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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.

GO - Molecular functioni

  1. cytokine activity Source: GO_Central
  2. heparin binding Source: UniProtKB-KW
  3. identical protein binding Source: MGI
  4. receptor binding Source: MGI
  5. transforming growth factor beta receptor binding Source: GO_Central

GO - Biological processi

  1. cell development Source: GO_Central
  2. cellular response to dexamethasone stimulus Source: MGI
  3. negative regulation of muscle hypertrophy Source: Ensembl
  4. negative regulation of myoblast proliferation Source: AgBase
  5. negative regulation of satellite cell differentiation Source: AgBase
  6. negative regulation of skeletal muscle satellite cell proliferation Source: AgBase
  7. negative regulation of skeletal muscle tissue growth Source: Ensembl
  8. ovulation cycle process Source: Ensembl
  9. positive regulation of pathway-restricted SMAD protein phosphorylation Source: GO_Central
  10. positive regulation of transcription, DNA-templated Source: MGI
  11. regulation of apoptotic process Source: GO_Central
  12. regulation of MAPK cascade Source: GO_Central
  13. response to electrical stimulus Source: Ensembl
  14. response to estrogen Source: Ensembl
  15. response to ethanol Source: Ensembl
  16. response to gravity Source: Ensembl
  17. response to heat Source: Ensembl
  18. response to muscle activity Source: Ensembl
  19. response to testosterone Source: Ensembl
  20. skeletal muscle atrophy Source: Ensembl
  21. skeletal muscle tissue regeneration Source: Ensembl
  22. SMAD protein signal transduction Source: GO_Central
  23. transforming growth factor beta receptor signaling pathway Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Growth factor

Keywords - Ligandi

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:95691. Mstn.

Subcellular locationi

Secreted By similarity

GO - Cellular componenti

  1. cytoplasm Source: Ensembl
  2. extracellular space Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Disruption phenotypei

Mutant animals exhibit muscle hypertrophy.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence AnalysisAdd
BLAST
Propeptidei25 – 267243Sequence AnalysisPRO_0000033956Add
BLAST
Chaini268 – 376109Growth/differentiation factor 8PRO_0000033957Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi72 – 721N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi282 ↔ 341
Disulfide bondi310 ↔ 373
Disulfide bondi314 ↔ 375
Disulfide bondi340 – 340Interchain

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiO08689.
PaxDbiO08689.
PRIDEiO08689.

PTM databases

PhosphoSiteiO08689.

Expressioni

Tissue specificityi

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

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.

Gene expression databases

BgeeiO08689.
CleanExiMM_MSTN.
ExpressionAtlasiO08689. baseline and differential.
GenevestigatoriO08689.

Interactioni

Subunit structurei

Homodimer; disulfide-linked (By similarity). Interacts with WFIKKN2, leading to inhibit its activity. Interacts with FST3 (By similarity).By similarity

Protein-protein interaction databases

BioGridi201535. 1 interaction.
IntActiO08689. 4 interactions.
MINTiMINT-7914794.

Structurei

Secondary structure

1
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi281 – 2855Combined sources
Beta strandi288 – 2903Combined sources
Helixi291 – 2944Combined sources
Beta strandi299 – 3013Combined sources
Beta strandi303 – 3064Combined sources
Beta strandi309 – 3113Combined sources
Turni316 – 3194Combined sources
Helixi324 – 3318Combined sources
Beta strandi340 – 35415Combined sources
Beta strandi360 – 37617Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3HH2X-ray2.15A/B268-376[»]
3SEKX-ray2.40B268-376[»]
ProteinModelPortaliO08689.
SMRiO08689. Positions 50-376.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO08689.

Family & Domainsi

Sequence similaritiesi

Belongs to the TGF-beta family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG310007.
HOGENOMiHOG000006566.
HOVERGENiHBG000217.
InParanoidiO08689.
KOiK05497.
OMAiNPFLEVR.
OrthoDBiEOG74R1Q4.
PhylomeDBiO08689.
TreeFamiTF318514.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR015616. GDF_8.
IPR001839. TGF-b_C.
IPR001111. TGF-b_N.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view]
PANTHERiPTHR11848. PTHR11848. 1 hit.
PTHR11848:SF13. PTHR11848:SF13. 1 hit.
PfamiPF00019. TGF_beta. 1 hit.
PF00688. TGFb_propeptide. 1 hit.
[Graphical view]
SMARTiSM00204. TGFB. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.
[Graphical view]

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_010834.2.
UniGeneiMm.3514.

Genome annotation databases

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

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U84005 mRNA. Translation: AAC53167.1.
CCDSiCCDS14950.1.
RefSeqiNP_034964.1. NM_010834.2.
UniGeneiMm.3514.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3HH2X-ray2.15A/B268-376[»]
3SEKX-ray2.40B268-376[»]
ProteinModelPortaliO08689.
SMRiO08689. Positions 50-376.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201535. 1 interaction.
IntActiO08689. 4 interactions.
MINTiMINT-7914794.

PTM databases

PhosphoSiteiO08689.

Proteomic databases

MaxQBiO08689.
PaxDbiO08689.
PRIDEiO08689.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi2660.
MGIiMGI:95691. Mstn.

Phylogenomic databases

eggNOGiNOG310007.
HOGENOMiHOG000006566.
HOVERGENiHBG000217.
InParanoidiO08689.
KOiK05497.
OMAiNPFLEVR.
OrthoDBiEOG74R1Q4.
PhylomeDBiO08689.
TreeFamiTF318514.

Miscellaneous databases

EvolutionaryTraceiO08689.
NextBioi292290.
PROiO08689.
SOURCEiSearch...

Gene expression databases

BgeeiO08689.
CleanExiMM_MSTN.
ExpressionAtlasiO08689. baseline and differential.
GenevestigatoriO08689.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR015616. GDF_8.
IPR001839. TGF-b_C.
IPR001111. TGF-b_N.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view]
PANTHERiPTHR11848. PTHR11848. 1 hit.
PTHR11848:SF13. PTHR11848:SF13. 1 hit.
PfamiPF00019. TGF_beta. 1 hit.
PF00688. TGFb_propeptide. 1 hit.
[Graphical view]
SMARTiSM00204. TGFB. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member."
    McPherron A.C., Lawler A.M., Lee S.-J.
    Nature 387:83-90(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: CD-1.
    Tissue: Skeletal muscle.
  2. "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(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH WFIKKN2.
  3. Cited for: DISRUPTION PHENOTYPE.
  4. "The structure of myostatin:follistatin 288: insights into receptor utilization and heparin binding."
    Cash J.N., Rejon C.A., McPherron A.C., Bernard D.J., Thompson T.B.
    EMBO J. 28:2662-2676(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 268-376 IN COMPLEX WITH HUMAN FOLLISTATIN, HEPARIN-BINDING, DISULFIDE BONDS.
  5. "Structure of myostatin.follistatin-like 3: N-terminal domains of follistatin-type molecules exhibit alternate modes of binding."
    Cash J.N., Angerman E.B., Kattamuri C., Nolan K., Zhao H., Sidis Y., Keutmann H.T., Thompson T.B.
    J. Biol. Chem. 287:1043-1053(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 268-376 IN COMPLEX WITH HUMAN FSTL3, DISULFIDE BONDS.

Entry informationi

Entry nameiGDF8_MOUSE
AccessioniPrimary (citable) accession number: O08689
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 1, 1997
Last modified: March 4, 2015
This is version 111 of the entry and version 1 of the sequence. [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

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.