                         SEQUENCE LISTING

<110>  Biopharm Gesellschaft zur biotechnologischen Entwicklung 
       von Pharmaka mbH
 
<120>  GDF-5 mutant for inducing cartilage formation

<130>  52328P EP

<160>  4     

<170>  PatentIn version 3.5

<210>  1
<211>  2703
<212>  DNA
<213>  homo sapiens


<220>
<221>  CDS
<222>  (640)..(2142)
<223>  GDF-5 precursor

<400>  1
ccatggcctc gaaagggcag cggtgatttt tttcacataa atatatcgca cttaaatgag       60

tttagacagc atgacatcag agagtaatta aattggtttg ggttggaatt ccgtttccaa      120

ttcctgagtt caggtttgta aaagattttt ctgagcacct gcaggcctgt gagtgtgtgt      180

gtgtgtgtgt gtgtgtgtgt gtgtgtgtga agtattttca ctggaaagga ttcaaaacta      240

gggggaaaaa aaaactggag cacacaggca gcattacgcc attcttcctt cttggaaaaa      300

tccctcagcc ttatacaagc ctccttcaag ccctcagtca gttgtgcagg agaaaggggg      360

cggttggctt tctcctttca agaacgagtt attttcagct gctgactgga gacggtgcac      420

gtctggatac gagagcattt ccactatggg actggataca aacacacacc cggcagactt      480

caagagtctc agactgagga gaaagccttt ccttctgctg ctactgctgc tgccgctgct      540

tttgaaagtc cactcctttc atggtttttc ctgccaaacc agaggcacct ttgctgctgc      600

cgctgttctc tttggtgtca ttcagcggct ggccagagg atg aga ctc ccc aaa         654
                                           Met Arg Leu Pro Lys            
                                           1               5              

ctc ctc act ttc ttg ctt tgg tac ctg gct tgg ctg gac ctg gaa ttc        702
Leu Leu Thr Phe Leu Leu Trp Tyr Leu Ala Trp Leu Asp Leu Glu Phe           
                10                  15                  20                

atc tgc act gtg ttg ggt gcc cct gac ttg ggc cag aga ccc cag ggg        750
Ile Cys Thr Val Leu Gly Ala Pro Asp Leu Gly Gln Arg Pro Gln Gly           
            25                  30                  35                    

acc agg cca gga ttg gcc aaa gca gag gcc aag gag agg ccc ccc ctg        798
Thr Arg Pro Gly Leu Ala Lys Ala Glu Ala Lys Glu Arg Pro Pro Leu           
        40                  45                  50                        

gcc cgg aac gtc ttc agg cca ggg ggt cac agc tat ggt ggg ggg gcc        846
Ala Arg Asn Val Phe Arg Pro Gly Gly His Ser Tyr Gly Gly Gly Ala           
    55                  60                  65                            

acc aat gcc aat gcc agg gca aag gga ggc acc ggg cag aca gga ggc        894
Thr Asn Ala Asn Ala Arg Ala Lys Gly Gly Thr Gly Gln Thr Gly Gly           
70                  75                  80                  85            

ctg aca cag ccc aag aag gat gaa ccc aaa aag ctg ccc ccc aga ccg        942
Leu Thr Gln Pro Lys Lys Asp Glu Pro Lys Lys Leu Pro Pro Arg Pro           
                90                  95                  100               

ggc ggc cct gaa ccc aag cca gga cac cct ccc caa aca agg cag gct        990
Gly Gly Pro Glu Pro Lys Pro Gly His Pro Pro Gln Thr Arg Gln Ala           
            105                 110                 115                   

aca gcc cgg act gtg acc cca aaa gga cag ctt ccc gga ggc aag gca       1038
Thr Ala Arg Thr Val Thr Pro Lys Gly Gln Leu Pro Gly Gly Lys Ala           
        120                 125                 130                       

ccc cca aaa gca gga tct gtc ccc agc tcc ttc ctg ctg aag aag gcc       1086
Pro Pro Lys Ala Gly Ser Val Pro Ser Ser Phe Leu Leu Lys Lys Ala           
    135                 140                 145                           

agg gag ccc ggg ccc cca cga gag ccc aag gag ccg ttt cgc cca ccc       1134
Arg Glu Pro Gly Pro Pro Arg Glu Pro Lys Glu Pro Phe Arg Pro Pro           
150                 155                 160                 165           

ccc atc aca ccc cac gag tac atg ctc tcg ctg tac agg acg ctg tcc       1182
Pro Ile Thr Pro His Glu Tyr Met Leu Ser Leu Tyr Arg Thr Leu Ser           
                170                 175                 180               

gat gct gac aga aag gga ggc aac agc agc gtg aag ttg gag gct ggc       1230
Asp Ala Asp Arg Lys Gly Gly Asn Ser Ser Val Lys Leu Glu Ala Gly           
            185                 190                 195                   

ctg gcc aac acc atc acc agc ttt att gac aaa ggg caa gat gac cga       1278
Leu Ala Asn Thr Ile Thr Ser Phe Ile Asp Lys Gly Gln Asp Asp Arg           
        200                 205                 210                       

ggt ccc gtg gtc agg aag cag agg tac gtg ttt gac att agt gcc ctg       1326
Gly Pro Val Val Arg Lys Gln Arg Tyr Val Phe Asp Ile Ser Ala Leu           
    215                 220                 225                           

gag aag gat ggg ctg ctg ggg gcc gag ctg cgg atc ttg cgg aag aag       1374
Glu Lys Asp Gly Leu Leu Gly Ala Glu Leu Arg Ile Leu Arg Lys Lys           
230                 235                 240                 245           

ccc tcg gac acg gcc aag cca gcg gcc ccc gga ggc ggg cgg gct gcc       1422
Pro Ser Asp Thr Ala Lys Pro Ala Ala Pro Gly Gly Gly Arg Ala Ala           
                250                 255                 260               

cag ctg aag ctg tcc agc tgc ccc agc ggc cgg cag ccg gcc tcc ttg       1470
Gln Leu Lys Leu Ser Ser Cys Pro Ser Gly Arg Gln Pro Ala Ser Leu           
            265                 270                 275                   

ctg gat gtg cgc tcc gtg cca ggc ctg gac gga tct ggc tgg gag gtg       1518
Leu Asp Val Arg Ser Val Pro Gly Leu Asp Gly Ser Gly Trp Glu Val           
        280                 285                 290                       

ttc gac atc tgg aag ctc ttc cga aac ttt aag aac tcg gcc cag ctg       1566
Phe Asp Ile Trp Lys Leu Phe Arg Asn Phe Lys Asn Ser Ala Gln Leu           
    295                 300                 305                           

tgc ctg gag ctg gag gcc tgg gaa cgg ggc agg gcc gtg gac ctc cgt       1614
Cys Leu Glu Leu Glu Ala Trp Glu Arg Gly Arg Ala Val Asp Leu Arg           
310                 315                 320                 325           

ggc ctg ggc ttc gac cgc gcc gcc cgg cag gtc cac gag aag gcc ctg       1662
Gly Leu Gly Phe Asp Arg Ala Ala Arg Gln Val His Glu Lys Ala Leu           
                330                 335                 340               

ttc ctg gtg ttt ggc cgc acc aag aaa cgg gac ctg ttc ttt aat gag       1710
Phe Leu Val Phe Gly Arg Thr Lys Lys Arg Asp Leu Phe Phe Asn Glu           
            345                 350                 355                   

att aag gcc cgc tct ggc cag gac gat aag acc gtg tat gag tac ctg       1758
Ile Lys Ala Arg Ser Gly Gln Asp Asp Lys Thr Val Tyr Glu Tyr Leu           
        360                 365                 370                       

ttc agc cag cgg cga aaa cgg cgg gcc cca ctg gcc act cgc cag ggc       1806
Phe Ser Gln Arg Arg Lys Arg Arg Ala Pro Leu Ala Thr Arg Gln Gly           
    375                 380                 385                           

aag cga ccc agc aag aac ctt aag gct cgc tgc agt cgg aag gca ctg       1854
Lys Arg Pro Ser Lys Asn Leu Lys Ala Arg Cys Ser Arg Lys Ala Leu           
390                 395                 400                 405           

cat gtc aac ttc aag gac atg ggc tgg gac gac tgg atc atc gca ccc       1902
His Val Asn Phe Lys Asp Met Gly Trp Asp Asp Trp Ile Ile Ala Pro           
                410                 415                 420               

ctt gag tac gag gct ttc cac tgc gag ggg ctg tgc gag ttc cca ttg       1950
Leu Glu Tyr Glu Ala Phe His Cys Glu Gly Leu Cys Glu Phe Pro Leu           
            425                 430                 435                   

cgc tcc cac ctg gag ccc acg aat cat gca gtc atc cag acc ctg atg       1998
Arg Ser His Leu Glu Pro Thr Asn His Ala Val Ile Gln Thr Leu Met           
        440                 445                 450                       

aac tcc atg gac ccc gag tcc aca cca ccc acc tgc tgt gtg ccc acg       2046
Asn Ser Met Asp Pro Glu Ser Thr Pro Pro Thr Cys Cys Val Pro Thr           
    455                 460                 465                           

cgg ctg agt ccc atc agc atc ctc ttc att gac tct gcc aac aac gtg       2094
Arg Leu Ser Pro Ile Ser Ile Leu Phe Ile Asp Ser Ala Asn Asn Val           
470                 475                 480                 485           

gtg tat aag cag tat gag gac atg gtc gtg gag tcg tgt ggc tgc agg       2142
Val Tyr Lys Gln Tyr Glu Asp Met Val Val Glu Ser Cys Gly Cys Arg           
                490                 495                 500               

tagcagcact ggccctctgt cttcctgggt ggcacatccc aagagcccct tcctgcactc     2202

ctggaatcac agaggggtca ggaagctgtg gcaggagcat ctacacagct tgggtgaaag     2262

gggattccaa taagcttgct cgctctctga gtgtgacttg ggctaaaggc ccccttttat     2322

ccacaagttc ccctggctga ggattgctgc ccgtctgctg atgtgaccag tggcaggcac     2382

aggtccaggg agacagactc tgaatgggac tgagtcccag gaaacagtgc tttccgatga     2442

gactcagccc accatttctc ctcacctggg ccttctcagc ctctggactc tcctaagcac     2502

ctctcaggag agccacaggt gccactgcct cctcaaatca catttgtgcc tggtgacttc     2562

ctgtccctgg gacagttgag aagctgactg ggcaagagtg ggagagaaga ggagagggct     2622

tggatagagt tgaggagtgt gaggctgtta gactgttaga tttaaatgta tattgatgag     2682

ataaaaagca aaactgtgcc t                                               2703


<210>  2
<211>  501
<212>  PRT
<213>  homo sapiens

<400>  2

Met Arg Leu Pro Lys Leu Leu Thr Phe Leu Leu Trp Tyr Leu Ala Trp 
1               5                   10                  15      


Leu Asp Leu Glu Phe Ile Cys Thr Val Leu Gly Ala Pro Asp Leu Gly 
            20                  25                  30          


Gln Arg Pro Gln Gly Thr Arg Pro Gly Leu Ala Lys Ala Glu Ala Lys 
        35                  40                  45              


Glu Arg Pro Pro Leu Ala Arg Asn Val Phe Arg Pro Gly Gly His Ser 
    50                  55                  60                  


Tyr Gly Gly Gly Ala Thr Asn Ala Asn Ala Arg Ala Lys Gly Gly Thr 
65                  70                  75                  80  


Gly Gln Thr Gly Gly Leu Thr Gln Pro Lys Lys Asp Glu Pro Lys Lys 
                85                  90                  95      


Leu Pro Pro Arg Pro Gly Gly Pro Glu Pro Lys Pro Gly His Pro Pro 
            100                 105                 110         


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


Pro Gly Gly Lys Ala Pro Pro Lys Ala Gly Ser Val Pro Ser Ser Phe 
    130                 135                 140                 


Leu Leu Lys Lys Ala Arg Glu Pro Gly Pro Pro Arg Glu Pro Lys Glu 
145                 150                 155                 160 


Pro Phe Arg Pro Pro Pro Ile Thr Pro His Glu Tyr Met Leu Ser Leu 
                165                 170                 175     


Tyr Arg Thr Leu Ser Asp Ala Asp Arg Lys Gly Gly Asn Ser Ser Val 
            180                 185                 190         


Lys Leu Glu Ala Gly Leu Ala Asn Thr Ile Thr Ser Phe Ile Asp Lys 
        195                 200                 205             


Gly Gln Asp Asp Arg Gly Pro Val Val Arg Lys Gln Arg Tyr Val Phe 
    210                 215                 220                 


Asp Ile Ser Ala Leu Glu Lys Asp Gly Leu Leu Gly Ala Glu Leu Arg 
225                 230                 235                 240 


Ile Leu Arg Lys Lys Pro Ser Asp Thr Ala Lys Pro Ala Ala Pro Gly 
                245                 250                 255     


Gly Gly Arg Ala Ala Gln Leu Lys Leu Ser Ser Cys Pro Ser Gly Arg 
            260                 265                 270         


Gln Pro Ala Ser Leu Leu Asp Val Arg Ser Val Pro Gly Leu Asp Gly 
        275                 280                 285             


Ser Gly Trp Glu Val Phe Asp Ile Trp Lys Leu Phe Arg Asn Phe Lys 
    290                 295                 300                 


Asn Ser Ala Gln Leu Cys Leu Glu Leu Glu Ala Trp Glu Arg Gly Arg 
305                 310                 315                 320 


Ala Val Asp Leu Arg Gly Leu Gly Phe Asp Arg Ala Ala Arg Gln Val 
                325                 330                 335     


His Glu Lys Ala Leu Phe Leu Val Phe Gly Arg Thr Lys Lys Arg Asp 
            340                 345                 350         


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


Val Tyr Glu Tyr Leu Phe Ser Gln Arg Arg Lys Arg Arg Ala Pro Leu 
    370                 375                 380                 


Ala Thr Arg Gln Gly Lys Arg Pro Ser Lys Asn Leu Lys Ala Arg Cys 
385                 390                 395                 400 


Ser Arg Lys Ala Leu His Val Asn Phe Lys Asp Met Gly Trp Asp Asp 
                405                 410                 415     


Trp Ile Ile Ala Pro Leu Glu Tyr Glu Ala Phe His Cys Glu Gly Leu 
            420                 425                 430         


Cys Glu Phe Pro Leu Arg Ser His Leu Glu Pro Thr Asn His Ala Val 
        435                 440                 445             


Ile Gln Thr Leu Met Asn Ser Met Asp Pro Glu Ser Thr Pro Pro Thr 
    450                 455                 460                 


Cys Cys Val Pro Thr Arg Leu Ser Pro Ile Ser Ile Leu Phe Ile Asp 
465                 470                 475                 480 


Ser Ala Asn Asn Val Val Tyr Lys Gln Tyr Glu Asp Met Val Val Glu 
                485                 490                 495     


Ser Cys Gly Cys Arg 
            500     


<210>  3
<211>  360
<212>  DNA
<213>  Homo sapiens


<220>
<221>  CDS
<222>  (1)..(360)
<223>  human mature monomeric GDF-5

<400>  3
gca cca cta gca act cgt cag ggc aag cga ccc agc aag aac ctt aag         48
Ala Pro Leu Ala Thr Arg Gln Gly Lys Arg Pro Ser Lys Asn Leu Lys           
1               5                   10                  15                

gct cgc tgc agt cgg aag gca ctg cat gtc aac ttc aag gac atg ggc         96
Ala Arg Cys Ser Arg Lys Ala Leu His Val Asn Phe Lys Asp Met Gly           
            20                  25                  30                    

tgg gac gac tgg atc atc gca ccc ctt gag tac gag gct ttc cac tgc        144
Trp Asp Asp Trp Ile Ile Ala Pro Leu Glu Tyr Glu Ala Phe His Cys           
        35                  40                  45                        

gag ggg ctg tgc gag ttc cca ttg cgc tcc cac ctg gag ccc acg aat        192
Glu Gly Leu Cys Glu Phe Pro Leu Arg Ser His Leu Glu Pro Thr Asn           
    50                  55                  60                            

cat gca gtc atc cag acc ctg atg aac tcc atg gac ccc gag tcc aca        240
His Ala Val Ile Gln Thr Leu Met Asn Ser Met Asp Pro Glu Ser Thr           
65                  70                  75                  80            

cca ccc acc gcc tgt gtg ccc acg cga ctg agt ccc atc agc atc ctc        288
Pro Pro Thr Ala Cys Val Pro Thr Arg Leu Ser Pro Ile Ser Ile Leu           
                85                  90                  95                

ttc att gac tct gcc aac aac gtg gtg tat aag cag tat gag gac atg        336
Phe Ile Asp Ser Ala Asn Asn Val Val Tyr Lys Gln Tyr Glu Asp Met           
            100                 105                 110                   

gtc gtg gag tcg tgt ggc tgt agg                                        360
Val Val Glu Ser Cys Gly Cys Arg                                           
        115                 120                                           


<210>  4
<211>  120
<212>  PRT
<213>  Homo sapiens

<400>  4

Ala Pro Leu Ala Thr Arg Gln Gly Lys Arg Pro Ser Lys Asn Leu Lys 
1               5                   10                  15      


Ala Arg Cys Ser Arg Lys Ala Leu His Val Asn Phe Lys Asp Met Gly 
            20                  25                  30          


Trp Asp Asp Trp Ile Ile Ala Pro Leu Glu Tyr Glu Ala Phe His Cys 
        35                  40                  45              


Glu Gly Leu Cys Glu Phe Pro Leu Arg Ser His Leu Glu Pro Thr Asn 
    50                  55                  60                  


His Ala Val Ile Gln Thr Leu Met Asn Ser Met Asp Pro Glu Ser Thr 
65                  70                  75                  80  


Pro Pro Thr Ala Cys Val Pro Thr Arg Leu Ser Pro Ile Ser Ile Leu 
                85                  90                  95      


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


Val Val Glu Ser Cys Gly Cys Arg 
        115                 120 


