GDF8_RAT
ID GDF8_RAT Reviewed; 376 AA.
AC O35312;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Growth/differentiation factor 8;
DE Short=GDF-8;
DE AltName: Full=Myostatin;
DE Flags: Precursor;
GN Name=Mstn; Synonyms=Gdf8;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC 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).
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; AF019624; AAB86691.1; -; mRNA.
DR RefSeq; NP_062024.1; NM_019151.1.
DR AlphaFoldDB; O35312; -.
DR SMR; O35312; -.
DR STRING; 10116.ENSRNOP00000038159; -.
DR GlyGen; O35312; 1 site.
DR PaxDb; O35312; -.
DR PRIDE; O35312; -.
DR ABCD; O35312; 2 sequenced antibodies.
DR Ensembl; ENSRNOT00000038093; ENSRNOP00000038159; ENSRNOG00000021294.
DR GeneID; 29152; -.
DR KEGG; rno:29152; -.
DR UCSC; RGD:3115; rat.
DR CTD; 2660; -.
DR RGD; 3115; Mstn.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000160657; -.
DR HOGENOM; CLU_020515_6_1_1; -.
DR InParanoid; O35312; -.
DR OMA; QICVYIY; -.
DR OrthoDB; 892873at2759; -.
DR PhylomeDB; O35312; -.
DR TreeFam; TF318514; -.
DR PRO; PR:O35312; -.
DR Proteomes; UP000002494; Chromosome 9.
DR Bgee; ENSRNOG00000021294; Expressed in quadriceps femoris and 7 other tissues.
DR Genevisible; O35312; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
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; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0005102; F:signaling receptor binding; ISO:RGD.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; ISO:RGD.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; ISO:RGD.
DR GO; GO:0014839; P:myoblast migration involved in skeletal muscle regeneration; ISS:UniProtKB.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISO:RGD.
DR GO; GO:0033673; P:negative regulation of kinase activity; ISO:RGD.
DR GO; GO:0014741; P:negative regulation of muscle hypertrophy; IMP:RGD.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; ISO:RGD.
DR GO; GO:2000818; P:negative regulation of myoblast proliferation; ISS:AgBase.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; ISO:RGD.
DR GO; GO:1902725; P:negative regulation of satellite cell differentiation; ISS:AgBase.
DR GO; GO:1902723; P:negative regulation of skeletal muscle satellite cell proliferation; ISS:AgBase.
DR GO; GO:0048632; P:negative regulation of skeletal muscle tissue growth; IMP:RGD.
DR GO; GO:0022602; P:ovulation cycle process; IEP:RGD.
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; ISO:RGD.
DR GO; GO:0051602; P:response to electrical stimulus; IEP:RGD.
DR GO; GO:0043627; P:response to estrogen; IEP:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0051384; P:response to glucocorticoid; IEP:RGD.
DR GO; GO:0009629; P:response to gravity; IEP:RGD.
DR GO; GO:0009408; P:response to heat; IEP:RGD.
DR GO; GO:0014850; P:response to muscle activity; IEP:RGD.
DR GO; GO:0033574; P:response to testosterone; IEP:RGD.
DR GO; GO:0014732; P:skeletal muscle atrophy; IEP:RGD.
DR GO; GO:0043403; P:skeletal muscle tissue regeneration; IEP:RGD.
DR GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISO:RGD.
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; Reference proteome; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT PROPEP 25..267
FT /evidence="ECO:0000255"
FT /id="PRO_0000033962"
FT CHAIN 268..376
FT /note="Growth/differentiation factor 8"
FT /id="PRO_0000033963"
FT SITE 99..100
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:O08689"
FT CARBOHYD 72
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 273..283
FT /evidence="ECO:0000250|UniProtKB:O14793"
FT DISULFID 282..341
FT /evidence="ECO:0000250|UniProtKB:O14793"
FT DISULFID 310..373
FT /evidence="ECO:0000250|UniProtKB:O14793"
FT DISULFID 314..375
FT /evidence="ECO:0000250|UniProtKB:O14793"
FT DISULFID 340
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:O14793"
SQ SEQUENCE 376 AA; 42829 MW; 933043D8C8C3294B CRC64;
MIQKPQMYVY IYLFVLIAAG PVDLNEDSER EANVEKEGLC NACAWRQNTR YSRIEAIKIQ
ILSKLRLETA PNISKDAIRQ LLPRAPPLRE LIDQYDVQRD DSSDGSLEDD DYHATTETII
TMPTESDFLM QADGKPKCCF FKFSSKIQYN KVVKAQLWIY LRAVKTPTTV FVQILRLIKP
MKDGTRYTGI RSLKLDMSPG TGIWQSIDVK TVLQNWLKQP ESNLGIEIKA LDENGHDLAV
TFPGPGEDGL NPFLEVKVTD TPKRSRRDFG LDCDEHSTES RCCRYPLTVD FEAFGWDWII
APKRYKANYC SGECEFVFLQ KYPHTHLVHQ ANPRGSAGPC CTPTKMSPIN MLYFNGKEQI
IYGKIPAMVV DRCGCS
