                               SEQUENCE LISTING

<110> BIOMARIN PHARMACEUTICAL INC.
 
<120> COMPOSITIONS OF BETA-HEXOSAMINIDASE VARIANTS AND USES THEREOF

<130> 58039-719.601

<140> PCT/US2022/034861
<141> 2022-06-24

<150> 63/215,328
<151> 2021-06-25

<160> 19    

<170> PatentIn version 3.5

<210> 1
<211> 529
<212> PRT
<213> Unknown

<220>
<223> Description of Unknown: 
      HexA alpha subunit sequence

<400> 1
Met Thr Ser Ser Arg Leu Trp Phe Ser Leu Leu Leu Ala Ala Ala Phe 
1               5                   10                  15      


Ala Gly Arg Ala Thr Ala Leu Trp Pro Trp Pro Gln Asn Phe Gln Thr 
            20                  25                  30          


Ser Asp Gln Arg Tyr Val Leu Tyr Pro Asn Asn Phe Gln Phe Gln Tyr 
        35                  40                  45              


Asp Val Ser Ser Ala Ala Gln Pro Gly Cys Ser Val Leu Asp Glu Ala 
    50                  55                  60                  


Phe Gln Arg Tyr Arg Asp Leu Leu Phe Gly Ser Gly Ser Trp Pro Arg 
65                  70                  75                  80  


Pro Tyr Leu Thr Gly Lys Arg His Thr Leu Glu Lys Asn Val Leu Val 
                85                  90                  95      


Val Ser Val Val Thr Pro Gly Cys Asn Gln Leu Pro Thr Leu Glu Ser 
            100                 105                 110         


Val Glu Asn Tyr Thr Leu Thr Ile Asn Asp Asp Gln Cys Leu Leu Leu 
        115                 120                 125             


Ser Glu Thr Val Trp Gly Ala Leu Arg Gly Leu Glu Thr Phe Ser Gln 
    130                 135                 140                 


Leu Val Trp Lys Ser Ala Glu Gly Thr Phe Phe Ile Asn Lys Thr Glu 
145                 150                 155                 160 


Ile Glu Asp Phe Pro Arg Phe Pro His Arg Gly Leu Leu Leu Asp Thr 
                165                 170                 175     


Ser Arg His Tyr Leu Pro Leu Ser Ser Ile Leu Asp Thr Leu Asp Val 
            180                 185                 190         


Met Ala Tyr Asn Lys Leu Asn Val Phe His Trp His Leu Val Asp Asp 
        195                 200                 205             


Pro Ser Phe Pro Tyr Glu Ser Phe Thr Phe Pro Glu Leu Met Arg Lys 
    210                 215                 220                 


Gly Ser Tyr Asn Pro Val Thr His Ile Tyr Thr Ala Gln Asp Val Lys 
225                 230                 235                 240 


Glu Val Ile Glu Tyr Ala Arg Leu Arg Gly Ile Arg Val Leu Ala Glu 
                245                 250                 255     


Phe Asp Thr Pro Gly His Thr Leu Ser Trp Gly Pro Gly Ile Pro Gly 
            260                 265                 270         


Leu Leu Thr Pro Cys Tyr Ser Gly Ser Glu Pro Ser Gly Thr Phe Gly 
        275                 280                 285             


Pro Val Asn Pro Ser Leu Asn Asn Thr Tyr Glu Phe Met Ser Thr Phe 
    290                 295                 300                 


Phe Leu Glu Val Ser Ser Val Phe Pro Asp Phe Tyr Leu His Leu Gly 
305                 310                 315                 320 


Gly Asp Glu Val Asp Phe Thr Cys Trp Lys Ser Asn Pro Glu Ile Gln 
                325                 330                 335     


Asp Phe Met Arg Lys Lys Gly Phe Gly Glu Asp Phe Lys Gln Leu Glu 
            340                 345                 350         


Ser Phe Tyr Ile Gln Thr Leu Leu Asp Ile Val Ser Ser Tyr Gly Lys 
        355                 360                 365             


Gly Tyr Val Val Trp Gln Glu Val Phe Asp Asn Lys Val Lys Ile Gln 
    370                 375                 380                 


Pro Asp Thr Ile Ile Gln Val Trp Arg Glu Asp Ile Pro Val Asn Tyr 
385                 390                 395                 400 


Met Lys Glu Leu Glu Leu Val Thr Lys Ala Gly Phe Arg Ala Leu Leu 
                405                 410                 415     


Ser Ala Pro Trp Tyr Leu Asn Arg Ile Ser Tyr Gly Pro Asp Trp Lys 
            420                 425                 430         


Asp Phe Tyr Ile Val Glu Pro Leu Ala Phe Glu Gly Thr Pro Glu Gln 
        435                 440                 445             


Lys Ala Leu Val Ile Gly Gly Glu Ala Cys Met Trp Gly Glu Tyr Val 
    450                 455                 460                 


Asp Asn Thr Asn Leu Val Pro Arg Leu Trp Pro Arg Ala Gly Ala Val 
465                 470                 475                 480 


Ala Glu Arg Leu Trp Ser Asn Lys Leu Thr Ser Asp Leu Thr Phe Ala 
                485                 490                 495     


Tyr Glu Arg Leu Ser His Phe Arg Cys Glu Leu Leu Arg Arg Gly Val 
            500                 505                 510         


Gln Ala Gln Pro Leu Asn Val Gly Phe Cys Glu Gln Glu Phe Glu Gln 
        515                 520                 525             


Thr 
    


<210> 2
<211> 555
<212> PRT
<213> Unknown

<220>
<223> Description of Unknown: 
      HexA beta subunit sequence

<400> 2
Met Glu Leu Cys Gly Leu Gly Leu Pro Arg Pro Pro Met Leu Leu Ala 
1               5                   10                  15      


Leu Leu Leu Ala Thr Leu Leu Ala Ala Met Leu Ala Leu Leu Thr Gln 
            20                  25                  30          


Val Ala Leu Val Val Gln Val Ala Glu Ala Ala Arg Ala Pro Ser Val 
        35                  40                  45              


Ser Ala Lys Pro Gly Pro Ala Leu Trp Pro Leu Pro Leu Ser Val Lys 
    50                  55                  60                  


Met Thr Pro Asn Leu Leu His Leu Ala Pro Glu Asn Phe Tyr Ile Ser 
65                  70                  75                  80  


His Ser Pro Asn Ser Thr Ala Gly Pro Ser Cys Thr Leu Leu Glu Glu 
                85                  90                  95      


Ala Phe Arg Tyr His Gly Tyr Ile Phe Gly Phe Tyr Lys Trp His His 
            100                 105                 110         


Glu Pro Ala Glu Phe Gln Ala Lys Thr Gln Val Gln Gln Leu Leu Val 
        115                 120                 125             


Ser Ile Thr Leu Gln Ser Glu Cys Asp Ala Phe Pro Asn Ile Ser Ser 
    130                 135                 140                 


Asp Glu Ser Tyr Thr Leu Leu Val Lys Glu Pro Val Ala Val Leu Lys 
145                 150                 155                 160 


Ala Asn Arg Val Trp Gly Ala Leu Arg Gly Leu Glu Thr Phe Ser Gln 
                165                 170                 175     


Leu Val Tyr Gln Asp Ser Tyr Gly Thr Phe Thr Ile Asn Glu Ser Thr 
            180                 185                 190         


Ile Ile Asp Ser Pro Arg Phe Ser His Arg Gly Ile Leu Ile Asp Thr 
        195                 200                 205             


Ser Arg His Tyr Leu Pro Val Lys Ile Ile Leu Lys Thr Leu Asp Ala 
    210                 215                 220                 


Met Ala Phe Asn Lys Phe Asn Val Leu His Trp His Ile Val Asp Asp 
225                 230                 235                 240 


Gln Ser Phe Pro Tyr Gln Ser Ile Thr Phe Pro Glu Leu Ser Asn Lys 
                245                 250                 255     


Gly Ser Tyr Ser Leu Ser His Val Tyr Thr Pro Asn Asp Val Arg Met 
            260                 265                 270         


Val Ile Glu Tyr Ala Arg Leu Arg Gly Ile Arg Val Leu Pro Glu Phe 
        275                 280                 285             


Asp Thr Pro Gly His Thr Leu Ser Trp Gly Lys Gly Gln Lys Asp Leu 
    290                 295                 300                 


Leu Thr Pro Cys Tyr Ser Arg Gln Asn Lys Leu Asp Ser Phe Gly Pro 
305                 310                 315                 320 


Ile Asn Pro Thr Leu Asn Thr Thr Tyr Ser Phe Leu Thr Thr Phe Phe 
                325                 330                 335     


Lys Glu Ile Ser Glu Val Phe Pro Asp Gln Phe Ile His Leu Gly Gly 
            340                 345                 350         


Asp Glu Val Glu Phe Lys Cys Trp Glu Ser Asn Pro Lys Ile Gln Asp 
        355                 360                 365             


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


Phe Tyr Ile Gln Lys Val Leu Asp Ile Ile Ala Thr Ile Asn Lys Gly 
385                 390                 395                 400 


Ser Ile Val Trp Gln Glu Val Phe Asp Asp Lys Ala Lys Leu Ala Pro 
                405                 410                 415     


Gly Thr Ile Val Glu Val Trp Lys Asp Ser Ala Tyr Pro Glu Glu Leu 
            420                 425                 430         


Ser Arg Val Thr Ala Ser Gly Phe Pro Val Ile Leu Ser Ala Pro Trp 
        435                 440                 445             


Tyr Leu Asp Leu Ile Ser Tyr Gly Gln Asp Trp Arg Lys Tyr Tyr Lys 
    450                 455                 460                 


Val Glu Pro Leu Asp Phe Gly Gly Thr Gln Lys Gln Lys Gln Leu Phe 
465                 470                 475                 480 


Ile Gly Gly Glu Ala Cys Leu Trp Gly Glu Tyr Val Asp Ala Thr Asn 
                485                 490                 495     


Leu Thr Pro Arg Leu Trp Pro Arg Ala Ser Ala Val Gly Glu Arg Leu 
            500                 505                 510         


Trp Ser Ser Lys Asp Val Arg Asp Met Asp Asp Ala Tyr Asp Arg Leu 
        515                 520                 525             


Thr Arg His Arg Cys Arg Met Val Glu Arg Gly Ile Ala Ala Gln Pro 
    530                 535                 540                 


Leu Tyr Ala Gly Tyr Cys Asn His Glu Asn Met 
545                 550                 555 


<210> 3
<211> 561
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 3
Met Glu Leu Cys Gly Leu Gly Leu Pro Arg Pro Pro Met Leu Leu Ala 
1               5                   10                  15      


Leu Leu Leu Ala Thr Leu Leu Ala Ala Met Leu Ala Leu Leu Thr Gln 
            20                  25                  30          


Val Ala Leu Val Val Gln Val Ala Glu Ala Ala Arg Ala Pro Ser Val 
        35                  40                  45              


Ser Ala Lys Pro Gly Pro Ala Leu Trp Pro Leu Pro Leu Ser Val Lys 
    50                  55                  60                  


Met Thr Pro Asn Leu Leu His Leu Ala Pro Glu Asn Phe Tyr Ile Ser 
65                  70                  75                  80  


His Ser Pro Asn Ser Thr Ala Gly Pro Ser Cys Thr Leu Leu Glu Glu 
                85                  90                  95      


Ala Phe Arg Arg Tyr His Gly Tyr Ile Phe Gly Phe Tyr Lys Trp His 
            100                 105                 110         


His Glu Pro Ala Glu Phe Gln Ala Lys Thr Gln Val Gln Gln Leu Leu 
        115                 120                 125             


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


Ser Asp Glu Ser Tyr Thr Leu Leu Val Lys Glu Pro Val Ala Val Leu 
145                 150                 155                 160 


Lys Ala Asn Arg Val Trp Gly Ala Leu Arg Gly Leu Glu Thr Phe Ser 
                165                 170                 175     


Gln Leu Val Tyr Gln Asp Ser Tyr Gly Thr Phe Thr Ile Asn Glu Ser 
            180                 185                 190         


Thr Ile Ile Asp Ser Pro Arg Phe Pro His Arg Gly Leu Leu Leu Asp 
        195                 200                 205             


Thr Ser Arg His Tyr Leu Pro Leu Lys Ser Ile Leu Asp Thr Leu Asp 
    210                 215                 220                 


Val Met Ala Tyr Asn Lys Leu Asn Val Phe His Trp His Leu Val Asp 
225                 230                 235                 240 


Asp Gln Ser Phe Pro Tyr Glu Ser Phe Thr Phe Pro Glu Leu Met Arg 
                245                 250                 255     


Lys Gly Ser Tyr Ser Leu Ser His Ile Tyr Thr Ala Gln Asp Val Lys 
            260                 265                 270         


Glu Val Ile Glu Tyr Ala Arg Leu Arg Gly Ile Arg Val Leu Ala Glu 
        275                 280                 285             


Phe Asp Thr Pro Gly His Thr Leu Ser Trp Gly Pro Gly Ile Pro Gly 
    290                 295                 300                 


Leu Leu Thr Pro Cys Tyr Ser Gly Ser Glu Pro Ser Gly Thr Phe Gly 
305                 310                 315                 320 


Pro Val Asn Pro Ser Leu Asn Asn Thr Tyr Glu Phe Met Ser Thr Phe 
                325                 330                 335     


Phe Leu Glu Val Ser Ser Val Phe Pro Asp Phe Tyr Leu His Leu Gly 
            340                 345                 350         


Gly Asp Glu Val Asp Phe Thr Cys Trp Lys Ser Asn Pro Glu Ile Gln 
        355                 360                 365             


Asp Phe Met Arg Lys Lys Gly Phe Gly Glu Asp Phe Lys Gln Leu Glu 
    370                 375                 380                 


Ser Phe Tyr Ile Gln Thr Leu Leu Asp Ile Val Ser Ser Tyr Gly Lys 
385                 390                 395                 400 


Gly Tyr Val Val Trp Gln Glu Val Phe Asp Asn Lys Val Lys Ile Gln 
                405                 410                 415     


Pro Asp Thr Ile Ile Gln Val Trp Arg Glu Asp Ile Pro Val Asn Tyr 
            420                 425                 430         


Met Lys Glu Leu Glu Leu Val Thr Lys Ala Gly Phe Arg Ala Leu Leu 
        435                 440                 445             


Ser Ala Pro Trp Tyr Leu Asn Arg Ile Ser Tyr Gly Gln Asp Trp Arg 
    450                 455                 460                 


Lys Phe Tyr Lys Val Glu Pro Leu Ala Phe Glu Gly Thr Pro Glu Gln 
465                 470                 475                 480 


Lys Ala Leu Val Ile Gly Gly Glu Ala Cys Met Trp Gly Glu Tyr Val 
                485                 490                 495     


Asp Ala Thr Asn Leu Val Pro Arg Leu Trp Pro Arg Ala Gly Ala Val 
            500                 505                 510         


Ala Glu Arg Leu Trp Ser Asn Lys Leu Thr Arg Asp Met Asp Asp Ala 
        515                 520                 525             


Tyr Asp Arg Leu Ser His Phe Arg Cys Glu Leu Val Arg Arg Gly Val 
    530                 535                 540                 


Ala Ala Gln Pro Leu Tyr Ala Gly Tyr Cys Asn Gln Glu Phe Glu Gln 
545                 550                 555                 560 


Thr 
    


<210> 4
<211> 1587
<212> DNA
<213> Unknown

<220>
<223> Description of Unknown: 
      HexA alpha subunit sequence

<400> 4
atgacttcct cccgcctttg gttctccctc ctgcttgccg ctgccttcgc cggacgcgcc       60

accgccctgt ggccgtggcc tcagaacttc cagactagcg accaaagata cgtgctgtac      120

ccgaacaact tccagtttca atacgacgtc agcagcgccg cccagcccgg ctgctcggtg      180

ctcgatgagg cattccagcg gtaccgggat ctcttgttcg gttccggatc atggcctcgg      240

ccgtacctca ctggaaagag gcacactctc gaaaagaacg tcctggtggt gtccgtggtc      300

acccctggct gcaatcagct gcccaccctg gaatcagtgg agaactacac tttgaccatc      360

aacgatgacc aatgcctgct gctgtcggag actgtgtggg gtgccctgcg cgggctggaa      420

acctttagcc aactggtctg gaagtcagcc gaggggacct tcttcattaa caagaccgaa      480

atcgaggact tccctcggtt cccgcaccgc ggcttgctgc tggatacctc gcggcactat      540

ctgccactgt cctccattct cgataccctg gacgtgatgg cctacaacaa gctgaacgtg      600

ttccactggc atctcgtgga cgacccatcc tttccctacg agtccttcac cttccctgag      660

ttgatgagaa agggctccta caaccccgtg acccatatct acacggctca ggacgtgaag      720

gaagtgatcg aatatgcccg gctgagaggg attagggtgc tggcagaatt tgacaccccg      780

ggacacaccc tgtcgtgggg ccctggtatc ccgggcctgc tgactccgtg ctactccggc      840

tccgagccat ccggaacctt cggacctgtg aatccctccc tgaacaacac ttacgagttc      900

atgtccacct tcttcctgga agtgtcgagc gtgttccccg acttctacct ccacctcggt      960

ggcgacgaag tcgatttcac ttgctggaag tctaaccccg agatccaaga tttcatgcga     1020

aagaaaggat tcggagagga ctttaagcag ctggagtcct tctacatcca aaccctgctg     1080

gacattgtgt catcgtatgg aaagggatac gtggtgtggc aggaagtgtt tgacaataag     1140

gtcaaaattc agcccgatac aatcatccaa gtctggcgcg aagatatccc cgtgaactac     1200

atgaaagaac tggaactggt cacgaaggct ggattcaggg cgcttctgag cgccccttgg     1260

tacttgaacc ggattagcta cggcccggac tggaaggact tctacatcgt cgaacctctg     1320

gccttcgagg gaacccccga gcagaaggcc ttggtgatcg gcggcgaagc ctgtatgtgg     1380

ggggaatacg tggacaacac caacctggtg ccgcgcctgt ggccgagagc gggagcagtg     1440

gccgagcggc tctggtcgaa caagctgact tccgacctca ccttcgcata cgagagactg     1500

agccacttcc gctgcgaact tcttcggcgg ggggtgcagg cccagccgct caacgtcggg     1560

ttctgtgaac aggagttcga gcagacc                                         1587


<210> 5
<211> 1670
<212> DNA
<213> Unknown

<220>
<223> Description of Unknown: 
      HexA beta subunit sequence

<400> 5
atggagctgt gcgggctggg gctgccccgg ccgcccatgc tgctggcgct gctgttggcg       60

acactgctgg cggcgatgtt ggcgctgctg actcaggtgg cgctggtggt gcaggtggcg      120

gaggcggctc gggccccgag cgtctcggcc aagccggggc cggcgctgtg gcccctgccg      180

ctcttggtga agatgacccc gaacctgctg catctcgccc cggagaactt ctacatcagc      240

cacagcccca attccacggc gggcccctcc tgcaccctgc tggaggaagc gtttcgacga      300

tatcatggct atatttttgg tttctacaag tggcatcatg aacctgctga attccaggct      360

aaaacccagg ttcagcaact tcttgtctca atcacccttc agtcagagtg tgatgctttc      420

cccaacatat cttcagatga gtcttatact ttacttgtga aagaaccagt ggctgtcctt      480

aaggccaaca gagtttgggg agcattacga ggtttagaga cctttagcca gttagtttat      540

caagattctt atggaacttt caccatcaat gaatccacca ttattgattc tccaaggttt      600

tctcacagag gaattttgat tgatacatcc agacattatc tgccagttaa gattattctt      660

aaaactctgg atgccatggc ttttaataag tttaatgttc ttcactggca catagttgat      720

gaccagtctt tcccatatca gagcatcact tttcctgagt taagcaataa aggaagctat      780

tctttgtctc atgtttatac accaaatgat gtccgtatgg tgattgaata tgccagatta      840

cgaggaattc gagtcctgcc agaatttgat acccctgggc atacactatc ttggggaaaa      900

ggtcagaaag acctcctgac tccatgttac agtagacaaa acaagttgga ctcttttgga      960

cctataaacc ctactctgaa tacaacatac gcttccttac tacatttttc aaagaaatta     1020

gtgaggtgtt tccagatcaa ttcattcatt tgggaggaga tgaagtggaa tttaaatgtt     1080

gggaatcaaa tccaaaaatt caagatttca tgaggcaaaa aggctttggc acagatttta     1140

agaaactaga atctttctac attcaaaagg ttttggatat tattgcaacc ataaacaagg     1200

gatccattgt ctggcaggag gtttttgatg ataaagcaaa gcttgcgccg ggcacaatag     1260

ttgaagtatg gaaagacagc gcatatcctg aggaactcag tagagtcaca gcatctggct     1320

tccctgtaat cctttctgct ccttggtact tagatttgat tagctatgga caagattgga     1380

ggaaatacta taaagtggaa cctcttgatt ttggcggtac tcagaaacag aaacaacttt     1440

tcattggtgg agaagcttgt ctatggggag aatatgtgga tgcaactaac ctcactccaa     1500

gattatggcc tcgggcaagt gctgttggtg agagactctg gagttccaaa gatgtcagag     1560

atatggatga cgcctatgac agactgacaa ggcaccgctg caggatggtc gaacgtggaa     1620

tagctgcaca acctctttat gctggatatt gtaaccatga gaacatgtaa                1670


<210> 6
<211> 528
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 6
Met Thr Ser Ser Arg Leu Trp Phe Ser Leu Leu Leu Ala Ala Ala Phe 
1               5                   10                  15      


Ala Gly Arg Ala Thr Ala Leu Trp Pro Trp Pro Gln Asn Phe Gln Thr 
            20                  25                  30          


Ser Asp Gln Arg Tyr Val Leu Tyr Pro Asn Asn Phe Gln Phe Gln Tyr 
        35                  40                  45              


Asp Val Ser Ser Ala Ala Gln Pro Gly Cys Ser Val Leu Asp Glu Ala 
    50                  55                  60                  


Phe Gln Arg Tyr Arg Asp Leu Leu Phe Gly Ser Gly Ser Trp Pro Arg 
65                  70                  75                  80  


Pro Tyr Leu Thr Gly Lys Arg His Thr Leu Glu Lys Asn Val Leu Val 
                85                  90                  95      


Val Ser Val Val Thr Pro Gly Cys Asn Gln Leu Pro Thr Leu Glu Ser 
            100                 105                 110         


Val Glu Asn Tyr Thr Leu Thr Ile Asn Asp Asp Gln Cys Leu Leu Leu 
        115                 120                 125             


Ser Glu Thr Val Trp Gly Ala Leu Arg Gly Leu Glu Thr Phe Ser Gln 
    130                 135                 140                 


Leu Val Trp Lys Ser Ala Glu Gly Thr Phe Phe Ile Asn Lys Thr Glu 
145                 150                 155                 160 


Ile Glu Asp Phe Pro Arg Phe Pro His Arg Gly Leu Leu Leu Asp Thr 
                165                 170                 175     


Ser Arg His Tyr Leu Pro Leu Lys Ser Ile Leu Asp Thr Leu Asp Val 
            180                 185                 190         


Met Ala Tyr Asn Lys Leu Asn Val Phe His Trp His Leu Val Asp Asp 
        195                 200                 205             


Gln Ser Phe Pro Tyr Glu Ser Phe Thr Phe Pro Glu Leu Met Arg Lys 
    210                 215                 220                 


Gly Ser Tyr Ser Leu Ser His Ile Tyr Thr Ala Gln Asp Val Lys Glu 
225                 230                 235                 240 


Val Ile Glu Tyr Ala Arg Leu Arg Gly Ile Arg Val Leu Ala Glu Phe 
                245                 250                 255     


Asp Thr Pro Gly His Thr Leu Ser Trp Gly Pro Gly Ile Pro Gly Leu 
            260                 265                 270         


Leu Thr Pro Cys Tyr Ser Gly Ser Glu Pro Ser Gly Thr Phe Gly Pro 
        275                 280                 285             


Val Asn Pro Ser Leu Asn Asn Thr Tyr Glu Phe Met Ser Thr Phe Phe 
    290                 295                 300                 


Leu Glu Val Ser Ser Val Phe Pro Asp Phe Tyr Leu His Leu Gly Gly 
305                 310                 315                 320 


Asp Glu Val Asp Phe Thr Cys Trp Lys Ser Asn Pro Glu Ile Gln Asp 
                325                 330                 335     


Phe Met Arg Lys Lys Gly Phe Gly Glu Asp Phe Lys Gln Leu Glu Ser 
            340                 345                 350         


Phe Tyr Ile Gln Thr Leu Leu Asp Ile Val Ser Ser Tyr Gly Lys Gly 
        355                 360                 365             


Tyr Val Val Trp Gln Glu Val Phe Asp Asn Lys Val Lys Ile Gln Pro 
    370                 375                 380                 


Asp Thr Ile Ile Gln Val Trp Arg Glu Asp Ile Pro Val Asn Tyr Met 
385                 390                 395                 400 


Lys Glu Leu Glu Leu Val Thr Lys Ala Gly Phe Arg Ala Leu Leu Ser 
                405                 410                 415     


Ala Pro Trp Tyr Leu Asn Arg Ile Ser Tyr Gly Gln Asp Trp Arg Lys 
            420                 425                 430         


Phe Tyr Lys Val Glu Pro Leu Ala Phe Glu Gly Thr Pro Glu Gln Lys 
        435                 440                 445             


Ala Leu Val Ile Gly Gly Glu Ala Cys Met Trp Gly Glu Tyr Val Asp 
    450                 455                 460                 


Ala Thr Asn Leu Val Pro Arg Leu Trp Pro Arg Ala Gly Ala Val Ala 
465                 470                 475                 480 


Glu Arg Leu Trp Ser Asn Lys Leu Thr Arg Asp Met Asp Asp Ala Tyr 
                485                 490                 495     


Asp Arg Leu Ser His Phe Arg Cys Glu Leu Val Arg Arg Gly Val Ala 
            500                 505                 510         


Ala Gln Pro Leu Tyr Ala Gly Tyr Cys Asn Gln Glu Phe Glu Gln Thr 
        515                 520                 525             


<210> 7
<211> 1584
<212> DNA
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polynucleotide

<400> 7
atgacttcct cccgcctttg gttctccctc ctgcttgccg ctgccttcgc cggacgcgcc       60

accgccctgt ggccgtggcc tcagaacttc cagactagcg accaaagata cgtgctgtac      120

ccgaacaact tccagtttca atacgacgtc agcagcgccg cccagcccgg ctgctcggtg      180

ctcgatgagg cattccagcg gtaccgggat ctcttgttcg gttccggatc atggcctcgg      240

ccgtacctca ctggaaagag gcacactctc gaaaagaacg tcctggtggt gtccgtggtc      300

acccctggct gcaatcagct gcccaccctg gaatcagtgg agaactacac tttgaccatc      360

aacgatgacc aatgcctgct gctgtcggag actgtgtggg gtgccctgcg cgggctggaa      420

acctttagcc aactggtctg gaagtcagcc gaggggacct tcttcattaa caagaccgaa      480

atcgaggact tccctcggtt cccgcaccgc ggcttgctgc tggatacctc gcggcactat      540

ctgccactga agtccattct cgataccctg gacgtgatgg cctacaacaa gctgaacgtg      600

ttccactggc atctcgtgga cgaccagtcc tttccctacg agtccttcac cttccctgag      660

ttgatgagaa agggctccta ctccctctcc catatctaca cggctcagga cgtgaaggaa      720

gtgatcgaat atgcccggct gagagggatt agggtgctgg cagaatttga caccccggga      780

cacaccctgt cgtggggccc tggtatcccg ggcctgctga ctccgtgcta ctccggctcc      840

gagccatccg gaaccttcgg acctgtgaat ccctccctga acaacactta cgagttcatg      900

tccaccttct tcctggaagt gtcgagcgtg ttccccgact tctacctcca cctcggtggc      960

gacgaagtcg atttcacttg ctggaagtct aaccccgaga tccaagattt catgcgaaag     1020

aaaggattcg gagaggactt taagcagctg gagtccttct acatccaaac cctgctggac     1080

attgtgtcat cgtatggaaa gggatacgtg gtgtggcagg aagtgtttga caataaggtc     1140

aaaattcagc ccgatacaat catccaagtc tggcgcgaag atatccccgt gaactacatg     1200

aaagaactgg aactggtcac gaaggctgga ttcagggcgc ttctgagcgc cccttggtac     1260

ttgaaccgga ttagctacgg ccaggactgg aggaagttct acaaggtcga acctctggcc     1320

ttcgagggaa cccccgagca gaaggccttg gtgatcggcg gcgaagcctg tatgtggggg     1380

gaatacgtgg acgcgaccaa cctggtgccg cgcctgtggc cgagagcggg agcagtggcc     1440

gagcggctct ggtcgaacaa gctgactagg gacatggacg atgcatacga cagactgagc     1500

cacttccgct gcgaacttgt gcggcggggg gtggcggccc agccgctcta cgcggggtac     1560

tgtaaccagg agttcgagca gacc                                            1584


<210> 8
<211> 1683
<212> DNA
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polynucleotide

<400> 8
atggaacttt gcggactcgg cctcccaaga ccacctatgc ttctcgccct gctgctcgcc       60

accttgctcg cggctatgct tgcgctcctg actcaagtgg cccttgtggt ccaagtggcc      120

gaggctgccc gcgccccgag cgtgtcagcc aagccaggac cggccctgtg gccgctgcct      180

ctgagcgtga agatgactcc caatctcctg cacctggccc cggaaaactt ctacatctcg      240

cactcgccga acagcaccgc cggtccctcc tgcaccctgc tcgaagaggc attccggcgg      300

taccacggat acatcttcgg tttctataag tggcatcacg agccggcaga gttccaggcc      360

aagactcagg tccagcagct gctcgtgtcc attaccctgc aatcggagtg cgacgccttc      420

cccaacatca gctcagacga gtcatacact ttgctcgtga aggaacctgt cgccgtgctg      480

aaggccaacc gcgtgtgggg tgccctgcgc gggctggaaa cctttagcca actggtctac      540

caagattcat acgggacctt caccattaac gagtccacca tcatcgactc ccctcggttc      600

ccgcaccgcg gcttgctgct ggatacctcg cggcactatc tgccactgaa gtccattctc      660

gataccctgg acgtgatggc ctacaacaag ctgaacgtgt tccactggca tctcgtggac      720

gaccagtcct ttccctacga gtccttcacc ttccctgagt tgatgagaaa gggctcctac      780

tccctctccc atatctacac ggctcaggac gtgaaggaag tgatcgaata tgcccggctg      840

agagggatta gggtgctggc agaatttgac accccgggac acaccctgtc gtggggccct      900

ggtatcccgg gcctgctgac tccgtgctac tccggctccg agccatccgg aaccttcgga      960

cctgtgaatc cctccctgaa caacacttac gagttcatgt ccaccttctt cctggaagtg     1020

tcgagcgtgt tccccgactt ctacctccac ctcggtggcg acgaagtcga tttcacttgc     1080

tggaagtcta accccgagat ccaagatttc atgcgaaaga aaggattcgg agaggacttt     1140

aagcagctgg agtccttcta catccaaacc ctgctggaca ttgtgtcatc gtatggaaag     1200

ggatacgtgg tgtggcagga agtgtttgac aataaggtca aaattcagcc cgatacaatc     1260

atccaagtct ggcgcgaaga tatccccgtg aactacatga aagaactgga actggtcacg     1320

aaggctggat tcagggcgct tctgagcgcc ccttggtact tgaaccggat tagctacggc     1380

caggactgga ggaagttcta caaggtcgaa cctctggcct tcgagggaac ccccgagcag     1440

aaggccttgg tgatcggcgg cgaagcctgt atgtgggggg aatacgtgga cgcgaccaac     1500

ctggtgccgc gcctgtggcc gagagcggga gcagtggccg agcggctctg gtcgaacaag     1560

ctgactaggg acatggacga tgcatacgac agactgagcc acttccgctg cgaacttgtg     1620

cggcgggggg tggcggccca gccgctctac gcggggtact gtaaccagga gttcgagcag     1680

acc                                                                   1683


<210> 9
<211> 1668
<212> DNA
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polynucleotide

<400> 9
atggaacttt gtggacttgg actccctcgc cctccgatgc tgcttgcact gctcctcgcc       60

actctcctcg ccgctatgct ggcgctgctg actcaagtgg cactggtggt ccaagtggcc      120

gaggcggccc gcgcaccatc cgtgtccgcg aagccgggcc cagccctgtg gcccctgcct      180

ctgagcgtga agatgacccc taaccttctg cacctggcgc cggagaactt ctacataagc      240

cactcgccca actcgaccgc gggtccctcc tgtaccctgc tggaggaggc cttcaggcgc      300

taccacggct acattttcgg gttctataag tggcaccacg agccggccga gttccaagcc      360

aagactcagg tccaacagct gctggtgtca atcacactgc agtccgaatg cgatgctttc      420

cctaatatct cctccgacga gtcctacacc ctgctcgtga aggaacctgt ggccgtgctc      480

aaggccaacc gcgtctgggg agccctcagg ggtctggaaa ccttcagcca gctggtgtac      540

caggacagct acggcacctt caccattaac gagtccacca tcatcgactc accgagattc      600

agccaccggg gaatcctgat tgatacttca agacactatt tgcccgtgaa gatcatcctg      660

aaaaccctcg acgctatggc ctttaacaag tttaacgtgt tgcattggca tatcgtggac      720

gatcagtcct tcccgtatca aagcatcact tttccggaac tgtccaacaa gggatcttac      780

tcgctgagcc acgtgtacac tcccaatgac gtgcgcatgg tcatcgaata cgcccggctg      840

aggggcatta gagtgctccc tgaatttgac acccccggcc ataccctctc ctggggaaaa      900

ggacagaaag atttgctcac accttgctac tccggctccg agccctctgg aactttcggc      960

cccatcaacc cgaccctgaa caccacttac tccttcttga ccacgttctt caaggagatt     1020

tccgaggtgt tcccggacca gttcatccac ctggggggcg acgaagtgga gttcaagtgc     1080

tgggaatcga acccaaagat ccaggacttc atgaggcaga aggggtttgg caccgatttc     1140

aagaagctgg agtcgttcta cattcaaaag gtcctggaca tcattgcaac catcaacaag     1200

gggtcaatcg tgtggcagga agtgttcgat gacaaggcta agctggcgcc cggcactatt     1260

gtggaagtct ggaaagactc cgcctaccct gaggagctgt cgagagtcac cgcctccgga     1320

ttccccgtca tcctgagcgc tccgtggtac ctgaaccgga tctcctacgg acaagattgg     1380

cgcaagtact acaaggtcga accgctggac ttcggaggga ctcagaagca gaagcagctc     1440

tttattggtg gagaggcctg cctttggggc gaatacgtgg acgccaccaa cctcaccccg     1500

cggctctggc cacgggccag cgccgtggga gaacgcctgt ggtcgtcaaa ggacgtccgc     1560

gatatggacg atgcctacga ccggctcact cggcatcggt gccggatggt ggaacgcggt     1620

atcgcagcgc agccactgta cgctggatac tgcaaccacg agaatatg                  1668


<210> 10
<211> 556
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 10
Met Glu Leu Cys Gly Leu Gly Leu Pro Arg Pro Pro Met Leu Leu Ala 
1               5                   10                  15      


Leu Leu Leu Ala Thr Leu Leu Ala Ala Met Leu Ala Leu Leu Thr Gln 
            20                  25                  30          


Val Ala Leu Val Val Gln Val Ala Glu Ala Ala Arg Ala Pro Ser Val 
        35                  40                  45              


Ser Ala Lys Pro Gly Pro Ala Leu Trp Pro Leu Pro Leu Ser Val Lys 
    50                  55                  60                  


Met Thr Pro Asn Leu Leu His Leu Ala Pro Glu Asn Phe Tyr Ile Ser 
65                  70                  75                  80  


His Ser Pro Asn Ser Thr Ala Gly Pro Ser Cys Thr Leu Leu Glu Glu 
                85                  90                  95      


Ala Phe Arg Arg Tyr His Gly Tyr Ile Phe Gly Phe Tyr Lys Trp His 
            100                 105                 110         


His Glu Pro Ala Glu Phe Gln Ala Lys Thr Gln Val Gln Gln Leu Leu 
        115                 120                 125             


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


Ser Asp Glu Ser Tyr Thr Leu Leu Val Lys Glu Pro Val Ala Val Leu 
145                 150                 155                 160 


Lys Ala Asn Arg Val Trp Gly Ala Leu Arg Gly Leu Glu Thr Phe Ser 
                165                 170                 175     


Gln Leu Val Tyr Gln Asp Ser Tyr Gly Thr Phe Thr Ile Asn Glu Ser 
            180                 185                 190         


Thr Ile Ile Asp Ser Pro Arg Phe Ser His Arg Gly Ile Leu Ile Asp 
        195                 200                 205             


Thr Ser Arg His Tyr Leu Pro Val Lys Ile Ile Leu Lys Thr Leu Asp 
    210                 215                 220                 


Ala Met Ala Phe Asn Lys Phe Asn Val Leu His Trp His Ile Val Asp 
225                 230                 235                 240 


Asp Gln Ser Phe Pro Tyr Gln Ser Ile Thr Phe Pro Glu Leu Ser Asn 
                245                 250                 255     


Lys Gly Ser Tyr Ser Leu Ser His Val Tyr Thr Pro Asn Asp Val Arg 
            260                 265                 270         


Met Val Ile Glu Tyr Ala Arg Leu Arg Gly Ile Arg Val Leu Pro Glu 
        275                 280                 285             


Phe Asp Thr Pro Gly His Thr Leu Ser Trp Gly Lys Gly Gln Lys Asp 
    290                 295                 300                 


Leu Leu Thr Pro Cys Tyr Ser Gly Ser Glu Pro Ser Gly Thr Phe Gly 
305                 310                 315                 320 


Pro Ile Asn Pro Thr Leu Asn Thr Thr Tyr Ser Phe Leu Thr Thr Phe 
                325                 330                 335     


Phe Lys Glu Ile Ser Glu Val Phe Pro Asp Gln Phe Ile His Leu Gly 
            340                 345                 350         


Gly Asp Glu Val Glu Phe Lys Cys Trp Glu Ser Asn Pro Lys Ile Gln 
        355                 360                 365             


Asp Phe Met Arg Gln Lys Gly Phe Gly Thr Asp Phe Lys Lys Leu Glu 
    370                 375                 380                 


Ser Phe Tyr Ile Gln Lys Val Leu Asp Ile Ile Ala Thr Ile Asn Lys 
385                 390                 395                 400 


Gly Ser Ile Val Trp Gln Glu Val Phe Asp Asp Lys Ala Lys Leu Ala 
                405                 410                 415     


Pro Gly Thr Ile Val Glu Val Trp Lys Asp Ser Ala Tyr Pro Glu Glu 
            420                 425                 430         


Leu Ser Arg Val Thr Ala Ser Gly Phe Pro Val Ile Leu Ser Ala Pro 
        435                 440                 445             


Trp Tyr Leu Asn Arg Ile Ser Tyr Gly Gln Asp Trp Arg Lys Tyr Tyr 
    450                 455                 460                 


Lys Val Glu Pro Leu Asp Phe Gly Gly Thr Gln Lys Gln Lys Gln Leu 
465                 470                 475                 480 


Phe Ile Gly Gly Glu Ala Cys Leu Trp Gly Glu Tyr Val Asp Ala Thr 
                485                 490                 495     


Asn Leu Thr Pro Arg Leu Trp Pro Arg Ala Ser Ala Val Gly Glu Arg 
            500                 505                 510         


Leu Trp Ser Ser Lys Asp Val Arg Asp Met Asp Asp Ala Tyr Asp Arg 
        515                 520                 525             


Leu Thr Arg His Arg Cys Arg Met Val Glu Arg Gly Ile Ala Ala Gln 
    530                 535                 540                 


Pro Leu Tyr Ala Gly Tyr Cys Asn His Glu Asn Met 
545                 550                 555     


<210> 11
<211> 339
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 11
Lys Ser Ile Leu Asp Thr Leu Asp Val Met Ala Tyr Asn Lys Leu Asn 
1               5                   10                  15      


Val Phe His Trp His Leu Val Asp Asp Gln Ser Phe Pro Tyr Glu Ser 
            20                  25                  30          


Phe Thr Phe Pro Glu Leu Met Arg Lys Gly Ser Tyr Ser Leu Ser His 
        35                  40                  45              


Ile Tyr Thr Ala Gln Asp Val Lys Glu Val Ile Glu Tyr Ala Arg Leu 
    50                  55                  60                  


Arg Gly Ile Arg Val Leu Ala Glu Phe Asp Thr Pro Gly His Thr Leu 
65                  70                  75                  80  


Ser Trp Gly Pro Gly Ile Pro Gly Leu Leu Thr Pro Cys Tyr Ser Gly 
                85                  90                  95      


Ser Glu Pro Ser Gly Thr Phe Gly Pro Val Asn Pro Ser Leu Asn Asn 
            100                 105                 110         


Thr Tyr Glu Phe Met Ser Thr Phe Phe Leu Glu Val Ser Ser Val Phe 
        115                 120                 125             


Pro Asp Phe Tyr Leu His Leu Gly Gly Asp Glu Val Asp Phe Thr Cys 
    130                 135                 140                 


Trp Lys Ser Asn Pro Glu Ile Gln Asp Phe Met Arg Lys Lys Gly Phe 
145                 150                 155                 160 


Gly Glu Asp Phe Lys Gln Leu Glu Ser Phe Tyr Ile Gln Thr Leu Leu 
                165                 170                 175     


Asp Ile Val Ser Ser Tyr Gly Lys Gly Tyr Val Val Trp Gln Glu Val 
            180                 185                 190         


Phe Asp Asn Lys Val Lys Ile Gln Pro Asp Thr Ile Ile Gln Val Trp 
        195                 200                 205             


Arg Glu Asp Ile Pro Val Asn Tyr Met Lys Glu Leu Glu Leu Val Thr 
    210                 215                 220                 


Lys Ala Gly Phe Arg Ala Leu Leu Ser Ala Pro Trp Tyr Leu Asn Arg 
225                 230                 235                 240 


Ile Ser Tyr Gly Gln Asp Trp Arg Lys Phe Tyr Lys Val Glu Pro Leu 
                245                 250                 255     


Ala Phe Glu Gly Thr Pro Glu Gln Lys Ala Leu Val Ile Gly Gly Glu 
            260                 265                 270         


Ala Cys Met Trp Gly Glu Tyr Val Asp Ala Thr Asn Leu Val Pro Arg 
        275                 280                 285             


Leu Trp Pro Arg Ala Gly Ala Val Ala Glu Arg Leu Trp Ser Asn Lys 
    290                 295                 300                 


Leu Thr Arg Asp Met Asp Asp Ala Tyr Asp Arg Leu Ser His Phe Arg 
305                 310                 315                 320 


Cys Glu Leu Val Arg Arg Gly Val Ala Ala Gln Pro Leu Tyr Ala Gly 
                325                 330                 335     


Tyr Cys Asn 
            


<210> 12
<211> 155
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 12
Ala Arg Ala Pro Ser Val Ser Ala Lys Pro Gly Pro Ala Leu Trp Pro 
1               5                   10                  15      


Leu Pro Leu Ser Val Lys Met Thr Pro Asn Leu Leu His Leu Ala Pro 
            20                  25                  30          


Glu Asn Phe Tyr Ile Ser His Ser Pro Asn Ser Thr Ala Gly Pro Ser 
        35                  40                  45              


Cys Thr Leu Leu Glu Glu Ala Phe Arg Arg Tyr His Gly Tyr Ile Phe 
    50                  55                  60                  


Gly Phe Tyr Lys Trp His His Glu Pro Ala Glu Phe Gln Ala Lys Thr 
65                  70                  75                  80  


Gln Val Gln Gln Leu Leu Val Ser Ile Thr Leu Gln Ser Glu Cys Asp 
                85                  90                  95      


Ala Phe Pro Asn Ile Ser Ser Asp Glu Ser Tyr Thr Leu Leu Val Lys 
            100                 105                 110         


Glu Pro Val Ala Val Leu Lys Ala Asn Arg Val Trp Gly Ala Leu Arg 
        115                 120                 125             


Gly Leu Glu Thr Phe Ser Gln Leu Val Tyr Gln Asp Ser Tyr Gly Thr 
    130                 135                 140                 


Phe Thr Ile Asn Glu Ser Thr Ile Ile Asp Ser 
145                 150                 155 


<210> 13
<211> 197
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 13
Met Glu Leu Cys Gly Leu Gly Leu Pro Arg Pro Pro Met Leu Leu Ala 
1               5                   10                  15      


Leu Leu Leu Ala Thr Leu Leu Ala Ala Met Leu Ala Leu Leu Thr Gln 
            20                  25                  30          


Val Ala Leu Val Val Gln Val Ala Glu Ala Ala Arg Ala Pro Ser Val 
        35                  40                  45              


Ser Ala Lys Pro Gly Pro Ala Leu Trp Pro Leu Pro Leu Ser Val Lys 
    50                  55                  60                  


Met Thr Pro Asn Leu Leu His Leu Ala Pro Glu Asn Phe Tyr Ile Ser 
65                  70                  75                  80  


His Ser Pro Asn Ser Thr Ala Gly Pro Ser Cys Thr Leu Leu Glu Glu 
                85                  90                  95      


Ala Phe Arg Arg Tyr His Gly Tyr Ile Phe Gly Phe Tyr Lys Trp His 
            100                 105                 110         


His Glu Pro Ala Glu Phe Gln Ala Lys Thr Gln Val Gln Gln Leu Leu 
        115                 120                 125             


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


Ser Asp Glu Ser Tyr Thr Leu Leu Val Lys Glu Pro Val Ala Val Leu 
145                 150                 155                 160 


Lys Ala Asn Arg Val Trp Gly Ala Leu Arg Gly Leu Glu Thr Phe Ser 
                165                 170                 175     


Gln Leu Val Tyr Gln Asp Ser Tyr Gly Thr Phe Thr Ile Asn Glu Ser 
            180                 185                 190         


Thr Ile Ile Asp Ser 
        195         


<210> 14
<211> 3
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      peptide


<220>
<221> MOD_RES
<222> (2)..(2)
<223> Any amino acid

<220>
<221> MOD_RES
<222> (3)..(3)
<223> Ser or Thr

<400> 14
Asn Xaa Xaa 
1           


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

<220>
<223> Description of Artificial Sequence: Synthetic
      peptide

<400> 15
Gly Ser Tyr Ser Leu Ser His Ile Tyr Thr Ala Gln Asp Val Lys 
1               5                   10                  15  


<210> 16
<211> 11
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      peptide

<400> 16
Ile Gln Pro Asp Thr Ile Ile Gln Val Trp Arg 
1               5                   10      


<210> 17
<211> 8
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      peptide

<400> 17
Ile Ser Tyr Gly Gln Asp Trp Arg 
1               5               


<210> 18
<211> 6
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      6xHis tag

<400> 18
His His His His His His 
1               5       


<210> 19
<211> 4
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      peptide

<400> 19
Asn Pro Val Thr 
1               


