ID   GDF8_MOUSE              Reviewed;         376 AA.
AC   O08689;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1997, sequence version 1.
DT   14-OCT-2015, entry version 117.
DE   RecName: Full=Growth/differentiation factor 8;
DE            Short=GDF-8;
DE   AltName: Full=Myostatin;
DE   Flags: Precursor;
GN   Name=Mstn; Synonyms=Gdf8;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC   Muroidea; Muridae; Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=CD-1; TISSUE=Skeletal muscle;
RX   PubMed=9139826; DOI=10.1038/387083a0;
RA   McPherron A.C., Lawler A.M., Lee S.-J.;
RT   "Regulation of skeletal muscle mass in mice by a new TGF-beta
RT   superfamily member.";
RL   Nature 387:83-90(1997).
RN   [2]
RP   INTERACTION WITH WFIKKN2.
RX   PubMed=12595574; DOI=10.1210/me.2002-0366;
RA   Hill J.J., Qiu Y., Hewick R.M., Wolfman N.M.;
RT   "Regulation of myostatin in vivo by growth and differentiation factor-
RT   associated serum protein-1: a novel protein with protease inhibitor
RT   and follistatin domains.";
RL   Mol. Endocrinol. 17:1144-1154(2003).
RN   [3]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=24076600; DOI=10.1038/ng.2772;
RA   Sartori R., Schirwis E., Blaauw B., Bortolanza S., Zhao J., Enzo E.,
RA   Stantzou A., Mouisel E., Toniolo L., Ferry A., Stricker S.,
RA   Goldberg A.L., Dupont S., Piccolo S., Amthor H., Sandri M.;
RT   "BMP signaling controls muscle mass.";
RL   Nat. Genet. 45:1309-1318(2013).
RN   [4]
RP   X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 268-376 IN COMPLEX WITH
RP   HUMAN FOLLISTATIN, HEPARIN-BINDING, AND DISULFIDE BONDS.
RX   PubMed=19644449; DOI=10.1038/emboj.2009.205;
RA   Cash J.N., Rejon C.A., McPherron A.C., Bernard D.J., Thompson T.B.;
RT   "The structure of myostatin:follistatin 288: insights into receptor
RT   utilization and heparin binding.";
RL   EMBO J. 28:2662-2676(2009).
RN   [5]
RP   X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 268-376 IN COMPLEX WITH HUMAN
RP   FSTL3, AND DISULFIDE BONDS.
RX   PubMed=22052913; DOI=10.1074/jbc.M111.270801;
RA   Cash J.N., Angerman E.B., Kattamuri C., Nolan K., Zhao H., Sidis Y.,
RA   Keutmann H.T., Thompson T.B.;
RT   "Structure of myostatin.follistatin-like 3: N-terminal domains of
RT   follistatin-type molecules exhibit alternate modes of binding.";
RL   J. Biol. Chem. 287:1043-1053(2012).
CC   -!- FUNCTION: Acts specifically as a negative regulator of skeletal
CC       muscle growth.
CC   -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Interacts
CC       with WFIKKN2, leading to inhibit its activity. Interacts with FST3
CC       (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Expressed specifically in developing and adult
CC       skeletal muscle. Weak expression in adipose tissue.
CC   -!- DEVELOPMENTAL STAGE: First detected 9.5 dpc in one-third of
CC       developing somites. At 10.5 dpc, expressed in the myotome
CC       compartment of somites. At later stages of development, detected
CC       in a wide range of developing muscles. Expression continues in
CC       adulthood.
CC   -!- DISRUPTION PHENOTYPE: Mutant animals exhibit muscle hypertrophy.
CC       {ECO:0000269|PubMed:24076600}.
CC   -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
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DR   EMBL; U84005; AAC53167.1; -; mRNA.
DR   CCDS; CCDS14950.1; -.
DR   RefSeq; NP_034964.1; NM_010834.2.
DR   UniGene; Mm.3514; -.
DR   PDB; 3HH2; X-ray; 2.15 A; A/B=268-376.
DR   PDB; 3SEK; X-ray; 2.40 A; B=268-376.
DR   PDBsum; 3HH2; -.
DR   PDBsum; 3SEK; -.
DR   ProteinModelPortal; O08689; -.
DR   SMR; O08689; 50-376.
DR   BioGrid; 201535; 1.
DR   IntAct; O08689; 4.
DR   MINT; MINT-7914794; -.
DR   STRING; 10090.ENSMUSP00000027269; -.
DR   PhosphoSite; O08689; -.
DR   MaxQB; O08689; -.
DR   PaxDb; O08689; -.
DR   PRIDE; O08689; -.
DR   GeneID; 17700; -.
DR   KEGG; mmu:17700; -.
DR   UCSC; uc007ayt.1; mouse.
DR   CTD; 2660; -.
DR   MGI; MGI:95691; Mstn.
DR   eggNOG; NOG310007; -.
DR   HOGENOM; HOG000006566; -.
DR   HOVERGEN; HBG000217; -.
DR   InParanoid; O08689; -.
DR   KO; K05497; -.
DR   OMA; NPFLEVR; -.
DR   OrthoDB; EOG74R1Q4; -.
DR   PhylomeDB; O08689; -.
DR   TreeFam; TF318514; -.
DR   EvolutionaryTrace; O08689; -.
DR   NextBio; 292290; -.
DR   PRO; PR:O08689; -.
DR   Proteomes; UP000000589; Unplaced.
DR   Bgee; O08689; -.
DR   CleanEx; MM_MSTN; -.
DR   ExpressionAtlas; O08689; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR   GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0005102; F:receptor binding; IPI:MGI.
DR   GO; GO:0005160; F:transforming growth factor beta receptor binding; IBA:GO_Central.
DR   GO; GO:0098779; P:activation of mitophagy in response to mitochondrial depolarization; ISO:MGI.
DR   GO; GO:0048468; P:cell development; IBA:GO_Central.
DR   GO; GO:0071549; P:cellular response to dexamethasone stimulus; IDA:MGI.
DR   GO; GO:0046716; P:muscle cell cellular homeostasis; ISO:MGI.
DR   GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IMP:CACAO.
DR   GO; GO:0033673; P:negative regulation of kinase activity; IMP:CACAO.
DR   GO; GO:0014741; P:negative regulation of muscle hypertrophy; IEA:Ensembl.
DR   GO; GO:0045662; P:negative regulation of myoblast differentiation; ISO:MGI.
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:MGI.
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:CACAO.
DR   GO; GO:0022602; P:ovulation cycle process; IEA:Ensembl.
DR   GO; GO:0002230; P:positive regulation of defense response to virus by host; ISO:MGI.
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:MGI.
DR   GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central.
DR   GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
DR   GO; GO:0051602; P:response to electrical stimulus; IEA:Ensembl.
DR   GO; GO:0043627; P:response to estrogen; IEA:Ensembl.
DR   GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR   GO; GO:0009629; P:response to gravity; IEA:Ensembl.
DR   GO; GO:0009408; P:response to heat; IEA:Ensembl.
DR   GO; GO:0014850; P:response to muscle activity; IEA:Ensembl.
DR   GO; GO:0033574; P:response to testosterone; IEA:Ensembl.
DR   GO; GO:0014732; P:skeletal muscle atrophy; IMP:CACAO.
DR   GO; GO:0043403; P:skeletal muscle tissue regeneration; 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; IDA:MGI.
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_N.
DR   InterPro; IPR015615; TGF-beta-rel.
DR   InterPro; IPR017948; TGFb_CS.
DR   PANTHER; PTHR11848; PTHR11848; 1.
DR   PANTHER; PTHR11848:SF13; PTHR11848:SF13; 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   3D-structure; Cleavage on pair of basic residues; Complete proteome;
KW   Cytokine; Disulfide bond; Glycoprotein; Growth factor;
KW   Heparin-binding; Reference proteome; Secreted; Signal.
FT   SIGNAL        1     24       {ECO:0000255}.
FT   PROPEP       25    267       {ECO:0000255}.
FT                                /FTId=PRO_0000033956.
FT   CHAIN       268    376       Growth/differentiation factor 8.
FT                                /FTId=PRO_0000033957.
FT   CARBOHYD     72     72       N-linked (GlcNAc...). {ECO:0000255}.
FT   DISULFID    282    341
FT   DISULFID    310    373
FT   DISULFID    314    375
FT   DISULFID    340    340       Interchain.
FT   STRAND      281    285       {ECO:0000244|PDB:3HH2}.
FT   STRAND      288    290       {ECO:0000244|PDB:3HH2}.
FT   HELIX       291    294       {ECO:0000244|PDB:3HH2}.
FT   STRAND      299    301       {ECO:0000244|PDB:3HH2}.
FT   STRAND      303    306       {ECO:0000244|PDB:3HH2}.
FT   STRAND      309    311       {ECO:0000244|PDB:3HH2}.
FT   TURN        316    319       {ECO:0000244|PDB:3HH2}.
FT   HELIX       324    331       {ECO:0000244|PDB:3HH2}.
FT   STRAND      340    354       {ECO:0000244|PDB:3HH2}.
FT   STRAND      360    376       {ECO:0000244|PDB:3HH2}.
SQ   SEQUENCE   376 AA;  42921 MW;  3E19814DD62C08BE CRC64;
     MMQKLQMYVY IYLFMLIAAG PVDLNEGSER EENVEKEGLC NACAWRQNTR YSRIEAIKIQ
     ILSKLRLETA PNISKDAIRQ LLPRAPPLRE LIDQYDVQRD DSSDGSLEDD DYHATTETII
     TMPTESDFLM QADGKPKCCF FKFSSKIQYN KVVKAQLWIY LRPVKTPTTV FVQILRLIKP
     MKDGTRYTGI RSLKLDMSPG TGIWQSIDVK TVLQNWLKQP ESNLGIEIKA LDENGHDLAV
     TFPGPGEDGL NPFLEVKVTD TPKRSRRDFG LDCDEHSTES RCCRYPLTVD FEAFGWDWII
     APKRYKANYC SGECEFVFLQ KYPHTHLVHQ ANPRGSAGPC CTPTKMSPIN MLYFNGKEQI
     IYGKIPAMVV DRCGCS
//