Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Growth/differentiation factor 8

Gene

MSTN

Organism
Homo sapiens (Human)
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.By similarity

GO - Molecular functioni

  • cytokine activity Source: GO_Central
  • growth factor activity Source: ProtInc
  • heparin binding Source: UniProtKB-KW
  • identical protein binding Source: UniProtKB
  • protein homodimerization activity Source: Ensembl
  • receptor binding Source: BHF-UCL
  • transforming growth factor beta receptor binding Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionCytokine, Growth factor, Heparin-binding

Enzyme and pathway databases

SIGNORiO14793.

Names & Taxonomyi

Protein namesi
Recommended name:
Growth/differentiation factor 8
Short name:
GDF-8
Alternative name(s):
Myostatin
Gene namesi
Name:MSTN
Synonyms:GDF8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000138379.4.
HGNCiHGNC:4223. 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

Involvement in diseasei

Muscle hypertrophy (MSLHP)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA condition characterized by increased muscle bulk and strength. Affected individuals are exceptionally strong.
See also OMIM:614160

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi267D → N: Decreases SMAD3 protein signal transduction; when associated with L-268. 1 Publication1
Mutagenesisi268F → L: Decreases SMAD3 protein signal transduction; when associated with N-267. 1 Publication1
Mutagenesisi312E → Q: Slightly decreased SMAD3 protein signal transduction. 1 Publication1
Mutagenesisi315F → Y: Increases SMAD3 protein signal transduction; when associated with M-316 and M-318. 1 Publication1
Mutagenesisi316V → M: Increases SMAD3 protein signal transduction; when associated with Y-315 and M-318. 1 Publication1
Mutagenesisi318L → M: Increases SMAD3 protein signal transduction; when associated with Y-315 and M-316. 1 Publication1
Mutagenesisi328H → Q: Increases SMAD3 protein signal transduction. 1 Publication1
Mutagenesisi355G → D: Increases SMAD3 protein signal transduction; when associated with Q-357. 1 Publication1
Mutagenesisi357E → Q: Increases SMAD3 protein signal transduction; when associated with D-355. 1 Publication1
Mutagenesisi366A → G: Increases SMAD3 protein signal transduction. 1 Publication1

Organism-specific databases

DisGeNETi2660.
GeneReviewsiMSTN.
MalaCardsiMSTN.
MIMi614160. phenotype.
OpenTargetsiENSG00000138379.
Orphaneti275534. Myostatin-related muscle hypertrophy.
PharmGKBiPA162396253.

Chemistry databases

ChEMBLiCHEMBL3407325.
DrugBankiDB05915. MYO-029.

Polymorphism and mutation databases

BioMutaiMSTN.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
PropeptideiPRO_000003395024 – 266Sequence analysisAdd BLAST243
ChainiPRO_0000033951267 – 375Growth/differentiation factor 8Add BLAST109

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi71N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi272 ↔ 282Combined sources1 Publication
Disulfide bondi281 ↔ 340Combined sources1 Publication
Disulfide bondi309 ↔ 372Combined sources1 Publication
Disulfide bondi313 ↔ 374Combined sources1 Publication
Disulfide bondi339InterchainCombined 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.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei98 – 99CleavageBy similarity2

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

EPDiO14793.
PaxDbiO14793.
PeptideAtlasiO14793.
PRIDEiO14793.

PTM databases

iPTMnetiO14793.
PhosphoSitePlusiO14793.

Expressioni

Gene expression databases

BgeeiENSG00000138379.
CleanExiHS_MSTN.
ExpressionAtlasiO14793. baseline and differential.
GenevisibleiO14793. HS.

Organism-specific databases

HPAiCAB009963.

Interactioni

Subunit structurei

Homodimer; disulfide-linked (PubMed:27625211). Interacts with WFIKKN2, leading to inhibit its activity (PubMed:12595574). Interacts with FST3 (PubMed:17878677).3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • cytokine activity Source: GO_Central
  • growth factor activity Source: ProtInc
  • identical protein binding Source: UniProtKB
  • protein homodimerization activity Source: Ensembl
  • receptor binding Source: BHF-UCL
  • transforming growth factor beta receptor binding Source: GO_Central

Protein-protein interaction databases

BioGridi108929. 3 interactors.
IntActiO14793. 4 interactors.
STRINGi9606.ENSP00000260950.

Chemistry databases

BindingDBiO14793.

Structurei

Secondary structure

1375
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi280 – 284Combined sources5
Beta strandi287 – 289Combined sources3
Helixi290 – 293Combined sources4
Beta strandi298 – 300Combined sources3
Beta strandi302 – 305Combined sources4
Beta strandi308 – 310Combined sources3
Helixi318 – 320Combined sources3
Helixi321 – 330Combined sources10
Beta strandi335 – 337Combined sources3
Beta strandi340 – 353Combined sources14
Beta strandi359 – 374Combined sources16

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5F3BX-ray1.76C/D267-375[»]
5F3HX-ray2.70I/J/K/L268-375[»]
ProteinModelPortaliO14793.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the TGF-beta family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3900. Eukaryota.
ENOG410XT8Z. LUCA.
GeneTreeiENSGT00760000119112.
HOGENOMiHOG000006566.
HOVERGENiHBG000217.
InParanoidiO14793.
KOiK05497.
OMAiKDGLCNA.
OrthoDBiEOG091G078V.
PhylomeDBiO14793.
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.

O14793-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQKLQLCVYI YLFMLIVAGP VDLNENSEQK ENVEKEGLCN ACTWRQNTKS
60 70 80 90 100
SRIEAIKIQI LSKLRLETAP NISKDVIRQL LPKAPPLREL IDQYDVQRDD
110 120 130 140 150
SSDGSLEDDD YHATTETIIT MPTESDFLMQ VDGKPKCCFF KFSSKIQYNK
160 170 180 190 200
VVKAQLWIYL RPVETPTTVF VQILRLIKPM KDGTRYTGIR SLKLDMNPGT
210 220 230 240 250
GIWQSIDVKT VLQNWLKQPE SNLGIEIKAL DENGHDLAVT FPGPGEDGLN
260 270 280 290 300
PFLEVKVTDT PKRSRRDFGL DCDEHSTESR CCRYPLTVDF EAFGWDWIIA
310 320 330 340 350
PKRYKANYCS GECEFVFLQK YPHTHLVHQA NPRGSAGPCC TPTKMSPINM
360 370
LYFNGKEQII YGKIPAMVVD RCGCS
Length:375
Mass (Da):42,750
Last modified:January 1, 1998 - v1
Checksum:iEBFF6129725E6AFA
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01447555A → T1 PublicationCorresponds to variant dbSNP:rs1805085Ensembl.1
Natural variantiVAR_014476153K → R1 PublicationCorresponds to variant dbSNP:rs1805086Ensembl.1
Natural variantiVAR_052575348I → T. Corresponds to variant dbSNP:rs34780010Ensembl.1
Natural variantiVAR_052576371R → G. Corresponds to variant dbSNP:rs16823988Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF019627 mRNA. Translation: AAB86694.1.
AF104922 mRNA. Translation: AAC96327.1.
DQ927096 Genomic DNA. Translation: ABI48419.1.
DQ927098 Genomic DNA. Translation: ABI48421.1.
DQ927099 Genomic DNA. Translation: ABI48422.1.
BC074757 mRNA. Translation: AAH74757.2.
CCDSiCCDS2303.1.
RefSeqiNP_005250.1. NM_005259.2.
UniGeneiHs.41565.

Genome annotation databases

EnsembliENST00000260950; ENSP00000260950; ENSG00000138379.
GeneIDi2660.
KEGGihsa:2660.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiGDF8_HUMAN
AccessioniPrimary (citable) accession number: O14793
Secondary accession number(s): A1C2J7, A1C2K0, Q6B0H2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 1, 1998
Last modified: September 27, 2017
This is version 154 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families