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O14793 (GDF8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Growth/differentiation factor 8

Short name=GDF-8
Alternative name(s):
Myostatin
Gene names
Name:MSTN
Synonyms:GDF8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length375 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Acts specifically as a negative regulator of skeletal muscle growth.

Subunit structure

Homodimer; disulfide-linked By similarity. Interacts with WFIKKN2, leading to inhibit its activity. Interacts with FST3. Ref.5 Ref.7

Subcellular location

Secreted.

Involvement in disease

Muscle hypertrophy (MSLHP) [MIM:614160]: A condition characterized by increased muscle bulk and strength. Affected individuals are exceptionally strong.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6

Sequence similarities

Belongs to the TGF-beta family.

Ontologies

Keywords
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DomainSignal
   LigandHeparin-binding
   Molecular functionCytokine
Growth factor
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processmuscle organ development

Traceable author statement Ref.2. Source: ProtInc

negative regulation of muscle hypertrophy

Inferred from electronic annotation. Source: Ensembl

negative regulation of skeletal muscle tissue growth

Inferred from electronic annotation. Source: Ensembl

ovulation cycle process

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 14517293. Source: HGNC

response to electrical stimulus

Inferred from electronic annotation. Source: Ensembl

response to estrogen

Inferred from electronic annotation. Source: Ensembl

response to ethanol

Inferred from electronic annotation. Source: Ensembl

response to glucocorticoid

Inferred from electronic annotation. Source: Ensembl

response to gravity

Inferred from electronic annotation. Source: Ensembl

response to heat

Inferred from electronic annotation. Source: Ensembl

response to muscle activity

Inferred from electronic annotation. Source: Ensembl

response to testosterone

Inferred from electronic annotation. Source: Ensembl

skeletal muscle atrophy

Inferred from electronic annotation. Source: Ensembl

skeletal muscle tissue regeneration

Inferred from electronic annotation. Source: Ensembl

transforming growth factor beta receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: Ensembl

extracellular space

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functiongrowth factor activity

Traceable author statement Ref.2. Source: ProtInc

heparin binding

Inferred from electronic annotation. Source: UniProtKB-KW

identical protein binding

Inferred from physical interaction PubMed 23829672. Source: IntAct

receptor binding

Inferred from physical interaction PubMed 14517293. Source: HGNC

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Potential
Propeptide24 – 266243 Potential
PRO_0000033950
Chain267 – 375109Growth/differentiation factor 8
PRO_0000033951

Amino acid modifications

Glycosylation711N-linked (GlcNAc...) Potential
Disulfide bond281 ↔ 340 By similarity
Disulfide bond309 ↔ 372 By similarity
Disulfide bond313 ↔ 374 By similarity
Disulfide bond339Interchain By similarity

Natural variations

Natural variant551A → T. Ref.3
Corresponds to variant rs1805085 [ dbSNP | Ensembl ].
VAR_014475
Natural variant1531K → R. Ref.3
Corresponds to variant rs1805086 [ dbSNP | Ensembl ].
VAR_014476
Natural variant3481I → T.
Corresponds to variant rs34780010 [ dbSNP | Ensembl ].
VAR_052575
Natural variant3711R → G.
Corresponds to variant rs16823988 [ dbSNP | Ensembl ].
VAR_052576

Sequences

Sequence LengthMass (Da)Tools
O14793 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: EBFF6129725E6AFA

FASTA37542,750
        10         20         30         40         50         60 
MQKLQLCVYI YLFMLIVAGP VDLNENSEQK ENVEKEGLCN ACTWRQNTKS SRIEAIKIQI 

        70         80         90        100        110        120 
LSKLRLETAP NISKDVIRQL LPKAPPLREL IDQYDVQRDD SSDGSLEDDD YHATTETIIT 

       130        140        150        160        170        180 
MPTESDFLMQ VDGKPKCCFF KFSSKIQYNK VVKAQLWIYL RPVETPTTVF VQILRLIKPM 

       190        200        210        220        230        240 
KDGTRYTGIR SLKLDMNPGT GIWQSIDVKT VLQNWLKQPE SNLGIEIKAL DENGHDLAVT 

       250        260        270        280        290        300 
FPGPGEDGLN PFLEVKVTDT PKRSRRDFGL DCDEHSTESR CCRYPLTVDF EAFGWDWIIA 

       310        320        330        340        350        360 
PKRYKANYCS GECEFVFLQK YPHTHLVHQA NPRGSAGPCC TPTKMSPINM LYFNGKEQII 

       370 
YGKIPAMVVD RCGCS 

« Hide

References

« Hide 'large scale' references
[1]"Double muscling in cattle due to mutations in the myostatin gene."
McPherron A.C., Lee S.-J.
Proc. Natl. Acad. Sci. U.S.A. 94:12457-12461(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Skeletal muscle.
[2]"Organization of the human myostatin gene and expression in healthy men and HIV-infected men with muscle wasting."
Gonzalez-Cadavid N.F., Taylor W.E., Yarasheski K., Sinha-Hikim I., Ma K., Ezzat S., Shen R., Lalani R., Asa S., Mamita M., Nair G., Arver S., Bhasin S.
Proc. Natl. Acad. Sci. U.S.A. 95:14938-14943(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Muscle.
[3]"Human adaptive evolution at myostatin (GDF8), a regulator of muscle growth."
Saunders M.A., Good J.M., Lawrence E.C., Ferrell R.E., Li W.H., Nachman M.W.
Am. J. Hum. Genet. 79:1089-1097(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-55 AND ARG-153.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Colon.
[5]"Regulation of myostatin in vivo by growth and differentiation factor-associated serum protein-1: a novel protein with protease inhibitor and follistatin domains."
Hill J.J., Qiu Y., Hewick R.M., Wolfman N.M.
Mol. Endocrinol. 17:1144-1154(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH WFIKKN2.
[6]"Myostatin mutation associated with gross muscle hypertrophy in a child."
Schuelke M., Wagner K.R., Stolz L.E., Hubner C., Riebel T., Komen W., Braun T., Tobin J.F., Lee S.J.
N. Engl. J. Med. 350:2682-2688(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN MSLHP.
[7]"Characterization of follistatin-related gene as a negative regulatory factor for activin family members during mouse heart development."
Takehara-Kasamatsu Y., Tsuchida K., Nakatani M., Murakami T., Kurisaki A., Hashimoto O., Ohuchi H., Kurose H., Mori K., Kagami S., Noji S., Sugino H.
J. Med. Invest. 54:276-288(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FSTL3.
+Additional computationally mapped references.

Web resources

GeneReviews
Wikipedia

Myostatin entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_005250.1. NM_005259.2.
UniGeneHs.41565.

3D structure databases

ProteinModelPortalO14793.
SMRO14793. Positions 49-375.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108929. 4 interactions.
IntActO14793. 4 interactions.
STRING9606.ENSP00000260950.

PTM databases

PhosphoSiteO14793.

Proteomic databases

PaxDbO14793.
PeptideAtlasO14793.
PRIDEO14793.

Protocols and materials databases

DNASU2660.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000260950; ENSP00000260950; ENSG00000138379.
GeneID2660.
KEGGhsa:2660.
UCSCuc002urp.3. human.

Organism-specific databases

CTD2660.
GeneCardsGC02M190920.
HGNCHGNC:4223. MSTN.
HPACAB009963.
MIM601788. gene.
614160. phenotype.
neXtProtNX_O14793.
Orphanet275534. Myostatin-related muscle hypertrophy.
PharmGKBPA162396253.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG310007.
HOGENOMHOG000006566.
HOVERGENHBG000217.
InParanoidO14793.
KOK05497.
OMADLLMQVE.
OrthoDBEOG74R1Q4.
PhylomeDBO14793.
TreeFamTF318514.

Gene expression databases

ArrayExpressO14793.
BgeeO14793.
CleanExHS_MSTN.
GenevestigatorO14793.

Family and domain databases

InterProIPR015616. GDF_8.
IPR001839. TGF-b_C.
IPR001111. TGF-b_N.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view]
PANTHERPTHR11848. PTHR11848. 1 hit.
PTHR11848:SF13. PTHR11848:SF13. 1 hit.
PfamPF00019. TGF_beta. 1 hit.
PF00688. TGFb_propeptide. 1 hit.
[Graphical view]
SMARTSM00204. TGFB. 1 hit.
[Graphical view]
PROSITEPS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMyostatin.
GenomeRNAi2660.
NextBio10500.
PROO14793.
SOURCESearch...

Entry information

Entry nameGDF8_HUMAN
AccessionPrimary (citable) accession number: O14793
Secondary accession number(s): A1C2J7, A1C2K0, Q6B0H2
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 1, 1998
Last modified: April 16, 2014
This is version 123 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM