O14793 (GDF8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Growth/differentiation factor 8
Short name=GDF-8

Alternative name(s):
Myostatin

Gene names

Name:	MSTN
Synonyms:	GDF8

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	375 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Ligand	Heparin-binding
Molecular function	Cytokine Growth factor
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	muscle organ development Traceable author statement Ref.2. Source: ProtInc negative regulation of muscle hypertrophy Inferred from electronic annotation. Source: Compara negative regulation of skeletal muscle tissue growth Inferred from electronic annotation. Source: Compara ovulation cycle process Inferred from electronic annotation. Source: Compara positive regulation of transcription, DNA-dependent Inferred from direct assay PubMed 14517293. Source: HGNC response to electrical stimulus Inferred from electronic annotation. Source: Compara response to estrogen stimulus Inferred from electronic annotation. Source: Compara response to ethanol Inferred from electronic annotation. Source: Compara response to glucocorticoid stimulus Inferred from electronic annotation. Source: Compara response to gravity Inferred from electronic annotation. Source: Compara response to heat Inferred from electronic annotation. Source: Compara response to muscle activity Inferred from electronic annotation. Source: Compara response to testosterone stimulus Inferred from electronic annotation. Source: Compara skeletal muscle atrophy Inferred from electronic annotation. Source: Compara skeletal muscle tissue regeneration Inferred from electronic annotation. Source: Compara transforming growth factor beta receptor signaling pathway Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from electronic annotation. Source: Compara extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	growth factor activity Traceable author statement Ref.2. Source: ProtInc heparin binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Potential
	Propeptide	24 – 266	243	Potential		PRO_0000033950
	Chain	267 – 375	109	Growth/differentiation factor 8		PRO_0000033951
Amino acid modifications
	Glycosylation	71	1	N-linked (GlcNAc...) Potential
	Disulfide bond	281 ↔ 340		By similarity
	Disulfide bond	309 ↔ 372		By similarity
	Disulfide bond	313 ↔ 374		By similarity
	Disulfide bond	339		Interchain By similarity
Natural variations
	Natural variant	55	1	A → T. Ref.3 Corresponds to variant rs1805085 [ dbSNP | Ensembl ].		VAR_014475
	Natural variant	153	1	K → R. Ref.3 Corresponds to variant rs1805086 [ dbSNP | Ensembl ].		VAR_014476
	Natural variant	348	1	I → T. Corresponds to variant rs34780010 [ dbSNP | Ensembl ].		VAR_052575
	Natural variant	371	1	R → G. Corresponds to variant rs16823988 [ dbSNP | Ensembl ].		VAR_052576

Sequences

	Sequence		Length	Mass (Da)
	O14793 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: EBFF6129725E6AFA	FASTA	375	42,750
	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

References

	« Hide 'large scale' referencesShow '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.
IPI	IPI00023751.
RefSeq	NP_005250.1. NM_005259.2.
UniGene	Hs.41565.
3D structure databases
ProteinModelPortal	O14793.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000260950.
PTM databases
PhosphoSite	O14793.
Proteomic databases
PaxDb	O14793.
PeptideAtlas	O14793.
PRIDE	O14793.
Protocols and materials databases
DNASU	2660.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000260950; ENSP00000260950; ENSG00000138379.
GeneID	2660.
KEGG	hsa:2660.
UCSC	uc002urp.3. human.
Organism-specific databases
CTD	2660.
GeneCards	GC02M190920.
HGNC	HGNC:4223. MSTN.
HPA	CAB009963.
MIM	601788. gene. 614160. phenotype.
neXtProt	NX_O14793.
Orphanet	275534. Myostatin-related muscle hypertrophy.
PharmGKB	PA162396253.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG310007.
HOGENOM	HOG000006566.
HOVERGEN	HBG000217.
InParanoid	O14793.
KO	K05497.
OMA	DLLMQVE.
OrthoDB	EOG4ZS93B.
PhylomeDB	O14793.
Gene expression databases
ArrayExpress	O14793.
Bgee	O14793.
CleanEx	HS_MSTN.
Genevestigator	O14793.
GermOnline	ENSG00000138379. Homo sapiens.
Family and domain databases
InterPro	IPR015616. GDF_8. IPR001839. TGF-b_C. IPR001111. TGF-b_N. IPR015615. TGF-beta-rel. IPR017948. TGFb_CS. [Graphical view]
PANTHER	PTHR11848. PTHR11848. 1 hit. PTHR11848:SF13. PTHR11848:SF13. 1 hit.
Pfam	PF00019. TGF_beta. 1 hit. PF00688. TGFb_propeptide. 1 hit. [Graphical view]
SMART	SM00204. TGFB. 1 hit. [Graphical view]
PROSITE	PS00250. TGF_BETA_1. 1 hit. PS51362. TGF_BETA_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	2660.
NextBio	10500.
SOURCE	Search...

Entry information

Entry name

GDF8_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 117 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.