val Ser Leu 
            100                 105                 110         


Asn Tyr Gly Glu Ile Ile Trp Thr Leu Gln Asp Thr Gln Glu Ile Lys 
        115                 120                 125             


Gln Arg Val Val Phe Lys Tyr Ser Gln Met Ile Asn Ile Ser Asp Tyr 
    130                 135                 140                 


Ile Asn Arg Trp Ile Phe Val Thr Ile Thr Asn Asn Arg Leu Asn Asn 
145                 150                 155                 160 


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


Asn Leu Gly Asn Ile His Ala Ser Asn Asn Ile Met Phe Lys Leu Asp 
            180                 185                 190         


Gly Cys Arg Asp Thr His Arg Tyr Ile Trp Ile Lys Tyr Phe Asn Leu 
        195                 200                 205             


Phe Asp Lys Glu Leu Asn Glu Lys Glu Ile Lys Asp Leu Tyr Asp Asn 
    210                 215                 220                 


Gln Ser Asn Ser Gly Ile Leu Lys Asp Phe Trp Gly Asp Tyr Leu Gln 
225                 230                 235                 240 


Tyr Asp Lys Pro Tyr Tyr Met Leu Asn Leu Tyr Asp Pro Asn Lys Tyr 
                245                 250                 255     


Val Asp Val Asn Asn Val Gly Ile Arg Gly Tyr Met Tyr Leu Lys Gly 
            260                 265                 270         


Pro Arg Gly Ser Val Met Thr Thr Asn Ile Tyr Leu Asn Ser Ser Leu 
        275                 280                 285             


Tyr Arg Gly Thr Lys Phe Ile Ile Lys Lys Tyr Ala Ser Gly Asn Lys 
    290                 295                 300                 


Asp Asn Ile Val Arg Asn Asn Asp Arg Val Tyr Ile Asn Val Val Val 
305                 310                 315                 320 


Lys Asn Lys Glu Tyr Arg Leu Ala Thr Asn Ala Ser Gln Ala Gly Val 
                325                 330                 335     


Glu Lys Ile Leu Ser Ala Leu Glu Ile Pro Asp Val Gly Asn Leu Ser 
            340                 345                 350         


Gln Val Val Val Met Lys Ser Lys Asn Asp Gln Gly Ile Thr Asn Lys 
        355                 360                 365             


Cys Lys Met Asn Leu Gln Asp Asn Asn Gly Asn Asp Ile Gly Phe Ile 
    370                 375                 380                 


Gly Phe His Gln Phe Asn Asn Ile Ala Lys Leu Val Ala Ser Asn Trp 
385                 390                 395                 400 


Tyr Asn Arg Gln Ile Glu Arg Ser Ser Arg Thr Leu Gly Cys Ser Trp 
                405                 410                 415     


Glu Phe Ile Pro Val Asp Asp Gly Trp Gly Glu Arg Pro Leu 
            420                 425                 430 


<210>  3
<211>  1346
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Neurotoxin B (BoNT/B)

<400>  3
ggatccgggc ccgccaccat ggactggaca tggattctgt tcctggtcgc tgctgctaca       60

cgagtgcatt ctgacaacaa cctgattgac ctgagcggct acggcgccaa agtggaagtc      120

tatgatgggg tggagctgaa cgacaagaat cagtttaaac tgacaagctc cgctaacagt      180

aagatcaggg tcactcagaa ccagaatatc atcttcaaca gcgtgttcct ggatttttct      240

gtcagtttct ggatcagaat ccccaagtac aaaaacgacg gcatccagaa ctacatccac      300

aacgagtaca ccatcattaa ttgcatgaag aacaatagtg gatggaaaat ctcaattagg      360

ggcaaccgca tcatttggac tctgatcgat attaatggga agaccaaatc cgtgttcttt      420

gaatataaca tccgagaaga catttctgag tacatcaatc ggtggttctt tgtgaccatc      480

acaaacaatc tgaacaatgc aaagatctac attaacggca aactggagag caatacagat      540

atcaaggaca ttcgggaagt gattgccaac ggggagatca tcttcaagct ggacggagat      600

attgacagaa ctcagttcat ctggatgaag tatttctcca tctttaacac cgagctgtca      660

cagagcaata ttgaggaaag atacaagatc cagtcctatt ctgaatacct gaaagatttt      720

tggggcaacc cactgatgta caataaggag tactacatgt tcaacgctgg gaacaagaat      780

tcttacatca agctgaagaa ggatagtccc gtgggagaaa tcctgaccag aagcaagtac      840

aaccagaact ccaagtacat caactacagg gacctgtaca tcggagagaa gttcatcatt      900

cggagaaaaa gtaactcaca gagcattaat gacgatatcg tgcgcaagga agattacatc      960

tatctggact tctttaacct gaatcaggag tggcgagtct acacatacaa gtactttaag     1020

aaggaggaag agaaactgtt cctggccccc atctccgatt ctgacgagtt ttacaacacc     1080

atccagatta aggaatatga tgagcagcct acatactcat gccagctgct gttcaagaaa     1140

gatgaagaga gcactgacga aatcggcctg atcgggattc atcgattcta tgagtccggc     1200

atcgtgttcg aagagtataa ggactacttc tgtatctcta agtggtacct gaaagaggtc     1260

aagcgcaaac cctataatct gaagctggga tgtaattggc agttcattcc taaagacgaa     1320

gggtggaccg aatgataagc ggccgc                                          1346


<210>  4
<211>  438
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Neurotoxin B (BoNT/B)

<400>  4

Met Asp Trp Thr Trp Ile Leu Phe Leu Val Ala Ala Ala Thr Arg Val 
1               5                   10                  15      


His Ser Asp Asn Asn Leu Ile Asp Leu Ser Gly Tyr Gly Ala Lys Val 
            20                  25                  30          


Glu Val Tyr Asp Gly Val Glu Leu Asn Asp Lys Asn Gln Phe Lys Leu 
        35                  40                  45              


Thr Ser Ser Ala Asn Ser Lys Ile Arg Val Thr Gln Asn Gln Asn Ile 
    50                  55                  60                  


Ile Phe Asn Ser Val Phe Leu Asp Phe Ser Val Ser Phe Trp Ile Arg 
65                  70                  75                  80  


Ile Pro Lys Tyr Lys Asn Asp Gly Ile Gln Asn Tyr Ile His Asn Glu 
                85                  90                  95      


Tyr Thr Ile Ile Asn Cys Met Lys Asn Asn Ser Gly Trp Lys Ile Ser 
            100                 105                 110         


Ile Arg Gly Asn Arg Ile Ile Trp Thr Leu Ile Asp Ile Asn Gly Lys 
        115                 120                 125             


Thr Lys Ser Val Phe Phe Glu Tyr Asn Ile Arg Glu Asp Ile Ser Glu 
    130                 135                 140                 


Tyr Ile Asn Arg Trp Phe Phe Val Thr Ile Thr Asn Asn Leu Asn Asn 
145                 150                 155                 160 


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


Asp Ile Arg Glu Val Ile Ala Asn Gly Glu Ile Ile Phe Lys Leu Asp 
            180                 185                 190         


Gly Asp Ile Asp Arg Thr Gln Phe Ile Trp Met Lys Tyr Phe Ser Ile 
        195                 200                 205             


Phe Asn Thr Glu Leu Ser Gln Ser Asn Ile Glu Glu Arg Tyr Lys Ile 
    210                 215                 220                 


Gln Ser Tyr Ser Glu Tyr Leu Lys Asp Phe Trp Gly Asn Pro Leu Met 
225                 230                 235                 240 


Tyr Asn Lys Glu Tyr Tyr Met Phe Asn Ala Gly Asn Lys Asn Ser Tyr 
                245                 250                 255     


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


Lys Tyr Asn Gln Asn Ser Lys Tyr Ile Asn Tyr Arg Asp Leu Tyr Ile 
        275                 280                 285             


Gly Glu Lys Phe Ile Ile Arg Arg Lys Ser Asn Ser Gln Ser Ile Asn 
    290                 295                 300                 


Asp Asp Ile Val Arg Lys Glu Asp Tyr Ile Tyr Leu Asp Phe Phe Asn 
305                 310                 315                 320 


Leu Asn Gln Glu Trp Arg Val Tyr Thr Tyr Lys Tyr Phe Lys Lys Glu 
                325                 330                 335     


Glu Glu Lys Leu Phe Leu Ala Pro Ile Ser Asp Ser Asp Glu Phe Tyr 
            340                 345                 350         


Asn Thr Ile Gln Ile Lys Glu Tyr Asp Glu Gln Pro Thr Tyr Ser Cys 
        355                 360                 365             


Gln Leu Leu Phe Lys Lys Asp Glu Glu Ser Thr Asp Glu Ile Gly Leu 
    370                 375                 380                 


Ile Gly Ile His Arg Phe Tyr Glu Ser Gly Ile Val Phe Glu Glu Tyr 
385                 390                 395                 400 


Lys Asp Tyr Phe Cys Ile Ser Lys Trp Tyr Leu Lys Glu Val Lys Arg 
                405                 410                 415     


Lys Pro Tyr Asn Leu Lys Leu Gly Cys Asn Trp Gln Phe Ile Pro Lys 
            420                 425                 430         


Asp Glu Gly Trp Thr Glu 
        435             


<210>  5
<211>  1271
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Neurotoxin E (BoNT/E)

<400>  5
ggatccgtcg acgccaccat ggactggact tggattctgt tcctggtcgc cgccgcaacc       60

cgcgtgcatt ctgacaaata tgtggacacc tcaggctatg actctaatat caacattaat      120

ggcgacgtgt acaagtatcc aaccaacaaa aatcagttcg gcatctacaa cgataagctg      180

tcagaggtga acatcagcca gaatgactac atcatctacg ataacaagta caagaatttc      240

agcatttcct tttgggtccg catccccaac tacgacaaca agattgtcaa cgtgaacaac      300

gagtacacaa tcattaattg catgcgagat aacaattccg ggtggaaggt gtctctgaac      360

cacaatgaaa tcatttggac tctgcaggac aacgccggaa tcaatcagaa actggctttc      420

aactacggaa acgcaaatgg catctctgat tacatcaaca agtggatctt cgtgactatt      480

accaatgacc ggctggggga tagtaaactg tacatcaacg gaaatctgat tgaccagaag      540

agtatcctga acctgggcaa tatccatgtc tcagataaca tcctgtttaa aatcgtgaac      600

tgtagctaca ccaggtatat cgggattcgc tacttcaaca tttttgacaa ggagctggat      660

gagacagaaa tccagactct gtatagcaat gaacccaaca caaatatcct gaaggacttc      720

tggggaaact acctgctgta tgataaggag tactatctgc tgaatgtgct gaaacctaat      780

aacttcatcg accggagaaa ggattctaca ctgagtatca acaatattcg aagcactatc      840

ctgctggcca accggctgta ctccgggatc aaggtcaaaa ttcagagagt gaacaatagc      900

tccaccaacg acaatctggt gaggaaaaac gatcaggtct acatcaattt cgtggctagc      960

aagacacacc tgtttcccct gtatgccgac actgctacca caaacaagga aaaaaccatc     1020

aagatttcta gttcaggcaa caggttcaat caggtggtcg tgatgaactc cgtgggcaac     1080

aactgcacta tgaatttcaa aaacaacaac gggaacaaca tcggcctgct ggggtttaag     1140

gcagacaccg tcgtggcctc tacctggtac tatacacaca tgcgggatca tacaaattca     1200

aatggatgtt tctggaactt tattagtgag gagcatgggt ggcaggaaaa atgataaacg     1260

cgtgcggccg c                                                          1271


<210>  6
<211>  411
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Neurotoxin E (BoNT/E)

<400>  6

Met Asp Trp Thr Trp Ile Leu Phe Leu Val Ala Ala Ala Thr Arg Val 
1               5                   10                  15      


His Ser Asp Lys Tyr Val Asp Thr Ser Gly Tyr Asp Ser Asn Ile Asn 
            20                  25                  30          


Ile Asn Gly Asp Val Tyr Lys Tyr Pro Thr Asn Lys Asn Gln Phe Gly 
        35                  40                  45              


Ile Tyr Asn Asp Lys Leu Ser Glu Val Asn Ile Ser Gln Asn Asp Tyr 
    50                  55                  60                  


Ile Ile Tyr Asp Asn Lys Tyr Lys Asn Phe Ser Ile Ser Phe Trp Val 
65                  70                  75                  80  


Arg Ile Pro Asn Tyr Asp Asn Lys Ile Val Asn Val Asn Asn Glu Tyr 
                85                  90                  95      


Thr Ile Ile Asn Cys Met Arg Asp Asn Asn Ser Gly Trp Lys Val Ser 
            100                 105                 110         


Leu Asn His Asn Glu Ile Ile Trp Thr Leu Gln Asp Asn Ala Gly Ile 
        115                 120                 125             


Asn Gln Lys Leu Ala Phe Asn Tyr Gly Asn Ala Asn Gly Ile Ser Asp 
    130                 135                 140                 


Tyr Ile Asn Lys Trp Ile Phe Val Thr Ile Thr Asn Asp Arg Leu Gly 
145                 150                 155                 160 


Asp Ser Lys Leu Tyr Ile Asn Gly Asn Leu Ile Asp Gln Lys Ser Ile 
                165                 170                 175     


Leu Asn Leu Gly Asn Ile His Val Ser Asp Asn Ile Leu Phe Lys Ile 
            180                 185                 190         


Val Asn Cys Ser Tyr Thr Arg Tyr Ile Gly Ile Arg Tyr Phe Asn Ile 
        195                 200                 205             


Phe Asp Lys Glu Leu Asp Glu Thr Glu Ile Gln Thr Leu Tyr Ser Asn 
    210                 215                 220                 


Glu Pro Asn Thr Asn Ile Leu Lys Asp Phe Trp Gly Asn Tyr Leu Leu 
225                 230                 235                 240 


Tyr Asp Lys Glu Tyr Tyr Leu Leu Asn Val Leu Lys Pro Asn Asn Phe 
                245                 250                 255     


Ile Asp Arg Arg Lys Asp Ser Thr Leu Ser Ile Asn Asn Ile Arg Ser 
            260                 265                 270         


Thr Ile Leu Leu Ala Asn Arg Leu Tyr Ser Gly Ile Lys Val Lys Ile 
        275                 280                 285             


Gln Arg Val Asn Asn Ser Ser Thr Asn Asp Asn Leu Val Arg Lys Asn 
    290                 295                 300                 


Asp Gln Val Tyr Ile Asn Phe Val Ala Ser Lys Thr His Leu Phe Pro 
305                 310                 315                 320 


Leu Tyr Ala Asp Thr Ala Thr Thr Asn Lys Glu Lys Thr Ile Lys Ile 
                325                 330                 335     


Ser Ser Ser Gly Asn Arg Phe Asn Gln Val Val Val Met Asn Ser Val 
            340                 345                 350         


Gly Asn Asn Cys Thr Met Asn Phe Lys Asn Asn Asn Gly Asn Asn Ile 
        355                 360                 365             


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


Tyr Thr His Met Arg Asp His Thr Asn Ser Asn Gly Cys Phe Trp Asn 
385                 390                 395                 400 


Phe Ile Ser Glu Glu His Gly Trp Gln Glu Lys 
                405                 410     


<210>  7
<211>  1289
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Neurotoxin F (BoNT/F)

<400>  7
ggatccgggc ccgccaccat ggactggaca tggattctgt tcctggtggc tgctgctaca       60

agagtgcatt caaataacaa attcattgac atctcaggct acggctctaa catcagtatt      120

aatggcgacg tgtacatcta cagcaccaac cgaaatcagt tcgggatcta cagctccaag      180

ccatccgagg tgaacattgc acagaacaat gatatcatct acaacggccg gtatcagaat      240

ttctcaatta gcttttgggt gagaatcccc aagtacttta acaaggtcaa tctgaacaac      300

gaatacacaa tcatcgactg catccgcaac aataactccg gatggaagat ctctctgaac      360

tacaataaga tcatctggac tctgcaggac accgccggca ataaccagaa actggtgttc      420

aattacactc agatgatctc catctctgat tacatcaaca agtggatctt cgtcaccatc      480

acaaataacc ggctggggaa ctctagaatc tatatcaacg gaaatctgat cgatgagaag      540

agtatctcaa acctgggcga catccacgtg agcgataata ttctgttcaa gatcgtcggc      600

tgtaacgaca ccagatacgt gggcatccgg tatttcaaag tctttgatac agagctgggg      660

aagacagaga tcgaaactct gtacagcgac gaacccgatc cttccattct gaaagacttt      720

tggggaaact acctgctgta taataagaga tactatctgc tgaatctgct gaggactgat      780

aagagtatca cccagaactc aaatttcctg aacatcaatc agcagagagg ggtgtaccag      840

aagcctaaca tctttagcaa tacccgcctg tatacaggag tggaagtcat cattcgaaaa      900

aacggctcaa cagacatcag caacactgat aatttcgtga ggaagaacga cctggcttac      960

attaatgtgg tcgaccgaga tgtcgagtac cggctgtatg ccgatatctc cattgctaag     1020

cccgaaaaaa tcattaagct gatccgcact agcaattcca ataactctct ggggcagatc     1080

attgtgatgg acagtatcgg aaataactgc accatgaact tccagaataa caatggcgga     1140

aatatcggac tgctgggctt tcattctaac aatctggtgg cctctagttg gtactataac     1200

aatatccgga agaacacttc atccaatggg tgtttctggt ccttcatctc caaagagcat     1260

gggtggcagg aaaattgata agcggccgc                                       1289


<210>  8
<211>  419
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Neurotoxin F (BoNT/F)

<400>  8

Met Asp Trp Thr Trp Ile Leu Phe Leu Val Ala Ala Ala Thr Arg Val 
1               5                   10                  15      


His Ser Asn Asn Lys Phe Ile Asp Ile Ser Gly Tyr Gly Ser Asn Ile 
            20                  25                  30          


Ser Ile Asn Gly Asp Val Tyr Ile Tyr Ser Thr Asn Arg Asn Gln Phe 
        35                  40                  45              


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


Asp Ile Ile Tyr Asn Gly Arg Tyr Gln Asn Phe Ser Ile Ser Phe Trp 
65                  70                  75                  80  


Val Arg Ile Pro Lys Tyr Phe Asn Lys Val Asn Leu Asn Asn Glu Tyr 
                85                  90                  95      


Thr Ile Ile Asp Cys Ile Arg Asn Asn Asn Ser Gly Trp Lys Ile Ser 
            100                 105                 110         


Leu Asn Tyr Asn Lys Ile Ile Trp Thr Leu Gln Asp Thr Ala Gly Asn 
        115                 120                 125             


Asn Gln Lys Leu Val Phe Asn Tyr Thr Gln Met Ile Ser Ile Ser Asp 
    130                 135                 140                 


Tyr Ile Asn Lys Trp Ile Phe Val Thr Ile Thr Asn Asn Arg Leu Gly 
145                 150                 155                 160 


Asn Ser Arg Ile Tyr Ile Asn Gly Asn Leu Ile Asp Glu Lys Ser Ile 
                165                 170                 175     


Ser Asn Leu Gly Asp Ile His Val Ser Asp Asn Ile Leu Phe Lys Ile 
            180                 185                 190         


Val Gly Cys Asn Asp Thr Arg Tyr Val Gly Ile Arg Tyr Phe Lys Val 
        195                 200                 205             


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


Glu Pro Asp Pro Ser Ile Leu Lys Asp Phe Trp Gly Asn Tyr Leu Leu 
225                 230                 235                 240 


Tyr Asn Lys Arg Tyr Tyr Leu Leu Asn Leu Leu Arg Thr Asp Lys Ser 
                245                 250                 255     


Ile Thr Gln Asn Ser Asn Phe Leu Asn Ile Asn Gln Gln Arg Gly Val 
            260                 265                 270         


Tyr Gln Lys Pro Asn Ile Phe Ser Asn Thr Arg Leu Tyr Thr Gly Val 
        275                 280                 285             


Glu Val Ile Ile Arg Lys Asn Gly Ser Thr Asp Ile Ser Asn Thr Asp 
    290                 295                 300                 


Asn Phe Val Arg Lys Asn Asp Leu Ala Tyr Ile Asn Val Val Asp Arg 
305                 310                 315                 320 


Asp Val Glu Tyr Arg Leu Tyr Ala Asp Ile Ser Ile Ala Lys Pro Glu 
                325                 330                 335     


Lys Ile Ile Lys Leu Ile Arg Thr Ser Asn Ser Asn Asn Ser Leu Gly 
            340                 345                 350         


Gln Ile Ile Val Met Asp Ser Ile Gly Asn Asn Cys Thr Met Asn Phe 
        355                 360                 365             


Gln Asn Asn Asn Gly Gly Asn Ile Gly Leu Leu Gly Phe His Ser Asn 
    370                 375                 380                 


Asn Leu Val Ala Ser Ser Trp Tyr Tyr Asn Asn Ile Arg Lys Asn Thr 
385                 390                 395                 400 


Ser Ser Asn Gly Cys Phe Trp Ser Phe Ile Ser Lys Glu His Gly Trp 
                405                 410                 415     


Gln Glu Asn 
            


<210>  9
<211>  857
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Neurotoxin A + B (BoNT/A + BoNT/B)

<400>  9

Met Asp Trp Thr Trp Ile Leu Phe Leu Val Ala Ala Ala Thr Arg Val 
1               5                   10                  15      


His Ser Ser Asn His Leu Ile Asp Leu Ser Arg Tyr Ala Ser Lys Ile 
            20                  25                  30          


Asn Ile Gly Ser Lys Val Asn Phe Asp Pro Ile Asp Lys Asn Gln Ile 
        35                  40                  45              


Gln Leu Phe Asn Leu Glu Ser Ser Lys Ile Glu Val Ile Leu Lys Asn 
    50                  55                  60                  


Ala Ile Val Tyr Asn Ser Met Tyr Glu Asn Phe Ser Thr Ser Phe Trp 
65                  70                  75                  80  


Ile Arg Ile Pro Lys Tyr Phe Asn Ser Ile Ser Leu Asn Asn Glu Tyr 
                85                  90                  95      


Thr Ile Ile Asn Cys Met Glu Asn Asn Ser Gly Trp Lys Val Ser Leu 
            100                 105                 110         


Asn Tyr Gly Glu Ile Ile Trp Thr Leu Gln Asp Thr Gln Glu Ile Lys 
        115                 120                 125             


Gln Arg Val Val Phe Lys Tyr Ser Gln Met Ile Asn Ile Ser Asp Tyr 
    130                 135                 140                 


Ile Asn Arg Trp Ile Phe Val Thr Ile Thr Asn Asn Arg Leu Asn Asn 
145                 150                 155                 160 


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


Asn Leu Gly Asn Ile His Ala Ser Asn Asn Ile Met Phe Lys Leu Asp 
            180                 185                 190         


Gly Cys Arg Asp Thr His Arg Tyr Ile Trp Ile Lys Tyr Phe Asn Leu 
        195                 200                 205             


Phe Asp Lys Glu Leu Asn Glu Lys Glu Ile Lys Asp Leu Tyr Asp Asn 
    210                 215                 220                 


Gln Ser Asn Ser Gly Ile Leu Lys Asp Phe Trp Gly Asp Tyr Leu Gln 
225                 230                 235                 240 


Tyr Asp Lys Pro Tyr Tyr Met Leu Asn Leu Tyr Asp Pro Asn Lys Tyr 
                245                 250                 255     


Val Asp Val Asn Asn Val Gly Ile Arg Gly Tyr Met Tyr Leu Lys Gly 
            260                 265                 270         


Pro Arg Gly Ser Val Met Thr Thr Asn Ile Tyr Leu Asn Ser Ser Leu 
        275                 280                 285             


Tyr Arg Gly Thr Lys Phe Ile Ile Lys Lys Tyr Ala Ser Gly Asn Lys 
    290                 295                 300                 


Asp Asn Ile Val Arg Asn Asn Asp Arg Val Tyr Ile Asn Val Val Val 
305                 310                 315                 320 


Lys Asn Lys Glu Tyr Arg Leu Ala Thr Asn Ala Ser Gln Ala Gly Val 
                325                 330                 335     


Glu Lys Ile Leu Ser Ala Leu Glu Ile Pro Asp Val Gly Asn Leu Ser 
            340                 345                 350         


Gln Val Val Val Met Lys Ser Lys Asn Asp Gln Gly Ile Thr Asn Lys 
        355                 360                 365             


Cys Lys Met Asn Leu Gln Asp Asn Asn Gly Asn Asp Ile Gly Phe Ile 
    370                 375                 380                 


Gly Phe His Gln Phe Asn Asn Ile Ala Lys Leu Val Ala Ser Asn Trp 
385                 390                 395                 400 


Tyr Asn Arg Gln Ile Glu Arg Ser Ser Arg Thr Leu Gly Cys Ser Trp 
                405                 410                 415     


Glu Phe Ile Pro Val Asp Asp Gly Trp Gly Glu Arg Pro Leu Arg Gly 
            420                 425                 430         


Arg Lys Arg Arg Ser Asp Asn Asn Leu Ile Asp Leu Ser Gly Tyr Gly 
        435                 440                 445             


Ala Lys Val Glu Val Tyr Asp Gly Val Glu Leu Asn Asp Lys Asn Gln 
    450                 455                 460                 


Phe Lys Leu Thr Ser Ser Ala Asn Ser Lys Ile Arg Val Thr Gln Asn 
465                 470                 475                 480 


Gln Asn Ile Ile Phe Asn Ser Val Phe Leu Asp Phe Ser Val Ser Phe 
                485                 490                 495     


Trp Ile Arg Ile Pro Lys Tyr Lys Asn Asp Gly Ile Gln Asn Tyr Ile 
            500                 505                 510         


His Asn Glu Tyr Thr Ile Ile Asn Cys Met Lys Asn Asn Ser Gly Trp 
        515                 520                 525             


Lys Ile Ser Ile Arg Gly Asn Arg Ile Ile Trp Thr Leu Ile Asp Ile 
    530                 535                 540                 


Asn Gly Lys Thr Lys Ser Val Phe Phe Glu Tyr Asn Ile Arg Glu Asp 
545                 550                 555                 560 


Ile Ser Glu Tyr Ile Asn Arg Trp Phe Phe Val Thr Ile Thr Asn Asn 
                565                 570                 575     


Leu Asn Asn Ala Lys Ile Tyr Ile Asn Gly Lys Leu Glu Ser Asn Thr 
            580                 585                 590         


Asp Ile Lys Asp Ile Arg Glu Val Ile Ala Asn Gly Glu Ile Ile Phe 
        595                 600                 605             


Lys Leu Asp Gly Asp Ile Asp Arg Thr Gln Phe Ile Trp Met Lys Tyr 
    610                 615                 620                 


Phe Ser Ile Phe Asn Thr Glu Leu Ser Gln Ser Asn Ile Glu Glu Arg 
625                 630                 635                 640 


Tyr Lys Ile Gln Ser Tyr Ser Glu Tyr Leu Lys Asp Phe Trp Gly Asn 
                645                 650                 655     


Pro Leu Met Tyr Asn Lys Glu Tyr Tyr Met Phe Asn Ala Gly Asn Lys 
            660                 665                 670         


Asn Ser Tyr Ile Lys Leu Lys Lys Asp Ser Pro Val Gly Glu Ile Leu 
        675                 680                 685             


Thr Arg Ser Lys Tyr Asn Gln Asn Ser Lys Tyr Ile Asn Tyr Arg Asp 
    690                 695                 700                 


Leu Tyr Ile Gly Glu Lys Phe Ile Ile Arg Arg Lys Ser Asn Ser Gln 
705                 710                 715                 720 


Ser Ile Asn Asp Asp Ile Val Arg Lys Glu Asp Tyr Ile Tyr Leu Asp 
                725                 730                 735     


Phe Phe Asn Leu Asn Gln Glu Trp Arg Val Tyr Thr Tyr Lys Tyr Phe 
            740                 745                 750         


Lys Lys Glu Glu Glu Lys Leu Phe Leu Ala Pro Ile Ser Asp Ser Asp 
        755                 760                 765             


Glu Phe Tyr Asn Thr Ile Gln Ile Lys Glu Tyr Asp Glu Gln Pro Thr 
    770                 775                 780                 


Tyr Ser Cys Gln Leu Leu Phe Lys Lys Asp Glu Glu Ser Thr Asp Glu 
785                 790                 795                 800 


Ile Gly Leu Ile Gly Ile His Arg Phe Tyr Glu Ser Gly Ile Val Phe 
                805                 810                 815     


Glu Glu Tyr Lys Asp Tyr Phe Cys Ile Ser Lys Trp Tyr Leu Lys Glu 
            820                 825                 830         


Val Lys Arg Lys Pro Tyr Asn Leu Lys Leu Gly Cys Asn Trp Gln Phe 
        835                 840                 845             


Ile Pro Lys Asp Glu Gly Trp Thr Glu 
    850                 855         


<210>  10
<211>  819
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Neurotoxin E + F (BoNT/E + BoNT/F)

<400>  10

Met Asp Trp Thr Trp Ile Leu Phe Leu Val Ala Ala Ala Thr Arg Val 
1               5                   10                  15      


His Ser Asp Lys Tyr Val Asp Thr Ser Gly Tyr Asp Ser Asn Ile Asn 
            20                  25                  30          


Ile Asn Gly Asp Val Tyr Lys Tyr Pro Thr Asn Lys Asn Gln Phe Gly 
        35                  40                  45              


Ile Tyr Asn Asp Lys Leu Ser Glu Val Asn Ile Ser Gln Asn Asp Tyr 
    50                  55                  60                  


Ile Ile Tyr Asp Asn Lys Tyr Lys Asn Phe Ser Ile Ser Phe Trp Val 
65                  70                  75                  80  


Arg Ile Pro Asn Tyr Asp Asn Lys Ile Val Asn Val Asn Asn Glu Tyr 
                85                  90                  95      


Thr Ile Ile Asn Cys Met Arg Asp Asn Asn Ser Gly Trp Lys Val Ser 
            100                 105                 110         


Leu Asn His Asn Glu Ile Ile Trp Thr Leu Gln Asp Asn Ala Gly Ile 
        115                 120                 125             


Asn Gln Lys Leu Ala Phe Asn Tyr Gly Asn Ala Asn Gly Ile Ser Asp 
    130                 135                 140                 


Tyr Ile Asn Lys Trp Ile Phe Val Thr Ile Thr Asn Asp Arg Leu Gly 
145                 150                 155                 160 


Asp Ser Lys Leu Tyr Ile Asn Gly Asn Leu Ile Asp Gln Lys Ser Ile 
                165                 170                 175     


Leu Asn Leu Gly Asn Ile His Val Ser Asp Asn Ile Leu Phe Lys Ile 
            180                 185                 190         


Val Asn Cys Ser Tyr Thr Arg Tyr Ile Gly Ile Arg Tyr Phe Asn Ile 
        195                 200                 205             


Phe Asp Lys Glu Leu Asp Glu Thr Glu Ile Gln Thr Leu Tyr Ser Asn 
    210                 215                 220                 


Glu Pro Asn Thr Asn Ile Leu Lys Asp Phe Trp Gly Asn Tyr Leu Leu 
225                 230                 235                 240 


Tyr Asp Lys Glu Tyr Tyr Leu Leu Asn Val Leu Lys Pro Asn Asn Phe 
                245                 250                 255     


Ile Asp Arg Arg Lys Asp Ser Thr Leu Ser Ile Asn Asn Ile Arg Ser 
            260                 265                 270         


Thr Ile Leu Leu Ala Asn Arg Leu Tyr Ser Gly Ile Lys Val Lys Ile 
        275                 280                 285             


Gln Arg Val Asn Asn Ser Ser Thr Asn Asp Asn Leu Val Arg Lys Asn 
    290                 295                 300                 


Asp Gln Val Tyr Ile Asn Phe Val Ala Ser Lys Thr His Leu Phe Pro 
305                 310                 315                 320 


Leu Tyr Ala Asp Thr Ala Thr Thr Asn Lys Glu Lys Thr Ile Lys Ile 
                325                 330                 335     


Ser Ser Ser Gly Asn Arg Phe Asn Gln Val Val Val Met Asn Ser Val 
            340                 345                 350         


Gly Asn Asn Cys Thr Met Asn Phe Lys Asn Asn Asn Gly Asn Asn Ile 
        355                 360                 365             


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


Tyr Thr His Met Arg Asp His Thr Asn Ser Asn Gly Cys Phe Trp Asn 
385                 390                 395                 400 


Phe Ile Ser Glu Glu His Gly Trp Gln Glu Lys Arg Gly Arg Lys Arg 
                405                 410                 415     


Arg Ser Asn Asn Lys Phe Ile Asp Ile Ser Gly Tyr Gly Ser Asn Ile 
            420                 425                 430         


Ser Ile Asn Gly Asp Val Tyr Ile Tyr Ser Thr Asn Arg Asn Gln Phe 
        435                 440                 445             


Gly Ile Tyr Ser Ser Lys Pro Ser Glu Val Asn Ile Ala Gln Asn Asn 
    450                 455                 460                 


Asp Ile Ile Tyr Asn Gly Arg Tyr Gln Asn Phe Ser Ile Ser Phe Trp 
465                 470                 475                 480 


Val Arg Ile Pro Lys Tyr Phe Asn Lys Val Asn Leu Asn Asn Glu Tyr 
                485                 490                 495     


Thr Ile Ile Asp Cys Ile Arg Asn Asn Asn Ser Gly Trp Lys Ile Ser 
            500                 505                 510         


Leu Asn Tyr Asn Lys Ile Ile Trp Thr Leu Gln Asp Thr Ala Gly Asn 
        515                 520                 525             


Asn Gln Lys Leu Val Phe Asn Tyr Thr Gln Met Ile Ser Ile Ser Asp 
    530                 535                 540                 


Tyr Ile Asn Lys Trp Ile Phe Val Thr Ile Thr Asn Asn Arg Leu Gly 
545                 550                 555                 560 


Asn Ser Arg Ile Tyr Ile Asn Gly Asn Leu Ile Asp Glu Lys Ser Ile 
                565                 570                 575     


Ser Asn Leu Gly Asp Ile His Val Ser Asp Asn Ile Leu Phe Lys Ile 
            580                 585                 590         


Val Gly Cys Asn Asp Thr Arg Tyr Val Gly Ile Arg Tyr Phe Lys Val 
        595                 600                 605             


Phe Asp Thr Glu Leu Gly Lys Thr Glu Ile Glu Thr Leu Tyr Ser Asp 
    610                 615                 620                 


Glu Pro Asp Pro Ser Ile Leu Lys Asp Phe Trp Gly Asn Tyr Leu Leu 
625                 630                 635                 640 


Tyr Asn Lys Arg Tyr Tyr Leu Leu Asn Leu Leu Arg Thr Asp Lys Ser 
                645                 650                 655     


Ile Thr Gln Asn Ser Asn Phe Leu Asn Ile Asn Gln Gln Arg Gly Val 
            660                 665                 670         


Tyr Gln Lys Pro Asn Ile Phe Ser Asn Thr Arg Leu Tyr Thr Gly Val 
        675                 680                 685             


Glu Val Ile Ile Arg Lys Asn Gly Ser Thr Asp Ile Ser Asn Thr Asp 
    690                 695                 700                 


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


Asp Val Glu Tyr Arg Leu Tyr Ala Asp Ile Ser Ile Ala Lys Pro Glu 
                725                 730                 735     


Lys Ile Ile Lys Leu Ile Arg Thr Ser Asn Ser Asn Asn Ser Leu Gly 
            740                 745                 750         


Gln Ile Ile Val Met Asp Ser Ile Gly Asn Asn Cys Thr Met Asn Phe 
        755                 760                 765             


Gln Asn Asn Asn Gly Gly Asn Ile Gly Leu Leu Gly Phe His Ser Asn 
    770                 775                 780                 


Asn Leu Val Ala Ser Ser Trp Tyr Tyr Asn Asn Ile Arg Lys Asn Thr 
785                 790                 795                 800 


Ser Ser Asn Gly Cys Phe Trp Ser Phe Ile Ser Lys Glu His Gly Trp 
                805                 810                 815     


Gln Glu Asn 
            


<210>  11
<211>  1665
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Neurotoxin A + B + E + F (BoNT/A + BoNT/B + BoNT/E + BoNT/F)

<400>  11

Met Asp Trp Thr Trp Ile Leu Phe Leu Val Ala Ala Ala Thr Arg Val 
1               5                   10                  15      


His Ser Ser Asn His Leu Ile Asp Leu Ser Arg Tyr Ala Ser Lys Ile 
            20                  25                  30          


Asn Ile Gly Ser Lys Val Asn Phe Asp Pro Ile Asp Lys Asn Gln Ile 
        35                  40                  45              


Gln Leu Phe Asn Leu Glu Ser Ser Lys Ile Glu Val Ile Leu Lys Asn 
    50                  55                  60                  


Ala Ile Val Tyr Asn Ser Met Tyr Glu Asn Phe Ser Thr Ser Phe Trp 
65                  70                  75                  80  


Ile Arg Ile Pro Lys Tyr Phe Asn Ser Ile Ser Leu Asn Asn Glu Tyr 
                85                  90                  95      


Thr Ile Ile Asn Cys Met Glu Asn Asn Ser Gly Trp Lys Val Ser Leu 
            100                 105                 110         


Asn Tyr Gly Glu Ile Ile Trp Thr Leu Gln Asp Thr Gln Glu Ile Lys 
        115                 120                 125             


Gln Arg Val Val Phe Lys Tyr Ser Gln Met Ile Asn Ile Ser Asp Tyr 
    130                 135                 140                 


Ile Asn Arg Trp Ile Phe Val Thr Ile Thr Asn Asn Arg Leu Asn Asn 
145                 150                 155                 160 


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


Asn Leu Gly Asn Ile His Ala Ser Asn Asn Ile Met Phe Lys Leu Asp 
            180                 185                 190         


Gly Cys Arg Asp Thr His Arg Tyr Ile Trp Ile Lys Tyr Phe Asn Leu 
        195                 200                 205             


Phe Asp Lys Glu Leu Asn Glu Lys Glu Ile Lys Asp Leu Tyr Asp Asn 
    210                 215                 220                 


Gln Ser Asn Ser Gly Ile Leu Lys Asp Phe Trp Gly Asp Tyr Leu Gln 
225                 230                 235                 240 


Tyr Asp Lys Pro Tyr Tyr Met Leu Asn Leu Tyr Asp Pro Asn Lys Tyr 
                245                 250                 255     


Val Asp Val Asn Asn Val Gly Ile Arg Gly Tyr Met Tyr Leu Lys Gly 
            260                 265                 270         


Pro Arg Gly Ser Val Met Thr Thr Asn Ile Tyr Leu Asn Ser Ser Leu 
        275                 280                 285             


Tyr Arg Gly Thr Lys Phe Ile Ile Lys Lys Tyr Ala Ser Gly Asn Lys 
    290                 295                 300                 


Asp Asn Ile Val Arg Asn Asn Asp Arg Val Tyr Ile Asn Val Val Val 
305                 310                 315                 320 


Lys Asn Lys Glu Tyr Arg Leu Ala Thr Asn Ala Ser Gln Ala Gly Val 
                325                 330                 335     


Glu Lys Ile Leu Ser Ala Leu Glu Ile Pro Asp Val Gly Asn Leu Ser 
            340                 345                 350         


Gln Val Val Val Met Lys Ser Lys Asn Asp Gln Gly Ile Thr Asn Lys 
        355                 360                 365             


Cys Lys Met Asn Leu Gln Asp Asn Asn Gly Asn Asp Ile Gly Phe Ile 
    370                 375                 380                 


Gly Phe His Gln Phe Asn Asn Ile Ala Lys Leu Val Ala Ser Asn Trp 
385                 390                 395                 400 


Tyr Asn Arg Gln Ile Glu Arg Ser Ser Arg Thr Leu Gly Cys Ser Trp 
                405                 410                 415     


Glu Phe Ile Pro Val Asp Asp Gly Trp Gly Glu Arg Pro Leu Arg Gly 
            420                 425                 430         


Arg Lys Arg Arg Ser Asp Asn Asn Leu Ile Asp Leu Ser Gly Tyr Gly 
        435                 440                 445             


Ala Lys Val Glu Val Tyr Asp Gly Val Glu Leu Asn Asp Lys Asn Gln 
    450                 455                 460                 


Phe Lys Leu Thr Ser Ser Ala Asn Ser Lys Ile Arg Val Thr Gln Asn 
465                 470                 475                 480 


Gln Asn Ile Ile Phe Asn Ser Val Phe Leu Asp Phe Ser Val Ser Phe 
                485                 490                 495     


Trp Ile Arg Ile Pro Lys Tyr Lys Asn Asp Gly Ile Gln Asn Tyr Ile 
            500                 505                 510         


His Asn Glu Tyr Thr Ile Ile Asn Cys Met Lys Asn Asn Ser Gly Trp 
        515                 520                 525             


Lys Ile Ser Ile Arg Gly Asn Arg Ile Ile Trp Thr Leu Ile Asp Ile 
    530                 535                 540                 


Asn Gly Lys Thr Lys Ser Val Phe Phe Glu Tyr Asn Ile Arg Glu Asp 
545                 550                 555                 560 


Ile Ser Glu Tyr Ile Asn Arg Trp Phe Phe Val Thr Ile Thr Asn Asn 
                565                 570                 575     


Leu Asn Asn Ala Lys Ile Tyr Ile Asn Gly Lys Leu Glu Ser Asn Thr 
            580                 585                 590         


Asp Ile Lys Asp Ile Arg Glu Val Ile Ala Asn Gly Glu Ile Ile Phe 
        595                 600                 605             


Lys Leu Asp Gly Asp Ile Asp Arg Thr Gln Phe Ile Trp Met Lys Tyr 
    610                 615                 620                 


Phe Ser Ile Phe Asn Thr Glu Leu Ser Gln Ser Asn Ile Glu Glu Arg 
625                 630                 635                 640 


Tyr Lys Ile Gln Ser Tyr Ser Glu Tyr Leu Lys Asp Phe Trp Gly Asn 
                645                 650                 655     


Pro Leu Met Tyr Asn Lys Glu Tyr Tyr Met Phe Asn Ala Gly Asn Lys 
            660                 665                 670         


Asn Ser Tyr Ile Lys Leu Lys Lys Asp Ser Pro Val Gly Glu Ile Leu 
        675                 680                 685             


Thr Arg Ser Lys Tyr Asn Gln Asn Ser Lys Tyr Ile Asn Tyr Arg Asp 
    690                 695                 700                 


Leu Tyr Ile Gly Glu Lys Phe Ile Ile Arg Arg Lys Ser Asn Ser Gln 
705                 710                 715                 720 


Ser Ile Asn Asp Asp Ile Val Arg Lys Glu Asp Tyr Ile Tyr Leu Asp 
                725                 730                 735     


Phe Phe Asn Leu Asn Gln Glu Trp Arg Val Tyr Thr Tyr Lys Tyr Phe 
            740                 745                 750         


Lys Lys Glu Glu Glu Lys Leu Phe Leu Ala Pro Ile Ser Asp Ser Asp 
        755                 760                 765             


Glu Phe Tyr Asn Thr Ile Gln Ile Lys Glu Tyr Asp Glu Gln Pro Thr 
    770                 775                 780                 


Tyr Ser Cys Gln Leu Leu Phe Lys Lys Asp Glu Glu Ser Thr Asp Glu 
785                 790                 795                 800 


Ile Gly Leu Ile Gly Ile His Arg Phe Tyr Glu Ser Gly Ile Val Phe 
                805                 810                 815     


Glu Glu Tyr Lys Asp Tyr Phe Cys Ile Ser Lys Trp Tyr Leu Lys Glu 
            820                 825                 830         


Val Lys Arg Lys Pro Tyr Asn Leu Lys Leu Gly Cys Asn Trp Gln Phe 
        835                 840                 845             


Ile Pro Lys Asp Glu Gly Trp Thr Glu Arg Gly Arg Lys Arg Arg Ser 
    850                 855                 860                 


Asp Lys Tyr Val Asp Thr Ser Gly Tyr Asp Ser Asn Ile Asn Ile Asn 
865                 870                 875                 880 


Gly Asp Val Tyr Lys Tyr Pro Thr Asn Lys Asn Gln Phe Gly Ile Tyr 
                885                 890                 895     


Asn Asp Lys Leu Ser Glu Val Asn Ile Ser Gln Asn Asp Tyr Ile Ile 
            900                 905                 910         


Tyr Asp Asn Lys Tyr Lys Asn Phe Ser Ile Ser Phe Trp Val Arg Ile 
        915                 920                 925             


Pro Asn Tyr Asp Asn Lys Ile Val Asn Val Asn Asn Glu Tyr Thr Ile 
    930                 935                 940                 


Ile Asn Cys Met Arg Asp Asn Asn Ser Gly Trp Lys Val Ser Leu Asn 
945                 950                 955                 960 


His Asn Glu Ile Ile Trp Thr Leu Gln Asp Asn Ala Gly Ile Asn Gln 
                965                 970                 975     


Lys Leu Ala Phe Asn Tyr Gly Asn Ala Asn Gly Ile Ser Asp Tyr Ile 
            980                 985                 990         


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


Lys Leu  Tyr Ile Asn Gly Asn  Leu Ile Asp Gln Lys  Ser Ile Leu 
    1010                 1015                 1020             


Asn Leu  Gly Asn Ile His Val  Ser Asp Asn Ile Leu  Phe Lys Ile 
    1025                 1030                 1035             


Val Asn  Cys Ser Tyr Thr Arg  Tyr Ile Gly Ile Arg  Tyr Phe Asn 
    1040                 1045                 1050             


Ile Phe  Asp Lys Glu Leu Asp  Glu Thr Glu Ile Gln  Thr Leu Tyr 
    1055                 1060                 1065             


Ser Asn  Glu Pro Asn Thr Asn  Ile Leu Lys Asp Phe  Trp Gly Asn 
    1070                 1075                 1080             


Tyr Leu  Leu Tyr Asp Lys Glu  Tyr Tyr Leu Leu Asn  Val Leu Lys 
    1085                 1090                 1095             


Pro Asn  Asn Phe Ile Asp Arg  Arg Lys Asp Ser Thr  Leu Ser Ile 
    1100                 1105                 1110             


Asn Asn  Ile Arg Ser Thr Ile  Leu Leu Ala Asn Arg  Leu Tyr Ser 
    1115                 1120                 1125             


Gly Ile  Lys Val Lys Ile Gln  Arg Val Asn Asn Ser  Ser Thr Asn 
    1130                 1135                 1140             


Asp Asn  Leu Val Arg Lys Asn  Asp Gln Val Tyr Ile  Asn Phe Val 
    1145                 1150                 1155             


Ala Ser  Lys Thr His Leu Phe  Pro Leu Tyr Ala Asp  Thr Ala Thr 
    1160                 1165                 1170             


Thr Asn  Lys Glu Lys Thr Ile  Lys Ile Ser Ser Ser  Gly Asn Arg 
    1175                 1180                 1185             


Phe Asn  Gln Val Val Val Met  Asn Ser Val Gly Asn  Asn Cys Thr 
    1190                 1195                 1200             


Met Asn  Phe Lys Asn Asn Asn  Gly Asn Asn Ile Gly  Leu Leu Gly 
    1205                 1210                 1215             


Phe Lys  Ala Asp Thr Val Val  Ala Ser Thr Trp Tyr  Tyr Thr His 
    1220                 1225                 1230             


Met Arg  Asp His Thr Asn Ser  Asn Gly Cys Phe Trp  Asn Phe Ile 
    1235                 1240                 1245             


Ser Glu  Glu His Gly Trp Gln  Glu Lys Arg Gly Arg  Lys Arg Arg 
    1250                 1255                 1260             


Ser Asn  Asn Lys Phe Ile Asp  Ile Ser Gly Tyr Gly  Ser Asn Ile 
    1265                 1270                 1275             


Ser Ile  Asn Gly Asp Val Tyr  Ile Tyr Ser Thr Asn  Arg Asn Gln 
    1280                 1285                 1290             


Phe Gly  Ile Tyr Ser Ser Lys  Pro Ser Glu Val Asn  Ile Ala Gln 
    1295                 1300                 1305             


Asn Asn  Asp Ile Ile Tyr Asn  Gly Arg Tyr Gln Asn  Phe Ser Ile 
    1310                 1315                 1320             


Ser Phe  Trp Val Arg Ile Pro  Lys Tyr Phe Asn Lys  Val Asn Leu 
    1325                 1330                 1335             


Asn Asn  Glu Tyr Thr Ile Ile  Asp Cys Ile Arg Asn  Asn Asn Ser 
    1340                 1345                 1350             


Gly Trp  Lys Ile Ser Leu Asn  Tyr Asn Lys Ile Ile  Trp Thr Leu 
    1355                 1360                 1365             


Gln Asp  Thr Ala Gly Asn Asn  Gln Lys Leu Val Phe  Asn Tyr Thr 
    1370                 1375                 1380             


Gln Met  Ile Ser Ile Ser Asp  Tyr Ile Asn Lys Trp  Ile Phe Val 
    1385                 1390                 1395             


Thr Ile  Thr Asn Asn Arg Leu  Gly Asn Ser Arg Ile  Tyr Ile Asn 
    1400                 1405                 1410             


Gly Asn  Leu Ile Asp Glu Lys  Ser Ile Ser Asn Leu  Gly Asp Ile 
    1415                 1420                 1425             


His Val  Ser Asp Asn Ile Leu  Phe Lys Ile Val Gly  Cys Asn Asp 
    1430                 1435                 1440             


Thr Arg  Tyr Val Gly Ile Arg  Tyr Phe Lys Val Phe  Asp Thr Glu 
    1445                 1450                 1455             


Leu Gly  Lys Thr Glu Ile Glu  Thr Leu Tyr Ser Asp  Glu Pro Asp 
    1460                 1465                 1470             


Pro Ser  Ile Leu Lys Asp Phe  Trp Gly Asn Tyr Leu  Leu Tyr Asn 
    1475                 1480                 1485             


Lys Arg  Tyr Tyr Leu Leu Asn  Leu Leu Arg Thr Asp  Lys Ser Ile 
    1490                 1495                 1500             


Thr Gln  Asn Ser Asn Phe Leu  Asn Ile Asn Gln Gln  Arg Gly Val 
    1505                 1510                 1515             


Tyr Gln  Lys Pro Asn Ile Phe  Ser Asn Thr Arg Leu  Tyr Thr Gly 
    1520                 1525                 1530             


Val Glu  Val Ile Ile Arg Lys  Asn Gly Ser Thr Asp  Ile Ser Asn 
    1535                 1540                 1545             


Thr Asp  Asn Phe Val Arg Lys  Asn Asp Leu Ala Tyr  Ile Asn Val 
    1550                 1555                 1560             


Val Asp  Arg Asp Val Glu Tyr  Arg Leu Tyr Ala Asp  Ile Ser Ile 
    1565                 1570                 1575             


Ala Lys  Pro Glu Lys Ile Ile  Lys Leu Ile Arg Thr  Ser Asn Ser 
    1580                 1585                 1590             


Asn Asn  Ser Leu Gly Gln Ile  Ile Val Met Asp Ser  Ile Gly Asn 
    1595                 1600                 1605             


Asn Cys  Thr Met Asn Phe Gln  Asn Asn Asn Gly Gly  Asn Ile Gly 
    1610                 1615                 1620             


Leu Leu  Gly Phe His Ser Asn  Asn Leu Val Ala Ser  Ser Trp Tyr 
    1625                 1630                 1635             


Tyr Asn  Asn Ile Arg Lys Asn  Thr Ser Ser Asn Gly  Cys Phe Trp 
    1640                 1645                 1650             


Ser Phe  Ile Ser Lys Glu His  Gly Trp Gln Glu Asn  
    1655                 1660                 1665 


