GDF8_BOVIN
ID GDF8_BOVIN Reviewed; 375 AA.
AC O18836; A4IFF8; O18829; Q564D4; Q8WNS6; Q95N97;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 27-MAY-2002, sequence version 2.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Growth/differentiation factor 8;
DE Short=GDF-8;
DE AltName: Full=Myostatin;
DE Flags: Precursor;
GN Name=MSTN; Synonyms=GDF8, MH;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT MH TYR-313.
RC STRAIN=Friesian; TISSUE=Embryo, and Muscle;
RX PubMed=9314496; DOI=10.1101/gr.7.9.910;
RA Kambadur R., Sharma M., Smith T.P.L., Bass J.J.;
RT "Mutations in myostatin (GDF8) in double-muscled Belgian Blue and
RT Piedmontese cattle.";
RL Genome Res. 7:910-916(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS MH LEU-94 AND TYR-313.
RC STRAIN=Holstein; TISSUE=Skeletal muscle;
RX PubMed=9356471; DOI=10.1073/pnas.94.23.12457;
RA McPherron A.C., Lee S.-J.;
RT "Double muscling in cattle due to mutations in the myostatin gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:12457-12461(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11451380; DOI=10.1023/a:1010801511963;
RA Jeanplong F., Sharma M., Somers W.G., Bass J.J., Kambadur R.;
RT "Genomic organization and neonatal expression of the bovine myostatin
RT gene.";
RL Mol. Cell. Biochem. 220:31-37(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Japanese black;
RA Shibata M., Ohshima K., Kojima T., Muramoto T., Matsumoto K., Komatsu M.,
RA Aikawa K., Fujimura S., Kadowaki M.;
RT "Nucleotide sequence of myostatin gene and its developmental expression in
RT skeletal muscles of Japanese Black cattle.";
RL Anim. Sci. J. 74:383-390(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Korean;
RA Kim D.Y., Yoo S.L., Sang B.C., Cho K.W., Lee J.H.;
RT "Characterization of the bovine myostatin gene in Korean native cattle.";
RL Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Beefmaster;
RA De la Rosa X.F., Sifuentes A.M.;
RT "Nucleotide sequence determination and molecular characterization of GDF-8
RT gene from Beefmaster cattle.";
RL Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Basal ganglia;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases.
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 -!- TISSUE SPECIFICITY: Specifically expressed in developing and adult
CC skeletal muscle. Highest levels found in the hindlimb semimembranosus
CC and biceps-femoris muscles; low levels in other hindlimb muscles.
CC -!- DEVELOPMENTAL STAGE: Widely expressed throughout development. Low
CC levels are found up to day 29 embryos. Levels increase from day 31 up
CC until late gestation.
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 -!- DISEASE: Note=Defects in MSTN are the cause of the double-muscle
CC phenotype or muscular hypertrophy (mh), an autosomal recessive disease
CC frequently found in the Belgian blue and Piedmontese cattle breeds.
CC This disease is characterized by an increased number of muscle fibers
CC (hyperplasia), resulting in an increase in muscle mass of 20-25%.
CC {ECO:0000269|PubMed:9314496, ECO:0000269|PubMed:9356471}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
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DR EMBL; AF019761; AAB81508.1; -; mRNA.
DR EMBL; AF019620; AAB86687.1; -; mRNA.
DR EMBL; AF320998; AAG48116.1; -; Genomic_DNA.
DR EMBL; AB076403; BAB79498.1; -; Genomic_DNA.
DR EMBL; AY160688; AAN65183.1; -; mRNA.
DR EMBL; AY850105; AAX51855.1; -; Genomic_DNA.
DR EMBL; BC134563; AAI34564.1; -; mRNA.
DR RefSeq; NP_001001525.1; NM_001001525.3.
DR AlphaFoldDB; O18836; -.
DR SMR; O18836; -.
DR STRING; 9913.ENSBTAP00000015674; -.
DR PaxDb; O18836; -.
DR PRIDE; O18836; -.
DR Ensembl; ENSBTAT00000015674; ENSBTAP00000015674; ENSBTAG00000011808.
DR GeneID; 281187; -.
DR KEGG; bta:281187; -.
DR CTD; 2660; -.
DR VEuPathDB; HostDB:ENSBTAG00000011808; -.
DR VGNC; VGNC:31709; MSTN.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000160657; -.
DR HOGENOM; CLU_020515_6_1_1; -.
DR InParanoid; O18836; -.
DR OMA; QICVYIY; -.
DR OrthoDB; 892873at2759; -.
DR TreeFam; TF318514; -.
DR Proteomes; UP000009136; Chromosome 2.
DR Bgee; ENSBTAG00000011808; Expressed in rectus femoris and 39 other tissues.
DR ExpressionAtlas; O18836; baseline and differential.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
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:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; IEA:Ensembl.
DR GO; GO:0014839; P:myoblast migration involved in skeletal muscle regeneration; ISS:UniProtKB.
DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; IDA:CACAO.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0033673; P:negative regulation of kinase activity; IEA:Ensembl.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; IEA:Ensembl.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IEA:Ensembl.
DR GO; GO:0048632; P:negative regulation of skeletal muscle tissue growth; IEA:Ensembl.
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 GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IBA:GO_Central.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IEA:Ensembl.
DR GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IEA:Ensembl.
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 1: Evidence at protein level;
KW Cleavage on pair of basic residues; Cytokine; Disease variant;
KW Disulfide bond; Glycoprotein; Growth factor; Heparin-binding;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..266
FT /evidence="ECO:0000255"
FT /id="PRO_0000033936"
FT CHAIN 267..375
FT /note="Growth/differentiation factor 8"
FT /id="PRO_0000033937"
FT SITE 98..99
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:O08689"
FT CARBOHYD 47
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"
FT VARIANT 94
FT /note="F -> L (in mh; Piedmontese breed)"
FT /evidence="ECO:0000269|PubMed:9356471"
FT VARIANT 313
FT /note="C -> Y (in mh; Piedmontese breed)"
FT /evidence="ECO:0000269|PubMed:9314496,
FT ECO:0000269|PubMed:9356471"
FT CONFLICT 14
FT /note="M -> T (in Ref. 1; AAB81508)"
FT /evidence="ECO:0000305"
FT CONFLICT 214
FT /note="N -> S (in Ref. 4; BAB79498)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 375 AA; 42551 MW; 84E1AB20650C05F6 CRC64;
MQKLQISVYI YLFMLIVAGP VDLNENSEQK ENVEKEGLCN ACLWRENTTS SRLEAIKIQI
LSKLRLETAP NISKDAIRQL LPKAPPLLEL IDQFDVQRDA SSDGSLEDDD YHARTETVIT
MPTESDLLTQ VEGKPKCCFF KFSSKIQYNK LVKAQLWIYL RPVKTPATVF VQILRLIKPM
KDGTRYTGIR SLKLDMNPGT GIWQSIDVKT VLQNWLKQPE SNLGIEIKAL DENGHDLAVT
FPEPGEDGLT PFLEVKVTDT PKRSRRDFGL DCDEHSTESR CCRYPLTVDF EAFGWDWIIA
PKRYKANYCS GECEFVFLQK YPHTHLVHQA NPRGSAGPCC TPTKMSPINM LYFNGEGQII
YGKIPAMVVD RCGCS
