                               SEQUENCE LISTING

<110> PRESIDENT AND FELLOWS OF HARVARD COLLEGE
 
<120> TGFBETA THERAPY FOR OCULAR AND NEURODEGENERATIVE DISEASES

<130> 002806-097280WOPT

<140> PCT/US2021/026389
<141> 2021-04-08

<150> 63/006,817
<151> 2020-04-08

<160> 46    

<170> PatentIn version 3.5

<210> 1
<211> 1172
<212> DNA
<213> Homo sapiens

<400> 1
atgccgccct ccgggctgcg gctgctgccg ctgctgctac cgctgctgtg gctactggtg       60

ctgacgcctg gccggccggc cgcgggacta tccacctgca agactatcga catggagctg      120

gtgaagcgga agcgcatcga ggccatccgc ggccagatcc tgtccaagct gcggctcgcc      180

agccccccga gccaggggga ggtgccgccc ggcccgctgc ccgaggccgt gctcgccctg      240

tacaacagca cccgcgaccg ggtggccggg gagagtgcag aaccggagcc cgagcctgag      300

gccgactact acgccaagga ggtcacccgc gtgctaatgg tggaaaccca caacgaaatc      360

tatgacaagt tcaagcagag tacacacagc atatatatgt tcttcaacac atcagagctc      420

cgagaagcgg tacctgaacc cgtgttgctc tcccgggcag agctgcgtct gctgaggctc      480

aagttaaaag tggagcagca cgtggagctg taccagaaat acagcaacaa ttcctggcga      540

tacctcagca accggctgct ggcacccagc gactcgccag agtggttatc ttttgatgtc      600

accggagttg tgcggcagtg gttgagccgt ggaggggaaa ttgagggctt tcgccttagc      660

gcccactgct cctgtgacag cagggataac acactgcaag tggacatcaa cgggttcact      720

accggccgcc gaggtgacct ggccaccatt catggcatga accggccttt cctgcttctc      780

atggccaccc cgctggagag ggcccagcat ctgcaaagct cccggcaccg ccgagccctg      840

gacaccaact attgcttcag ctccacggag aagaactgct gcgtgcggca gctgtacatt      900

gacttccgca aggacctcgg ctggaagtgg atccacgagc ccaagggcta ccatgccaac      960

ttctgcctcg ggccctgccc ctacatttgg agcctggaca cgcagtacag caaggtcctg     1020

gccctgtaca accagcataa cccgggcgcc tcggcggcgc cgtgctgcgt gccgcaggcg     1080

ctggagccgc tgcccatcgt gtactacgtg ggccgcaagc ccaaggtgga gcagctgtcc     1140

aacatgatcg tgcgctcctg caagtgcagc tg                                   1172


<210> 2
<211> 1329
<212> DNA
<213> Homo sapiens

<400> 2
atgcactact gtgtgctgag cgcttttctg atcctgcatc tggtcacggt cgcgctcagc       60

ctgtctacct gcagcacact cgatatggac cagttcatgc gcaagaggat cgaggcgatc      120

cgcgggcaga tcctgagcaa gctgaagctc accagtcccc cagaagacta tcctgagccc      180

gaggaagtcc ccccggaggt gatttccatc tacaacagca ccagggactt gctccaggag      240

aaggcgagcc ggagggcggc cgcctgcgag cgcgagagga gcgacgaaga gtactacgcc      300

aaggaggttt acaaaataga catgccgccc ttcttcccct ccgaaactgt ctgcccagtt      360

gttacaacac cctctggctc agtgggcagc ttgtgctcca gacagtccca ggtgctctgt      420

gggtaccttg atgccatccc gcccactttc tacagaccct acttcagaat tgttcgattt      480

gacgtctcag caatggagaa gaatgcttcc aatttggtga aagcagagtt cagagtcttt      540

cgtttgcaga acccaaaagc cagagtgcct gaacaacgga ttgagctata tcagattctc      600

aagtccaaag atttaacatc tccaacccag cgctacatcg acagcaaagt tgtgaaaaca      660

agagcagaag gcgaatggct ctccttcgat gtaactgatg ctgttcatga atggcttcac      720

cataaagaca ggaacctggg atttaaaata agcttacact gtccctgctg cacttttgta      780

ccatctaata attacatcat cccaaataaa agtgaagaac tagaagcaag atttgcaggt      840

attgatggca cctccacata taccagtggt gatcagaaaa ctataaagtc cactaggaaa      900

aaaaacagtg ggaagacccc acatctcctg ctaatgttat tgccctccta cagacttgag      960

tcacaacaga ccaaccggcg gaagaagcgt gctttggatg cggcctattg ctttagaaat     1020

gtgcaggata attgctgcct acgtccactt tacattgatt tcaagaggga tctagggtgg     1080

aaatggatac acgaacccaa agggtacaat gccaacttct gtgctggagc atgcccgtat     1140

ttatggagtt cagacactca gcacagcagg gtcctgagct tatataatac cataaatcca     1200

gaagcatctg cttctccttg ctgcgtgtcc caagatttag aacctctaac cattctctac     1260

tacattggca aaacacccaa gattgaacag ctttctaata tgattgtaaa gtcttgcaaa     1320

tgcagctaa                                                             1329


<210> 3
<211> 1245
<212> DNA
<213> Homo sapiens

<400> 3
atgcactact gtgtgctgag cgcttttctg atcctgcatc tggtcacggt cgcgctcagc       60

ctgtctacct gcagcacact cgatatggac cagttcatgc gcaagaggat cgaggcgatc      120

cgcgggcaga tcctgagcaa gctgaagctc accagtcccc cagaagacta tcctgagccc      180

gaggaagtcc ccccggaggt gatttccatc tacaacagca ccagggactt gctccaggag      240

aaggcgagcc ggagggcggc cgcctgcgag cgcgagagga gcgacgaaga gtactacgcc      300

aaggaggttt acaaaataga catgccgccc ttcttcccct ccgaaaatgc catcccgccc      360

actttctaca gaccctactt cagaattgtt cgatttgacg tctcagcaat ggagaagaat      420

gcttccaatt tggtgaaagc agagttcaga gtctttcgtt tgcagaaccc aaaagccaga      480

gtgcctgaac aacggattga gctatatcag attctcaagt ccaaagattt aacatctcca      540

acccagcgct acatcgacag caaagttgtg aaaacaagag cagaaggcga atggctctcc      600

ttcgatgtaa ctgatgctgt tcatgaatgg cttcaccata aagacaggaa cctgggattt      660

aaaataagct tacactgtcc ctgctgcact tttgtaccat ctaataatta catcatccca      720

aataaaagtg aagaactaga agcaagattt gcaggtattg atggcacctc cacatatacc      780

agtggtgatc agaaaactat aaagtccact aggaaaaaaa acagtgggaa gaccccacat      840

ctcctgctaa tgttattgcc ctcctacaga cttgagtcac aacagaccaa ccggcggaag      900

aagcgtgctt tggatgcggc ctattgcttt agaaatgtgc aggataattg ctgcctacgt      960

ccactttaca ttgatttcaa gagggatcta gggtggaaat ggatacacga acccaaaggg     1020

tacaatgcca acttctgtgc tggagcatgc ccgtatttat ggagttcaga cactcagcac     1080

agcagggtcc tgagcttata taataccata aatccagaag catctgcttc tccttgctgc     1140

gtgtcccaag atttagaacc tctaaccatt ctctactaca ttggcaaaac acccaagatt     1200

gaacagcttt ctaatatgat tgtaaagtct tgcaaatgca gctaa                     1245


<210> 4
<211> 1239
<212> DNA
<213> Homo sapiens

<400> 4
atgaagatgc acttgcaaag ggctctggtg gtcctggccc tgctgaactt tgccacggtc       60

agcctctctc tgtccacttg caccaccttg gacttcggcc acatcaagaa gaagagggtg      120

gaagccatta ggggacagat cttgagcaag ctcaggctca ccagcccccc tgagccaacg      180

gtgatgaccc acgtccccta tcaggtcctg gccctttaca acagcacccg ggagctgctg      240

gaggagatgc atggggagag ggaggaaggc tgcacccagg aaaacaccga gtcggaatac      300

tatgccaaag aaatccataa attcgacatg atccaggggc tggcggagca caacgaactg      360

gctgtctgcc ctaaaggaat tacctccaag gttttccgct tcaatgtgtc ctcagtggag      420

aaaaatagaa ccaacctatt ccgagcagaa ttccgggtct tgcgggtgcc caaccccagc      480

tctaagcgga atgagcagag gatcgagctc ttccagatcc ttcggccaga tgagcacatt      540

gccaaacagc gctatatcgg tggcaagaat ctgcccacac ggggcactgc cgagtggctg      600

tcctttgatg tcactgacac tgtgcgtgag tggctgttga gaagagagtc caacttaggt      660

ctagaaatca gcattcactg tccatgtcac acctttcagc ccaatggaga tatcctggaa      720

aacattcacg aggtgatgga aatcaaattc aaaggcgtgg acaatgagga tgaccatggc      780

cgtggagatc tggggcgcct caagaagcag aaggatcacc acaaccctca tctaatcctc      840

atgatgattc ccccacaccg gctcgacaac ccgggccagg ggggtcagag gaagaagcgg      900

gctttggaca ccaattactg cttccgcaac ttggaggaga actgctgtgt gcgccccctc      960

tacattgact tccgacagga tctgggctgg aagtgggtcc atgaacctaa gggctactat     1020

gccaacttct gctcaggccc ttgcccatac ctccgcagtg cagacacaac ccacagcacg     1080

gtgctgggac tgtacaacac tctgaaccct gaagcatctg cctcgccttg ctgcgtgccc     1140

caggacctgg agcccctgac catcctgtac tatgttggga ggacccccaa agtggagcag     1200

ctctccaaca tggtggtgaa gtcttgtaaa tgtagctga                            1239


<210> 5
<211> 930
<212> DNA
<213> Homo sapiens

<400> 5
atgaagatgc acttgcaaag ggctctggtg gtcctggccc tgctgaactt tgccacggtc       60

agcctctctc tgtccacttg caccaccttg gacttcggcc acatcaagaa gaagagggtg      120

gaagccatta ggggacagat cttgagcaag ctcaggctca ccagcccccc tgagccaacg      180

gtgatgaccc acgtccccta tcaggtcctg gccctttaca acagcacccg ggagctgctg      240

gaggagatgc atggggagag ggaggaaggc tgcacccagg aaaacaccga gtcggaatac      300

tatgccaaag aaatccataa attcgacatg atccaggggc tggcggagca caacgaactg      360

gctgtctgcc ctaaaggaat tacctccaag gttttccgct tcaatgtgtc ctcagtggag      420

aaaaatagaa ccaacctatt ccgagcagaa ttccgggtct tgcgggtgcc caaccccagc      480

tctaagcgga atgagcagag gatcgagctc ttccagatcc ttcggccaga tgagcacatt      540

gccaaacagc gctatatcgg tggcaagaat ctgcccacac ggggcactgc cgagtggctg      600

tcctttgatg tcactgacac tgtgcgtgag tggctgttga gaagagagtc caacttaggt      660

ctagaaatca gcattcactg tccatgtcac acctttcagc ccaatggaga tatcctggaa      720

aacattcacg aggtgatgga aatcaaattc aaaggcgtgg acaatgagga tgaccatggc      780

cgtggagatc tggggcgcct caagaagcag aaggatcacc acaaccctca tctaatcctc      840

atgatgattc ccccacaccg gctcgacaac ccgggccagg ggggtcagag gaagaagcgg      900

gctttggaca ccaattactg cttccggtga                                       930


<210> 6
<211> 390
<212> PRT
<213> Homo sapiens

<400> 6
Met Pro Pro Ser Gly Leu Arg Leu Leu Pro Leu Leu Leu Pro Leu Leu 
1               5                   10                  15      


Trp Leu Leu Val Leu Thr Pro Gly Arg Pro Ala Ala Gly Leu Ser Thr 
            20                  25                  30          


Cys Lys Thr Ile Asp Met Glu Leu Val Lys Arg Lys Arg Ile Glu Ala 
        35                  40                  45              


Ile Arg Gly Gln Ile Leu Ser Lys Leu Arg Leu Ala Ser Pro Pro Ser 
    50                  55                  60                  


Gln Gly Glu Val Pro Pro Gly Pro Leu Pro Glu Ala Val Leu Ala Leu 
65                  70                  75                  80  


Tyr Asn Ser Thr Arg Asp Arg Val Ala Gly Glu Ser Ala Glu Pro Glu 
                85                  90                  95      


Pro Glu Pro Glu Ala Asp Tyr Tyr Ala Lys Glu Val Thr Arg Val Leu 
            100                 105                 110         


Met Val Glu Thr His Asn Glu Ile Tyr Asp Lys Phe Lys Gln Ser Thr 
        115                 120                 125             


His Ser Ile Tyr Met Phe Phe Asn Thr Ser Glu Leu Arg Glu Ala Val 
    130                 135                 140                 


Pro Glu Pro Val Leu Leu Ser Arg Ala Glu Leu Arg Leu Leu Arg Leu 
145                 150                 155                 160 


Lys Leu Lys Val Glu Gln His Val Glu Leu Tyr Gln Lys Tyr Ser Asn 
                165                 170                 175     


Asn Ser Trp Arg Tyr Leu Ser Asn Arg Leu Leu Ala Pro Ser Asp Ser 
            180                 185                 190         


Pro Glu Trp Leu Ser Phe Asp Val Thr Gly Val Val Arg Gln Trp Leu 
        195                 200                 205             


Ser Arg Gly Gly Glu Ile Glu Gly Phe Arg Leu Ser Ala His Cys Ser 
    210                 215                 220                 


Cys Asp Ser Arg Asp Asn Thr Leu Gln Val Asp Ile Asn Gly Phe Thr 
225                 230                 235                 240 


Thr Gly Arg Arg Gly Asp Leu Ala Thr Ile His Gly Met Asn Arg Pro 
                245                 250                 255     


Phe Leu Leu Leu Met Ala Thr Pro Leu Glu Arg Ala Gln His Leu Gln 
            260                 265                 270         


Ser Ser Arg His Arg Arg Ala Leu Asp Thr Asn Tyr Cys Phe Ser Ser 
        275                 280                 285             


Thr Glu Lys Asn Cys Cys Val Arg Gln Leu Tyr Ile Asp Phe Arg Lys 
    290                 295                 300                 


Asp Leu Gly Trp Lys Trp Ile His Glu Pro Lys Gly Tyr His Ala Asn 
305                 310                 315                 320 


Phe Cys Leu Gly Pro Cys Pro Tyr Ile Trp Ser Leu Asp Thr Gln Tyr 
                325                 330                 335     


Ser Lys Val Leu Ala Leu Tyr Asn Gln His Asn Pro Gly Ala Ser Ala 
            340                 345                 350         


Ala Pro Cys Cys Val Pro Gln Ala Leu Glu Pro Leu Pro Ile Val Tyr 
        355                 360                 365             


Tyr Val Gly Arg Lys Pro Lys Val Glu Gln Leu Ser Asn Met Ile Val 
    370                 375                 380                 


Arg Ser Cys Lys Cys Ser 
385                 390 


<210> 7
<211> 442
<212> PRT
<213> Homo sapiens

<400> 7
Met His Tyr Cys Val Leu Ser Ala Phe Leu Ile Leu His Leu Val Thr 
1               5                   10                  15      


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


Met Arg Lys Arg Ile Glu Ala Ile Arg Gly Gln Ile Leu Ser Lys Leu 
        35                  40                  45              


Lys Leu Thr Ser Pro Pro Glu Asp Tyr Pro Glu Pro Glu Glu Val Pro 
    50                  55                  60                  


Pro Glu Val Ile Ser Ile Tyr Asn Ser Thr Arg Asp Leu Leu Gln Glu 
65                  70                  75                  80  


Lys Ala Ser Arg Arg Ala Ala Ala Cys Glu Arg Glu Arg Ser Asp Glu 
                85                  90                  95      


Glu Tyr Tyr Ala Lys Glu Val Tyr Lys Ile Asp Met Pro Pro Phe Phe 
            100                 105                 110         


Pro Ser Glu Thr Val Cys Pro Val Val Thr Thr Pro Ser Gly Ser Val 
        115                 120                 125             


Gly Ser Leu Cys Ser Arg Gln Ser Gln Val Leu Cys Gly Tyr Leu Asp 
    130                 135                 140                 


Ala Ile Pro Pro Thr Phe Tyr Arg Pro Tyr Phe Arg Ile Val Arg Phe 
145                 150                 155                 160 


Asp Val Ser Ala Met Glu Lys Asn Ala Ser Asn Leu Val Lys Ala Glu 
                165                 170                 175     


Phe Arg Val Phe Arg Leu Gln Asn Pro Lys Ala Arg Val Pro Glu Gln 
            180                 185                 190         


Arg Ile Glu Leu Tyr Gln Ile Leu Lys Ser Lys Asp Leu Thr Ser Pro 
        195                 200                 205             


Thr Gln Arg Tyr Ile Asp Ser Lys Val Val Lys Thr Arg Ala Glu Gly 
    210                 215                 220                 


Glu Trp Leu Ser Phe Asp Val Thr Asp Ala Val His Glu Trp Leu His 
225                 230                 235                 240 


His Lys Asp Arg Asn Leu Gly Phe Lys Ile Ser Leu His Cys Pro Cys 
                245                 250                 255     


Cys Thr Phe Val Pro Ser Asn Asn Tyr Ile Ile Pro Asn Lys Ser Glu 
            260                 265                 270         


Glu Leu Glu Ala Arg Phe Ala Gly Ile Asp Gly Thr Ser Thr Tyr Thr 
        275                 280                 285             


Ser Gly Asp Gln Lys Thr Ile Lys Ser Thr Arg Lys Lys Asn Ser Gly 
    290                 295                 300                 


Lys Thr Pro His Leu Leu Leu Met Leu Leu Pro Ser Tyr Arg Leu Glu 
305                 310                 315                 320 


Ser Gln Gln Thr Asn Arg Arg Lys Lys Arg Ala Leu Asp Ala Ala Tyr 
                325                 330                 335     


Cys Phe Arg Asn Val Gln Asp Asn Cys Cys Leu Arg Pro Leu Tyr Ile 
            340                 345                 350         


Asp Phe Lys Arg Asp Leu Gly Trp Lys Trp Ile His Glu Pro Lys Gly 
        355                 360                 365             


Tyr Asn Ala Asn Phe Cys Ala Gly Ala Cys Pro Tyr Leu Trp Ser Ser 
    370                 375                 380                 


Asp Thr Gln His Ser Arg Val Leu Ser Leu Tyr Asn Thr Ile Asn Pro 
385                 390                 395                 400 


Glu Ala Ser Ala Ser Pro Cys Cys Val Ser Gln Asp Leu Glu Pro Leu 
                405                 410                 415     


Thr Ile Leu Tyr Tyr Ile Gly Lys Thr Pro Lys Ile Glu Gln Leu Ser 
            420                 425                 430         


Asn Met Ile Val Lys Ser Cys Lys Cys Ser 
        435                 440         


<210> 8
<211> 414
<212> PRT
<213> Homo sapiens

<400> 8
Met His Tyr Cys Val Leu Ser Ala Phe Leu Ile Leu His Leu Val Thr 
1               5                   10                  15      


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


Met Arg Lys Arg Ile Glu Ala Ile Arg Gly Gln Ile Leu Ser Lys Leu 
        35                  40                  45              


Lys Leu Thr Ser Pro Pro Glu Asp Tyr Pro Glu Pro Glu Glu Val Pro 
    50                  55                  60                  


Pro Glu Val Ile Ser Ile Tyr Asn Ser Thr Arg Asp Leu Leu Gln Glu 
65                  70                  75                  80  


Lys Ala Ser Arg Arg Ala Ala Ala Cys Glu Arg Glu Arg Ser Asp Glu 
                85                  90                  95      


Glu Tyr Tyr Ala Lys Glu Val Tyr Lys Ile Asp Met Pro Pro Phe Phe 
            100                 105                 110         


Pro Ser Glu Asn Ala Ile Pro Pro Thr Phe Tyr Arg Pro Tyr Phe Arg 
        115                 120                 125             


Ile Val Arg Phe Asp Val Ser Ala Met Glu Lys Asn Ala Ser Asn Leu 
    130                 135                 140                 


Val Lys Ala Glu Phe Arg Val Phe Arg Leu Gln Asn Pro Lys Ala Arg 
145                 150                 155                 160 


Val Pro Glu Gln Arg Ile Glu Leu Tyr Gln Ile Leu Lys Ser Lys Asp 
                165                 170                 175     


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


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


Glu Trp Leu His His Lys Asp Arg Asn Leu Gly Phe Lys Ile Ser Leu 
    210                 215                 220                 


His Cys Pro Cys Cys Thr Phe Val Pro Ser Asn Asn Tyr Ile Ile Pro 
225                 230                 235                 240 


Asn Lys Ser Glu Glu Leu Glu Ala Arg Phe Ala Gly Ile Asp Gly Thr 
                245                 250                 255     


Ser Thr Tyr Thr Ser Gly Asp Gln Lys Thr Ile Lys Ser Thr Arg Lys 
            260                 265                 270         


Lys Asn Ser Gly Lys Thr Pro His Leu Leu Leu Met Leu Leu Pro Ser 
        275                 280                 285             


Tyr Arg Leu Glu Ser Gln Gln Thr Asn Arg Arg Lys Lys Arg Ala Leu 
    290                 295                 300                 


Asp Ala Ala Tyr Cys Phe Arg Asn Val Gln Asp Asn Cys Cys Leu Arg 
305                 310                 315                 320 


Pro Leu Tyr Ile Asp Phe Lys Arg Asp Leu Gly Trp Lys Trp Ile His 
                325                 330                 335     


Glu Pro Lys Gly Tyr Asn Ala Asn Phe Cys Ala Gly Ala Cys Pro Tyr 
            340                 345                 350         


Leu Trp Ser Ser Asp Thr Gln His Ser Arg Val Leu Ser Leu Tyr Asn 
        355                 360                 365             


Thr Ile Asn Pro Glu Ala Ser Ala Ser Pro Cys Cys Val Ser Gln Asp 
    370                 375                 380                 


Leu Glu Pro Leu Thr Ile Leu Tyr Tyr Ile Gly Lys Thr Pro Lys Ile 
385                 390                 395                 400 


Glu Gln Leu Ser Asn Met Ile Val Lys Ser Cys Lys Cys Ser 
                405                 410                 


<210> 9
<211> 412
<212> PRT
<213> Homo sapiens

<400> 9
Met Lys Met His Leu Gln Arg Ala Leu Val Val Leu Ala Leu Leu Asn 
1               5                   10                  15      


Phe Ala Thr Val Ser Leu Ser Leu Ser Thr Cys Thr Thr Leu Asp Phe 
            20                  25                  30          


Gly His Ile Lys Lys Lys Arg Val Glu Ala Ile Arg Gly Gln Ile Leu 
        35                  40                  45              


Ser Lys Leu Arg Leu Thr Ser Pro Pro Glu Pro Thr Val Met Thr His 
    50                  55                  60                  


Val Pro Tyr Gln Val Leu Ala Leu Tyr Asn Ser Thr Arg Glu Leu Leu 
65                  70                  75                  80  


Glu Glu Met His Gly Glu Arg Glu Glu Gly Cys Thr Gln Glu Asn Thr 
                85                  90                  95      


Glu Ser Glu Tyr Tyr Ala Lys Glu Ile His Lys Phe Asp Met Ile Gln 
            100                 105                 110         


Gly Leu Ala Glu His Asn Glu Leu Ala Val Cys Pro Lys Gly Ile Thr 
        115                 120                 125             


Ser Lys Val Phe Arg Phe Asn Val Ser Ser Val Glu Lys Asn Arg Thr 
    130                 135                 140                 


Asn Leu Phe Arg Ala Glu Phe Arg Val Leu Arg Val Pro Asn Pro Ser 
145                 150                 155                 160 


Ser Lys Arg Asn Glu Gln Arg Ile Glu Leu Phe Gln Ile Leu Arg Pro 
                165                 170                 175     


Asp Glu His Ile Ala Lys Gln Arg Tyr Ile Gly Gly Lys Asn Leu Pro 
            180                 185                 190         


Thr Arg Gly Thr Ala Glu Trp Leu Ser Phe Asp Val Thr Asp Thr Val 
        195                 200                 205             


Arg Glu Trp Leu Leu Arg Arg Glu Ser Asn Leu Gly Leu Glu Ile Ser 
    210                 215                 220                 


Ile His Cys Pro Cys His Thr Phe Gln Pro Asn Gly Asp Ile Leu Glu 
225                 230                 235                 240 


Asn Ile His Glu Val Met Glu Ile Lys Phe Lys Gly Val Asp Asn Glu 
                245                 250                 255     


Asp Asp His Gly Arg Gly Asp Leu Gly Arg Leu Lys Lys Gln Lys Asp 
            260                 265                 270         


His His Asn Pro His Leu Ile Leu Met Met Ile Pro Pro His Arg Leu 
        275                 280                 285             


Asp Asn Pro Gly Gln Gly Gly Gln Arg Lys Lys Arg Ala Leu Asp Thr 
    290                 295                 300                 


Asn Tyr Cys Phe Arg Asn Leu Glu Glu Asn Cys Cys Val Arg Pro Leu 
305                 310                 315                 320 


Tyr Ile Asp Phe Arg Gln Asp Leu Gly Trp Lys Trp Val His Glu Pro 
                325                 330                 335     


Lys Gly Tyr Tyr Ala Asn Phe Cys Ser Gly Pro Cys Pro Tyr Leu Arg 
            340                 345                 350         


Ser Ala Asp Thr Thr His Ser Thr Val Leu Gly Leu Tyr Asn Thr Leu 
        355                 360                 365             


Asn Pro Glu Ala Ser Ala Ser Pro Cys Cys Val Pro Gln Asp Leu Glu 
    370                 375                 380                 


Pro Leu Thr Ile Leu Tyr Tyr Val Gly Arg Thr Pro Lys Val Glu Gln 
385                 390                 395                 400 


Leu Ser Asn Met Val Val Lys Ser Cys Lys Cys Ser 
                405                 410         


<210> 10
<211> 309
<212> PRT
<213> Homo sapiens

<400> 10
Met Lys Met His Leu Gln Arg Ala Leu Val Val Leu Ala Leu Leu Asn 
1               5                   10                  15      


Phe Ala Thr Val Ser Leu Ser Leu Ser Thr Cys Thr Thr Leu Asp Phe 
            20                  25                  30          


Gly His Ile Lys Lys Lys Arg Val Glu Ala Ile Arg Gly Gln Ile Leu 
        35                  40                  45              


Ser Lys Leu Arg Leu Thr Ser Pro Pro Glu Pro Thr Val Met Thr His 
    50                  55                  60                  


Val Pro Tyr Gln Val Leu Ala Leu Tyr Asn Ser Thr Arg Glu Leu Leu 
65                  70                  75                  80  


Glu Glu Met His Gly Glu Arg Glu Glu Gly Cys Thr Gln Glu Asn Thr 
                85                  90                  95      


Glu Ser Glu Tyr Tyr Ala Lys Glu Ile His Lys Phe Asp Met Ile Gln 
            100                 105                 110         


Gly Leu Ala Glu His Asn Glu Leu Ala Val Cys Pro Lys Gly Ile Thr 
        115                 120                 125             


Ser Lys Val Phe Arg Phe Asn Val Ser Ser Val Glu Lys Asn Arg Thr 
    130                 135                 140                 


Asn Leu Phe Arg Ala Glu Phe Arg Val Leu Arg Val Pro Asn Pro Ser 
145                 150                 155                 160 


Ser Lys Arg Asn Glu Gln Arg Ile Glu Leu Phe Gln Ile Leu Arg Pro 
                165                 170                 175     


Asp Glu His Ile Ala Lys Gln Arg Tyr Ile Gly Gly Lys Asn Leu Pro 
            180                 185                 190         


Thr Arg Gly Thr Ala Glu Trp Leu Ser Phe Asp Val Thr Asp Thr Val 
        195                 200                 205             


Arg Glu Trp Leu Leu Arg Arg Glu Ser Asn Leu Gly Leu Glu Ile Ser 
    210                 215                 220                 


Ile His Cys Pro Cys His Thr Phe Gln Pro Asn Gly Asp Ile Leu Glu 
225                 230                 235                 240 


Asn Ile His Glu Val Met Glu Ile Lys Phe Lys Gly Val Asp Asn Glu 
                245                 250                 255     


Asp Asp His Gly Arg Gly Asp Leu Gly Arg Leu Lys Lys Gln Lys Asp 
            260                 265                 270         


His His Asn Pro His Leu Ile Leu Met Met Ile Pro Pro His Arg Leu 
        275                 280                 285             


Asp Asn Pro Gly Gln Gly Gly Gln Arg Lys Lys Arg Ala Leu Asp Thr 
    290                 295                 300                 


Asn Tyr Cys Phe Arg 
305                 


<210> 11
<211> 1173
<212> DNA
<213> Mus musculus

<400> 11
atgccgccct cggggctgcg gctactgccg cttctgctcc cactcccgtg gcttctagtg       60

ctgacgcccg ggaggccagc cgcgggactc tccacctgca agaccatcga catggagctg      120

gtgaaacgga agcgcatcga agccatccgt ggccagatcc tgtccaaact aaggctcgcc      180

agtcccccaa gccaggggga ggtaccgccc ggcccgctgc ccgaggcggt gctcgctttg      240

tacaacagca cccgcgaccg ggtggcaggc gagagcgccg acccagagcc ggagcccgaa      300

gcggactact atgctaaaga ggtcacccgc gtgctaatgg tggaccgcaa caacgccatc      360

tatgagaaaa ccaaagacat ctcacacagt atatatatgt tcttcaatac gtcagacatt      420

cgggaagcag tgcccgaacc cccattgctg tcccgtgcag agctgcgctt gcagagatta      480

aaatcaagtg tggagcaaca tgtggaactc taccagaaat atagcaacaa ttcctggcgt      540

taccttggta accggctgct gacccccact gatacgcctg agtggctgtc ttttgacgtc      600

actggagttg tacggcagtg gctgaaccaa ggagacggaa tacagggctt tcgattcagc      660

gctcactgct cttgtgacag caaagataac aaactccacg tggaaatcaa cgggatcagc      720

cccaaacgtc ggggcgacct gggcaccatc catgacatga accggccctt cctgctcctc      780

atggccaccc ccctggaaag ggcccagcac ctgcacagct cacggcaccg gagagccctg      840

gataccaact attgcttcag ctccacagag aagaactgct gtgtgcggca gctgtacatt      900

gactttagga aggacctggg ttggaagtgg atccacgagc ccaagggcta ccatgccaac      960

ttctgtctgg gaccctgccc ctatatttgg agcctggaca cacagtacag caaggtcctt     1020

gccctctaca accaacacaa cccgggcgct tcggcgtcac cgtgctgcgt gccgcaggct     1080

ttggagccac tgcccatcgt ctactacgtg ggtcgcaagc ccaaggtgga gcagttgtcc     1140

aacatgattg tgcgctcctg caagtgcagc tga                                  1173


<210> 12
<211> 1245
<212> DNA
<213> Mus musculus

<400> 12
atgcactact gtgtgctgag cacctttttg ctcctgcatc tggtcccggt ggcgctcagt       60

ctgtctacct gcagcaccct cgacatggat cagtttatgc gcaagaggat cgaggccatc      120

cgcgggcaga tcctgagcaa gctgaagctc accagccccc cggaagacta tccggagccg      180

gatgaggtcc ccccggaggt gatttccatc tacaacagta ccagggactt actgcaggag      240

aaggcaagcc ggagggcagc cgcctgcgag cgcgagcgga gcgacgagga gtactacgcc      300

aaggaggttt ataaaatcga catgccgtcc cacctcccct ccgaaaatgc catcccgccc      360

actttctaca gaccctactt cagaatcgtc cgctttgatg tctcaacaat ggagaaaaat      420

gcttcgaatc tggtgaaggc agagttcagg gtcttccgct tgcaaaaccc caaagccaga      480

gtggccgagc agcggattga actgtatcag atccttaaat ccaaagactt aacatctccc      540

acccagcgct acatcgatag caaggttgtg aaaaccagag cggagggtga atggctctcc      600

ttcgacgtga cagacgctgt gcaggagtgg cttcaccaca aagacaggaa cctggggttt      660

aaaataagtt tacactgccc ctgctgtacc ttcgtgccgt ctaataatta catcatcccg      720

aataaaagcg aagagctcga ggcgagattt gcaggtattg atggcacctc tacatatgcc      780

agtggtgatc agaaaactat aaagtccact aggaaaaaaa ccagtgggaa gaccccacat      840

ctcctgctaa tgttgttgcc ctcctacaga ctggagtcac aacagtccag ccggcggaag      900

aagcgcgctt tggatgctgc ctactgcttt agaaatgtgc aggataattg ctgccttcgc      960

cctctttaca ttgattttaa gagggatctt ggatggaaat ggatccatga acccaaaggg     1020

tacaatgcta acttctgtgc tggggcatgc ccatatctat ggagttcaga cactcaacac     1080

accaaagtcc tcagcctgta caacaccata aatcccgaag cttccgcttc cccttgctgt     1140

gtgtcccagg atctggaacc actgaccatt ctctattaca ttggaaatac gcccaagatc     1200

gaacagcttt ccaatatgat tgtcaagtct tgtaaatgca gctaa                     1245


<210> 13
<211> 1239
<212> DNA
<213> Mus musculus

<400> 13
atgaagatgc acttgcaaag ggctctggta gtcctggccc tgctgaactt ggccacaatc       60

agcctctctc tgtccacttg caccacgttg gacttcggcc acatcaagaa gaagagggtg      120

gaagccatta ggggacagat cttgagcaag ctcaggctca ccagcccccc tgagccatcg      180

gtgatgaccc acgtccccta tcaggtcctg gcactttaca acagcacccg ggagttgctg      240

gaagagatgc acggggagag ggaggaaggc tgcactcagg agacctcgga gtctgagtac      300

tatgccaaag agatccataa attcgacatg atccagggac tggcggagca caatgaactg      360

gccgtctgcc ccaaaggaat tacctctaag gtttttcgtt tcaatgtgtc ctcagtggag      420

aaaaatggaa ccaatctgtt ccgggcagag ttccgggtct tgcgggtgcc caaccccagc      480

tccaagcgca cagagcagag aattgagctc ttccagatac ttcgaccgga tgagcacata      540

gccaagcagc gctacatagg tggcaagaat ctgcccacaa ggggcaccgc tgaatggctg      600

tctttcgatg tcactgacac tgtgcgcgag tggctgttga ggagagagtc caacttgggt      660

ctggaaatca gcatccactg tccatgtcac acctttcagc ccaatggaga catactggaa      720

aatgttcatg aggtgatgga aatcaaattc aaaggagtgg acaatgaaga tgaccatggc      780

cgtggagacc tggggcgtct caagaagcaa aaggatcacc acaacccaca cctgatcctc      840

atgatgatcc ccccacaccg actggacagc ccaggccagg gcagtcagag gaagaagagg      900

gccctggaca ccaattactg cttccgcaac ctggaggaga actgctgtgt acgccccctt      960

tatattgact tccggcagga tctaggctgg aaatgggtcc acgaacctaa gggttactat     1020

gccaacttct gctcaggccc ttgcccatac ctccgcagcg cagacacaac ccatagcacg     1080

gtgcttggac tatacaacac cctgaaccca gaggcgtctg cctcgccatg ctgcgtcccc     1140

caggacctgg agcccctgac catcttgtac tatgtgggca gaacccccaa ggtggagcag     1200

ctgtccaaca tggtggtgaa gtcgtgtaag tgcagctga                            1239


<210> 14
<211> 130
<212> DNA
<213> Artificial Sequence

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

<400> 14
ctgcgcgctc gctcgctcac tgaggccgcc cgggcaaagc ccgggcgtcg ggcgaccttt       60

ggtcgcccgg cctcagtgag cgagcgagcg cgcagagagg gagtggccaa ctccatcact      120

aggggttcct                                                             130


<210> 15
<211> 130
<212> DNA
<213> Artificial Sequence

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

<400> 15
aggaacccct agtgatggag ttggccactc cctctctgcg cgctcgctcg ctcactgagg       60

ccgggcgacc aaaggtcgcc cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc      120

gagcgcgcag                                                             130


<210> 16
<211> 2056
<212> DNA
<213> Homo sapiens

<400> 16
cctacagcag ccagggtgag attatgaggc tgagctgaga atatcaagac tgtaccgagt       60

agggggcctt ggcaagtgtg gagagcccgg cagctggggc agagggcgga gtacggtgtg      120

cgtttacgga cctcttcaaa cgaggtagga aggtcagaag tcaaaaaggg aacaaatgat      180

gtttaaccac acaaaaatga aaatccaatg gttggatatc cattccaaat acacaaaggc      240

aacggataag tgatccgggc caggcacaga aggccatgca cccgtaggat tgcactcaga      300

gctcccaaat gcataggaat agaagggtgg gtgcaggagg ctgaggggtg gggaaagggc      360

atgggtgttt catgaggaca gagcttccgt ttcatgcaat gaaaagagtt tggagacgga      420

tggtggtgac tggactatac acttacacac ggtagcgatg gtacactttg tattatgtat      480

attttaccac gatcttttta aagtgtcaaa ggcaaatggc caaatggttc cttgtcctat      540

agctgtagca gccatcggct gttagtgaca aagcccctga gtcaagatga cagcagcccc      600

cataactcct aatcggctct cccgcgtgga gtcatttagg agtagtcgca ttagagacaa      660

gtccaacatc taatcttcca ccctggccag ggccccagct ggcagcgagg gtgggagact      720

ccgggcagag cagagggcgc tgacattggg gcccggcctg gcttgggtcc ctctggcctt      780

tccccagggg ccctctttcc ttggggcttt cttgggccgc cactgctccc gctcctctcc      840

ccccatccca ccccctcacc ccctcgttct tcatatcctt ctctagtgct ccctccactt      900

tcatccaccc ttctgcaaga gtgtgggacc acaaatgagt tttcacctgg cctggggaca      960

cacgtgcccc cacaggtgct gagtgacttt ctaggacagt aatctgcttt aggctaaaat     1020

gggacttgat cttctgttag ccctaatcat caattagcag agccggtgaa ggtgcagaac     1080

ctaccgcctt tccaggcctc ctcccacctc tgccacctcc actctccttc ctgggatgtg     1140

ggggctggca cacgtgtggc ccagggcatt ggtgggattg cactgagctg ggtcattagc     1200

gtaatcctgg acaagggcag acagggcgag cggagggcca gctccggggc tcaggcaagg     1260

ctgggggctt cccccagaca ccccactcct cctctgctgg acccccactt catagggcac     1320

ttcgtgttct caaagggctt ccaaatagca tggtggcctt ggatgcccag ggaagcctca     1380

gagttgctta tctccctcta gacagaaggg gaatctcggt caagagggag aggtcgccct     1440

gttcaaggcc acccagccag ctcatggcgg taatgggaca aggctggcca gccatcccac     1500

cctcagaagg gacccggtgg ggcaggtgat ctcagaggag gctcacttct gggtctcaca     1560

ttcttggatc cggttccagg cctcggccct aaatagtctc cctgggcttt caagagaacc     1620

acatgagaaa ggaggattcg ggctctgagc agtttcacca cccacccccc agtctgcaaa     1680

tcctgacccg tgggtccacc tgccccaaag gcggacgcag gacagtagaa gggaacagag     1740

aacacataaa cacagagagg gccacagcgg ctcccacagt caccgccacc ttcctggcgg     1800

ggatgggtgg ggcgtctgag tttggttccc agcaaatccc tctgagccgc ccttgcgggc     1860

tcgcctcagg agcaggggag caagaggtgg gaggaggagg tctaagtccc aggcccaatt     1920

aagagatcag gtagtgtagg gtttgggagc ttttaaggtg aagaggcccg ggctgatccc     1980

acaggccagt ataaagcgcc gtgaccctca ggtgatgcgc cagggccggc tgccgtcggg     2040

gacagggctt tccata                                                     2056


<210> 17
<211> 542
<212> DNA
<213> Artificial Sequence

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

<400> 17
aatcaacctc tggattacaa aatttgtgaa agattgactg gtattcttaa ctatgttgct       60

ccttttacgc tatgtggata cgctgcttta atgcctttgt atcatgctat tgcttcccgt      120

atggctttca ttttctcctc cttgtataaa tcctggttgc tgtctcttta tgaggagttg      180

tggcccgttg tcaggcaacg tggcgtggtg tgcactgtgt ttgctgacgc aacccccact      240

ggttggggca ttgccaccac ctgtcagctc ctttccggga ctttcgcttt ccccctccct      300

attgccacgg cggaactcat cgccgcctgc cttgcccgct gctggacagg ggctcggctg      360

ttgggcactg acaattccgt ggtgttgtcg gggaagctga cgtcctttcc atggctgctc      420

gcctgtgttg ccacctggat tctgcgcggg acgtccttct gctacgtccc ttcggccctc      480

aatccagcgg accttccttc ccgcggcctg ctgccggctc tgcggcctct tccgcgtctt      540

cg                                                                     542


<210> 18
<211> 215
<212> DNA
<213> Artificial Sequence

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

<400> 18
gcctcgactg tgccttctag ttgccagcca tctgttgttt gcccctcccc cgtgccttcc       60

ttgaccctgg aaggtgccac tcccactgtc ctttcctaat aaaatgagga aattgcatcg      120

cattgtctga gtaggtgtca ttctattctg gggggtgggg tggggcagga cagcaagggg      180

gaggattggg aagacaatag caggcatgct gggga                                 215


<210> 19
<211> 22
<212> DNA
<213> Artificial Sequence

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

<400> 19
aaaggcaatc caggcaatat ca                                                22


<210> 20
<211> 21
<212> DNA
<213> Artificial Sequence

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

<400> 20
tggttctggt atggactctc c                                                 21


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

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

<400> 21
aggtcggtgt gaacggattt g                                                 21


<210> 22
<211> 23
<212> DNA
<213> Artificial Sequence

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

<400> 22
tgtagaccat gtagttgagg tca                                               23


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

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

<400> 23
tgacctcaac tacatggtct aca                                               23


<210> 24
<211> 19
<212> DNA
<213> Artificial Sequence

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

<400> 24
cttcccattc tcggccttg                                                    19


<210> 25
<211> 19
<212> DNA
<213> Artificial Sequence

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

<400> 25
tgctggcttc cgagtcttc                                                    19


<210> 26
<211> 19
<212> DNA
<213> Artificial Sequence

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

<400> 26
cggggtcgtt ctcgaacac                                                    19


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

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

<400> 27
cgaagactac agttctgcca tt                                                22


<210> 28
<211> 22
<212> DNA
<213> Artificial Sequence

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

<400> 28
gacgtttcag aggttctcag ag                                                22


<210> 29
<211> 22
<212> DNA
<213> Artificial Sequence

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

<400> 29
gcaactgttc ctgaactcaa ct                                                22


<210> 30
<211> 21
<212> DNA
<213> Artificial Sequence

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

<400> 30
atcttttggg gtccgtcaac t                                                 21


<210> 31
<211> 23
<212> DNA
<213> Artificial Sequence

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

<400> 31
tagtccttcc taccccaatt tcc                                               23


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

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

<400> 32
ttggtcctta gccactcctt c                                                 21


<210> 33
<211> 22
<212> DNA
<213> Artificial Sequence

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

<400> 33
agcaagaaac tcttccaagc aa                                                22


<210> 34
<211> 23
<212> DNA
<213> Artificial Sequence

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

<400> 34
gtgagattcg tcagattcat ccg                                               23


<210> 35
<211> 19
<212> DNA
<213> Artificial Sequence

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

<400> 35
ctcccgtggc ttctagtgc                                                    19


<210> 36
<211> 22
<212> DNA
<213> Artificial Sequence

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

<400> 36
gccttagttt ggacaggatc tg                                                22


<210> 37
<211> 20
<212> DNA
<213> Artificial Sequence

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

<400> 37
gagcccgaag cggactacta                                                   20


<210> 38
<211> 23
<212> DNA
<213> Artificial Sequence

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

<400> 38
tggttttctc atagatggcg ttg                                               23


<210> 39
<211> 19
<212> DNA
<213> Artificial Sequence

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

<400> 39
cttcgacgtg acagacgct                                                    19


<210> 40
<211> 22
<212> DNA
<213> Artificial Sequence

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

<400> 40
gcaggggcag tgtaaactta tt                                                22


<210> 41
<211> 19
<212> DNA
<213> Artificial Sequence

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

<400> 41
cctggccctg ctgaacttg                                                    19


<210> 42
<211> 21
<212> DNA
<213> Artificial Sequence

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

<400> 42
ttgatgtggc cgaagtccaa c                                                 21


<210> 43
<211> 20
<212> DNA
<213> Artificial Sequence

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

<400> 43
cctactctgt gtcactcccg                                                   20


<210> 44
<211> 21
<212> DNA
<213> Artificial Sequence

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

<400> 44
cacgtactgc cggaagaaat c                                                 21


<210> 45
<211> 23
<212> DNA
<213> Artificial Sequence

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

<400> 45
ccctcacact cagatcatct tct                                               23


<210> 46
<211> 19
<212> DNA
<213> Artificial Sequence

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

<400> 46
gctacgacgt gggctacag                                                    19


