ID   GDF8_HEMJE              Reviewed;         375 AA.
AC   Q5USV8;
DT   12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT   07-DEC-2004, sequence version 1.
DT   25-MAY-2022, entry version 52.
DE   RecName: Full=Growth/differentiation factor 8;
DE            Short=GDF-8;
DE   AltName: Full=Myostatin;
DE   Flags: Precursor;
GN   Name=MSTN; Synonyms=GDF8;
OS   Hemitragus jemlahicus (Himalayan tahr).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Caprinae; Hemitragus.
OX   NCBI_TaxID=37179;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=15522803; DOI=10.1016/j.ympev.2004.07.004;
RA   Tellgren S., Berglund A.C., Savolainen P., Janis C.M., Liberles D.A.;
RT   "Myostatin rapid sequence evolution in ruminants predates domestication.";
RL   Mol. Phylogenet. Evol. 33:782-790(2004).
CC   -!- FUNCTION: Acts specifically as a negative regulator of skeletal muscle
CC       growth. {ECO:0000250|UniProtKB:O08689}.
CC   -!- SUBUNIT: Homodimer; disulfide-linked. Interacts with WFIKKN2, leading
CC       to inhibit its activity. Interacts with FSTL3.
CC       {ECO:0000250|UniProtKB:O08689}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:O08689}.
CC   -!- PTM: Synthesized as large precursor molecule that undergoes proteolytic
CC       cleavage to generate an N-terminal propeptide and a disulfide linked C-
CC       terminal dimer, which is the biologically active molecule. The
CC       circulating form consists of a latent complex of the C-terminal dimer
CC       and other proteins, including its propeptide, which maintain the C-
CC       terminal dimer in a latent, inactive state. Ligand activation requires
CC       additional cleavage of the prodomain by a tolloid-like
CC       metalloproteinase. {ECO:0000250|UniProtKB:O08689}.
CC   -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
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DR   EMBL; AY629306; AAT40570.1; -; mRNA.
DR   AlphaFoldDB; Q5USV8; -.
DR   SMR; Q5USV8; -.
DR   GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR   GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR   GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR   GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR   GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR   GO; GO:0014839; P:myoblast migration involved in skeletal muscle regeneration; ISS:UniProtKB.
DR   GO; GO:0010592; P:positive regulation of lamellipodium assembly; ISS:UniProtKB.
DR   GO; GO:0010759; P:positive regulation of macrophage chemotaxis; ISS:UniProtKB.
DR   Gene3D; 2.10.90.10; -; 1.
DR   InterPro; IPR029034; Cystine-knot_cytokine.
DR   InterPro; IPR015616; GDF_8.
DR   InterPro; IPR001839; TGF-b_C.
DR   InterPro; IPR001111; TGF-b_propeptide.
DR   InterPro; IPR015615; TGF-beta-rel.
DR   InterPro; IPR017948; TGFb_CS.
DR   PANTHER; PTHR11848; PTHR11848; 1.
DR   PANTHER; PTHR11848:SF150; PTHR11848:SF150; 1.
DR   Pfam; PF00019; TGF_beta; 1.
DR   Pfam; PF00688; TGFb_propeptide; 1.
DR   SMART; SM00204; TGFB; 1.
DR   SUPFAM; SSF57501; SSF57501; 1.
DR   PROSITE; PS00250; TGF_BETA_1; 1.
DR   PROSITE; PS51362; TGF_BETA_2; 1.
PE   2: Evidence at transcript level;
KW   Cleavage on pair of basic residues; Cytokine; Disulfide bond; Glycoprotein;
KW   Growth factor; Heparin-binding; Secreted; Signal.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000255"
FT   PROPEP          19..266
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000033946"
FT   CHAIN           267..375
FT                   /note="Growth/differentiation factor 8"
FT                   /id="PRO_0000033947"
FT   SITE            98..99
FT                   /note="Cleavage"
FT                   /evidence="ECO:0000250|UniProtKB:O08689"
FT   CARBOHYD        48
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        71
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        272..282
FT                   /evidence="ECO:0000250|UniProtKB:O14793"
FT   DISULFID        281..340
FT                   /evidence="ECO:0000250|UniProtKB:O14793"
FT   DISULFID        309..372
FT                   /evidence="ECO:0000250|UniProtKB:O14793"
FT   DISULFID        313..374
FT                   /evidence="ECO:0000250|UniProtKB:O14793"
FT   DISULFID        339
FT                   /note="Interchain"
FT                   /evidence="ECO:0000250|UniProtKB:O14793"
SQ   SEQUENCE   375 AA;  42827 MW;  1C36F3833BB11241 CRC64;
     MQKLQIFVYI YLFMLLVAGP VDLNENSEQK ENVEKKGLCN ACLWRQNNKS SRLEAIKIQI
     LSKLRLETAP NISKDAIRQL LPKAPPLREL IDQYDVQRDD SSDGSLEDDD YHVTTETVIT
     MPTESDLLAE VQEKPKCCFF KFSSKIQHNK VVKAQLWIYL RPVKTPTTVF VQILRLIKPM
     KDGTRYTGIR SLKLDMNPGT GIWQSIDVKT VLQNWLKQPE SNLGIEIKAL DENGHDLAVT
     FPEPGEEGLN PFLEVKVTDT PKRSRRDFGL DCDEHSTESR CCRYPLTVDF EAFGWDWIIA
     PKRYKANYCS GECEFLFLQK YPHTHLVHQA NPKGSAGPCC TPTKMSPINM LYFNGKEQII
     YGKIPGMVVD RCGCS