                         SEQUENCE LISTING

<110>  Pfizer Inc.
 
<120>  Modified Nucleic Acids Encoding Aspartoacylase (ASPA) and Vector 
       for Gene Therapy

<130>  323429.00101

<150>  63/016,507
<151>  2020-04-28

<150>  63/077,144
<151>  2020-09-11

<160>  20    

<170>  PatentIn version 3.5

<210>  1
<211>  942
<212>  DNA
<213>  Artificial

<220>
<223>  Synthetic

<400>  1
atgacctcct gtcatatagc cgaggagcac atccagaaag tggccatttt cggcgggaca       60

catgggaacg agctgactgg cgttttcctg gtcaagcact ggctcgaaaa tggcgcggaa      120

attcagagaa cgggcctgga ggtcaaacct tttattacta acccccgcgc ggtgaagaaa      180

tgtacccggt acatcgactg cgatcttaac cgaatctttg atctggaaaa tctgggaaaa      240

aaaatgagcg aggacctgcc ctacgaagtc cgcagagcac aggagattaa tcatctcttc      300

ggacccaagg actccgagga cagctacgat atcatcttcg acttgcacaa tactacttcc      360

aatatgggat gtaccttgat actggaggac tcacgaaata acttcttgat tcagatgttc      420

cattacatca aaacctctct cgctcctctc ccttgctacg tatatttgat cgagcaccct      480

agtctgaaat atgccactac acgaagcata gctaagtatc ccgttggtat tgaggtgggc      540

ccccagcccc agggagtgct gcgggctgac atccttgacc agatgagaaa aatgatcaaa      600

cacgcccttg acttcatcca ccactttaat gaaggcaaag agtttcctcc ctgtgccata      660

gaggtgtata aaatcatcga aaaagttgac tatccacggg atgagaacgg cgagatcgct      720

gccatcatcc atcccaattt gcaagatcag gattggaaac ctttgcaccc aggcgaccct      780

atgttcctga cattggatgg caagaccata cccctgggtg gtgattgcac tgtgtaccca      840

gttttcgtaa acgaggcagc gtactatgaa aagaaagagg catttgcaaa aaccactaag      900

ttgacactga atgccaagag cattagatgc tgtcttcatt aa                         942


<210>  2
<211>  942
<212>  DNA
<213>  Artificial

<220>
<223>  Synthetic

<400>  2
atgacctcct gtcatatagc cgaggagcac atccagaaag tggccatttt cggcgggaca       60

cacggaaacg aacttacagg agtgtttctg gtgaaacact ggcttgaaaa tggtgcggag      120

atccaaagga ccggcctgga ggtcaaacct tttattacaa atccccgggc ggtcaagaag      180

tgcacacggt acattgattg tgatcttaat cgcatattcg acctggagaa ccttgggaag      240

aaaatgtctg aagatctgcc ctacgaagtg aggcgagcac aagagataaa ccacctgttc      300

ggaccgaaag acagtgaaga ctcctatgac atcattttcg acctgcacaa cactacgagt      360

aacatggggt gtaccctgat cctcgaagac tcccgaaaca atttcctgat acagatgttt      420

cattacatca aaactagtct ggcccctctc ccctgctacg tttatctgat cgaacaccct      480

tctctcaaat acgctaccac ccgctctatt gctaagtacc ccgtcgggat cgaggtcggc      540

ccacaacctc aaggtgtgct ccgggccgat attttggacc agatgagaaa gatgattaaa      600

cacgctctcg acttcattca ccactttaac gaggggaagg aatttccccc ttgtgccatc      660

gaggtttata agattatcga gaaggtggac tacccaagag acgaaaacgg ggagatagct      720

gccatcatcc accctaattt gcaagatcag gactggaagc ccctgcaccc aggagacccc      780

atgtttctga ccttggatgg aaagacgatc cccctgggcg gtgattgtac agtgtaccca      840

gtctttgtca acgaggccgc ttactatgag aaaaaggagg cttttgcaaa gacaacaaag      900

ctcactttga atgcaaagtc catcaggtgc tgtctgcact aa                         942


<210>  3
<211>  942
<212>  DNA
<213>  Homo sapiens

<400>  3
atgacttctt gtcacattgc tgaagaacat atacaaaagg ttgctatctt tggaggaacc       60

catgggaatg agctaaccgg agtatttctg gttaagcatt ggctagagaa tggcgctgag      120

attcagagaa cagggctgga ggtaaaacca tttattacta accccagagc agtgaagaag      180

tgtaccagat atattgactg tgacctgaat cgcatttttg accttgaaaa tcttggcaaa      240

aaaatgtcag aagatttgcc atatgaagtg agaagggctc aagaaataaa tcatttattt      300

ggtccaaaag acagtgaaga ttcctatgac attatttttg accttcacaa caccacctct      360

aacatggggt gcactcttat tcttgaggat tccaggaata actttttaat tcagatgttt      420

cattacatta agacttctct ggctccacta ccctgctacg tttatctgat tgagcatcct      480

tccctcaaat atgcgaccac tcgttccata gccaagtatc ctgtgggtat agaagttggt      540

cctcagcctc aaggggttct gagagctgat atcttggatc aaatgagaaa aatgattaaa      600

catgctcttg attttataca tcatttcaat gaaggaaaag aatttcctcc ctgcgccatt      660

gaggtctata aaattataga gaaagttgat tacccccggg atgaaaatgg agaaattgct      720

gctatcatcc atcctaatct gcaggatcaa gactggaaac cactgcatcc tggggatccc      780

atgtttttaa ctcttgatgg gaagacgatc ccactgggcg gagactgtac cgtgtacccc      840

gtgtttgtga atgaggccgc atattacgaa aagaaagaag cttttgcaaa gacaactaaa      900

ctaacgctca atgcaaaaag tattcgctgc tgtttacatt ag                         942


<210>  4
<211>  313
<212>  PRT
<213>  Homo sapiens

<400>  4

Met Thr Ser Cys His Ile Ala Glu Glu His Ile Gln Lys Val Ala Ile 
1               5                   10                  15      


Phe Gly Gly Thr His Gly Asn Glu Leu Thr Gly Val Phe Leu Val Lys 
            20                  25                  30          


His Trp Leu Glu Asn Gly Ala Glu Ile Gln Arg Thr Gly Leu Glu Val 
        35                  40                  45              


Lys Pro Phe Ile Thr Asn Pro Arg Ala Val Lys Lys Cys Thr Arg Tyr 
    50                  55                  60                  


Ile Asp Cys Asp Leu Asn Arg Ile Phe Asp Leu Glu Asn Leu Gly Lys 
65                  70                  75                  80  


Lys Met Ser Glu Asp Leu Pro Tyr Glu Val Arg Arg Ala Gln Glu Ile 
                85                  90                  95      


Asn His Leu Phe Gly Pro Lys Asp Ser Glu Asp Ser Tyr Asp Ile Ile 
            100                 105                 110         


Phe Asp Leu His Asn Thr Thr Ser Asn Met Gly Cys Thr Leu Ile Leu 
        115                 120                 125             


Glu Asp Ser Arg Asn Asn Phe Leu Ile Gln Met Phe His Tyr Ile Lys 
    130                 135                 140                 


Thr Ser Leu Ala Pro Leu Pro Cys Tyr Val Tyr Leu Ile Glu His Pro 
145                 150                 155                 160 


Ser Leu Lys Tyr Ala Thr Thr Arg Ser Ile Ala Lys Tyr Pro Val Gly 
                165                 170                 175     


Ile Glu Val Gly Pro Gln Pro Gln Gly Val Leu Arg Ala Asp Ile Leu 
            180                 185                 190         


Asp Gln Met Arg Lys Met Ile Lys His Ala Leu Asp Phe Ile His His 
        195                 200                 205             


Phe Asn Glu Gly Lys Glu Phe Pro Pro Cys Ala Ile Glu Val Tyr Lys 
    210                 215                 220                 


Ile Ile Glu Lys Val Asp Tyr Pro Arg Asp Glu Asn Gly Glu Ile Ala 
225                 230                 235                 240 


Ala Ile Ile His Pro Asn Leu Gln Asp Gln Asp Trp Lys Pro Leu His 
                245                 250                 255     


Pro Gly Asp Pro Met Phe Leu Thr Leu Asp Gly Lys Thr Ile Pro Leu 
            260                 265                 270         


Gly Gly Asp Cys Thr Val Tyr Pro Val Phe Val Asn Glu Ala Ala Tyr 
        275                 280                 285             


Tyr Glu Lys Lys Glu Ala Phe Ala Lys Thr Thr Lys Leu Thr Leu Asn 
    290                 295                 300                 


Ala Lys Ser Ile Arg Cys Cys Leu His 
305                 310             


<210>  5
<211>  106
<212>  DNA
<213>  Artificial

<220>
<223>  Synthetic

<400>  5
ctgcgcgctc gctcgctcac tgaggccgcc cgggcaaagc ccgggcgtcg ggcgaccttt       60

ggtcgcccgg cctcagtgag cgagcgagcg cgcagagagg gagtgg                     106


<210>  6
<211>  284
<212>  DNA
<213>  Artificial

<220>
<223>  Synthetic

<400>  6
cgttacataa cttacggtaa atggcccgcc tggctgaccg cccaacgacc cccgcccatt       60

gacgtcaata gtaacgccaa tagggacttt ccattgacgt caatgggtgg agtatttacg      120

gtaaactgcc cacttggcag tacatcaagt gtatcatatg ccaagtacgc cccctattga      180

cgtcaatgac ggtaaatggc ccgcctggca tttgcccagt acatgacctt atgggacttt      240

cctacttggc agtacatcta cgtattagtc atcgctatta ccat                       284


<210>  7
<211>  278
<212>  DNA
<213>  Artificial

<220>
<223>  Synthetic

<400>  7
tcgaggtgag ccccacgttc tgcttcactc tccccatctc ccccccctcc ccacccccaa       60

ttttgtattt atttattttt taattatttt gtgcagcgat gggggcgggg gggggggggg      120

ggcgcgcgcc aggcggggcg gggcggggcg aggggcgggg cggggcgagg cggagaggtg      180

cggcggcagc caatcagagc ggcgcgctcc gaaagtttcc ttttatggcg aggcggcggc      240

ggcggcggcc ctataaaaag cgaagcgcgc ggcgggcg                              278


<210>  8
<211>  82
<212>  DNA
<213>  Artificial

<220>
<223>  Synthetic

<400>  8
ggagtcgctg cgcgctgcct tcgccccgtg ccccgctccg ccgccgcctc gcgccgcccg       60

ccccggctct gactgaccgc gt                                                82


<210>  9
<211>  43
<212>  DNA
<213>  Artificial

<220>
<223>  Synthetic

<400>  9
gtgagcgggc gggacggccc ttctcctccg ggctgtaatt agc                         43


<210>  10
<211>  92
<212>  DNA
<213>  Artificial

<220>
<223>  Synthetic

<400>  10
aagaggtaag ggtttaaggg atggttggtt ggtggggtat taatgtttaa ttacctggag       60

cacctgcctg aaatcacttt ttttcaggtt gg                                     92


<210>  11
<211>  225
<212>  DNA
<213>  Artificial

<220>
<223>  Synthetic

<400>  11
ctgtgccttc tagttgccag ccatctgttg tttgcccctc ccccgtgcct tccttgaccc       60

tggaaggtgc cactcccact gtcctttcct aataaaatga ggaaattgca tcgcattgtc      120

tgagtaggtg tcattctatt ctggggggtg gggtggggca ggacagcaag ggggaggatt      180

gggaagacaa cagcaggcat gctggggatg cggtgggctc tatgg                      225


<210>  12
<211>  113
<212>  DNA
<213>  Artificial

<220>
<223>  Synthetic

<400>  12
tcgcccgacg cccgggcttt gcccgggcgg cctcagtgag cgagcgagcg cgcagctggc       60

gtaatagcga agaggcccgc accgatcgcc cttcccaaca gttgcgcagc ctg             113


<210>  13
<211>  2214
<212>  DNA
<213>  Artificial

<220>
<223>  Synthetic

<400>  13
atggctgccg atggttatct tccagattgg ctcgaggaca ctctctctga aggaataaga       60

cagtggtgga agctcaaacc tggcccacca ccaccaaagc ccgcagagcg gcataaggac      120

gacagcaggg gtcttgtgct tcctgggtac aagtacctcg gacccttcaa cggactcgac      180

aagggagagc cggtcaacga ggcagacgcc gcggccctcg agcacgacaa agcctacgac      240

cggcagctcg acagcggaga caacccgtac ctcaagtaca accacgccga cgcggagttt      300

caggagcgcc ttaaagaaga tacgtctttt gggggcaacc tcgggcgagc agtcttccag      360

gccaaaaaga ggcttcttga acctcttggt ctggttgagg aagcggctaa gacggctcct      420

ggaaagaaga ggcctgtaga gcagtctcct caggaaccgg actcctcctc gggcatcggc      480

aagacaggcc agcagcccgc taaaaagaga ctcaatttcg gtcagactgg cgacacagag      540

tcagtcccag accctcaacc aatcggagaa cctcccgcag ccccctcagg tgtgggatct      600

cttacaatgg cttcaggtgg tggcgcacca gtggcagaca ataacgaagg tgccgatgga      660

gtgggtagtt cctcgggaaa ttggcattgc gattcccaat ggctggggga cagagtcatc      720

accaccagca cccgaacctg ggccctgccc acctacaaca atcacctcta caagcaaatc      780

tccaacggga catcgggagg agccaccaac gacaacacct acttcggcta cagcaccccc      840

tgggggtatt ttgactttaa cagattccac tgccactttt caccacgtga ctggcagcga      900

ctcatcaaca acaactgggg attccggccc aagagactca gcttcaagct cttcaacatc      960

caggtcaagg aggtcacgca gaatgaaggc accaagacca tcgccaataa ccttaccagc     1020

acggtccagg tcttcacgga ctcggagtac cagctgccgt acgttctcgg ctctgcccac     1080

cagggctgcc tgcctccgtt cccggcggac gtgttcatga ttccccagta cggctaccta     1140

acactcaaca acggtagtca ggccgtggga cgctcctcct tctactgcct ggaatacttt     1200

ccttcgcaga tgctgagaac cggcaacaac ttccagttta cttacacctt cgaggacgtg     1260

cctttccaca gcagctacgc ccacagccag agcttggacc ggctgatgaa tcctctgatt     1320

gaccagtacc tgtactactt gtctcggact caaacaacag gaggcacggc aaatacgcag     1380

actctgggct tcagccaagg tgggcctaat acaatggcca atcaggcaaa gaactggctg     1440

ccaggaccct gttaccgcca acaacgcgtc tcaacgacaa ccgggcaaaa caacaatagc     1500

aactttgcct ggactgctgg gaccaaatac catctgaatg gaagaaattc attggctaat     1560

cctggcatcg ctatggcaac acacaaagac gacaaggagc gtttttttcc cagtaacggg     1620

atcctgattt ttggcaaaca aaatgctgcc agagacaatg cggattacag cgatgtcatg     1680

ctcaccagcg aggaagaaat caaaaccact aaccctgtgg ctacagagga atacggtatc     1740

gtggcagata acttgcagca gcaaaacacg gctcctcaaa ttggaactgt caacagccag     1800

ggggccttac ccggtatggt ttggcagaac cgggacgtgt acctgcaggg tcccatctgg     1860

gccaagattc ctcacacgga cggcaacttc cacccgtctc cgctgatggg cggctttggc     1920

ctgaaacatc ctccgcctca gatcctgatc aagaacacgc ctgtacctgc ggatcctccg     1980

accaccttca accagtcaaa gctgaactct ttcatcacgc aatacagcac cggacaggtc     2040

agcgtggaaa ttgaatggga gctgcagaag gaaaacagca agcgctggaa ccccgagatc     2100

cagtacacct ccaactacta caaatctaca agtgtggact ttgctgttaa tacagaaggc     2160

gtgtactctg aaccccaccc cattggcacc cgttacctca cccgtcccct gtaa           2214


<210>  14
<211>  737
<212>  PRT
<213>  Artificial

<220>
<223>  Synthetic

<400>  14

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Thr Leu Ser 
1               5                   10                  15      


Glu Gly Ile Arg Gln Trp Trp Lys Leu Lys Pro Gly Pro Pro Pro Pro 
            20                  25                  30          


Lys Pro Ala Glu Arg His Lys Asp Asp Ser Arg Gly Leu Val Leu Pro 
        35                  40                  45              


Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro 
    50                  55                  60                  


Val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 
65                  70                  75                  80  


Arg Gln Leu Asp Ser Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala 
                85                  90                  95      


Asp Ala Glu Phe Gln Glu Arg Leu Lys Glu Asp Thr Ser Phe Gly Gly 
            100                 105                 110         


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


Leu Gly Leu Val Glu Glu Ala Ala Lys Thr Ala Pro Gly Lys Lys Arg 
    130                 135                 140                 


Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ser Gly Ile Gly 
145                 150                 155                 160 


Lys Thr Gly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr 
                165                 170                 175     


Gly Asp Thr Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro Pro 
            180                 185                 190         


Ala Ala Pro Ser Gly Val Gly Ser Leu Thr Met Ala Ser Gly Gly Gly 
        195                 200                 205             


Ala Pro Val Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser Ser 
    210                 215                 220                 


Ser Gly Asn Trp His Cys Asp Ser Gln Trp Leu Gly Asp Arg Val Ile 
225                 230                 235                 240 


Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu 
                245                 250                 255     


Tyr Lys Gln Ile Ser Asn Gly Thr Ser Gly Gly Ala Thr Asn Asp Asn 
            260                 265                 270         


Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg 
        275                 280                 285             


Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn 
    290                 295                 300                 


Asn Trp Gly Phe Arg Pro Lys Arg Leu Ser Phe Lys Leu Phe Asn Ile 
305                 310                 315                 320 


Gln Val Lys Glu Val Thr Gln Asn Glu Gly Thr Lys Thr Ile Ala Asn 
                325                 330                 335     


Asn Leu Thr Ser Thr Val Gln Val Phe Thr Asp Ser Glu Tyr Gln Leu 
            340                 345                 350         


Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro 
        355                 360                 365             


Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn 
    370                 375                 380                 


Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe 
385                 390                 395                 400 


Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Gln Phe Thr Tyr Thr 
                405                 410                 415     


Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu 
            420                 425                 430         


Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser 
        435                 440                 445             


Arg Thr Gln Thr Thr Gly Gly Thr Ala Asn Thr Gln Thr Leu Gly Phe 
    450                 455                 460                 


Ser Gln Gly Gly Pro Asn Thr Met Ala Asn Gln Ala Lys Asn Trp Leu 
465                 470                 475                 480 


Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Thr Gly Gln 
                485                 490                 495     


Asn Asn Asn Ser Asn Phe Ala Trp Thr Ala Gly Thr Lys Tyr His Leu 
            500                 505                 510         


Asn Gly Arg Asn Ser Leu Ala Asn Pro Gly Ile Ala Met Ala Thr His 
        515                 520                 525             


Lys Asp Asp Lys Glu Arg Phe Phe Pro Ser Asn Gly Ile Leu Ile Phe 
    530                 535                 540                 


Gly Lys Gln Asn Ala Ala Arg Asp Asn Ala Asp Tyr Ser Asp Val Met 
545                 550                 555                 560 


Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr Glu 
                565                 570                 575     


Glu Tyr Gly Ile Val Ala Asp Asn Leu Gln Gln Gln Asn Thr Ala Pro 
            580                 585                 590         


Gln Ile Gly Thr Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val Trp 
        595                 600                 605             


Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro 
    610                 615                 620                 


His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly 
625                 630                 635                 640 


Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro 
                645                 650                 655     


Ala Asp Pro Pro Thr Thr Phe Asn Gln Ser Lys Leu Asn Ser Phe Ile 
            660                 665                 670         


Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu 
        675                 680                 685             


Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser 
    690                 695                 700                 


Asn Tyr Tyr Lys Ser Thr Ser Val Asp Phe Ala Val Asn Thr Glu Gly 
705                 710                 715                 720 


Val Tyr Ser Glu Pro His Pro Ile Gly Thr Arg Tyr Leu Thr Arg Pro 
                725                 730                 735     


Leu 
    


<210>  15
<211>  736
<212>  PRT
<213>  Artificial

<220>
<223>  Synthetic

<400>  15

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 
1               5                   10                  15      


Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 
            20                  25                  30          


Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro 
        35                  40                  45              


Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro 
    50                  55                  60                  


Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 
65                  70                  75                  80  


Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala 
                85                  90                  95      


Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly 
            100                 105                 110         


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


Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg 
    130                 135                 140                 


Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ser Gly Ile Gly 
145                 150                 155                 160 


Lys Thr Gly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr 
                165                 170                 175     


Gly Asp Thr Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro Pro 
            180                 185                 190         


Ala Ala Pro Ser Gly Val Gly Ser Leu Thr Met Ala Ser Gly Gly Gly 
        195                 200                 205             


Ala Pro Val Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser Ser 
    210                 215                 220                 


Ser Gly Asn Trp His Cys Asp Ser Gln Trp Leu Gly Asp Arg Val Ile 
225                 230                 235                 240 


Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu 
                245                 250                 255     


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


Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe 
        275                 280                 285             


His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn 
    290                 295                 300                 


Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gln 
305                 310                 315                 320 


Val Lys Glu Val Thr Asp Asn Asn Gly Val Lys Thr Ile Ala Asn Asn 
                325                 330                 335     


Leu Thr Ser Thr Val Gln Val Phe Thr Asp Ser Asp Tyr Gln Leu Pro 
            340                 345                 350         


Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala 
        355                 360                 365             


Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly 
    370                 375                 380                 


Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro 
385                 390                 395                 400 


Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Gln Phe Thr Tyr Thr Phe 
                405                 410                 415     


Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp 
            420                 425                 430         


Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser Arg 
        435                 440                 445             


Thr Gln Thr Thr Gly Gly Thr Ala Asn Thr Gln Thr Leu Gly Phe Ser 
    450                 455                 460                 


Gln Gly Gly Pro Asn Thr Met Ala Asn Gln Ala Lys Asn Trp Leu Pro 
465                 470                 475                 480 


Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Thr Gly Gln Asn 
                485                 490                 495     


Asn Asn Ser Asn Phe Ala Trp Thr Ala Gly Thr Lys Tyr His Leu Asn 
            500                 505                 510         


Gly Arg Asn Ser Leu Ala Asn Pro Gly Ile Ala Met Ala Thr His Lys 
        515                 520                 525             


Asp Asp Lys Glu Arg Phe Phe Pro Ser Asn Gly Ile Leu Ile Phe Gly 
    530                 535                 540                 


Lys Gln Asn Ala Ala Arg Asp Asn Ala Asp Tyr Ser Asp Val Met Leu 
545                 550                 555                 560 


Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Glu 
                565                 570                 575     


Tyr Gly Ile Val Ala Asp Asn Leu Gln Gln Gln Asn Thr Ala Pro Gln 
            580                 585                 590         


Ile Gly Thr Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val Trp Gln 
        595                 600                 605             


Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His 
    610                 615                 620                 


Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu 
625                 630                 635                 640 


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


Asp Pro Pro Thr Thr Phe Asn Gln Ser Lys Leu Asn Ser Phe Ile Thr 
            660                 665                 670         


Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln 
        675                 680                 685             


Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn 
    690                 695                 700                 


Tyr Tyr Lys Ser Thr Ser Val Asp Phe Ala Val Asn Thr Glu Gly Val 
705                 710                 715                 720 


Tyr Ser Glu Pro His Pro Ile Gly Thr Arg Tyr Leu Thr Arg Pro Leu 
                725                 730                 735     


<210>  16
<211>  736
<212>  PRT
<213>  Artificial

<220>
<223>  Synthetic

<400>  16

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Thr Leu Ser 
1               5                   10                  15      


Glu Gly Ile Arg Gln Trp Trp Lys Leu Lys Pro Gly Pro Pro Pro Pro 
            20                  25                  30          


Lys Pro Ala Glu Arg His Lys Asp Asp Ser Arg Gly Leu Val Leu Pro 
        35                  40                  45              


Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro 
    50                  55                  60                  


Val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 
65                  70                  75                  80  


Arg Gln Leu Asp Ser Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala 
                85                  90                  95      


Asp Ala Glu Phe Gln Glu Arg Leu Gln Gly Asp Thr Ser Phe Gly Gly 
            100                 105                 110         


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


Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg 
    130                 135                 140                 


Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ser Gly Ile Gly 
145                 150                 155                 160 


Glu Thr Gly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr 
                165                 170                 175     


Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro Pro 
            180                 185                 190         


Ala Thr Pro Ala Ala Val Gly Pro Thr Thr Met Ala Ser Gly Gly Gly 
        195                 200                 205             


Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser Ser 
    210                 215                 220                 


Ser Gly Asn Trp His Cys Asp Ser Gln Trp Leu Gly Asp Arg Val Ile 
225                 230                 235                 240 


Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu 
                245                 250                 255     


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


Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe 
        275                 280                 285             


His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn 
    290                 295                 300                 


Trp Gly Phe Arg Pro Lys Arg Leu Ser Phe Lys Leu Phe Asn Ile Gln 
305                 310                 315                 320 


Val Lys Glu Val Thr Asp Asn Asn Gly Val Lys Thr Ile Ala Asn Asn 
                325                 330                 335     


Leu Thr Ser Thr Val Gln Val Phe Thr Asp Ser Glu Tyr Gln Leu Pro 
            340                 345                 350         


Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala 
        355                 360                 365             


Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly 
    370                 375                 380                 


Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro 
385                 390                 395                 400 


Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe 
                405                 410                 415     


Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp 
            420                 425                 430         


Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser Arg 
        435                 440                 445             


Thr Gln Thr Thr Gly Gly Thr Ala Asn Thr Gln Thr Leu Gly Phe Ser 
    450                 455                 460                 


Gln Gly Gly Pro Asn Thr Met Ala Asn Gln Ala Lys Asn Trp Leu Pro 
465                 470                 475                 480 


Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Thr Gly Gln Asn 
                485                 490                 495     


Asn Asn Ser Asn Phe Ala Trp Thr Ala Gly Thr Lys Tyr His Leu Asn 
            500                 505                 510         


Gly Arg Asn Ser Leu Ala Asn Pro Gly Ile Ala Met Ala Thr His Lys 
        515                 520                 525             


Asp Asp Lys Glu Arg Phe Phe Pro Ser Asn Gly Ile Leu Ile Phe Gly 
    530                 535                 540                 


Lys Gln Asn Ala Ala Arg Asp Asn Ala Asp Tyr Ser Asp Val Met Leu 
545                 550                 555                 560 


Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Glu 
                565                 570                 575     


Tyr Gly Ile Val Ala Asp Asn Leu Gln Gln Gln Asn Thr Ala Pro Gln 
            580                 585                 590         


Ile Gly Thr Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val Trp Gln 
        595                 600                 605             


Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His 
    610                 615                 620                 


Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu 
625                 630                 635                 640 


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


Asp Pro Pro Thr Thr Phe Asn Gln Ser Lys Leu Asn Ser Phe Ile Thr 
            660                 665                 670         


Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln 
        675                 680                 685             


Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn 
    690                 695                 700                 


Tyr Tyr Lys Ser Thr Ser Val Asp Phe Ala Val Asn Thr Glu Gly Val 
705                 710                 715                 720 


Tyr Ser Glu Pro His Pro Ile Gly Thr Arg Tyr Leu Thr Arg Pro Leu 
                725                 730                 735     


<210>  17
<211>  286
<212>  DNA
<213>  Artificial

<220>
<223>  Synthetic

<400>  17
cgttacataa cttacggtaa atggcccgcc tggctgaccg cccaacgacc cccgcccatt       60

gacgtcaata gtaacgccaa tagggacttt ccattgacgt caatgggtgg agtatttacg      120

gtaaactgcc cacttggcag tacatcaagt gtatcatatg ccaagtacgc cccctattga      180

cgtcaatgac ggtaaatggc ccgcctggca ttgtgcccag tacatgacct tatgggactt      240

tcctacttgg cagtacatct acgtattagt catcgctatt accatg                     286


<210>  18
<211>  94
<212>  DNA
<213>  Artificial

<220>
<223>  Synthetic

<400>  18
ggagtcgctg cgacgctgcc ttcgccccgt gccccgctcc gccgccgcct cgcgccgccc       60

gccccggctc tgactgaccg cgttactccc acag                                   94


<210>  19
<211>  113
<212>  DNA
<213>  Artificial

<220>
<223>  Synthetic

<400>  19
cgcccgacgc ccgggctttg cccgggcggc ctcagtgagc gagcgagcgc gccagctggc       60

gtaatagcga agaggcccgc accgatcgcc cttcccaaca gttgcgcagc ctg             113


<210>  20
<211>  2333
<212>  DNA
<213>  Artificial

<220>
<223>  Synthetic

<400>  20
ctgcgcgctc gctcgctcac tgaggccgcc cgggcaaagc ccgggcgtcg ggcgaccttt       60

ggtcgcccgg cctcagtgag cgagcgagcg cgcagagagg gagtggggtt cggtacccgt      120

tacataactt acggtaaatg gcccgcctgg ctgaccgccc aacgaccccc gcccattgac      180

gtcaatagta acgccaatag ggactttcca ttgacgtcaa tgggtggagt atttacggta      240

aactgcccac ttggcagtac atcaagtgta tcatatgcca agtacgcccc ctattgacgt      300

caatgacggt aaatggcccg cctggcattg tgcccagtac atgaccttat gggactttcc      360

tacttggcag tacatctacg tattagtcat cgctattacc atggtcgagg tgagccccac      420

gttctgcttc actctcccca tctccccccc ctccccaccc ccaattttgt atttatttat      480

tttttaatta ttttgtgcag cgatgggggc gggggggggg ggggggcgcg cgccaggcgg      540

ggcggggcgg ggcgaggggc ggggcggggc gaggcggaga ggtgcggcgg cagccaatca      600

gagcggcgcg ctccgaaagt ttccttttat ggcgaggcgg cggcggcggc ggccctataa      660

aaagcgaagc gcgcggcggg cgggagtcgc tgcgacgctg ccttcgcccc gtgccccgct      720

ccgccgccgc ctcgcgccgc ccgccccggc tctgactgac cgcgttactc ccacaggtga      780

gcgggcggga cggcccttct cctccgggct gtaattagct gagcaagagg taagggttta      840

agggatggtt ggttggtggg gtattaatgt ttaattacct ggagcacctg cctgaaatca      900

ctttttttca ggttggaccg gtatgacctc ctgtcatata gccgaggagc acatccagaa      960

agtggccatt ttcggcggga cacacggaaa cgaacttaca ggagtgtttc tggtgaaaca     1020

ctggcttgaa aatggtgcgg agatccaaag gaccggcctg gaggtcaaac cttttattac     1080

aaatccccgg gcggtcaaga agtgcacacg gtacattgat tgtgatctta atcgcatatt     1140

cgacctggag aaccttggga agaaaatgtc tgaagatctg ccctacgaag tgaggcgagc     1200

acaagagata aaccacctgt tcggaccgaa agacagtgaa gactcctatg acatcatttt     1260

cgacctgcac aacactacga gtaacatggg gtgtaccctg atcctcgaag actcccgaaa     1320

caatttcctg atacagatgt ttcattacat caaaactagt ctggcccctc tcccctgcta     1380

cgtttatctg atcgaacacc cttctctcaa atacgctacc acccgctcta ttgctaagta     1440

ccccgtcggg atcgaggtcg gcccacaacc tcaaggtgtg ctccgggccg atattttgga     1500

ccagatgaga aagatgatta aacacgctct cgacttcatt caccacttta acgaggggaa     1560

ggaatttccc ccttgtgcca tcgaggttta taagattatc gagaaggtgg actacccaag     1620

agacgaaaac ggggagatag ctgccatcat ccaccctaat ttgcaagatc aggactggaa     1680

gcccctgcac ccaggagacc ccatgtttct gaccttggat ggaaagacga tccccctggg     1740

cggtgattgt acagtgtacc cagtctttgt caacgaggcc gcttactatg agaaaaagga     1800

ggcttttgca aagacaacaa agctcacttt gaatgcaaag tccatcaggt gctgtctgca     1860

ctaagcggcc gcggggatcc ctcgactgtg ccttctagtt gccagccatc tgttgtttgc     1920

ccctcccccg tgccttcctt gaccctggaa ggtgccactc ccactgtcct ttcctaataa     1980

aatgaggaaa ttgcatcgca ttgtctgagt aggtgtcatt ctattctggg gggtggggtg     2040

gggcaggaca gcaaggggga ggattgggaa gacaacagca ggcatgctgg ggatgcggtg     2100

ggctctatgg cttctgaggc ggaaagaacc agctttggac gcgtaggaac ccctagtgat     2160

ggagttggcc actccctctc tgcgcgctcg ctcgctcact gaggccgggc gaccaaaggt     2220

cgcccgacgc ccgggctttg cccgggcggc ctcagtgagc gagcgagcgc gccagctggc     2280

gtaatagcga agaggcccgc accgatcgcc cttcccaaca gttgcgcagc ctg            2333


