                         SEQUENCE LISTING

<110>  Joslin Diabetes Center
 
<120>  METHODS OF USE OF BETATROPHIN

<130>  01123-0005-00PCT

<150>  US 62/237,374
<151>  2015-10-05

<160>  14    

<170>  PatentIn version 3.5

<210>  1
<211>  198
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Pro Val Pro Ala Leu Cys Leu Leu Trp Ala Leu Ala Met Val Thr 
1               5                   10                  15      


Arg Pro Ala Ser Ala Ala Pro Met Gly Gly Pro Glu Leu Ala Gln His 
            20                  25                  30          


Glu Glu Leu Thr Leu Leu Phe His Gly Thr Leu Gln Leu Gly Gln Ala 
        35                  40                  45              


Leu Asn Gly Val Tyr Arg Thr Thr Glu Gly Arg Leu Thr Lys Ala Arg 
    50                  55                  60                  


Asn Ser Leu Gly Leu Tyr Gly Arg Thr Ile Glu Leu Leu Gly Gln Glu 
65                  70                  75                  80  


Val Ser Arg Gly Arg Asp Ala Ala Gln Glu Leu Arg Ala Ser Leu Leu 
                85                  90                  95      


Glu Thr Gln Met Glu Glu Asp Ile Leu Gln Leu Gln Ala Glu Ala Thr 
            100                 105                 110         


Ala Glu Val Leu Gly Glu Val Ala Gln Ala Gln Lys Val Leu Arg Asp 
        115                 120                 125             


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


Ala Tyr Arg Glu Phe Glu Val Leu Lys Ala His Ala Asp Lys Gln Ser 
145                 150                 155                 160 


His Ile Leu Trp Ala Leu Thr Gly His Val Gln Arg Gln Arg Arg Glu 
                165                 170                 175     


Met Val Ala Gln Gln His Arg Leu Arg Gln Ile Gln Glu Arg Leu His 
            180                 185                 190         


Thr Ala Ala Leu Pro Ala 
        195             


<210>  2
<211>  198
<212>  PRT
<213>  Mus musculus

<400>  2

Met Ala Val Leu Ala Leu Cys Leu Leu Trp Thr Leu Ala Ser Ala Val 
1               5                   10                  15      


Arg Pro Ala Pro Val Ala Pro Leu Gly Gly Pro Glu Pro Ala Gln Tyr 
            20                  25                  30          


Glu Glu Leu Thr Leu Leu Phe His Gly Ala Leu Gln Leu Gly Gln Ala 
        35                  40                  45              


Leu Asn Gly Val Tyr Arg Ala Thr Glu Ala Arg Leu Thr Glu Ala Gly 
    50                  55                  60                  


His Ser Leu Gly Leu Tyr Asp Arg Ala Leu Glu Phe Leu Gly Thr Glu 
65                  70                  75                  80  


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


Glu Ile Gln Val Glu Glu Asp Ala Leu His Leu Arg Ala Glu Ala Thr 
            100                 105                 110         


Ala Arg Ser Leu Gly Glu Val Ala Arg Ala Gln Gln Ala Leu Arg Asp 
        115                 120                 125             


Thr Val Arg Arg Leu Gln Val Gln Leu Arg Gly Ala Trp Leu Gly Gln 
    130                 135                 140                 


Ala His Gln Glu Phe Glu Thr Leu Lys Ala Arg Ala Asp Lys Gln Ser 
145                 150                 155                 160 


His Leu Leu Trp Ala Leu Thr Gly His Val Gln Arg Gln Gln Arg Glu 
                165                 170                 175     


Met Ala Glu Gln Gln Gln Trp Leu Arg Gln Ile Gln Gln Arg Leu His 
            180                 185                 190         


Thr Ala Ala Leu Pro Ala 
        195             


<210>  3
<211>  198
<212>  PRT
<213>  Rattus norvegicus

<400>  3

Met Val Val Pro Ile Leu Cys Leu Leu Trp Ala Ile Ala Thr Ala Val 
1               5                   10                  15      


Arg Pro Ala Pro Val Ala Pro Leu Gly Gly Pro Glu Pro Ala Gln Tyr 
            20                  25                  30          


Glu Glu Leu Thr Leu Leu Phe His Gly Ala Leu Gln Leu Gly Gln Ala 
        35                  40                  45              


Leu Asn Gly Val Tyr Lys Ala Thr Glu Ala Arg Leu Thr Glu Ala Gly 
    50                  55                  60                  


Arg Asn Leu Gly Leu Phe Asp Gln Ala Leu Glu Phe Leu Gly Arg Glu 
65                  70                  75                  80  


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


Glu Ile Gln Ala Glu Glu Asp Thr Leu His Leu Arg Ala Glu Ala Thr 
            100                 105                 110         


Ala Arg Ser Leu Arg Glu Val Ala Arg Ala Gln His Ala Leu Arg Asn 
        115                 120                 125             


Ser Val Arg Arg Leu Gln Val Gln Leu Arg Gly Ala Trp Leu Gly Gln 
    130                 135                 140                 


Ala His Gln Glu Phe Glu Asn Leu Lys Asp Arg Ala Asp Lys Gln Asn 
145                 150                 155                 160 


His Leu Leu Trp Ala Leu Thr Gly His Val Gln Arg Gln Gln Arg Glu 
                165                 170                 175     


Met Ala Glu Gln Gln Gln Trp Leu Arg Gln Ile Gln Gln Arg Leu His 
            180                 185                 190         


Met Ala Ala Leu Pro Ala 
        195             


<210>  4
<211>  198
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Consensus betatrophin sequence


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa is Pro, Ala or Val

<220>
<221>  MISC_FEATURE
<222>  (14)..(14)
<223>  Xaa is Met, Ser or Thr

<220>
<221>  MISC_FEATURE
<222>  (65)..(65)
<223>  Xaa is Asn, His or Arg

<220>
<221>  MISC_FEATURE
<222>  (79)..(79)
<223>  Xaa is Gln, Thr or Arg

<220>
<221>  MISC_FEATURE
<222>  (82)..(82)
<223>  Xaa is Ser, Arg or Asn

<220>
<221>  MISC_FEATURE
<222>  (100)..(100)
<223>  Xaa is Met, Val or Ala

<220>
<221>  MISC_FEATURE
<222>  (104)..(104)
<223>  Xaa is Ile, Ala or Thr

<220>
<221>  MISC_FEATURE
<222>  (124)..(124)
<223>  Xaa is Lys, Gln or His

<220>
<221>  MISC_FEATURE
<222>  (151)..(151)
<223>  Xaa is Val, Thr or Asn

<400>  4

Met Xaa Val Pro Ala Leu Cys Leu Leu Trp Ala Leu Ala Xaa Ala Val 
1               5                   10                  15      


Arg Pro Ala Pro Val Ala Pro Leu Gly Gly Pro Glu Pro Ala Gln Tyr 
            20                  25                  30          


Glu Glu Leu Thr Leu Leu Phe His Gly Ala Leu Gln Leu Gly Gln Ala 
        35                  40                  45              


Leu Asn Gly Val Tyr Arg Ala Thr Glu Ala Arg Leu Thr Glu Ala Gly 
    50                  55                  60                  


Xaa Ser Leu Gly Leu Tyr Asp Arg Ala Leu Glu Phe Leu Gly Xaa Glu 
65                  70                  75                  80  


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


Glu Ile Gln Xaa Glu Glu Asp Xaa Leu His Leu Arg Ala Glu Ala Thr 
            100                 105                 110         


Ala Arg Ser Leu Gly Glu Val Ala Arg Ala Gln Xaa Ala Leu Arg Asp 
        115                 120                 125             


Ser Val Arg Arg Leu Gln Val Gln Leu Arg Gly Ala Trp Leu Gly Gln 
    130                 135                 140                 


Ala His Gln Glu Phe Glu Xaa Leu Lys Ala Arg Ala Asp Lys Gln Ser 
145                 150                 155                 160 


His Leu Leu Trp Ala Leu Thr Gly His Val Gln Arg Gln Gln Arg Glu 
                165                 170                 175     


Met Ala Glu Gln Gln Gln Trp Leu Arg Gln Ile Gln Gln Arg Leu His 
            180                 185                 190         


Thr Ala Ala Leu Pro Ala 
        195             


<210>  5
<211>  1227
<212>  DNA
<213>  Escherichia coli

<400>  5
atgaaaatcg aagaaggtaa actggtaatc tggattaacg gcgataaagg ctataacggt       60

ctcgctgaag tcggtaagaa attcgagaaa gataccggaa ttaaagtcac cgttgagcat      120

ccggataaac tggaagagaa attcccacag gttgcggcaa ctggcgatgg ccctgacatt      180

atcttctggg cacacgaccg ctttggtggc tacgctcaat ctggcctgtt ggctgaaatc      240

accccggaca aagcgttcca ggacaagctg tatccgttta cctgggatgc cgtacgttac      300

aacggcaagc tgattgctta cccgatcgct gttgaagcgt tatcgctgat ttataacaaa      360

gatctgctgc cgaacccgcc aaaaacctgg gaagagatcc cggcgctgga taaagaactg      420

aaagcgaaag gtaagagcgc gctgatgttc aacctgcaag aaccgtactt cacctggccg      480

ctgattgctg ctgacggggg ttatgcgttc aagtatgaaa acggcaagta cgacattaaa      540

gacgtgggcg tggataacgc tggcgcgaaa gcgggtctga ccttcctggt tgacctgatt      600

aaaaacaaac acatgaatgc agacaccgat tactccatcg cagaagctgc ctttaataaa      660

ggcgaaacag cgatgaccat caacggcccg tgggcatggt ccaacatcga caccagcaaa      720

gtgaattatg gtgtaacggt actgccgacc ttcaagggtc aaccatccaa accgttcgtt      780

ggcgtgctga gcgcaggtat taacgccgcc agtccgaaca aagagctggc aaaagagttc      840

ctcgaaaact atctgctgac tgatgaaggt ctggaagcgg ttaataaaga caaaccgctg      900

ggtgccgtag cgctgaagtc ttacgaggaa gagttggtga aagatccgcg tattgccgcc      960

actatggaaa acgcccagaa aggtgaaatc atgccgaaca tcccgcagat gtccgctttc     1020

tggtatgccg tgcgtactgc ggtgatcaac gccgccagcg gtcgtcagac tgtcgatgaa     1080

gccctgaaag acgcgcagac taattcgagc tcgaacaaca acaacaataa caataacaac     1140

aacctcggga tcgagggaag gatttcacat atgtccatgg gcggccgcga tatcgtcgac     1200

ggatccgaat tccctgcagg taattaa                                         1227


<210>  6
<211>  408
<212>  PRT
<213>  Escherichia coli

<400>  6

Met Lys Ile Glu Glu Gly Lys Leu Val Ile Trp Ile Asn Gly Asp Lys 
1               5                   10                  15      


Gly Tyr Asn Gly Leu Ala Glu Val Gly Lys Lys Phe Glu Lys Asp Thr 
            20                  25                  30          


Gly Ile Lys Val Thr Val Glu His Pro Asp Lys Leu Glu Glu Lys Phe 
        35                  40                  45              


Pro Gln Val Ala Ala Thr Gly Asp Gly Pro Asp Ile Ile Phe Trp Ala 
    50                  55                  60                  


His Asp Arg Phe Gly Gly Tyr Ala Gln Ser Gly Leu Leu Ala Glu Ile 
65                  70                  75                  80  


Thr Pro Asp Lys Ala Phe Gln Asp Lys Leu Tyr Pro Phe Thr Trp Asp 
                85                  90                  95      


Ala Val Arg Tyr Asn Gly Lys Leu Ile Ala Tyr Pro Ile Ala Val Glu 
            100                 105                 110         


Ala Leu Ser Leu Ile Tyr Asn Lys Asp Leu Leu Pro Asn Pro Pro Lys 
        115                 120                 125             


Thr Trp Glu Glu Ile Pro Ala Leu Asp Lys Glu Leu Lys Ala Lys Gly 
    130                 135                 140                 


Lys Ser Ala Leu Met Phe Asn Leu Gln Glu Pro Tyr Phe Thr Trp Pro 
145                 150                 155                 160 


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


Tyr Asp Ile Lys Asp Val Gly Val Asp Asn Ala Gly Ala Lys Ala Gly 
            180                 185                 190         


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


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


Met Thr Ile Asn Gly Pro Trp Ala Trp Ser Asn Ile Asp Thr Ser Lys 
225                 230                 235                 240 


Val Asn Tyr Gly Val Thr Val Leu Pro Thr Phe Lys Gly Gln Pro Ser 
                245                 250                 255     


Lys Pro Phe Val Gly Val Leu Ser Ala Gly Ile Asn Ala Ala Ser Pro 
            260                 265                 270         


Asn Lys Glu Leu Ala Lys Glu Phe Leu Glu Asn Tyr Leu Leu Thr Asp 
        275                 280                 285             


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


Leu Lys Ser Tyr Glu Glu Glu Leu Val Lys Asp Pro Arg Ile Ala Ala 
305                 310                 315                 320 


Thr Met Glu Asn Ala Gln Lys Gly Glu Ile Met Pro Asn Ile Pro Gln 
                325                 330                 335     


Met Ser Ala Phe Trp Tyr Ala Val Arg Thr Ala Val Ile Asn Ala Ala 
            340                 345                 350         


Ser Gly Arg Gln Thr Val Asp Glu Ala Leu Lys Asp Ala Gln Thr Asn 
        355                 360                 365             


Ser Ser Ser Asn Asn Asn Asn Asn Asn Asn Asn Asn Asn Leu Gly Ile 
    370                 375                 380                 


Glu Gly Arg Ile Ser His Met Ser Met Gly Gly Arg Asp Ile Val Asp 
385                 390                 395                 400 


Gly Ser Glu Phe Pro Ala Gly Asn 
                405             


<210>  7
<211>  1782
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Sequence of MBP-mouse betatrophin (MBP-mBT)

<400>  7
atgaaaatcg aagaaggtaa actggtaatc tggattaacg gcgataaagg ctataacggt       60

ctcgctgaag tcggtaagaa attcgagaaa gataccggaa ttaaagtcac cgttgagcat      120

ccggataaac tggaagagaa attcccacag gttgcggcaa ctggcgatgg ccctgacatt      180

atcttctggg cacacgaccg ctttggtggc tacgctcaat ctggcctgtt ggctgaaatc      240

accccggaca aagcgttcca ggacaagctg tatccgttta cctgggatgc cgtacgttac      300

aacggcaagc tgattgctta cccgatcgct gttgaagcgt tatcgctgat ttataacaaa      360

gatctgctgc cgaacccgcc aaaaacctgg gaagagatcc cggcgctgga taaagaactg      420

aaagcgaaag gtaagagcgc gctgatgttc aacctgcaag aaccgtactt cacctggccg      480

ctgattgctg ctgacggggg ttatgcgttc aagtatgaaa acggcaagta cgacattaaa      540

gacgtgggcg tggataacgc tggcgcgaaa gcgggtctga ccttcctggt tgacctgatt      600

aaaaacaaac acatgaatgc agacaccgat tactccatcg cagaagctgc ctttaataaa      660

ggcgaaacag cgatgaccat caacggcccg tgggcatggt ccaacatcga caccagcaaa      720

gtgaattatg gtgtaacggt actgccgacc ttcaagggtc aaccatccaa accgttcgtt      780

ggcgtgctga gcgcaggtat taacgccgcc agtccgaaca aagagctggc aaaagagttc      840

ctcgaaaact atctgctgac tgatgaaggt ctggaagcgg ttaataaaga caaaccgctg      900

ggtgccgtag cgctgaagtc ttacgaggaa gagttggtga aagatccgcg tattgccgcc      960

actatggaaa acgcccagaa aggtgaaatc atgccgaaca tcccgcagat gtccgctttc     1020

tggtatgccg tgcgtactgc ggtgatcaac gccgccagcg gtcgtcagac tgtcgatgaa     1080

gccctgaaag acgcgcagac taattcgagc tcgaacaaca acaacaataa caataacaac     1140

aacctcggga tcgagggaag gatttcacat atgtccatgg gcggccgcga tatcgtcgac     1200

ggatccgaat tccctgcagg taatgaaaac ctatacttcc aatcaggagc ccccatgggc     1260

ggcccagaac tggcacagca tgaggagctg accctgctct tccatgggac cctgcagctg     1320

ggccaggccc tcaacggtgt gtacaggacc acggagggac ggctgacaaa ggccaggaac     1380

agcctgggtc tctatggccg cacaatagaa ctcctggggc aggaggtcag ccggggccgg     1440

gatgcagccc aggaacttcg ggcaagcctg ttggagactc agatggagga ggatattctg     1500

cagctgcagg cagaggccac agctgaggtg ctgggggagg tggcccaggc acagaaggtg     1560

ctacgggaca gcgtgcagcg gctagaagtc cagctgagga gcgcctggct gggccctgcc     1620

taccgagaat ttgaggtctt aaaggctcac gctgacaagc agagccacat cctatgggcc     1680

ctcacaggcc acgtgcagcg gcagaggcgg gagatggtgg cacagcagca tcggctgcga     1740

cagatccagg agagactcca cacagcggcg ctcccagcct ga                        1782


<210>  8
<211>  596
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Sequence of MBP-mouse betatrophin (MBP-mBT)

<400>  8

Met Lys Ile Glu Glu Gly Lys Leu Val Ile Trp Ile Asn Gly Asp Lys 
1               5                   10                  15      


Gly Tyr Asn Gly Leu Ala Glu Val Gly Lys Lys Phe Glu Lys Asp Thr 
            20                  25                  30          


Gly Ile Lys Val Thr Val Glu His Pro Asp Lys Leu Glu Glu Lys Phe 
        35                  40                  45              


Pro Gln Val Ala Ala Thr Gly Asp Gly Pro Asp Ile Ile Phe Trp Ala 
    50                  55                  60                  


His Asp Arg Phe Gly Gly Tyr Ala Gln Ser Gly Leu Leu Ala Glu Ile 
65                  70                  75                  80  


Thr Pro Asp Lys Ala Phe Gln Asp Lys Leu Tyr Pro Phe Thr Trp Asp 
                85                  90                  95      


Ala Val Arg Tyr Asn Gly Lys Leu Ile Ala Tyr Pro Ile Ala Val Glu 
            100                 105                 110         


Ala Leu Ser Leu Ile Tyr Asn Lys Asp Leu Leu Pro Asn Pro Pro Lys 
        115                 120                 125             


Thr Trp Glu Glu Ile Pro Ala Leu Asp Lys Glu Leu Lys Ala Lys Gly 
    130                 135                 140                 


Lys Ser Ala Leu Met Phe Asn Leu Gln Glu Pro Tyr Phe Thr Trp Pro 
145                 150                 155                 160 


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


Tyr Asp Ile Lys Asp Val Gly Val Asp Asn Ala Gly Ala Lys Ala Gly 
            180                 185                 190         


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


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


Met Thr Ile Asn Gly Pro Trp Ala Trp Ser Asn Ile Asp Thr Ser Lys 
225                 230                 235                 240 


Val Asn Tyr Gly Val Thr Val Leu Pro Thr Phe Lys Gly Gln Pro Ser 
                245                 250                 255     


Lys Pro Phe Val Gly Val Leu Ser Ala Gly Ile Asn Ala Ala Ser Pro 
            260                 265                 270         


Asn Lys Glu Leu Ala Lys Glu Phe Leu Glu Asn Tyr Leu Leu Thr Asp 
        275                 280                 285             


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


Leu Lys Ser Tyr Glu Glu Glu Leu Val Lys Asp Pro Arg Ile Ala Ala 
305                 310                 315                 320 


Thr Met Glu Asn Ala Gln Lys Gly Glu Ile Met Pro Asn Ile Pro Gln 
                325                 330                 335     


Met Ser Ala Phe Trp Tyr Ala Val Arg Thr Ala Val Ile Asn Ala Ala 
            340                 345                 350         


Ser Gly Arg Gln Thr Val Asp Glu Ala Leu Lys Asp Ala Gln Thr Asn 
        355                 360                 365             


Ser Ser Ser Asn Asn Asn Asn Asn Asn Asn Asn Asn Asn Leu Gly Ile 
    370                 375                 380                 


Glu Gly Arg Ile Ser His Met Ser Met Gly Gly Arg Asp Ile Val Asp 
385                 390                 395                 400 


Gly Ser Glu Phe Pro Ala Gly Asn Glu Asn Leu Tyr Phe Gln Ser Gly 
                405                 410                 415     


Ala Pro Val Ala Pro Leu Gly Gly Pro Glu Pro Ala Gln Tyr Glu Glu 
            420                 425                 430         


Leu Thr Leu Leu Phe His Gly Ala Leu Gln Leu Gly Gln Ala Leu Asn 
        435                 440                 445             


Gly Val Tyr Arg Ala Thr Glu Ala Arg Leu Thr Glu Ala Gly His Ser 
    450                 455                 460                 


Leu Gly Leu Tyr Asp Arg Ala Leu Glu Phe Leu Gly Thr Glu Val Arg 
465                 470                 475                 480 


Gln Gly Gln Asp Ala Thr Gln Glu Leu Arg Thr Ser Leu Ser Glu Ile 
                485                 490                 495     


Gln Val Glu Glu Asp Ala Leu His Leu Arg Ala Glu Ala Thr Ala Arg 
            500                 505                 510         


Ser Leu Gly Glu Val Ala Arg Ala Gln Gln Ala Leu Arg Asp Thr Val 
        515                 520                 525             


Arg Arg Leu Gln Val Gln Leu Arg Gly Ala Trp Leu Gly Gln Ala His 
    530                 535                 540                 


Gln Glu Phe Glu Thr Leu Lys Ala Arg Ala Asp Lys Gln Ser His Leu 
545                 550                 555                 560 


Leu Trp Ala Leu Thr Gly His Val Gln Arg Gln Gln Arg Glu Met Ala 
                565                 570                 575     


Glu Gln Gln Gln Trp Leu Arg Gln Ile Gln Gln Arg Leu His Thr Ala 
            580                 585                 590         


Ala Leu Pro Ala 
        595     


<210>  9
<211>  1782
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Sequence of MBP-human betatrophin (MBP-hBT)

<400>  9
atgaaaatcg aagaaggtaa actggtaatc tggattaacg gcgataaagg ctataacggt       60

ctcgctgaag tcggtaagaa attcgagaaa gataccggaa ttaaagtcac cgttgagcat      120

ccggataaac tggaagagaa attcccacag gttgcggcaa ctggcgatgg ccctgacatt      180

atcttctggg cacacgaccg ctttggtggc tacgctcaat ctggcctgtt ggctgaaatc      240

accccggaca aagcgttcca ggacaagctg tatccgttta cctgggatgc cgtacgttac      300

aacggcaagc tgattgctta cccgatcgct gttgaagcgt tatcgctgat ttataacaaa      360

gatctgctgc cgaacccgcc aaaaacctgg gaagagatcc cggcgctgga taaagaactg      420

aaagcgaaag gtaagagcgc gctgatgttc aacctgcaag aaccgtactt cacctggccg      480

ctgattgctg ctgacggggg ttatgcgttc aagtatgaaa acggcaagta cgacattaaa      540

gacgtgggcg tggataacgc tggcgcgaaa gcgggtctga ccttcctggt tgacctgatt      600

aaaaacaaac acatgaatgc agacaccgat tactccatcg cagaagctgc ctttaataaa      660

ggcgaaacag cgatgaccat caacggcccg tgggcatggt ccaacatcga caccagcaaa      720

gtgaattatg gtgtaacggt actgccgacc ttcaagggtc aaccatccaa accgttcgtt      780

ggcgtgctga gcgcaggtat taacgccgcc agtccgaaca aagagctggc aaaagagttc      840

ctcgaaaact atctgctgac tgatgaaggt ctggaagcgg ttaataaaga caaaccgctg      900

ggtgccgtag cgctgaagtc ttacgaggaa gagttggtga aagatccgcg tattgccgcc      960

actatggaaa acgcccagaa aggtgaaatc atgccgaaca tcccgcagat gtccgctttc     1020

tggtatgccg tgcgtactgc ggtgatcaac gccgccagcg gtcgtcagac tgtcgatgaa     1080

gccctgaaag acgcgcagac taattcgagc tcgaacaaca acaacaataa caataacaac     1140

aacctcggga tcgagggaag gatttcacat atgtccatgg gcggccgcga tatcgtcgac     1200

ggatccgaat tccctgcagg taatgaaaac ctatacttcc aatcaggagc ccccatgggc     1260

ggcccagaac tggcacagca tgaggagctg accctgctct tccatgggac cctgcagctg     1320

ggccaggccc tcaacggtgt gtacaggacc acggagggac ggctgacaaa ggccaggaac     1380

agcctgggtc tctatggccg cacaatagaa ctcctggggc aggaggtcag ccggggccgg     1440

gatgcagccc aggaacttcg ggcaagcctg ttggagactc agatggagga ggatattctg     1500

cagctgcagg cagaggccac agctgaggtg ctgggggagg tggcccaggc acagaaggtg     1560

ctacgggaca gcgtgcagcg gctagaagtc cagctgagga gcgcctggct gggccctgcc     1620

taccgagaat ttgaggtctt aaaggctcac gctgacaagc agagccacat cctatgggcc     1680

ctcacaggcc acgtgcagcg gcagaggcgg gagatggtgg cacagcagca tcggctgcga     1740

cagatccagg agagactcca cacagcggcg ctcccagcct ga                        1782


<210>  10
<211>  593
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Sequence of MBP-human betatrophin (MBP-hBT)

<400>  10

Met Lys Ile Glu Glu Gly Lys Leu Val Ile Trp Ile Asn Gly Asp Lys 
1               5                   10                  15      


Gly Tyr Asn Gly Leu Ala Glu Val Gly Lys Lys Phe Glu Lys Asp Thr 
            20                  25                  30          


Gly Ile Lys Val Thr Val Glu His Pro Asp Lys Leu Glu Glu Lys Phe 
        35                  40                  45              


Pro Gln Val Ala Ala Thr Gly Asp Gly Pro Asp Ile Ile Phe Trp Ala 
    50                  55                  60                  


His Asp Arg Phe Gly Gly Tyr Ala Gln Ser Gly Leu Leu Ala Glu Ile 
65                  70                  75                  80  


Thr Pro Asp Lys Ala Phe Gln Asp Lys Leu Tyr Pro Phe Thr Trp Asp 
                85                  90                  95      


Ala Val Arg Tyr Asn Gly Lys Leu Ile Ala Tyr Pro Ile Ala Val Glu 
            100                 105                 110         


Ala Leu Ser Leu Ile Tyr Asn Lys Asp Leu Leu Pro Asn Pro Pro Lys 
        115                 120                 125             


Thr Trp Glu Glu Ile Pro Ala Leu Asp Lys Glu Leu Lys Ala Lys Gly 
    130                 135                 140                 


Lys Ser Ala Leu Met Phe Asn Leu Gln Glu Pro Tyr Phe Thr Trp Pro 
145                 150                 155                 160 


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


Tyr Asp Ile Lys Asp Val Gly Val Asp Asn Ala Gly Ala Lys Ala Gly 
            180                 185                 190         


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


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


Met Thr Ile Asn Gly Pro Trp Ala Trp Ser Asn Ile Asp Thr Ser Lys 
225                 230                 235                 240 


Val Asn Tyr Gly Val Thr Val Leu Pro Thr Phe Lys Gly Gln Pro Ser 
                245                 250                 255     


Lys Pro Phe Val Gly Val Leu Ser Ala Gly Ile Asn Ala Ala Ser Pro 
            260                 265                 270         


Asn Lys Glu Leu Ala Lys Glu Phe Leu Glu Asn Tyr Leu Leu Thr Asp 
        275                 280                 285             


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


Leu Lys Ser Tyr Glu Glu Glu Leu Val Lys Asp Pro Arg Ile Ala Ala 
305                 310                 315                 320 


Thr Met Glu Asn Ala Gln Lys Gly Glu Ile Met Pro Asn Ile Pro Gln 
                325                 330                 335     


Met Ser Ala Phe Trp Tyr Ala Val Arg Thr Ala Val Ile Asn Ala Ala 
            340                 345                 350         


Ser Gly Arg Gln Thr Val Asp Glu Ala Leu Lys Asp Ala Gln Thr Asn 
        355                 360                 365             


Ser Ser Ser Asn Asn Asn Asn Asn Asn Asn Asn Asn Asn Leu Gly Ile 
    370                 375                 380                 


Glu Gly Arg Ile Ser His Met Ser Met Gly Gly Arg Asp Ile Val Asp 
385                 390                 395                 400 


Gly Ser Glu Phe Pro Ala Gly Asn Glu Asn Leu Tyr Phe Gln Ser Gly 
                405                 410                 415     


Ala Pro Met Gly Gly Pro Glu Leu Ala Gln His Glu Glu Leu Thr Leu 
            420                 425                 430         


Leu Phe His Gly Thr Leu Gln Leu Gly Gln Ala Leu Asn Gly Val Tyr 
        435                 440                 445             


Arg Thr Thr Glu Gly Arg Leu Thr Lys Ala Arg Asn Ser Leu Gly Leu 
    450                 455                 460                 


Tyr Gly Arg Thr Ile Glu Leu Leu Gly Gln Glu Val Ser Arg Gly Arg 
465                 470                 475                 480 


Asp Ala Ala Gln Glu Leu Arg Ala Ser Leu Leu Glu Thr Gln Met Glu 
                485                 490                 495     


Glu Asp Ile Leu Gln Leu Gln Ala Glu Ala Thr Ala Glu Val Leu Gly 
            500                 505                 510         


Glu Val Ala Gln Ala Gln Lys Val Leu Arg Asp Ser Val Gln Arg Leu 
        515                 520                 525             


Glu Val Gln Leu Arg Ser Ala Trp Leu Gly Pro Ala Tyr Arg Glu Phe 
    530                 535                 540                 


Glu Val Leu Lys Ala His Ala Asp Lys Gln Ser His Ile Leu Trp Ala 
545                 550                 555                 560 


Leu Thr Gly His Val Gln Arg Gln Arg Arg Glu Met Val Ala Gln Gln 
                565                 570                 575     


His Arg Leu Arg Gln Ile Gln Glu Arg Leu His Thr Ala Ala Leu Pro 
            580                 585                 590         


Ala 
    


<210>  11
<211>  30
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Sequence of Myc tag

<400>  11
gaacaaaagc tgatttctga agaagacctc                                        30


<210>  12
<211>  10
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Sequence of Myc tag

<400>  12

Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 
1               5                   10  


<210>  13
<211>  627
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Sequence of Myc-tagged mouse betatrophin

<400>  13
atggctgtgc ttgctctctg cctcctgtgg accttagcat cagcagtgcg acccgctcca       60

gtggcccctc tgggtggtcc agagccagct caatatgaag agctgaccct gctctttcac      120

ggggccctgc agctaggcca ggccctcaat ggcgtgtaca gagccacaga ggctcgcctg      180

acagaagctg ggcacagcct gggcctctat gacagagcac tggaattcct ggggacagaa      240

gtcaggcagg gccaggatgc cacacaggag cttcgcacca gcctgtcgga gattcaggtg      300

gaagaggacg ctttacacct tcgagctgaa gccacagccc gatcactggg ggaagtggcc      360

cgggcccagc aggctctgcg ggacactgta cggagactac aagtgcagct gagaggcgcc      420

tggctcggtc aagcccacca agaatttgag accttaaagg ctcgagctga taagcagagc      480

cacctcttat gggctctcac tggccacgtg cagcgacagc agcgggagat ggcagagcag      540

caacagtggc tgcgacagat ccagcagaga ctccacacag cagccctccc agccgaacaa      600

aagctgattt ctgaagaaga cctctga                                          627


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

<220>
<223>  Sequence of Myc-tagged mouse betatrophin

<400>  14

Met Ala Val Leu Ala Leu Cys Leu Leu Trp Thr Leu Ala Ser Ala Val 
1               5                   10                  15      


Arg Pro Ala Pro Val Ala Pro Leu Gly Gly Pro Glu Pro Ala Gln Tyr 
            20                  25                  30          


Glu Glu Leu Thr Leu Leu Phe His Gly Ala Leu Gln Leu Gly Gln Ala 
        35                  40                  45              


Leu Asn Gly Val Tyr Arg Ala Thr Glu Ala Arg Leu Thr Glu Ala Gly 
    50                  55                  60                  


His Ser Leu Gly Leu Tyr Asp Arg Ala Leu Glu Phe Leu Gly Thr Glu 
65                  70                  75                  80  


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


Glu Ile Gln Val Glu Glu Asp Ala Leu His Leu Arg Ala Glu Ala Thr 
            100                 105                 110         


Ala Arg Ser Leu Gly Glu Val Ala Arg Ala Gln Gln Ala Leu Arg Asp 
        115                 120                 125             


Thr Val Arg Arg Leu Gln Val Gln Leu Arg Gly Ala Trp Leu Gly Gln 
    130                 135                 140                 


Ala His Gln Glu Phe Glu Thr Leu Lys Ala Arg Ala Asp Lys Gln Ser 
145                 150                 155                 160 


His Leu Leu Trp Ala Leu Thr Gly His Val Gln Arg Gln Gln Arg Glu 
                165                 170                 175     


Met Glu Thr Ala Glu Gln Gln Gln Trp Leu Arg Gln Ile Gln Gln Arg 
            180                 185                 190         


Leu His Thr Ala Ala Leu Pro Ala Glu Gln Lys Leu Ile Ser Glu Glu 
        195                 200                 205             


Asp Leu 
    210 


