                         SEQUENCE LISTING

<110>  CELGENE CORPORATION
 
<120>  METHODS FOR TREATING MYELOPROLIFERATIVE NEOPLASM-ASSOCIATED 
       MYELOFIBROSIS AND ANEMIA

<130>  14247-306-228

<140>  To Be Assigned
<141>  Herewith

<150>  62/679,210
<151>  2018-06-01

<150>  62/519,725
<151>  2017-06-14

<160>  34    

<170>  PatentIn version 3.5

<210>  1
<211>  344
<212>  PRT
<213>  Homo sapiens

<220>
<223>  Extracellular domain of human ActRIIA fused to a human Fc domain

<400>  1

Ile Leu Gly Arg Ser Glu Thr Gln Glu Cys Leu Phe Phe Asn Ala Asn 
1               5                   10                  15      


Trp Glu Lys Asp Arg Thr Asn Gln Thr Gly Val Glu Pro Cys Tyr Gly 
            20                  25                  30          


Asp Lys Asp Lys Arg Arg His Cys Phe Ala Thr Trp Lys Asn Ile Ser 
        35                  40                  45              


Gly Ser Ile Glu Ile Val Lys Gln Gly Cys Trp Leu Asp Asp Ile Asn 
    50                  55                  60                  


Cys Tyr Asp Arg Thr Asp Cys Val Glu Lys Lys Asp Ser Pro Glu Val 
65                  70                  75                  80  


Tyr Phe Cys Cys Cys Glu Gly Asn Met Cys Asn Glu Lys Phe Ser Tyr 
                85                  90                  95      


Phe Pro Glu Met Glu Val Thr Gln Pro Thr Ser Asn Pro Val Thr Pro 
            100                 105                 110         


Lys Pro Pro Thr Gly Gly Gly Thr His Thr Cys Pro Pro Cys Pro Ala 
        115                 120                 125             


Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
    130                 135                 140                 


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
145                 150                 155                 160 


Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
                165                 170                 175     


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
            180                 185                 190         


Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
        195                 200                 205             


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
    210                 215                 220                 


Leu Pro Val Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
225                 230                 235                 240 


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr 
                245                 250                 255     


Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 
            260                 265                 270         


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


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
    290                 295                 300                 


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
305                 310                 315                 320 


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
                325                 330                 335     


Ser Leu Ser Leu Ser Pro Gly Lys 
            340                 


<210>  2
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Leader sequence of Honey bee mellitin (HBML)

<400>  2

Met Lys Phe Leu Val Asn Val Ala Leu Val Phe Met Val Val Tyr Ile 
1               5                   10                  15      


Ser Tyr Ile Tyr Ala 
            20      


<210>  3
<211>  512
<212>  PRT
<213>  Homo sapiens

<220>
<223>  human ActRIIB precursor protein sequence (A64)

<400>  3

Met Thr Ala Pro Trp Val Ala Leu Ala Leu Leu Trp Gly Ser Leu Trp 
1               5                   10                  15      


Pro Gly Ser Gly Arg Gly Glu Ala Glu Thr Arg Glu Cys Ile Tyr Tyr 
            20                  25                  30          


Asn Ala Asn Trp Glu Leu Glu Arg Thr Asn Gln Ser Gly Leu Glu Arg 
        35                  40                  45              


Cys Glu Gly Glu Gln Asp Lys Arg Leu His Cys Tyr Ala Ser Trp Ala 
    50                  55                  60                  


Asn Ser Ser Gly Thr Ile Glu Leu Val Lys Lys Gly Cys Trp Leu Asp 
65                  70                  75                  80  


Asp Phe Asn Cys Tyr Asp Arg Gln Glu Cys Val Ala Thr Glu Glu Asn 
                85                  90                  95      


Pro Gln Val Tyr Phe Cys Cys Cys Glu Gly Asn Phe Cys Asn Glu Arg 
            100                 105                 110         


Phe Thr His Leu Pro Glu Ala Gly Gly Pro Glu Val Thr Tyr Glu Pro 
        115                 120                 125             


Pro Pro Thr Ala Pro Thr Leu Leu Thr Val Leu Ala Tyr Ser Leu Leu 
    130                 135                 140                 


Pro Ile Gly Gly Leu Ser Leu Ile Val Leu Leu Ala Phe Trp Met Tyr 
145                 150                 155                 160 


Arg His Arg Lys Pro Pro Tyr Gly His Val Asp Ile His Glu Asp Pro 
                165                 170                 175     


Gly Pro Pro Pro Pro Ser Pro Leu Val Gly Leu Lys Pro Leu Gln Leu 
            180                 185                 190         


Leu Glu Ile Lys Ala Arg Gly Arg Phe Gly Cys Val Trp Lys Ala Gln 
        195                 200                 205             


Leu Met Asn Asp Phe Val Ala Val Lys Ile Phe Pro Leu Gln Asp Lys 
    210                 215                 220                 


Gln Ser Trp Gln Ser Glu Arg Glu Ile Phe Ser Thr Pro Gly Met Lys 
225                 230                 235                 240 


His Glu Asn Leu Leu Gln Phe Ile Ala Ala Glu Lys Arg Gly Ser Asn 
                245                 250                 255     


Leu Glu Val Glu Leu Trp Leu Ile Thr Ala Phe His Asp Lys Gly Ser 
            260                 265                 270         


Leu Thr Asp Tyr Leu Lys Gly Asn Ile Ile Thr Trp Asn Glu Leu Cys 
        275                 280                 285             


His Val Ala Glu Thr Met Ser Arg Gly Leu Ser Tyr Leu His Glu Asp 
    290                 295                 300                 


Val Pro Trp Cys Arg Gly Glu Gly His Lys Pro Ser Ile Ala His Arg 
305                 310                 315                 320 


Asp Phe Lys Ser Lys Asn Val Leu Leu Lys Ser Asp Leu Thr Ala Val 
                325                 330                 335     


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


Gly Asp Thr His Gly Gln Val Gly Thr Arg Arg Tyr Met Ala Pro Glu 
        355                 360                 365             


Val Leu Glu Gly Ala Ile Asn Phe Gln Arg Asp Ala Phe Leu Arg Ile 
    370                 375                 380                 


Asp Met Tyr Ala Met Gly Leu Val Leu Trp Glu Leu Val Ser Arg Cys 
385                 390                 395                 400 


Lys Ala Ala Asp Gly Pro Val Asp Glu Tyr Met Leu Pro Phe Glu Glu 
                405                 410                 415     


Glu Ile Gly Gln His Pro Ser Leu Glu Glu Leu Gln Glu Val Val Val 
            420                 425                 430         


His Lys Lys Met Arg Pro Thr Ile Lys Asp His Trp Leu Lys His Pro 
        435                 440                 445             


Gly Leu Ala Gln Leu Cys Val Thr Ile Glu Glu Cys Trp Asp His Asp 
    450                 455                 460                 


Ala Glu Ala Arg Leu Ser Ala Gly Cys Val Glu Glu Arg Val Ser Leu 
465                 470                 475                 480 


Ile Arg Arg Ser Val Asn Gly Thr Thr Ser Asp Cys Leu Val Ser Leu 
                485                 490                 495     


Val Thr Ser Val Thr Asn Val Asp Leu Pro Pro Lys Glu Ser Ser Ile 
            500                 505                 510         


<210>  4
<211>  116
<212>  PRT
<213>  Homo sapiens

<220>
<223>  human ActRIIB soluble (extracellular), processed polypeptide 
       sequence (amino acids 19-134 of SEQ ID NO:3)

<400>  4

Ser Gly Arg Gly Glu Ala Glu Thr Arg Glu Cys Ile Tyr Tyr Asn Ala 
1               5                   10                  15      


Asn Trp Glu Leu Glu Arg Thr Asn Gln Ser Gly Leu Glu Arg Cys Glu 
            20                  25                  30          


Gly Glu Gln Asp Lys Arg Leu His Cys Tyr Ala Ser Trp Ala Asn Ser 
        35                  40                  45              


Ser Gly Thr Ile Glu Leu Val Lys Lys Gly Cys Trp Leu Asp Asp Phe 
    50                  55                  60                  


Asn Cys Tyr Asp Arg Gln Glu Cys Val Ala Thr Glu Glu Asn Pro Gln 
65                  70                  75                  80  


Val Tyr Phe Cys Cys Cys Glu Gly Asn Phe Cys Asn Glu Arg Phe Thr 
                85                  90                  95      


His Leu Pro Glu Ala Gly Gly Pro Glu Val Thr Tyr Glu Pro Pro Pro 
            100                 105                 110         


Thr Ala Pro Thr 
        115     


<210>  5
<211>  101
<212>  PRT
<213>  Homo sapiens

<220>
<223>  human ActRIIB soluble (extracellular), processed polypeptide 
       sequence with the C-terminal 15 amino acids deleted (amino acids 
       19-119 of SEQ ID NO:3)

<400>  5

Ser Gly Arg Gly Glu Ala Glu Thr Arg Glu Cys Ile Tyr Tyr Asn Ala 
1               5                   10                  15      


Asn Trp Glu Leu Glu Arg Thr Asn Gln Ser Gly Leu Glu Arg Cys Glu 
            20                  25                  30          


Gly Glu Gln Asp Lys Arg Leu His Cys Tyr Ala Ser Trp Ala Asn Ser 
        35                  40                  45              


Ser Gly Thr Ile Glu Leu Val Lys Lys Gly Cys Trp Leu Asp Asp Phe 
    50                  55                  60                  


Asn Cys Tyr Asp Arg Gln Glu Cys Val Ala Thr Glu Glu Asn Pro Gln 
65                  70                  75                  80  


Val Tyr Phe Cys Cys Cys Glu Gly Asn Phe Cys Asn Glu Arg Phe Thr 
                85                  90                  95      


His Leu Pro Glu Ala 
            100     


<210>  6
<211>  1539
<212>  DNA
<213>  Homo sapiens

<220>
<223>  human ActRIIB (A64) precursor protein

<400>  6
atgacggcgc cctgggtggc cctcgccctc ctctggggat cgctgtggcc cggctctggg       60

cgtggggagg ctgagacacg ggagtgcatc tactacaacg ccaactggga gctggagcgc      120

accaaccaga gcggcctgga gcgctgcgaa ggcgagcagg acaagcggct gcactgctac      180

gcctcctggg ccaacagctc tggcaccatc gagctcgtga agaagggctg ctggctagat      240

gacttcaact gctacgatag gcaggagtgt gtggccactg aggagaaccc ccaggtgtac      300

ttctgctgct gtgaaggcaa cttctgcaac gagcgcttca ctcatttgcc agaggctggg      360

ggcccggaag tcacgtacga gccacccccg acagccccca ccctgctcac ggtgctggcc      420

tactcactgc tgcccatcgg gggcctttcc ctcatcgtcc tgctggcctt ttggatgtac      480

cggcatcgca agccccccta cggtcatgtg gacatccatg aggaccctgg gcctccacca      540

ccatcccctc tggtgggcct gaagccactg cagctgctgg agatcaaggc tcgggggcgc      600

tttggctgtg tctggaaggc ccagctcatg aatgactttg tagctgtcaa gatcttccca      660

ctccaggaca agcagtcgtg gcagagtgaa cgggagatct tcagcacacc tggcatgaag      720

cacgagaacc tgctacagtt cattgctgcc gagaagcgag gctccaacct cgaagtagag      780

ctgtggctca tcacggcctt ccatgacaag ggctccctca cggattacct caaggggaac      840

atcatcacat ggaacgaact gtgtcatgta gcagagacga tgtcacgagg cctctcatac      900

ctgcatgagg atgtgccctg gtgccgtggc gagggccaca agccgtctat tgcccacagg      960

gactttaaaa gtaagaatgt attgctgaag agcgacctca cagccgtgct ggctgacttt     1020

ggcttggctg ttcgatttga gccagggaaa cctccagggg acacccacgg acaggtaggc     1080

acgagacggt acatggctcc tgaggtgctc gagggagcca tcaacttcca gagagatgcc     1140

ttcctgcgca ttgacatgta tgccatgggg ttggtgctgt gggagcttgt gtctcgctgc     1200

aaggctgcag acggacccgt ggatgagtac atgctgccct ttgaggaaga gattggccag     1260

cacccttcgt tggaggagct gcaggaggtg gtggtgcaca agaagatgag gcccaccatt     1320

aaagatcact ggttgaaaca cccgggcctg gcccagcttt gtgtgaccat cgaggagtgc     1380

tgggaccatg atgcagaggc tcgcttgtcc gcgggctgtg tggaggagcg ggtgtccctg     1440

attcggaggt cggtcaacgg cactacctcg gactgtctcg tttccctggt gacctctgtc     1500

accaatgtgg acctgccccc taaagagtca agcatctaa                            1539


<210>  7
<211>  344
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  fusion protein comprising a soluble extracellular domain of 
       ActRIIB (A64; SEQ ID NO:17) fused to an Fc domain

<400>  7

Ser Gly Arg Gly Glu Ala Glu Thr Arg Glu Cys Ile Tyr Tyr Asn Ala 
1               5                   10                  15      


Asn Trp Glu Leu Glu Arg Thr Asn Gln Ser Gly Leu Glu Arg Cys Glu 
            20                  25                  30          


Gly Glu Gln Asp Lys Arg Leu His Cys Tyr Ala Ser Trp Ala Asn Ser 
        35                  40                  45              


Ser Gly Thr Ile Glu Leu Val Lys Lys Gly Cys Trp Leu Asp Asp Phe 
    50                  55                  60                  


Asn Cys Tyr Asp Arg Gln Glu Cys Val Ala Thr Glu Glu Asn Pro Gln 
65                  70                  75                  80  


Val Tyr Phe Cys Cys Cys Glu Gly Asn Phe Cys Asn Glu Arg Phe Thr 
                85                  90                  95      


His Leu Pro Glu Ala Gly Gly Pro Glu Val Thr Tyr Glu Pro Pro Pro 
            100                 105                 110         


Thr Ala Pro Thr Gly Gly Gly Thr His Thr Cys Pro Pro Cys Pro Ala 
        115                 120                 125             


Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
    130                 135                 140                 


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
145                 150                 155                 160 


Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
                165                 170                 175     


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
            180                 185                 190         


Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
        195                 200                 205             


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
    210                 215                 220                 


Leu Pro Val Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
225                 230                 235                 240 


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr 
                245                 250                 255     


Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 
            260                 265                 270         


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


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
    290                 295                 300                 


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
305                 310                 315                 320 


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
                325                 330                 335     


Ser Leu Ser Leu Ser Pro Gly Lys 
            340                 


<210>  8
<211>  329
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  fusion protein comprising a soluble extracellular domain of 
       ActRIIB (A64) with the C-terminal 15 amino acids deleted (SEQ ID 
       NO:5) fused to an Fc domain

<400>  8

Ser Gly Arg Gly Glu Ala Glu Thr Arg Glu Cys Ile Tyr Tyr Asn Ala 
1               5                   10                  15      


Asn Trp Glu Leu Glu Arg Thr Asn Gln Ser Gly Leu Glu Arg Cys Glu 
            20                  25                  30          


Gly Glu Gln Asp Lys Arg Leu His Cys Tyr Ala Ser Trp Ala Asn Ser 
        35                  40                  45              


Ser Gly Thr Ile Glu Leu Val Lys Lys Gly Cys Trp Leu Asp Asp Phe 
    50                  55                  60                  


Asn Cys Tyr Asp Arg Gln Glu Cys Val Ala Thr Glu Glu Asn Pro Gln 
65                  70                  75                  80  


Val Tyr Phe Cys Cys Cys Glu Gly Asn Phe Cys Asn Glu Arg Phe Thr 
                85                  90                  95      


His Leu Pro Glu Ala Gly Gly Gly Thr His Thr Cys Pro Pro Cys Pro 
            100                 105                 110         


Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
        115                 120                 125             


Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
    130                 135                 140                 


Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
145                 150                 155                 160 


Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
                165                 170                 175     


Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
            180                 185                 190         


Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
        195                 200                 205             


Ala Leu Pro Val Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
    210                 215                 220                 


Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met 
225                 230                 235                 240 


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


Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
            260                 265                 270         


Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
        275                 280                 285             


Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
    290                 295                 300                 


Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
305                 310                 315                 320 


Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                325                 


<210>  9
<211>  107
<212>  PRT
<213>  Homo sapiens

<220>
<223>  human ActRIIB soluble (extracellular), processed polypeptide 
       sequence with the N-terminal 6 amino acids of the EC domain 
       deleted and the C-terminal 3 amino acids of the EC domain deleted
       (amino acids 25-131 of SEQ ID NO:14) and with an L79D mutation

<400>  9

Glu Thr Arg Glu Cys Ile Tyr Tyr Asn Ala Asn Trp Glu Leu Glu Arg 
1               5                   10                  15      


Thr Asn Gln Ser Gly Leu Glu Arg Cys Glu Gly Glu Gln Asp Lys Arg 
            20                  25                  30          


Leu His Cys Tyr Ala Ser Trp Arg Asn Ser Ser Gly Thr Ile Glu Leu 
        35                  40                  45              


Val Lys Lys Gly Cys Trp Asp Asp Asp Phe Asn Cys Tyr Asp Arg Gln 
    50                  55                  60                  


Glu Cys Val Ala Thr Glu Glu Asn Pro Gln Val Tyr Phe Cys Cys Cys 
65                  70                  75                  80  


Glu Gly Asn Phe Cys Asn Glu Arg Phe Thr His Leu Pro Glu Ala Gly 
                85                  90                  95      


Gly Pro Glu Val Thr Tyr Glu Pro Pro Pro Thr 
            100                 105         


<210>  10
<211>  360
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Unprocessed ActRIIB-Fc fusion protein with the N-terminal 6 amino
       acids of the EC domain deleted and the C-terminal 3 amino acids 
       of the EC domain deleted (amino acids 25-131 of SEQ ID NO:14) and
       with an L79D mutation and with TPA leader sequence

<400>  10

Met Asp Ala Met Lys Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly 
1               5                   10                  15      


Ala Val Phe Val Ser Pro Gly Ala Ala Glu Thr Arg Glu Cys Ile Tyr 
            20                  25                  30          


Tyr Asn Ala Asn Trp Glu Leu Glu Arg Thr Asn Gln Ser Gly Leu Glu 
        35                  40                  45              


Arg Cys Glu Gly Glu Gln Asp Lys Arg Leu His Cys Tyr Ala Ser Trp 
    50                  55                  60                  


Arg Asn Ser Ser Gly Thr Ile Glu Leu Val Lys Lys Gly Cys Trp Asp 
65                  70                  75                  80  


Asp Asp Phe Asn Cys Tyr Asp Arg Gln Glu Cys Val Ala Thr Glu Glu 
                85                  90                  95      


Asn Pro Gln Val Tyr Phe Cys Cys Cys Glu Gly Asn Phe Cys Asn Glu 
            100                 105                 110         


Arg Phe Thr His Leu Pro Glu Ala Gly Gly Pro Glu Val Thr Tyr Glu 
        115                 120                 125             


Pro Pro Pro Thr Gly Gly Gly Thr His Thr Cys Pro Pro Cys Pro Ala 
    130                 135                 140                 


Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
145                 150                 155                 160 


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
                165                 170                 175     


Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
            180                 185                 190         


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
        195                 200                 205             


Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
    210                 215                 220                 


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
225                 230                 235                 240 


Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
                245                 250                 255     


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr 
            260                 265                 270         


Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 
        275                 280                 285             


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
    290                 295                 300                 


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
305                 310                 315                 320 


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
                325                 330                 335     


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
            340                 345                 350         


Ser Leu Ser Leu Ser Pro Gly Lys 
        355                 360 


<210>  11
<211>  335
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Processed ActRIIB-Fc fusion protein with the N-terminal 6 amino 
       acids of the EC domain deleted and the C-terminal 3 amino acids 
       of the EC domain deleted (amino acids 25-131 of SEQ ID NO:14) and
       with an L79D mutation (i.e., luspatercept)

<400>  11

Glu Thr Arg Glu Cys Ile Tyr Tyr Asn Ala Asn Trp Glu Leu Glu Arg 
1               5                   10                  15      


Thr Asn Gln Ser Gly Leu Glu Arg Cys Glu Gly Glu Gln Asp Lys Arg 
            20                  25                  30          


Leu His Cys Tyr Ala Ser Trp Arg Asn Ser Ser Gly Thr Ile Glu Leu 
        35                  40                  45              


Val Lys Lys Gly Cys Trp Asp Asp Asp Phe Asn Cys Tyr Asp Arg Gln 
    50                  55                  60                  


Glu Cys Val Ala Thr Glu Glu Asn Pro Gln Val Tyr Phe Cys Cys Cys 
65                  70                  75                  80  


Glu Gly Asn Phe Cys Asn Glu Arg Phe Thr His Leu Pro Glu Ala Gly 
                85                  90                  95      


Gly Pro Glu Val Thr Tyr Glu Pro Pro Pro Thr Gly Gly Gly Thr His 
            100                 105                 110         


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


Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
    130                 135                 140                 


Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
145                 150                 155                 160 


Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
                165                 170                 175     


Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
            180                 185                 190         


Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
        195                 200                 205             


Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
    210                 215                 220                 


Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
225                 230                 235                 240 


Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
                245                 250                 255     


Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
            260                 265                 270         


Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
        275                 280                 285             


Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
    290                 295                 300                 


Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
305                 310                 315                 320 


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                325                 330                 335 


<210>  12
<211>  115
<212>  PRT
<213>  Homo sapiens

<220>
<223>  human ActRIIB soluble (extracellular), processed polypeptide 
       sequence (amino acids 20-134 of SEQ ID NO:3)

<400>  12

Gly Arg Gly Glu Ala Glu Thr Arg Glu Cys Ile Tyr Tyr Asn Ala Asn 
1               5                   10                  15      


Trp Glu Leu Glu Arg Thr Asn Gln Ser Gly Leu Glu Arg Cys Glu Gly 
            20                  25                  30          


Glu Gln Asp Lys Arg Leu His Cys Tyr Ala Ser Trp Ala Asn Ser Ser 
        35                  40                  45              


Gly Thr Ile Glu Leu Val Lys Lys Gly Cys Trp Leu Asp Asp Phe Asn 
    50                  55                  60                  


Cys Tyr Asp Arg Gln Glu Cys Val Ala Thr Glu Glu Asn Pro Gln Val 
65                  70                  75                  80  


Tyr Phe Cys Cys Cys Glu Gly Asn Phe Cys Asn Glu Arg Phe Thr His 
                85                  90                  95      


Leu Pro Glu Ala Gly Gly Pro Glu Val Thr Tyr Glu Pro Pro Pro Thr 
            100                 105                 110         


Ala Pro Thr 
        115 


<210>  13
<211>  100
<212>  PRT
<213>  Homo sapiens

<220>
<223>  human ActRIIB soluble (extracellular), processed polypeptide 
       sequence with the C-terminal 15 amino acids deleted (amino acids 
       20-119 of SEQ ID NO:3)

<400>  13

Gly Arg Gly Glu Ala Glu Thr Arg Glu Cys Ile Tyr Tyr Asn Ala Asn 
1               5                   10                  15      


Trp Glu Leu Glu Arg Thr Asn Gln Ser Gly Leu Glu Arg Cys Glu Gly 
            20                  25                  30          


Glu Gln Asp Lys Arg Leu His Cys Tyr Ala Ser Trp Ala Asn Ser Ser 
        35                  40                  45              


Gly Thr Ile Glu Leu Val Lys Lys Gly Cys Trp Leu Asp Asp Phe Asn 
    50                  55                  60                  


Cys Tyr Asp Arg Gln Glu Cys Val Ala Thr Glu Glu Asn Pro Gln Val 
65                  70                  75                  80  


Tyr Phe Cys Cys Cys Glu Gly Asn Phe Cys Asn Glu Arg Phe Thr His 
                85                  90                  95      


Leu Pro Glu Ala 
            100 


<210>  14
<211>  512
<212>  PRT
<213>  Homo sapiens

<220>
<223>  human ActRIIB precursor protein sequence (R64)

<400>  14

Met Thr Ala Pro Trp Val Ala Leu Ala Leu Leu Trp Gly Ser Leu Trp 
1               5                   10                  15      


Pro Gly Ser Gly Arg Gly Glu Ala Glu Thr Arg Glu Cys Ile Tyr Tyr 
            20                  25                  30          


Asn Ala Asn Trp Glu Leu Glu Arg Thr Asn Gln Ser Gly Leu Glu Arg 
        35                  40                  45              


Cys Glu Gly Glu Gln Asp Lys Arg Leu His Cys Tyr Ala Ser Trp Arg 
    50                  55                  60                  


Asn Ser Ser Gly Thr Ile Glu Leu Val Lys Lys Gly Cys Trp Leu Asp 
65                  70                  75                  80  


Asp Phe Asn Cys Tyr Asp Arg Gln Glu Cys Val Ala Thr Glu Glu Asn 
                85                  90                  95      


Pro Gln Val Tyr Phe Cys Cys Cys Glu Gly Asn Phe Cys Asn Glu Arg 
            100                 105                 110         


Phe Thr His Leu Pro Glu Ala Gly Gly Pro Glu Val Thr Tyr Glu Pro 
        115                 120                 125             


Pro Pro Thr Ala Pro Thr Leu Leu Thr Val Leu Ala Tyr Ser Leu Leu 
    130                 135                 140                 


Pro Ile Gly Gly Leu Ser Leu Ile Val Leu Leu Ala Phe Trp Met Tyr 
145                 150                 155                 160 


Arg His Arg Lys Pro Pro Tyr Gly His Val Asp Ile His Glu Asp Pro 
                165                 170                 175     


Gly Pro Pro Pro Pro Ser Pro Leu Val Gly Leu Lys Pro Leu Gln Leu 
            180                 185                 190         


Leu Glu Ile Lys Ala Arg Gly Arg Phe Gly Cys Val Trp Lys Ala Gln 
        195                 200                 205             


Leu Met Asn Asp Phe Val Ala Val Lys Ile Phe Pro Leu Gln Asp Lys 
    210                 215                 220                 


Gln Ser Trp Gln Ser Glu Arg Glu Ile Phe Ser Thr Pro Gly Met Lys 
225                 230                 235                 240 


His Glu Asn Leu Leu Gln Phe Ile Ala Ala Glu Lys Arg Gly Ser Asn 
                245                 250                 255     


Leu Glu Val Glu Leu Trp Leu Ile Thr Ala Phe His Asp Lys Gly Ser 
            260                 265                 270         


Leu Thr Asp Tyr Leu Lys Gly Asn Ile Ile Thr Trp Asn Glu Leu Cys 
        275                 280                 285             


His Val Ala Glu Thr Met Ser Arg Gly Leu Ser Tyr Leu His Glu Asp 
    290                 295                 300                 


Val Pro Trp Cys Arg Gly Glu Gly His Lys Pro Ser Ile Ala His Arg 
305                 310                 315                 320 


Asp Phe Lys Ser Lys Asn Val Leu Leu Lys Ser Asp Leu Thr Ala Val 
                325                 330                 335     


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


Gly Asp Thr His Gly Gln Val Gly Thr Arg Arg Tyr Met Ala Pro Glu 
        355                 360                 365             


Val Leu Glu Gly Ala Ile Asn Phe Gln Arg Asp Ala Phe Leu Arg Ile 
    370                 375                 380                 


Asp Met Tyr Ala Met Gly Leu Val Leu Trp Glu Leu Val Ser Arg Cys 
385                 390                 395                 400 


Lys Ala Ala Asp Gly Pro Val Asp Glu Tyr Met Leu Pro Phe Glu Glu 
                405                 410                 415     


Glu Ile Gly Gln His Pro Ser Leu Glu Glu Leu Gln Glu Val Val Val 
            420                 425                 430         


His Lys Lys Met Arg Pro Thr Ile Lys Asp His Trp Leu Lys His Pro 
        435                 440                 445             


Gly Leu Ala Gln Leu Cys Val Thr Ile Glu Glu Cys Trp Asp His Asp 
    450                 455                 460                 


Ala Glu Ala Arg Leu Ser Ala Gly Cys Val Glu Glu Arg Val Ser Leu 
465                 470                 475                 480 


Ile Arg Arg Ser Val Asn Gly Thr Thr Ser Asp Cys Leu Val Ser Leu 
                485                 490                 495     


Val Thr Ser Val Thr Asn Val Asp Leu Pro Pro Lys Glu Ser Ser Ile 
            500                 505                 510         


<210>  15
<211>  116
<212>  PRT
<213>  Homo sapiens

<220>
<223>  human ActRIIB soluble (extracellular), processed polypeptide 
       sequence (amino acids 19-134 of SEQ ID NO:14)

<400>  15

Ser Gly Arg Gly Glu Ala Glu Thr Arg Glu Cys Ile Tyr Tyr Asn Ala 
1               5                   10                  15      


Asn Trp Glu Leu Glu Arg Thr Asn Gln Ser Gly Leu Glu Arg Cys Glu 
            20                  25                  30          


Gly Glu Gln Asp Lys Arg Leu His Cys Tyr Ala Ser Trp Arg Asn Ser 
        35                  40                  45              


Ser Gly Thr Ile Glu Leu Val Lys Lys Gly Cys Trp Leu Asp Asp Phe 
    50                  55                  60                  


Asn Cys Tyr Asp Arg Gln Glu Cys Val Ala Thr Glu Glu Asn Pro Gln 
65                  70                  75                  80  


Val Tyr Phe Cys Cys Cys Glu Gly Asn Phe Cys Asn Glu Arg Phe Thr 
                85                  90                  95      


His Leu Pro Glu Ala Gly Gly Pro Glu Val Thr Tyr Glu Pro Pro Pro 
            100                 105                 110         


Thr Ala Pro Thr 
        115     


<210>  16
<211>  101
<212>  PRT
<213>  Homo sapiens

<220>
<223>  human ActRIIB soluble (extracellular), processed polypeptide 
       sequence with the C-terminal 15 amino acids deleted (amino acids 
       19-119 of SEQ ID NO:14)

<400>  16

Ser Gly Arg Gly Glu Ala Glu Thr Arg Glu Cys Ile Tyr Tyr Asn Ala 
1               5                   10                  15      


Asn Trp Glu Leu Glu Arg Thr Asn Gln Ser Gly Leu Glu Arg Cys Glu 
            20                  25                  30          


Gly Glu Gln Asp Lys Arg Leu His Cys Tyr Ala Ser Trp Arg Asn Ser 
        35                  40                  45              


Ser Gly Thr Ile Glu Leu Val Lys Lys Gly Cys Trp Leu Asp Asp Phe 
    50                  55                  60                  


Asn Cys Tyr Asp Arg Gln Glu Cys Val Ala Thr Glu Glu Asn Pro Gln 
65                  70                  75                  80  


Val Tyr Phe Cys Cys Cys Glu Gly Asn Phe Cys Asn Glu Arg Phe Thr 
                85                  90                  95      


His Leu Pro Glu Ala 
            100     


<210>  17
<211>  115
<212>  PRT
<213>  Homo sapiens

<220>
<223>  human ActRIIB soluble (extracellular), processed polypeptide 
       sequence (amino acids 20-134 of SEQ ID NO:14)

<400>  17

Gly Arg Gly Glu Ala Glu Thr Arg Glu Cys Ile Tyr Tyr Asn Ala Asn 
1               5                   10                  15      


Trp Glu Leu Glu Arg Thr Asn Gln Ser Gly Leu Glu Arg Cys Glu Gly 
            20                  25                  30          


Glu Gln Asp Lys Arg Leu His Cys Tyr Ala Ser Trp Arg Asn Ser Ser 
        35                  40                  45              


Gly Thr Ile Glu Leu Val Lys Lys Gly Cys Trp Leu Asp Asp Phe Asn 
    50                  55                  60                  


Cys Tyr Asp Arg Gln Glu Cys Val Ala Thr Glu Glu Asn Pro Gln Val 
65                  70                  75                  80  


Tyr Phe Cys Cys Cys Glu Gly Asn Phe Cys Asn Glu Arg Phe Thr His 
                85                  90                  95      


Leu Pro Glu Ala Gly Gly Pro Glu Val Thr Tyr Glu Pro Pro Pro Thr 
            100                 105                 110         


Ala Pro Thr 
        115 


<210>  18
<211>  100
<212>  PRT
<213>  Homo sapiens

<220>
<223>  human ActRIIB soluble (extracellular), processed polypeptide 
       sequence with the C-terminal 15 amino acids deleted (amino acids 
       20-119 of SEQ ID NO:14)

<400>  18

Gly Arg Gly Glu Ala Glu Thr Arg Glu Cys Ile Tyr Tyr Asn Ala Asn 
1               5                   10                  15      


Trp Glu Leu Glu Arg Thr Asn Gln Ser Gly Leu Glu Arg Cys Glu Gly 
            20                  25                  30          


Glu Gln Asp Lys Arg Leu His Cys Tyr Ala Ser Trp Arg Asn Ser Ser 
        35                  40                  45              


Gly Thr Ile Glu Leu Val Lys Lys Gly Cys Trp Leu Asp Asp Phe Asn 
    50                  55                  60                  


Cys Tyr Asp Arg Gln Glu Cys Val Ala Thr Glu Glu Asn Pro Gln Val 
65                  70                  75                  80  


Tyr Phe Cys Cys Cys Glu Gly Asn Phe Cys Asn Glu Arg Phe Thr His 
                85                  90                  95      


Leu Pro Glu Ala 
            100 


<210>  19
<211>  107
<212>  PRT
<213>  Homo sapiens

<220>
<223>  human ActRIIB soluble (extracellular), processed polypeptide 
       sequence with the N-terminal 6 amino acids of the EC domain 
       deleted and the C-terminal 3 amino acids of the EC domain deleted
       (amino acids 25-131 of SEQ ID NO:3) and with an L79D mutation

<400>  19

Glu Thr Arg Glu Cys Ile Tyr Tyr Asn Ala Asn Trp Glu Leu Glu Arg 
1               5                   10                  15      


Thr Asn Gln Ser Gly Leu Glu Arg Cys Glu Gly Glu Gln Asp Lys Arg 
            20                  25                  30          


Leu His Cys Tyr Ala Ser Trp Ala Asn Ser Ser Gly Thr Ile Glu Leu 
        35                  40                  45              


Val Lys Lys Gly Cys Trp Asp Asp Asp Phe Asn Cys Tyr Asp Arg Gln 
    50                  55                  60                  


Glu Cys Val Ala Thr Glu Glu Asn Pro Gln Val Tyr Phe Cys Cys Cys 
65                  70                  75                  80  


Glu Gly Asn Phe Cys Asn Glu Arg Phe Thr His Leu Pro Glu Ala Gly 
                85                  90                  95      


Gly Pro Glu Val Thr Tyr Glu Pro Pro Pro Thr 
            100                 105         


<210>  20
<211>  360
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Unprocessed ActRIIB-Fc fusion protein with the N-terminal 6 amino
       acids of the EC domain deleted and the C-terminal 3 amino acids 
       of the EC domain deleted (amino acids 25-131 of SEQ ID NO:3) and 
       with an L79D mutation and with TPA leader sequence

<400>  20

Met Asp Ala Met Lys Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly 
1               5                   10                  15      


Ala Val Phe Val Ser Pro Gly Ala Ala Glu Thr Arg Glu Cys Ile Tyr 
            20                  25                  30          


Tyr Asn Ala Asn Trp Glu Leu Glu Arg Thr Asn Gln Ser Gly Leu Glu 
        35                  40                  45              


Arg Cys Glu Gly Glu Gln Asp Lys Arg Leu His Cys Tyr Ala Ser Trp 
    50                  55                  60                  


Ala Asn Ser Ser Gly Thr Ile Glu Leu Val Lys Lys Gly Cys Trp Asp 
65                  70                  75                  80  


Asp Asp Phe Asn Cys Tyr Asp Arg Gln Glu Cys Val Ala Thr Glu Glu 
                85                  90                  95      


Asn Pro Gln Val Tyr Phe Cys Cys Cys Glu Gly Asn Phe Cys Asn Glu 
            100                 105                 110         


Arg Phe Thr His Leu Pro Glu Ala Gly Gly Pro Glu Val Thr Tyr Glu 
        115                 120                 125             


Pro Pro Pro Thr Gly Gly Gly Thr His Thr Cys Pro Pro Cys Pro Ala 
    130                 135                 140                 


Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
145                 150                 155                 160 


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
                165                 170                 175     


Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
            180                 185                 190         


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
        195                 200                 205             


Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
    210                 215                 220                 


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
225                 230                 235                 240 


Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
                245                 250                 255     


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr 
            260                 265                 270         


Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 
        275                 280                 285             


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
    290                 295                 300                 


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
305                 310                 315                 320 


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
                325                 330                 335     


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
            340                 345                 350         


Ser Leu Ser Leu Ser Pro Gly Lys 
        355                 360 


<210>  21
<211>  335
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Processed ActRIIB-Fc fusion protein with the N-terminal 6 amino 
       acids of the EC domain deleted and the C-terminal 3 amino acids 
       of the EC domain deleted (amino acids 25-131 of SEQ ID NO:3) and 
       with an L79D mutation

<400>  21

Glu Thr Arg Glu Cys Ile Tyr Tyr Asn Ala Asn Trp Glu Leu Glu Arg 
1               5                   10                  15      


Thr Asn Gln Ser Gly Leu Glu Arg Cys Glu Gly Glu Gln Asp Lys Arg 
            20                  25                  30          


Leu His Cys Tyr Ala Ser Trp Ala Asn Ser Ser Gly Thr Ile Glu Leu 
        35                  40                  45              


Val Lys Lys Gly Cys Trp Asp Asp Asp Phe Asn Cys Tyr Asp Arg Gln 
    50                  55                  60                  


Glu Cys Val Ala Thr Glu Glu Asn Pro Gln Val Tyr Phe Cys Cys Cys 
65                  70                  75                  80  


Glu Gly Asn Phe Cys Asn Glu Arg Phe Thr His Leu Pro Glu Ala Gly 
                85                  90                  95      


Gly Pro Glu Val Thr Tyr Glu Pro Pro Pro Thr Gly Gly Gly Thr His 
            100                 105                 110         


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


Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
    130                 135                 140                 


Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
145                 150                 155                 160 


Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
                165                 170                 175     


Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
            180                 185                 190         


Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
        195                 200                 205             


Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
    210                 215                 220                 


Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
225                 230                 235                 240 


Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
                245                 250                 255     


Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
            260                 265                 270         


Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
        275                 280                 285             


Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
    290                 295                 300                 


Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
305                 310                 315                 320 


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                325                 330                 335 


<210>  22
<211>  115
<212>  PRT
<213>  Homo sapiens

<220>
<223>  human ActRIIB soluble (extracellular), processed polypeptide 
       sequence (amino acids 20-134 of SEQ ID NO:14) with L79D mutation

<400>  22

Gly Arg Gly Glu Ala Glu Thr Arg Glu Cys Ile Tyr Tyr Asn Ala Asn 
1               5                   10                  15      


Trp Glu Leu Glu Arg Thr Asn Gln Ser Gly Leu Glu Arg Cys Glu Gly 
            20                  25                  30          


Glu Gln Asp Lys Arg Leu His Cys Tyr Ala Ser Trp Arg Asn Ser Ser 
        35                  40                  45              


Gly Thr Ile Glu Leu Val Lys Lys Gly Cys Trp Asp Asp Asp Phe Asn 
    50                  55                  60                  


Cys Tyr Asp Arg Gln Glu Cys Val Ala Thr Glu Glu Asn Pro Gln Val 
65                  70                  75                  80  


Tyr Phe Cys Cys Cys Glu Gly Asn Phe Cys Asn Glu Arg Phe Thr His 
                85                  90                  95      


Leu Pro Glu Ala Gly Gly Pro Glu Val Thr Tyr Glu Pro Pro Pro Thr 
            100                 105                 110         


Ala Pro Thr 
        115 


<210>  23
<211>  115
<212>  PRT
<213>  Homo sapiens

<220>
<223>  human ActRIIB soluble (extracellular), processed polypeptide 
       sequence (amino acids 20-134 of SEQ ID NO:3) with L79D mutation

<400>  23

Gly Arg Gly Glu Ala Glu Thr Arg Glu Cys Ile Tyr Tyr Asn Ala Asn 
1               5                   10                  15      


Trp Glu Leu Glu Arg Thr Asn Gln Ser Gly Leu Glu Arg Cys Glu Gly 
            20                  25                  30          


Glu Gln Asp Lys Arg Leu His Cys Tyr Ala Ser Trp Ala Asn Ser Ser 
        35                  40                  45              


Gly Thr Ile Glu Leu Val Lys Lys Gly Cys Trp Asp Asp Asp Phe Asn 
    50                  55                  60                  


Cys Tyr Asp Arg Gln Glu Cys Val Ala Thr Glu Glu Asn Pro Gln Val 
65                  70                  75                  80  


Tyr Phe Cys Cys Cys Glu Gly Asn Phe Cys Asn Glu Arg Phe Thr His 
                85                  90                  95      


Leu Pro Glu Ala Gly Gly Pro Glu Val Thr Tyr Glu Pro Pro Pro Thr 
            100                 105                 110         


Ala Pro Thr 
        115 


<210>  24
<211>  343
<212>  PRT
<213>  Homo sapiens

<220>
<223>  human ActRIIB soluble (extracellular), processed polypeptide 
       sequence (amino acids 20-134 of SEQ ID NO:14) with L79D mutation 
       fused to an Fc domain with a GGG linker

<400>  24

Gly Arg Gly Glu Ala Glu Thr Arg Glu Cys Ile Tyr Tyr Asn Ala Asn 
1               5                   10                  15      


Trp Glu Leu Glu Arg Thr Asn Gln Ser Gly Leu Glu Arg Cys Glu Gly 
            20                  25                  30          


Glu Gln Asp Lys Arg Leu His Cys Tyr Ala Ser Trp Arg Asn Ser Ser 
        35                  40                  45              


Gly Thr Ile Glu Leu Val Lys Lys Gly Cys Trp Asp Asp Asp Phe Asn 
    50                  55                  60                  


Cys Tyr Asp Arg Gln Glu Cys Val Ala Thr Glu Glu Asn Pro Gln Val 
65                  70                  75                  80  


Tyr Phe Cys Cys Cys Glu Gly Asn Phe Cys Asn Glu Arg Phe Thr His 
                85                  90                  95      


Leu Pro Glu Ala Gly Gly Pro Glu Val Thr Tyr Glu Pro Pro Pro Thr 
            100                 105                 110         


Ala Pro Thr Gly Gly Gly Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
        115                 120                 125             


Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
    130                 135                 140                 


Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
145                 150                 155                 160 


Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
                165                 170                 175     


Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
            180                 185                 190         


Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
        195                 200                 205             


Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
    210                 215                 220                 


Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
225                 230                 235                 240 


Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 
                245                 250                 255     


Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
            260                 265                 270         


Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
        275                 280                 285             


Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
    290                 295                 300                 


Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
305                 310                 315                 320 


Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
                325                 330                 335     


Leu Ser Leu Ser Pro Gly Lys 
            340             


<210>  25
<211>  343
<212>  PRT
<213>  Homo sapiens

<220>
<223>  human ActRIIB soluble (extracellular), processed polypeptide 
       sequence (amino acids 20-134 of SEQ ID NO:3) with L79D mutation 
       fused to an Fc domain

<400>  25

Gly Arg Gly Glu Ala Glu Thr Arg Glu Cys Ile Tyr Tyr Asn Ala Asn 
1               5                   10                  15      


Trp Glu Leu Glu Arg Thr Asn Gln Ser Gly Leu Glu Arg Cys Glu Gly 
            20                  25                  30          


Glu Gln Asp Lys Arg Leu His Cys Tyr Ala Ser Trp Ala Asn Ser Ser 
        35                  40                  45              


Gly Thr Ile Glu Leu Val Lys Lys Gly Cys Trp Asp Asp Asp Phe Asn 
    50                  55                  60                  


Cys Tyr Asp Arg Gln Glu Cys Val Ala Thr Glu Glu Asn Pro Gln Val 
65                  70                  75                  80  


Tyr Phe Cys Cys Cys Glu Gly Asn Phe Cys Asn Glu Arg Phe Thr His 
                85                  90                  95      


Leu Pro Glu Ala Gly Gly Pro Glu Val Thr Tyr Glu Pro Pro Pro Thr 
            100                 105                 110         


Ala Pro Thr Gly Gly Gly Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
        115                 120                 125             


Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
    130                 135                 140                 


Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
145                 150                 155                 160 


Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
                165                 170                 175     


Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
            180                 185                 190         


Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
        195                 200                 205             


Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
    210                 215                 220                 


Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
225                 230                 235                 240 


Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 
                245                 250                 255     


Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
            260                 265                 270         


Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
        275                 280                 285             


Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
    290                 295                 300                 


Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
305                 310                 315                 320 


Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
                325                 330                 335     


Leu Ser Leu Ser Pro Gly Lys 
            340             


<210>  26
<211>  368
<212>  PRT
<213>  Homo sapiens

<220>
<223>  human ActRIIB soluble (extracellular), processed polypeptide 
       sequence (amino acids 20-134 of SEQ ID NO:14) with L79D mutation 
       fused to an Fc domain and with TPA leader sequence

<400>  26

Met Asp Ala Met Lys Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly 
1               5                   10                  15      


Ala Val Phe Val Ser Pro Gly Ala Ser Gly Arg Gly Glu Ala Glu Thr 
            20                  25                  30          


Arg Glu Cys Ile Tyr Tyr Asn Ala Asn Trp Glu Leu Glu Arg Thr Asn 
        35                  40                  45              


Gln Ser Gly Leu Glu Arg Cys Glu Gly Glu Gln Asp Lys Arg Leu His 
    50                  55                  60                  


Cys Tyr Ala Ser Trp Arg Asn Ser Ser Gly Thr Ile Glu Leu Val Lys 
65                  70                  75                  80  


Lys Gly Cys Trp Asp Asp Asp Phe Asn Cys Tyr Asp Arg Gln Glu Cys 
                85                  90                  95      


Val Ala Thr Glu Glu Asn Pro Gln Val Tyr Phe Cys Cys Cys Glu Gly 
            100                 105                 110         


Asn Phe Cys Asn Glu Arg Phe Thr His Leu Pro Glu Ala Gly Gly Pro 
        115                 120                 125             


Glu Val Thr Tyr Glu Pro Pro Pro Thr Ala Pro Thr Gly Gly Gly Thr 
    130                 135                 140                 


His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser 
145                 150                 155                 160 


Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 
                165                 170                 175     


Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 
            180                 185                 190         


Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
        195                 200                 205             


Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 
    210                 215                 220                 


Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
225                 230                 235                 240 


Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 
                245                 250                 255     


Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
            260                 265                 270         


Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys 
        275                 280                 285             


Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
    290                 295                 300                 


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
305                 310                 315                 320 


Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 
                325                 330                 335     


Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
            340                 345                 350         


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
        355                 360                 365             


<210>  27
<211>  368
<212>  PRT
<213>  Homo sapiens

<220>
<223>  human ActRIIB soluble (extracellular), processed polypeptide 
       sequence (amino acids 20-134 of SEQ ID NO:3) with L79D mutation 
       fused to an Fc domain and with TPA leader sequence

<400>  27

Met Asp Ala Met Lys Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly 
1               5                   10                  15      


Ala Val Phe Val Ser Pro Gly Ala Ser Gly Arg Gly Glu Ala Glu Thr 
            20                  25                  30          


Arg Glu Cys Ile Tyr Tyr Asn Ala Asn Trp Glu Leu Glu Arg Thr Asn 
        35                  40                  45              


Gln Ser Gly Leu Glu Arg Cys Glu Gly Glu Gln Asp Lys Arg Leu His 
    50                  55                  60                  


Cys Tyr Ala Ser Trp Ala Asn Ser Ser Gly Thr Ile Glu Leu Val Lys 
65                  70                  75                  80  


Lys Gly Cys Trp Asp Asp Asp Phe Asn Cys Tyr Asp Arg Gln Glu Cys 
                85                  90                  95      


Val Ala Thr Glu Glu Asn Pro Gln Val Tyr Phe Cys Cys Cys Glu Gly 
            100                 105                 110         


Asn Phe Cys Asn Glu Arg Phe Thr His Leu Pro Glu Ala Gly Gly Pro 
        115                 120                 125             


Glu Val Thr Tyr Glu Pro Pro Pro Thr Ala Pro Thr Gly Gly Gly Thr 
    130                 135                 140                 


His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser 
145                 150                 155                 160 


Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 
                165                 170                 175     


Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 
            180                 185                 190         


Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
        195                 200                 205             


Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 
    210                 215                 220                 


Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
225                 230                 235                 240 


Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 
                245                 250                 255     


Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
            260                 265                 270         


Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys 
        275                 280                 285             


Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
    290                 295                 300                 


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
305                 310                 315                 320 


Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 
                325                 330                 335     


Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
            340                 345                 350         


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
        355                 360                 365             


<210>  28
<211>  141
<212>  PRT
<213>  Homo sapiens

<220>
<223>  human ActRIIB soluble (extracellular), processed polypeptide 
       sequence having a variant C-terminal sequence (disclosed in 
       WO2007/053775)

<400>  28

Gly Arg Gly Glu Ala Glu Thr Arg Glu Cys Ile Tyr Tyr Asn Ala Asn 
1               5                   10                  15      


Trp Glu Leu Glu Arg Thr Asn Gln Ser Gly Leu Glu Arg Cys Glu Gly 
            20                  25                  30          


Glu Gln Asp Lys Arg Leu His Cys Tyr Ala Ser Trp Arg Asn Ser Ser 
        35                  40                  45              


Gly Thr Ile Glu Leu Val Lys Lys Gly Cys Trp Leu Asp Asp Phe Asn 
    50                  55                  60                  


Cys Tyr Asp Arg Gln Glu Cys Val Ala Thr Glu Glu Asn Pro Gln Val 
65                  70                  75                  80  


Tyr Phe Cys Cys Cys Glu Gly Asn Phe Cys Asn Glu Arg Phe Thr His 
                85                  90                  95      


Leu Pro Glu Ala Gly Gly Pro Glu Gly Pro Trp Ala Ser Thr Thr Ile 
            100                 105                 110         


Pro Ser Gly Gly Pro Glu Ala Thr Ala Ala Ala Gly Asp Gln Gly Ser 
        115                 120                 125             


Gly Ala Leu Trp Leu Cys Leu Glu Gly Pro Ala His Glu 
    130                 135                 140     


<210>  29
<211>  141
<212>  PRT
<213>  Homo sapiens

<220>
<223>  human ActRIIB soluble (extracellular), processed polypeptide 
       sequence having a variant C-terminal sequence (disclosed in 
       WO2007/053775) having an L79D mutation

<400>  29

Gly Arg Gly Glu Ala Glu Thr Arg Glu Cys Ile Tyr Tyr Asn Ala Asn 
1               5                   10                  15      


Trp Glu Leu Glu Arg Thr Asn Gln Ser Gly Leu Glu Arg Cys Glu Gly 
            20                  25                  30          


Glu Gln Asp Lys Arg Leu His Cys Tyr Ala Ser Trp Arg Asn Ser Ser 
        35                  40                  45              


Gly Thr Ile Glu Leu Val Lys Lys Gly Cys Trp Asp Asp Asp Phe Asn 
    50                  55                  60                  


Cys Tyr Asp Arg Gln Glu Cys Val Ala Thr Glu Glu Asn Pro Gln Val 
65                  70                  75                  80  


Tyr Phe Cys Cys Cys Glu Gly Asn Phe Cys Asn Glu Arg Phe Thr His 
                85                  90                  95      


Leu Pro Glu Ala Gly Gly Pro Glu Gly Pro Trp Ala Ser Thr Thr Ile 
            100                 105                 110         


Pro Ser Gly Gly Pro Glu Ala Thr Ala Ala Ala Gly Asp Gln Gly Ser 
        115                 120                 125             


Gly Ala Leu Trp Leu Cys Leu Glu Gly Pro Ala His Glu 
    130                 135                 140     


<210>  30
<211>  370
<212>  PRT
<213>  Homo sapiens

<220>
<223>  human ActRIIB soluble (extracellular), processed polypeptide 
       sequence having a variant C-terminal sequence (disclosed in 
       WO2007/053775) having an L79D mutation fused to an Fc domain with
       a TGGG linker

<400>  30

Gly Arg Gly Glu Ala Glu Thr Arg Glu Cys Ile Tyr Tyr Asn Ala Asn 
1               5                   10                  15      


Trp Glu Leu Glu Arg Thr Asn Gln Ser Gly Leu Glu Arg Cys Glu Gly 
            20                  25                  30          


Glu Gln Asp Lys Arg Leu His Cys Tyr Ala Ser Trp Arg Asn Ser Ser 
        35                  40                  45              


Gly Thr Ile Glu Leu Val Lys Lys Gly Cys Trp Asp Asp Asp Phe Asn 
    50                  55                  60                  


Cys Tyr Asp Arg Gln Glu Cys Val Ala Thr Glu Glu Asn Pro Gln Val 
65                  70                  75                  80  


Tyr Phe Cys Cys Cys Glu Gly Asn Phe Cys Asn Glu Arg Phe Thr His 
                85                  90                  95      


Leu Pro Glu Ala Gly Gly Pro Glu Gly Pro Trp Ala Ser Thr Thr Ile 
            100                 105                 110         


Pro Ser Gly Gly Pro Glu Ala Thr Ala Ala Ala Gly Asp Gln Gly Ser 
        115                 120                 125             


Gly Ala Leu Trp Leu Cys Leu Glu Gly Pro Ala His Glu Thr Gly Gly 
    130                 135                 140                 


Gly Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
145                 150                 155                 160 


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


Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
            180                 185                 190         


Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
        195                 200                 205             


Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 
    210                 215                 220                 


Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
225                 230                 235                 240 


Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                245                 250                 255     


Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
            260                 265                 270         


Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
        275                 280                 285             


Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
    290                 295                 300                 


Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
305                 310                 315                 320 


Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                325                 330                 335     


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
            340                 345                 350         


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
        355                 360                 365             


Gly Lys 
    370 


<210>  31
<211>  1083
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Nucleic Acid Sequence Encoding SEQ ID NO:10

<400>  31
atggatgcaa tgaagagagg gctctgctgt gtgctgctgc tgtgtggagc agtcttcgtt       60

tcgcccggcg ccgccgaaac ccgcgaatgt atttattaca atgctaattg ggaactcgaa      120

cggacgaacc aatccgggct cgaacggtgt gagggggaac aggataaacg cctccattgc      180

tatgcgtcgt ggaggaactc ctccgggacg attgaactgg tcaagaaagg gtgctgggac      240

gacgatttca attgttatga ccgccaggaa tgtgtcgcga ccgaagagaa tccgcaggtc      300

tatttctgtt gttgcgaggg gaatttctgt aatgaacggt ttacccacct ccccgaagcc      360

ggcgggcccg aggtgaccta tgaacccccg cccaccggtg gtggaactca cacatgccca      420

ccgtgcccag cacctgaact cctgggggga ccgtcagtct tcctcttccc cccaaaaccc      480

aaggacaccc tcatgatctc ccggacccct gaggtcacat gcgtggtggt ggacgtgagc      540

cacgaagacc ctgaggtcaa gttcaactgg tacgtggacg gcgtggaggt gcataatgcc      600

aagacaaagc cgcgggagga gcagtacaac agcacgtacc gtgtggtcag cgtcctcacc      660

gtcctgcacc aggactggct gaatggcaag gagtacaagt gcaaggtctc caacaaagcc      720

ctcccagccc ccatcgagaa aaccatctcc aaagccaaag ggcagccccg agaaccacag      780

gtgtacaccc tgcccccatc ccgggaggag atgaccaaga accaggtcag cctgacctgc      840

ctggtcaaag gcttctatcc cagcgacatc gccgtggagt gggagagcaa tgggcagccg      900

gagaacaact acaagaccac gcctcccgtg ctggactccg acggctcctt cttcctctat      960

agcaagctca ccgtggacaa gagcaggtgg cagcagggga acgtcttctc atgctccgtg     1020

atgcatgagg ctctgcacaa ccactacacg cagaagagcc tctccctgtc cccgggtaaa     1080

tga                                                                   1083


<210>  32
<211>  344
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  fusion protein comprising a soluble extracellular domain of 
       ActRIIB (R64; SEQ ID NO:15) fused to an Fc domain

<400>  32

Ser Gly Arg Gly Glu Ala Glu Thr Arg Glu Cys Ile Tyr Tyr Asn Ala 
1               5                   10                  15      


Asn Trp Glu Leu Glu Arg Thr Asn Gln Ser Gly Leu Glu Arg Cys Glu 
            20                  25                  30          


Gly Glu Gln Asp Lys Arg Leu His Cys Tyr Ala Ser Trp Arg Asn Ser 
        35                  40                  45              


Ser Gly Thr Ile Glu Leu Val Lys Lys Gly Cys Trp Leu Asp Asp Phe 
    50                  55                  60                  


Asn Cys Tyr Asp Arg Gln Glu Cys Val Ala Thr Glu Glu Asn Pro Gln 
65                  70                  75                  80  


Val Tyr Phe Cys Cys Cys Glu Gly Asn Phe Cys Asn Glu Arg Phe Thr 
                85                  90                  95      


His Leu Pro Glu Ala Gly Gly Pro Glu Val Thr Tyr Glu Pro Pro Pro 
            100                 105                 110         


Thr Ala Pro Thr Gly Gly Gly Thr His Thr Cys Pro Pro Cys Pro Ala 
        115                 120                 125             


Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
    130                 135                 140                 


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
145                 150                 155                 160 


Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
                165                 170                 175     


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
            180                 185                 190         


Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
        195                 200                 205             


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
    210                 215                 220                 


Leu Pro Val Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
225                 230                 235                 240 


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr 
                245                 250                 255     


Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 
            260                 265                 270         


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


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
    290                 295                 300                 


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
305                 310                 315                 320 


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
                325                 330                 335     


Ser Leu Ser Leu Ser Pro Gly Lys 
            340                 


<210>  33
<211>  329
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  fusion protein comprising a soluble extracellular domain of 
       ActRIIB (R64) with the C-terminal 15 amino acids deleted (SEQ ID 
       NO:16) fused to an Fc domain

<400>  33

Ser Gly Arg Gly Glu Ala Glu Thr Arg Glu Cys Ile Tyr Tyr Asn Ala 
1               5                   10                  15      


Asn Trp Glu Leu Glu Arg Thr Asn Gln Ser Gly Leu Glu Arg Cys Glu 
            20                  25                  30          


Gly Glu Gln Asp Lys Arg Leu His Cys Tyr Ala Ser Trp Arg Asn Ser 
        35                  40                  45              


Ser Gly Thr Ile Glu Leu Val Lys Lys Gly Cys Trp Leu Asp Asp Phe 
    50                  55                  60                  


Asn Cys Tyr Asp Arg Gln Glu Cys Val Ala Thr Glu Glu Asn Pro Gln 
65                  70                  75                  80  


Val Tyr Phe Cys Cys Cys Glu Gly Asn Phe Cys Asn Glu Arg Phe Thr 
                85                  90                  95      


His Leu Pro Glu Ala Gly Gly Gly Thr His Thr Cys Pro Pro Cys Pro 
            100                 105                 110         


Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
        115                 120                 125             


Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
    130                 135                 140                 


Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
145                 150                 155                 160 


Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
                165                 170                 175     


Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
            180                 185                 190         


Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
        195                 200                 205             


Ala Leu Pro Val Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
    210                 215                 220                 


Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met 
225                 230                 235                 240 


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


Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
            260                 265                 270         


Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
        275                 280                 285             


Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
    290                 295                 300                 


Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
305                 310                 315                 320 


Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                325                 


<210>  34
<211>  344
<212>  PRT
<213>  Homo sapiens

<220>
<223>  Extracellular domain of human ActRIIA fused to a human Fc domain

<400>  34

Ile Leu Gly Arg Ser Glu Thr Gln Glu Cys Leu Phe Phe Asn Ala Asn 
1               5                   10                  15      


Trp Glu Lys Asp Arg Thr Asn Gln Thr Gly Val Glu Pro Cys Tyr Gly 
            20                  25                  30          


Asp Lys Asp Lys Arg Arg His Cys Phe Ala Thr Trp Lys Asn Ile Ser 
        35                  40                  45              


Gly Ser Ile Glu Ile Val Lys Gln Gly Cys Trp Leu Asp Asp Ile Asn 
    50                  55                  60                  


Cys Tyr Asp Arg Thr Asp Cys Val Glu Lys Lys Asp Ser Pro Glu Val 
65                  70                  75                  80  


Tyr Phe Cys Cys Cys Glu Gly Asn Met Cys Asn Glu Lys Phe Ser Tyr 
                85                  90                  95      


Phe Pro Glu Met Glu Val Thr Gln Pro Thr Ser Asn Pro Val Thr Pro 
            100                 105                 110         


Lys Pro Pro Thr Gly Gly Gly Thr His Thr Cys Pro Pro Cys Pro Ala 
        115                 120                 125             


Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
    130                 135                 140                 


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
145                 150                 155                 160 


Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
                165                 170                 175     


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
            180                 185                 190         


Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
        195                 200                 205             


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
    210                 215                 220                 


Leu Pro Val Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
225                 230                 235                 240 


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr 
                245                 250                 255     


Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 
            260                 265                 270         


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


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
    290                 295                 300                 


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
305                 310                 315                 320 


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
                325                 330                 335     


Ser Leu Ser Leu Ser Pro Gly Lys 
            340                 


