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Protein

Growth/differentiation factor 8

Gene

Mstn

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Acts specifically as a negative regulator of skeletal muscle growth.3 Publications

GO - Molecular functioni

  • cytokine activity Source: GO_Central
  • growth factor activity Source: UniProtKB-KW
  • heparin binding Source: UniProtKB
  • identical protein binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • receptor binding Source: MGI
  • transforming growth factor beta receptor binding Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionCytokine, Growth factor, Heparin-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Growth/differentiation factor 8
Short name:
GDF-8
Alternative name(s):
Myostatin
Gene namesi
Name:Mstn
Synonyms:Gdf8
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:95691. Mstn.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Disruption phenotypei

Mutant animals exhibit muscle hypertrophy.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi99R → Q: No effect on proteolytic cleavage. 1 Publication1
Mutagenesisi100D → A: Blocks proteolytic cleavage; increases muscle mass when injected into adult mice. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL3588736.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
PropeptideiPRO_000003395625 – 267Sequence analysisAdd BLAST243
ChainiPRO_0000033957268 – 376Growth/differentiation factor 8Add BLAST109

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi72N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi273 ↔ 283Combined sources2 Publications
Disulfide bondi282 ↔ 341Combined sources2 Publications
Disulfide bondi310 ↔ 373Combined sources2 Publications
Disulfide bondi314 ↔ 375Combined sources2 Publications
Disulfide bondi340InterchainCombined sources1 Publication

Post-translational modificationi

Synthesized as large precursor molecule that undergoes proteolytic cleavage to generate an N-terminal propeptide and a disulfide linked C-terminal dimer, which is the biologically active molecule. The circulating form consists of a latent complex of the C-terminal dimer and other proteins, including its propeptide, which maintain the C-terminal dimer in a latent, inactive state. Ligand activation requires additional cleavage of the prodomain by a tolloid-like metalloproteinase (PubMed:14671324).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei99 – 100Cleavage1 Publication2

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO08689.
PeptideAtlasiO08689.
PRIDEiO08689.

PTM databases

iPTMnetiO08689.
PhosphoSitePlusiO08689.

Expressioni

Tissue specificityi

Expressed specifically in developing and adult skeletal muscle. Weak expression in adipose tissue.1 Publication

Developmental stagei

First detected 9.5 dpc in one-third of developing somites. At 10.5 dpc, expressed in the myotome compartment of somites. At later stages of development, detected in a wide range of developing muscles. Expression continues in adulthood.1 Publication

Gene expression databases

BgeeiENSMUSG00000026100.
CleanExiMM_MSTN.
ExpressionAtlasiO08689. baseline and differential.

Interactioni

Subunit structurei

Homodimer; disulfide-linked (PubMed:19644449). Interacts with WFIKKN2, leading to inhibit its activity (PubMed:12595574). Interacts with FSTL3 (PubMed:22052913).3 Publications

GO - Molecular functioni

  • cytokine activity Source: GO_Central
  • growth factor activity Source: UniProtKB-KW
  • identical protein binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • receptor binding Source: MGI
  • transforming growth factor beta receptor binding Source: GO_Central

Protein-protein interaction databases

BioGridi201535. 1 interactor.
IntActiO08689. 4 interactors.
MINTiMINT-7914794.
STRINGi10090.ENSMUSP00000027269.

Chemistry databases

BindingDBiO08689.

Structurei

Secondary structure

1376
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi281 – 285Combined sources5
Beta strandi288 – 290Combined sources3
Helixi291 – 294Combined sources4
Beta strandi299 – 301Combined sources3
Beta strandi303 – 306Combined sources4
Beta strandi309 – 311Combined sources3
Turni316 – 319Combined sources4
Helixi324 – 331Combined sources8
Beta strandi340 – 354Combined sources15
Beta strandi356 – 358Combined sources3
Beta strandi360 – 376Combined sources17

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3HH2X-ray2.15A/B268-376[»]
3SEKX-ray2.40B268-376[»]
5JI1X-ray2.25A/B268-376[»]
ProteinModelPortaliO08689.
SMRiO08689.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO08689.

Family & Domainsi

Sequence similaritiesi

Belongs to the TGF-beta family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3900. Eukaryota.
ENOG410XT8Z. LUCA.
GeneTreeiENSGT00760000119112.
HOGENOMiHOG000006566.
HOVERGENiHBG000217.
InParanoidiO08689.
KOiK05497.
OMAiKDGLCNA.
OrthoDBiEOG091G078V.
PhylomeDBiO08689.
TreeFamiTF318514.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiView protein in InterPro
IPR029034. Cystine-knot_cytokine.
IPR015616. GDF_8.
IPR001839. TGF-b_C.
IPR001111. TGF-b_propeptide.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
PANTHERiPTHR11848. PTHR11848. 1 hit.
PTHR11848:SF168. PTHR11848:SF168. 1 hit.
PfamiView protein in Pfam
PF00019. TGF_beta. 1 hit.
PF00688. TGFb_propeptide. 1 hit.
SMARTiView protein in SMART
SM00204. TGFB. 1 hit.
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiView protein in PROSITE
PS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O08689-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MMQKLQMYVY IYLFMLIAAG PVDLNEGSER EENVEKEGLC NACAWRQNTR
60 70 80 90 100
YSRIEAIKIQ ILSKLRLETA PNISKDAIRQ LLPRAPPLRE LIDQYDVQRD
110 120 130 140 150
DSSDGSLEDD DYHATTETII TMPTESDFLM QADGKPKCCF FKFSSKIQYN
160 170 180 190 200
KVVKAQLWIY LRPVKTPTTV FVQILRLIKP MKDGTRYTGI RSLKLDMSPG
210 220 230 240 250
TGIWQSIDVK TVLQNWLKQP ESNLGIEIKA LDENGHDLAV TFPGPGEDGL
260 270 280 290 300
NPFLEVKVTD TPKRSRRDFG LDCDEHSTES RCCRYPLTVD FEAFGWDWII
310 320 330 340 350
APKRYKANYC SGECEFVFLQ KYPHTHLVHQ ANPRGSAGPC CTPTKMSPIN
360 370
MLYFNGKEQI IYGKIPAMVV DRCGCS
Length:376
Mass (Da):42,921
Last modified:July 1, 1997 - v1
Checksum:i3E19814DD62C08BE
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U84005 mRNA. Translation: AAC53167.1.
CCDSiCCDS14950.1.
RefSeqiNP_034964.1. NM_010834.3.
UniGeneiMm.3514.

Genome annotation databases

EnsembliENSMUST00000027269; ENSMUSP00000027269; ENSMUSG00000026100.
GeneIDi17700.
KEGGimmu:17700.
UCSCiuc007ayt.1. mouse.

Similar proteinsi

Entry informationi

Entry nameiGDF8_MOUSE
AccessioniPrimary (citable) accession number: O08689
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 1, 1997
Last modified: September 27, 2017
This is version 134 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families