                               SEQUENCE LISTING

<110> THE GENERAL HOSPITAL CORPORATION
 
<120> COMPOSITIONS AND METHODS FOR IMPROVING MITOCHONDRIAL FUNCTION

<130> 030258-091760WOPT

<140> PCT/US2019/014725
<141> 2019-01-23

<150> 62/721,979
<151> 2018-08-23

<150> 62/620,641
<151> 2018-01-23

<160> 44    

<170> PatentIn version 3.5

<210> 1
<211> 2427
<212> DNA
<213> Artificial Sequence

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

<400> 1
atgagcacaa tttcccggcc agggctctgg gccctgataa cggccgcggt attcgcgctt       60

tgcggcgcga tccttaccgt tggcggcgca tgggtcgctg ccatcggcgg ccctctttat      120

tatgtcatcc ttggcctggc acttctcgcc acggctttcc tctcattccg gcgcaatccg      180

gctgccctct atctgttcgc agtcgtcgtc ttcggaacgg tcatctggga actcaccgtt      240

gtcggtctcg acatctgggc cctgatcccg cgctcggaca tcgtcatcat cctcggcatc      300

tggctgctgc tgccgttcgt ctcgcgccag atcggtggca cgcggacgac cgtcctgccg      360

ctcgccggcg ccgttggcgt tgcggttctg gccctgttcg ccagcctctt caccgacccg      420

catgacatca gcggcgaact gccgacgcag atcgcaaacg cctcccccgc cgacccggac      480

aacgttccgg ccagcgagtg gcacgcttat ggtcgtacgc aggccggtga ccgctggtcc      540

ccgctgaacc agatcaatgc gacgaacgtc agcaacctca aggtcgcatg gcatatccac      600

accaaggata tgatgaactc caacgacccg ggcgaagcga cgaacgaagc gacgccgatc      660

gagttcaaca acacgcttta tatgtgctca ctgcatcaga agctgtttgc ggttgatggt      720

gccaccggca acgtcaagtg ggtctacgat ccgaagctcc agatcaaccc tggcttccag      780

catctgacct gccgtggcgt cagcttccac gaaacgccgg ccaatgccat ggattccgat      840

ggcaatcctg ctccgacgga ctgcgccaag cgcatcatcc tgccggtcaa tgatggccgt      900

ctggttgaag tcgatgccga cacgggcaag acctgctccg gcttcggcaa caatggcgag      960

atcgacctgc gcgttccgaa ccagccttac acgacgcctg gccagtacga gccgacgtcc     1020

ccgccggtca tcacagacaa gctgatcatc gccaacagcg ccatcaccga taacggttcg     1080

gtcaagcagg cttcgggcgc cacgcaggca ttcgacgtct acaccggcaa gcgcgtctgg     1140

gtgttcgatg cgtccaaccc ggatccgaac cagcttccgg atgagagcca ccctgtcttc     1200

cacccgaact cgccaaactc ctggatcgtg tcgtcctacg acgccaacct gaacctcgtg     1260

tacatcccga tgggcgtggg gactcccgac cagtggggcg gtgaccgcac gaaggattcc     1320

gagcgtttcg ctccgggtat cgttgcgctg aacgccgata cgggcaagct cgcctggttc     1380

taccagaccg ttcatcacga tctgtgggac atggacgttc cgtcccagcc gagcctcgtg     1440

gatgtgacac agaaggacgg cacgcttgtt ccggccatct acgctccgac caagaccggc     1500

gacattttcg tcctcgaccg tcgtaccggc aaggaaatcg tcccggctcc ggaaaccccg     1560

gttccccagg gtgctgctcc gggtgaccac accagcccga cccagccgat gtcgcagctg     1620

accctgcgtc cgaagaaccc gctgaacgac tccgatatct ggggcggcac gatcttcgac     1680

cagatgttct gcagcatcta tttccacacc ctccgctacg aaggcccctt cacgccgccg     1740

tcgctcaagg gctcgctcat cttcccgggt gatctgggaa tgttcgaatg gggtggtctg     1800

gccgtcgatc cgcagcgtca ggtggctttc gccaacccga tttccctgcc gttcgtctct     1860

cagcttgttc cccgcggacc gggcaacccg ctctggcctg aaggaaatgc caagggcacg     1920

ggtggtgaaa ccggcctgca gcacaactat ggcatcccgt atgccgtcaa cctgcatccg     1980

ttcctggatc cggtgctgct gccgttcggc atcaagatgc cgtgccgcac gccgccctgg     2040

ggctatgtcg ccggtattga cctgaagacc aacaaggtcg tctggcagca ccgcaacggc     2100

accctgcgtg actcgatgta tggcagctcc ctgccgatcc cgctgccgcc gatcaagatc     2160

ggtgtcccga gcctcggtgg cccgctctcc acggctggca atctcggctt cctgacggcg     2220

tccatggatt actacatccg tgcgtacaac ctgacgacgg gcaaggtgct gtggcaggac     2280

cgtctgccgg ctggtgctca ggcaacgccg atcacctatg ccatcaacgg caagcagtac     2340

atcgtgacct atgcaggcgg acacaactcg ttcccgaccc gcatgggcga cgacatcatc     2400

gcctacgccc tgcccgatca gaaatga                                         2427


<210> 2
<211> 808
<212> PRT
<213> Artificial Sequence

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

<400> 2
Met Ser Thr Ile Ser Arg Pro Gly Leu Trp Ala Leu Ile Thr Ala Ala 
1               5                   10                  15      


Val Phe Ala Leu Cys Gly Ala Ile Leu Thr Val Gly Gly Ala Trp Val 
            20                  25                  30          


Ala Ala Ile Gly Gly Pro Leu Tyr Tyr Val Ile Leu Gly Leu Ala Leu 
        35                  40                  45              


Leu Ala Thr Ala Phe Leu Ser Phe Arg Arg Asn Pro Ala Ala Leu Tyr 
    50                  55                  60                  


Leu Phe Ala Val Val Val Phe Gly Thr Val Ile Trp Glu Leu Thr Val 
65                  70                  75                  80  


Val Gly Leu Asp Ile Trp Ala Leu Ile Pro Arg Ser Asp Ile Val Ile 
                85                  90                  95      


Ile Leu Gly Ile Trp Leu Leu Leu Pro Phe Val Ser Arg Gln Ile Gly 
            100                 105                 110         


Gly Thr Arg Thr Thr Val Leu Pro Leu Ala Gly Ala Val Gly Val Ala 
        115                 120                 125             


Val Leu Ala Leu Phe Ala Ser Leu Phe Thr Asp Pro His Asp Ile Ser 
    130                 135                 140                 


Gly Glu Leu Pro Thr Gln Ile Ala Asn Ala Ser Pro Ala Asp Pro Asp 
145                 150                 155                 160 


Asn Val Pro Ala Ser Glu Trp His Ala Tyr Gly Arg Thr Gln Ala Gly 
                165                 170                 175     


Asp Arg Trp Ser Pro Leu Asn Gln Ile Asn Ala Thr Asn Val Ser Asn 
            180                 185                 190         


Leu Lys Val Ala Trp His Ile His Thr Lys Asp Met Met Asn Ser Asn 
        195                 200                 205             


Asp Pro Gly Glu Ala Thr Asn Glu Ala Thr Pro Ile Glu Phe Asn Asn 
    210                 215                 220                 


Thr Leu Tyr Met Cys Ser Leu His Gln Lys Leu Phe Ala Val Asp Gly 
225                 230                 235                 240 


Ala Thr Gly Asn Val Lys Trp Val Tyr Asp Pro Lys Leu Gln Ile Asn 
                245                 250                 255     


Pro Gly Phe Gln His Leu Thr Cys Arg Gly Val Ser Phe His Glu Thr 
            260                 265                 270         


Pro Ala Asn Ala Met Asp Ser Asp Gly Asn Pro Ala Pro Thr Asp Cys 
        275                 280                 285             


Ala Lys Arg Ile Ile Leu Pro Val Asn Asp Gly Arg Leu Val Glu Val 
    290                 295                 300                 


Asp Ala Asp Thr Gly Lys Thr Cys Ser Gly Phe Gly Asn Asn Gly Glu 
305                 310                 315                 320 


Ile Asp Leu Arg Val Pro Asn Gln Pro Tyr Thr Thr Pro Gly Gln Tyr 
                325                 330                 335     


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


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


Gln Ala Phe Asp Val Tyr Thr Gly Lys Arg Val Trp Val Phe Asp Ala 
    370                 375                 380                 


Ser Asn Pro Asp Pro Asn Gln Leu Pro Asp Glu Ser His Pro Val Phe 
385                 390                 395                 400 


His Pro Asn Ser Pro Asn Ser Trp Ile Val Ser Ser Tyr Asp Ala Asn 
                405                 410                 415     


Leu Asn Leu Val Tyr Ile Pro Met Gly Val Gly Thr Pro Asp Gln Trp 
            420                 425                 430         


Gly Gly Asp Arg Thr Lys Asp Ser Glu Arg Phe Ala Pro Gly Ile Val 
        435                 440                 445             


Ala Leu Asn Ala Asp Thr Gly Lys Leu Ala Trp Phe Tyr Gln Thr Val 
    450                 455                 460                 


His His Asp Leu Trp Asp Met Asp Val Pro Ser Gln Pro Ser Leu Val 
465                 470                 475                 480 


Asp Val Thr Gln Lys Asp Gly Thr Leu Val Pro Ala Ile Tyr Ala Pro 
                485                 490                 495     


Thr Lys Thr Gly Asp Ile Phe Val Leu Asp Arg Arg Thr Gly Lys Glu 
            500                 505                 510         


Ile Val Pro Ala Pro Glu Thr Pro Val Pro Gln Gly Ala Ala Pro Gly 
        515                 520                 525             


Asp His Thr Ser Pro Thr Gln Pro Met Ser Gln Leu Thr Leu Arg Pro 
    530                 535                 540                 


Lys Asn Pro Leu Asn Asp Ser Asp Ile Trp Gly Gly Thr Ile Phe Asp 
545                 550                 555                 560 


Gln Met Phe Cys Ser Ile Tyr Phe His Thr Leu Arg Tyr Glu Gly Pro 
                565                 570                 575     


Phe Thr Pro Pro Ser Leu Lys Gly Ser Leu Ile Phe Pro Gly Asp Leu 
            580                 585                 590         


Gly Met Phe Glu Trp Gly Gly Leu Ala Val Asp Pro Gln Arg Gln Val 
        595                 600                 605             


Ala Phe Ala Asn Pro Ile Ser Leu Pro Phe Val Ser Gln Leu Val Pro 
    610                 615                 620                 


Arg Gly Pro Gly Asn Pro Leu Trp Pro Glu Gly Asn Ala Lys Gly Thr 
625                 630                 635                 640 


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


Asn Leu His Pro Phe Leu Asp Pro Val Leu Leu Pro Phe Gly Ile Lys 
            660                 665                 670         


Met Pro Cys Arg Thr Pro Pro Trp Gly Tyr Val Ala Gly Ile Asp Leu 
        675                 680                 685             


Lys Thr Asn Lys Val Val Trp Gln His Arg Asn Gly Thr Leu Arg Asp 
    690                 695                 700                 


Ser Met Tyr Gly Ser Ser Leu Pro Ile Pro Leu Pro Pro Ile Lys Ile 
705                 710                 715                 720 


Gly Val Pro Ser Leu Gly Gly Pro Leu Ser Thr Ala Gly Asn Leu Gly 
                725                 730                 735     


Phe Leu Thr Ala Ser Met Asp Tyr Tyr Ile Arg Ala Tyr Asn Leu Thr 
            740                 745                 750         


Thr Gly Lys Val Leu Trp Gln Asp Arg Leu Pro Ala Gly Ala Gln Ala 
        755                 760                 765             


Thr Pro Ile Thr Tyr Ala Ile Asn Gly Lys Gln Tyr Ile Val Thr Tyr 
    770                 775                 780                 


Ala Gly Gly His Asn Ser Phe Pro Thr Arg Met Gly Asp Asp Ile Ile 
785                 790                 795                 800 


Ala Tyr Ala Leu Pro Asp Gln Lys 
                805             


<210> 3
<211> 657
<212> DNA
<213> Artificial Sequence

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

<400> 3
atgacccagg acgatgcctc tctcatttct gatccaacgt cttccagaca ggaggagggg       60

tctcgccgca gggatgtgct ggcaacggta acagttgcca tgggatgtgc aggcgcgtgt      120

gctgtggcct atccttttct ggacagcctg aatgggacgc gcgccaatca tgtcggggag      180

agcgacatcc tggacgtgga tctctctacc ctcaaagccg gccagcagat tgttgtgaca      240

tggcgggggt ggcccgtgtt cgtgcagaga agaacgccag aaatgctgaa aacgcttcag      300

gatccggcaa tcctgcagaa actacgagat cctgagtcct gcattttcca acaacccaaa      360

gacgcaacaa actggcatcg ttccgtcagc cccgatatcg gcgtcatgat tgggatctgt      420

acccatctcg gctgcgtgcc gactttcgac gccccgacgc aggcagaacc tgccgggaaa      480

tacctctgcc cctgtcatgg ttcacagttt gacagtgcag gccgcgccta caggaacgcc      540

cctgcaccat acaatctgcc ggttccgccc gtgacaatga tttccgatac gcatctgcga      600

attggagaaa gcaaaaacga tcctgacttt gatattgcta acatccagca gatctga         657


<210> 4
<211> 218
<212> PRT
<213> Artificial Sequence

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

<400> 4
Met Thr Gln Asp Asp Ala Ser Leu Ile Ser Asp Pro Thr Ser Ser Arg 
1               5                   10                  15      


Gln Glu Glu Gly Ser Arg Arg Arg Asp Val Leu Ala Thr Val Thr Val 
            20                  25                  30          


Ala Met Gly Cys Ala Gly Ala Cys Ala Val Ala Tyr Pro Phe Leu Asp 
        35                  40                  45              


Ser Leu Asn Gly Thr Arg Ala Asn His Val Gly Glu Ser Asp Ile Leu 
    50                  55                  60                  


Asp Val Asp Leu Ser Thr Leu Lys Ala Gly Gln Gln Ile Val Val Thr 
65                  70                  75                  80  


Trp Arg Gly Trp Pro Val Phe Val Gln Arg Arg Thr Pro Glu Met Leu 
                85                  90                  95      


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


Ser Cys Ile Phe Gln Gln Pro Lys Asp Ala Thr Asn Trp His Arg Ser 
        115                 120                 125             


Val Ser Pro Asp Ile Gly Val Met Ile Gly Ile Cys Thr His Leu Gly 
    130                 135                 140                 


Cys Val Pro Thr Phe Asp Ala Pro Thr Gln Ala Glu Pro Ala Gly Lys 
145                 150                 155                 160 


Tyr Leu Cys Pro Cys His Gly Ser Gln Phe Asp Ser Ala Gly Arg Ala 
                165                 170                 175     


Tyr Arg Asn Ala Pro Ala Pro Tyr Asn Leu Pro Val Pro Pro Val Thr 
            180                 185                 190         


Met Ile Ser Asp Thr His Leu Arg Ile Gly Glu Ser Lys Asn Asp Pro 
        195                 200                 205             


Asp Phe Asp Ile Ala Asn Ile Gln Gln Ile 
    210                 215             


<210> 5
<211> 2940
<212> DNA
<213> Artificial Sequence

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

<400> 5
atgatcgtat cgcgtcgcaa tacgttactt tgcgcatcgg tgctggggat gggggcgctt       60

tcgagcgttg ctcatgcggc aaccgaaagc actcacacgt cctcacatgt gcgccacaag      120

actgtgactc atggtccggt gcgttctgct gcgacgcctg caacaacagc tccggtctcg      180

gtagctcgtc cggtggcagc tccgcagttt tctgcacctg tagcggtcaa ccggtcccat      240

gccgttcgtt ccattgattc cggaacgcag gaaagcgttg tggtcacggg gtcggctctg      300

agcacgtcta acaatcagaa cgcgaacccg gtccagatcg tgaccagcaa gcagatcgag      360

cagactggca tcaacactct gggtgattac ctgcagcgcc tgccgtctgt cggttcttcg      420

ggtacgacga acagccaaac caacaatacg gcgggtgttt cttgcacgga tatccgtaac      480

cttggcaaaa gccgtgttct ggttctgatt gatggcaagc gtgcagcaat tgacggctcg      540

tcaagctgct ttgatctgaa caccatcaat attcaccagg tggcgagtgt cgaaatcctc      600

aaggatggtg gttctgagct gtatggtgct gatgccgttt ccggtgtcat caacatcaag      660

ctcaaacaca atctggatga cgcgaacctg acggttcgtg gaggcatcac tgaccgtgga      720

gatggccagt ccggcatgat ttctggctac aagggctgga attttgatca tggccgcggc      780

aacgtgacgg tctccggatc ttacatgacc cagagcggga tccgtcagaa cagccgtgac      840

tgggccaacc cggttgtgtc tggtctgatt gcaccgggtg gttcgccgac ttacggatcg      900

tccatcccga cggcgggtcg tttcatcact gatactgcgg ataatgttcc caatggtgat      960

ggatcgttcc acaatttcag caagaaagat cgctacaact acggtaatga tcagagcctg     1020

acgaactcct tgcaggatgc cacgctgtcg ttcgatgcac attacgacgt gaaccgtcat     1080

ttcacgccgt atggcaactt cctgtattcg catcgtaact ctaatacgca gatggcgccg     1140

attccggtgt ctggtagcat ctacccgtcc actctgccgg tagccatcac cattccagga     1200

agtgcgccgt acaattcgct tggcgaagat gccacgatgt acaagcgtat gggtgaatgg     1260

ggtgatcgcg tcagtcagac tgctaccgac acatacacgg caaagattgg cgcttcgggt     1320

gatatcaccc acggttggaa atatgacctg tcctatacct acggatggaa ccaggtcatg     1380

tcccagactt ctggcgttgg taattattcc aagctgcttc agagctacgg tctatccgct     1440

gaagagccgg gcaatcctga cagtgcgctg gtttacaacc cgtcgatctg cactgcagcg     1500

gctggctgca cactgtccaa ccctttcaac aagctttcgc cgcaagcggc tgattactcg     1560

aactacacgt cgcacgatca ctactactat cagctgcgtg atctgaacct gcgtattaac     1620

aataaccatg ttgttcacat gccgtggaag aacggtggcg atctaggtat cgcgctgggt     1680

atggagcatc gtggtgagca gcttgcctat catccggatg ccctcgttga atctggccag     1740

acgctgacga actctgcttc ctacacgggt ggtggattca acgtcacgga aggctacctc     1800

gaaggtaaag ccacgctgct gcacaatgca ttccttgcca aggatctgac gattgacggt     1860

cagggccgtt actcgtctta caacacgttc ggcagcacga agaactggaa ggcgtccatc     1920

aactgggcac cggttcagga catccgcttc cgtgcaacgc ttggcacgtc ctaccgtcag     1980

cctaacgtct atgagctgta tggcggtcag tctctcggct atgcatcagc aactgaccca     2040

tgcgacagcg ggcaggtcgg cacatatggc agtctgacgc caattgtggc ggcaaattgc     2100

gccaagcagg ggattaacag cagtaatttc gtgtctgctt cctccagtca ggttccgacc     2160

ctgtttggtg gcaatcccaa gctgaagcct gaaactggcc gtacctacac gtttggtaca     2220

acggtcacgc cgcgttggat tccaggcctc tcggcttccg tggaatactg gcattacacg     2280

ctcaagaaca tgatttcgta cctgagcagt cagtacatca tgaaccagtg ctacacgggt     2340

gcaaacacgt catattgcaa tgacattacc cgcgttggca gcacgaacca gctaaactcc     2400

gtgacagctc tgtatggcaa catcggcgga ctgaagacga gcggcatcga ctttgacctt     2460

gactaccgta tccgcgttac atctcgcgac gttctgacat tgtccaacaa ctttcagcaa     2520

cttgtgagct atcttcagca gaacgagctc ggcggaaagt ggtacaatta tgcaggtcgc     2580

atgttctacc aaaacggtac tggcaacccc cgcgttcgtg attatgcgac cgttggctgg     2640

cagcatggtg caattggcgt cacatatatg atgagctata tgggtggtat gcgttggaac     2700

gactcggaaa ctgatgtgac ccgttcagct tcgggccgca tcaagacgcc tggcatcttc     2760

tctcatgatg ttacggtgac ttatcgttgg aaaaagtgga acttcgaagc tggtgtgaac     2820

aacctgctcg acaagaagcc tccctttgtt tctggtggga cagacaacag cgcggctgcc     2880

ctttatggca acctttacat gggacgtaac gtcttcctgc aggcaggcgt gaacttctga     2940


<210> 6
<211> 979
<212> PRT
<213> Artificial Sequence

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

<400> 6
Met Ile Val Ser Arg Arg Asn Thr Leu Leu Cys Ala Ser Val Leu Gly 
1               5                   10                  15      


Met Gly Ala Leu Ser Ser Val Ala His Ala Ala Thr Glu Ser Thr His 
            20                  25                  30          


Thr Ser Ser His Val Arg His Lys Thr Val Thr His Gly Pro Val Arg 
        35                  40                  45              


Ser Ala Ala Thr Pro Ala Thr Thr Ala Pro Val Ser Val Ala Arg Pro 
    50                  55                  60                  


Val Ala Ala Pro Gln Phe Ser Ala Pro Val Ala Val Asn Arg Ser His 
65                  70                  75                  80  


Ala Val Arg Ser Ile Asp Ser Gly Thr Gln Glu Ser Val Val Val Thr 
                85                  90                  95      


Gly Ser Ala Leu Ser Thr Ser Asn Asn Gln Asn Ala Asn Pro Val Gln 
            100                 105                 110         


Ile Val Thr Ser Lys Gln Ile Glu Gln Thr Gly Ile Asn Thr Leu Gly 
        115                 120                 125             


Asp Tyr Leu Gln Arg Leu Pro Ser Val Gly Ser Ser Gly Thr Thr Asn 
    130                 135                 140                 


Ser Gln Thr Asn Asn Thr Ala Gly Val Ser Cys Thr Asp Ile Arg Asn 
145                 150                 155                 160 


Leu Gly Lys Ser Arg Val Leu Val Leu Ile Asp Gly Lys Arg Ala Ala 
                165                 170                 175     


Ile Asp Gly Ser Ser Ser Cys Phe Asp Leu Asn Thr Ile Asn Ile His 
            180                 185                 190         


Gln Val Ala Ser Val Glu Ile Leu Lys Asp Gly Gly Ser Glu Leu Tyr 
        195                 200                 205             


Gly Ala Asp Ala Val Ser Gly Val Ile Asn Ile Lys Leu Lys His Asn 
    210                 215                 220                 


Leu Asp Asp Ala Asn Leu Thr Val Arg Gly Gly Ile Thr Asp Arg Gly 
225                 230                 235                 240 


Asp Gly Gln Ser Gly Met Ile Ser Gly Tyr Lys Gly Trp Asn Phe Asp 
                245                 250                 255     


His Gly Arg Gly Asn Val Thr Val Ser Gly Ser Tyr Met Thr Gln Ser 
            260                 265                 270         


Gly Ile Arg Gln Asn Ser Arg Asp Trp Ala Asn Pro Val Val Ser Gly 
        275                 280                 285             


Leu Ile Ala Pro Gly Gly Ser Pro Thr Tyr Gly Ser Ser Ile Pro Thr 
    290                 295                 300                 


Ala Gly Arg Phe Ile Thr Asp Thr Ala Asp Asn Val Pro Asn Gly Asp 
305                 310                 315                 320 


Gly Ser Phe His Asn Phe Ser Lys Lys Asp Arg Tyr Asn Tyr Gly Asn 
                325                 330                 335     


Asp Gln Ser Leu Thr Asn Ser Leu Gln Asp Ala Thr Leu Ser Phe Asp 
            340                 345                 350         


Ala His Tyr Asp Val Asn Arg His Phe Thr Pro Tyr Gly Asn Phe Leu 
        355                 360                 365             


Tyr Ser His Arg Asn Ser Asn Thr Gln Met Ala Pro Ile Pro Val Ser 
    370                 375                 380                 


Gly Ser Ile Tyr Pro Ser Thr Leu Pro Val Ala Ile Thr Ile Pro Gly 
385                 390                 395                 400 


Ser Ala Pro Tyr Asn Ser Leu Gly Glu Asp Ala Thr Met Tyr Lys Arg 
                405                 410                 415     


Met Gly Glu Trp Gly Asp Arg Val Ser Gln Thr Ala Thr Asp Thr Tyr 
            420                 425                 430         


Thr Ala Lys Ile Gly Ala Ser Gly Asp Ile Thr His Gly Trp Lys Tyr 
        435                 440                 445             


Asp Leu Ser Tyr Thr Tyr Gly Trp Asn Gln Val Met Ser Gln Thr Ser 
    450                 455                 460                 


Gly Val Gly Asn Tyr Ser Lys Leu Leu Gln Ser Tyr Gly Leu Ser Ala 
465                 470                 475                 480 


Glu Glu Pro Gly Asn Pro Asp Ser Ala Leu Val Tyr Asn Pro Ser Ile 
                485                 490                 495     


Cys Thr Ala Ala Ala Gly Cys Thr Leu Ser Asn Pro Phe Asn Lys Leu 
            500                 505                 510         


Ser Pro Gln Ala Ala Asp Tyr Ser Asn Tyr Thr Ser His Asp His Tyr 
        515                 520                 525             


Tyr Tyr Gln Leu Arg Asp Leu Asn Leu Arg Ile Asn Asn Asn His Val 
    530                 535                 540                 


Val His Met Pro Trp Lys Asn Gly Gly Asp Leu Gly Ile Ala Leu Gly 
545                 550                 555                 560 


Met Glu His Arg Gly Glu Gln Leu Ala Tyr His Pro Asp Ala Leu Val 
                565                 570                 575     


Glu Ser Gly Gln Thr Leu Thr Asn Ser Ala Ser Tyr Thr Gly Gly Gly 
            580                 585                 590         


Phe Asn Val Thr Glu Gly Tyr Leu Glu Gly Lys Ala Thr Leu Leu His 
        595                 600                 605             


Asn Ala Phe Leu Ala Lys Asp Leu Thr Ile Asp Gly Gln Gly Arg Tyr 
    610                 615                 620                 


Ser Ser Tyr Asn Thr Phe Gly Ser Thr Lys Asn Trp Lys Ala Ser Ile 
625                 630                 635                 640 


Asn Trp Ala Pro Val Gln Asp Ile Arg Phe Arg Ala Thr Leu Gly Thr 
                645                 650                 655     


Ser Tyr Arg Gln Pro Asn Val Tyr Glu Leu Tyr Gly Gly Gln Ser Leu 
            660                 665                 670         


Gly Tyr Ala Ser Ala Thr Asp Pro Cys Asp Ser Gly Gln Val Gly Thr 
        675                 680                 685             


Tyr Gly Ser Leu Thr Pro Ile Val Ala Ala Asn Cys Ala Lys Gln Gly 
    690                 695                 700                 


Ile Asn Ser Ser Asn Phe Val Ser Ala Ser Ser Ser Gln Val Pro Thr 
705                 710                 715                 720 


Leu Phe Gly Gly Asn Pro Lys Leu Lys Pro Glu Thr Gly Arg Thr Tyr 
                725                 730                 735     


Thr Phe Gly Thr Thr Val Thr Pro Arg Trp Ile Pro Gly Leu Ser Ala 
            740                 745                 750         


Ser Val Glu Tyr Trp His Tyr Thr Leu Lys Asn Met Ile Ser Tyr Leu 
        755                 760                 765             


Ser Ser Gln Tyr Ile Met Asn Gln Cys Tyr Thr Gly Ala Asn Thr Ser 
    770                 775                 780                 


Tyr Cys Asn Asp Ile Thr Arg Val Gly Ser Thr Asn Gln Leu Asn Ser 
785                 790                 795                 800 


Val Thr Ala Leu Tyr Gly Asn Ile Gly Gly Leu Lys Thr Ser Gly Ile 
                805                 810                 815     


Asp Phe Asp Leu Asp Tyr Arg Ile Arg Val Thr Ser Arg Asp Val Leu 
            820                 825                 830         


Thr Leu Ser Asn Asn Phe Gln Gln Leu Val Ser Tyr Leu Gln Gln Asn 
        835                 840                 845             


Glu Leu Gly Gly Lys Trp Tyr Asn Tyr Ala Gly Arg Met Phe Tyr Gln 
    850                 855                 860                 


Asn Gly Thr Gly Asn Pro Arg Val Arg Asp Tyr Ala Thr Val Gly Trp 
865                 870                 875                 880 


Gln His Gly Ala Ile Gly Val Thr Tyr Met Met Ser Tyr Met Gly Gly 
                885                 890                 895     


Met Arg Trp Asn Asp Ser Glu Thr Asp Val Thr Arg Ser Ala Ser Gly 
            900                 905                 910         


Arg Ile Lys Thr Pro Gly Ile Phe Ser His Asp Val Thr Val Thr Tyr 
        915                 920                 925             


Arg Trp Lys Lys Trp Asn Phe Glu Ala Gly Val Asn Asn Leu Leu Asp 
    930                 935                 940                 


Lys Lys Pro Pro Phe Val Ser Gly Gly Thr Asp Asn Ser Ala Ala Ala 
945                 950                 955                 960 


Leu Tyr Gly Asn Leu Tyr Met Gly Arg Asn Val Phe Leu Gln Ala Gly 
                965                 970                 975     


Val Asn Phe 
            


<210> 7
<211> 843
<212> DNA
<213> Artificial Sequence

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

<400> 7
atgcgcgttg ccctgatcca gatggctcct tcggcggacc ggagtgccaa tatccttcaa       60

gctcagcggc tggtttcaga agctgtcaaa gctcggaagc cagatcttgt ggtgctgcct      120

gaaatctgga gctgtctggg tggttcggct gcgaccaagc aggctaatgc agagcttcta      180

cctgatccag gcgatgctgg aggtgtactc tacgaagcgt tgagggccat ggcccgggaa      240

cataatgtct gggttcacgg tggttcaatc ggagaacttg tagggcctga gtcgggcgac      300

aagcttgcca atacttcact cgttttcaac cctgatggcg aggaatgtgg gcgttacaga      360

aaaatccatc tcttcgatgt tattacaccc aatggggacg gctatcgtga aagcgataat      420

tatgtgcccg gggaagcgat cgaagtcgtc gatattgatg gcgtcccaac cggcctcgcg      480

atttgctatg atttgaggtt tgctgagctg tttcttgcac ttcgggctgc ggatgttgag      540

atgattgttc tgcccgcagc gtttacgcag caaacgggtg aagctcactg ggacattctt      600

gtccgtgctc gcgctattga gtctcagacg tgggtgatag cgtgtggaac aacgggctgg      660

catgtcgatg ggcaaggcaa tcagcgccag acctatggcc attccatgat cgtcagccca      720

tggggcgagg ttgttcttca attgggtagt gaagaaggct ggggggtggc tgatcttgat      780

atggatgagg ttcgacaggt gcgggagaga atgcctgtgc agataaacag gcggctgatt      840

tga                                                                    843


<210> 8
<211> 280
<212> PRT
<213> Artificial Sequence

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

<400> 8
Met Arg Val Ala Leu Ile Gln Met Ala Pro Ser Ala Asp Arg Ser Ala 
1               5                   10                  15      


Asn Ile Leu Gln Ala Gln Arg Leu Val Ser Glu Ala Val Lys Ala Arg 
            20                  25                  30          


Lys Pro Asp Leu Val Val Leu Pro Glu Ile Trp Ser Cys Leu Gly Gly 
        35                  40                  45              


Ser Ala Ala Thr Lys Gln Ala Asn Ala Glu Leu Leu Pro Asp Pro Gly 
    50                  55                  60                  


Asp Ala Gly Gly Val Leu Tyr Glu Ala Leu Arg Ala Met Ala Arg Glu 
65                  70                  75                  80  


His Asn Val Trp Val His Gly Gly Ser Ile Gly Glu Leu Val Gly Pro 
                85                  90                  95      


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


Gly Glu Glu Cys Gly Arg Tyr Arg Lys Ile His Leu Phe Asp Val Ile 
        115                 120                 125             


Thr Pro Asn Gly Asp Gly Tyr Arg Glu Ser Asp Asn Tyr Val Pro Gly 
    130                 135                 140                 


Glu Ala Ile Glu Val Val Asp Ile Asp Gly Val Pro Thr Gly Leu Ala 
145                 150                 155                 160 


Ile Cys Tyr Asp Leu Arg Phe Ala Glu Leu Phe Leu Ala Leu Arg Ala 
                165                 170                 175     


Ala Asp Val Glu Met Ile Val Leu Pro Ala Ala Phe Thr Gln Gln Thr 
            180                 185                 190         


Gly Glu Ala His Trp Asp Ile Leu Val Arg Ala Arg Ala Ile Glu Ser 
        195                 200                 205             


Gln Thr Trp Val Ile Ala Cys Gly Thr Thr Gly Trp His Val Asp Gly 
    210                 215                 220                 


Gln Gly Asn Gln Arg Gln Thr Tyr Gly His Ser Met Ile Val Ser Pro 
225                 230                 235                 240 


Trp Gly Glu Val Val Leu Gln Leu Gly Ser Glu Glu Gly Trp Gly Val 
                245                 250                 255     


Ala Asp Leu Asp Met Asp Glu Val Arg Gln Val Arg Glu Arg Met Pro 
            260                 265                 270         


Val Gln Ile Asn Arg Arg Leu Ile 
        275                 280 


<210> 9
<211> 939
<212> DNA
<213> Artificial Sequence

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

<400> 9
atgatgaaag caggaccgat gaaaaaactc tggcgatatc tcccagcgtt gccggcgctg       60

atgctatcgg gttgcacggt tgatctgctt cagccgcgcg gtccgatcgc agaaatgaac      120

cgcgacgtta tggtggcaga atttgccatc atgatggcga ttgtggttcc gacctgtatc      180

gcaacgcttt attttgcttg gaagtatcgc gcttccaata cccaggccga atatctgccg      240

acctgggatc actcaacgaa gattgagtat gtcatctggg gcgtccctgc tctgatcatt      300

attgcccttg gcgcgatcag ctggtacagc acccatgctt atgacccgta ccgcccgctc      360

cagacggctg acaacgtcaa gccgctgaac gttcaggtgg tctctctcga ctggaaatgg      420

ctgttcatct atccggatct ggggatcgcc acgatcaacc agctggatgt gcccacgaac      480

acgccgctga acttccagat cacctctgac actgtcatga cgtcgttctt catcccgcgt      540

ctgggatcaa tgatctactc catgccgggt cagcagacac agctgcatct tcttgcaact      600

gagtcgggtg actatctggg tgaagcttcc cagttcagtg gtcgcggttt ctctgacatg      660

aagttccgca ccctcgccat ggcacctgaa gaattcagcg cctgggtcga gaaggtgaag      720

agcggcagcg aaaacctcga tgacacgact tatccgaagt acgccgcccc gcaggaagct      780

gcgccggttc agtatttcgc gcatgtccag ccggatctct tcgacggcat cgtcgccaag      840

tacaacaatg gcatgatggt tgagaagacg acgggcaagg tcatgcatat gcagtccgct      900

tccagcgctg caccgtccga cactggcatg aaggaataa                             939


<210> 10
<211> 312
<212> PRT
<213> Artificial Sequence

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

<400> 10
Met Met Lys Ala Gly Pro Met Lys Lys Leu Trp Arg Tyr Leu Pro Ala 
1               5                   10                  15      


Leu Pro Ala Leu Met Leu Ser Gly Cys Thr Val Asp Leu Leu Gln Pro 
            20                  25                  30          


Arg Gly Pro Ile Ala Glu Met Asn Arg Asp Val Met Val Ala Glu Phe 
        35                  40                  45              


Ala Ile Met Met Ala Ile Val Val Pro Thr Cys Ile Ala Thr Leu Tyr 
    50                  55                  60                  


Phe Ala Trp Lys Tyr Arg Ala Ser Asn Thr Gln Ala Glu Tyr Leu Pro 
65                  70                  75                  80  


Thr Trp Asp His Ser Thr Lys Ile Glu Tyr Val Ile Trp Gly Val Pro 
                85                  90                  95      


Ala Leu Ile Ile Ile Ala Leu Gly Ala Ile Ser Trp Tyr Ser Thr His 
            100                 105                 110         


Ala Tyr Asp Pro Tyr Arg Pro Leu Gln Thr Ala Asp Asn Val Lys Pro 
        115                 120                 125             


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


Pro Asp Leu Gly Ile Ala Thr Ile Asn Gln Leu Asp Val Pro Thr Asn 
145                 150                 155                 160 


Thr Pro Leu Asn Phe Gln Ile Thr Ser Asp Thr Val Met Thr Ser Phe 
                165                 170                 175     


Phe Ile Pro Arg Leu Gly Ser Met Ile Tyr Ser Met Pro Gly Gln Gln 
            180                 185                 190         


Thr Gln Leu His Leu Leu Ala Thr Glu Ser Gly Asp Tyr Leu Gly Glu 
        195                 200                 205             


Ala Ser Gln Phe Ser Gly Arg Gly Phe Ser Asp Met Lys Phe Arg Thr 
    210                 215                 220                 


Leu Ala Met Ala Pro Glu Glu Phe Ser Ala Trp Val Glu Lys Val Lys 
225                 230                 235                 240 


Ser Gly Ser Glu Asn Leu Asp Asp Thr Thr Tyr Pro Lys Tyr Ala Ala 
                245                 250                 255     


Pro Gln Glu Ala Ala Pro Val Gln Tyr Phe Ala His Val Gln Pro Asp 
            260                 265                 270         


Leu Phe Asp Gly Ile Val Ala Lys Tyr Asn Asn Gly Met Met Val Glu 
        275                 280                 285             


Lys Thr Thr Gly Lys Val Met His Met Gln Ser Ala Ser Ser Ala Ala 
    290                 295                 300                 


Pro Ser Asp Thr Gly Met Lys Glu 
305                 310         


<210> 11
<211> 20
<212> DNA
<213> Artificial Sequence

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

<400> 11
aacaagccag ggatgtaacg                                                   20


<210> 12
<211> 20
<212> DNA
<213> Artificial Sequence

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

<400> 12
cagcaacacc ttcttcacga                                                   20


<210> 13
<211> 60
<212> DNA
<213> Artificial Sequence

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

<400> 13
cagctgacgc ttcgtccgaa gaacccgctc tccgatgccg atatctgggg tggcacaatc       60


<210> 14
<211> 59
<212> DNA
<213> Artificial Sequence

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

<400> 14
ctacatcccg accaagacgg gcgatatctt tgtcctcgac cgccgtacgg gcaaggaag        59


<210> 15
<211> 59
<212> DNA
<213> Artificial Sequence

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

<400> 15
agcacccacg cctacgaccc gtaccgcccc cttcagacgg ctgacaacgt caagccctg        59


<210> 16
<211> 60
<212> DNA
<213> Artificial Sequence

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

<400> 16
cgcaccaaca aggtggtctg gcagcatcgt aacggtacgc tccgtgactc catgcacggc       60


<210> 17
<211> 60
<212> DNA
<213> Artificial Sequence

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

<400> 17
tacaagtggt atcgattggg attttgatta tcggatccgt ctgactagca tggattccat       60


<210> 18
<211> 37
<212> DNA
<213> Artificial Sequence

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

<400> 18
catcggcgtc atgatcggga tctgcacgca tctgggc                                37


<210> 19
<211> 59
<212> DNA
<213> Artificial Sequence

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

<400> 19
cgatgcagaa accgggcaga agtgttccgg ctttggcaac gacggcgaac tggaacctg        59


<210> 20
<211> 40
<212> DNA
<213> Artificial Sequence

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

<400> 20
tcttaatgcg cttctatgtg tttgtccgaa ggtcaagtgc                             40


<210> 21
<211> 47
<212> DNA
<213> Artificial Sequence

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

<400> 21
gcagtaattt cgtgtctgct tcctccagtc aggttccgac cctgttt                     47


<210> 22
<211> 60
<212> DNA
<213> Artificial Sequence

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

<400> 22
tggcgatcgc tggtctccgc tgaagcagat caattcgacc aatgttcaga acctcaaggt       60


<210> 23
<211> 60
<212> DNA
<213> Artificial Sequence

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

<400> 23
agactcaata gcgcgagcac ggacaagaat gtcccagtga gcttcacccg tttgctgcgt       60


<210> 24
<211> 20
<212> DNA
<213> Artificial Sequence

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

<400> 24
agagtttgat cmtggctcag                                                   20


<210> 25
<211> 22
<212> DNA
<213> Artificial Sequence

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

<400> 25
tacggytacc ttgttacgac tt                                                22


<210> 26
<211> 20
<212> DNA
<213> Artificial Sequence

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

<400> 26
caccagccta accagatttc                                                   20


<210> 27
<211> 22
<212> DNA
<213> Artificial Sequence

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

<400> 27
gggttgtatt gatgagatta gt                                                22


<210> 28
<211> 27
<212> DNA
<213> Artificial Sequence

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

<400> 28
gcttctgaca caactgtgtt cactagc                                           27


<210> 29
<211> 23
<212> DNA
<213> Artificial Sequence

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

<400> 29
caccaacttc atccacgttc acc                                               23


<210> 30
<211> 20
<212> DNA
<213> Artificial Sequence

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

<400> 30
tgttcacaat ggataggcac                                                   20


<210> 31
<211> 20
<212> DNA
<213> Artificial Sequence

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

<400> 31
tctgggtttt ccaaagcaag                                                   20


<210> 32
<211> 21
<212> DNA
<213> Artificial Sequence

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

<400> 32
tgaagacgga ttgccctcat t                                                 21


<210> 33
<211> 20
<212> DNA
<213> Artificial Sequence

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

<400> 33
gctggtgcca gtaagagctt                                                   20


<210> 34
<211> 60
<212> DNA
<213> Artificial Sequence

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

<400> 34
ggcacaatct tcgaccagat gttctgcagc atctacttcc actccctgcg ctacgaaggt       60


<210> 35
<211> 60
<212> DNA
<213> Artificial Sequence

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

<400> 35
gggcaaggaa gtcgtcgctg ctcctgaaac accagttcca ggtggtgcag ctccgggcga       60


<210> 36
<211> 60
<212> DNA
<213> Artificial Sequence

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

<400> 36
gacagcgtca agccactgaa tgttcaggtg gtctctctcg actggaaatg gctgttcatc       60


<210> 37
<211> 60
<212> DNA
<213> Artificial Sequence

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

<400> 37
atgcacggca gctccctgcc catcccgctg cctccgatca agatcggtgt tccgagcctt       60


<210> 38
<211> 60
<212> DNA
<213> Artificial Sequence

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

<400> 38
ggattccatc actgtcagca ataacctgca gaacctggtc aatttttccc agcagcagac       60


<210> 39
<211> 47
<212> DNA
<213> Artificial Sequence

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

<400> 39
tgcgtgccga ctttcgacgc cccgacgcag gcagaacctg ccgggaa                     47


<210> 40
<211> 60
<212> DNA
<213> Artificial Sequence

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

<400> 40
gaactggaac tgcgcgagcc gaaccagcct tacgtcacgc caggcatgta tgagccgacg       60


<210> 41
<211> 58
<212> DNA
<213> Artificial Sequence

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

<400> 41
aggtcaagtg ctgcaccaaa taacagctct aggaacatca tgagcacatc ttcccggc         58


<210> 42
<211> 51
<212> DNA
<213> Artificial Sequence

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

<400> 42
ggtggtaata caaagctgcg tccagaagca gggcgtacct acacctttgg t                51


<210> 43
<211> 60
<212> DNA
<213> Artificial Sequence

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

<400> 43
cctcaaggtg gcatggcaca tccacaccaa ggatctgatg ggaccgaatg atccgggcga       60


<210> 44
<211> 45
<212> DNA
<213> Artificial Sequence

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

<400> 44
aaacgctgcg ggcagaacaa tcatctcaac atccgcagcc cgaag                       45


