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 9

Gene

GDF9

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Required for ovarian folliculogenesis. Promotes primordial follicle development. Stimulates granulosa cell proliferation. Promotes cell transition from G0/G1 to S and G2/M phases, through an increase of CCND1 and CCNE1 expression, and RB1 phosphorylation. It regulates STAR expression and cAMP-dependent progesterone release in granulosa and thecal cells. Attenuates the suppressive effects of activin A on STAR expression and progesterone production by increasing the expression of inhibin B. It suppresses FST and FSTL3 production in granulosa-lutein cells.5 Publications

GO - Molecular functioni

  • cytokine activity Source: GO_Central
  • growth factor activity Source: ProtInc
  • transforming growth factor beta receptor binding Source: GO_Central

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Growth factor

Enzyme and pathway databases

BioCyciZFISH:ENSG00000164404-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Growth/differentiation factor 9
Short name:
GDF-9
Gene namesi
Name:GDF9
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:4224. GDF9.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Altered GDF9 function may be involved in ovarian disorders. Rare variants in GDF9 have been found in patients with premature ovarian failure and mothers of dizygotic twins.

Organism-specific databases

DisGeNETi2661.
OpenTargetsiENSG00000164404.
Orphaneti619. Primary ovarian failure.
PharmGKBiPA28639.

Polymorphism and mutation databases

BioMutaiGDF9.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
PropeptideiPRO_000003398025 – 319Sequence analysisAdd BLAST295
ChainiPRO_0000033981320 – 454Growth/differentiation factor 9Add BLAST135

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi106N-linked (GlcNAc...)Sequence analysis1
Glycosylationi163N-linked (GlcNAc...)Sequence analysis1
Glycosylationi236N-linked (GlcNAc...)Sequence analysis1
Glycosylationi255N-linked (GlcNAc...)Sequence analysis1
Glycosylationi268N-linked (GlcNAc...)Sequence analysis1
Modified residuei325Phosphoserine; by CK1 Publication1
Glycosylationi338N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi353 ↔ 419By similarity
Disulfide bondi382 ↔ 451By similarity
Disulfide bondi386 ↔ 453By similarity

Post-translational modificationi

Phosphorylated; phosphorylation is critical for GDF9 function. In vitro, can be phosphorylated by CK at Ser-325.2 Publications

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiO60383.
PeptideAtlasiO60383.
PRIDEiO60383.

PTM databases

iPTMnetiO60383.
PhosphoSitePlusiO60383.

Expressioni

Tissue specificityi

Expressed in ovarian granulosa cells. Present in oocytes of primary follicles (at protein level).2 Publications

Gene expression databases

BgeeiENSG00000164404.
CleanExiHS_GDF9.
ExpressionAtlasiO60383. baseline and differential.
GenevisibleiO60383. HS.

Organism-specific databases

HPAiHPA069146.

Interactioni

Subunit structurei

Homodimer or heterodimer (Potential). But, in contrast to other members of this family, cannot be disulfide-linked (By similarity).By similarityCurated

GO - Molecular functioni

  • cytokine activity Source: GO_Central
  • growth factor activity Source: ProtInc
  • transforming growth factor beta receptor binding Source: GO_Central

Protein-protein interaction databases

BioGridi108930. 49 interactors.
IntActiO60383. 39 interactors.
MINTiMINT-1430245.
STRINGi9606.ENSP00000296875.

Structurei

3D structure databases

ProteinModelPortaliO60383.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the TGF-beta family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3900. Eukaryota.
ENOG410XT8Z. LUCA.
GeneTreeiENSGT00740000114888.
HOGENOMiHOG000073526.
HOVERGENiHBG004660.
InParanoidiO60383.
KOiK05498.
OMAiSQLKWDN.
OrthoDBiEOG091G09RN.
PhylomeDBiO60383.
TreeFamiTF351788.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR015617. Growth_differentiation_fac-9.
IPR001839. TGF-b_C.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view]
PANTHERiPTHR11848. PTHR11848. 3 hits.
PTHR11848:SF19. PTHR11848:SF19. 3 hits.
PfamiPF00019. TGF_beta. 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.

O60383-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MARPNKFLLW FCCFAWLCFP ISLGSQASGG EAQIAASAEL ESGAMPWSLL
60 70 80 90 100
QHIDERDRAG LLPALFKVLS VGRGGSPRLQ PDSRALHYMK KLYKTYATKE
110 120 130 140 150
GIPKSNRSHL YNTVRLFTPC TRHKQAPGDQ VTGILPSVEL LFNLDRITTV
160 170 180 190 200
EHLLKSVLLY NINNSVSFSS AVKCVCNLMI KEPKSSSRTL GRAPYSFTFN
210 220 230 240 250
SQFEFGKKHK WIQIDVTSLL QPLVASNKRS IHMSINFTCM KDQLEHPSAQ
260 270 280 290 300
NGLFNMTLVS PSLILYLNDT SAQAYHSWYS LHYKRRPSQG PDQERSLSAY
310 320 330 340 350
PVGEEAAEDG RSSHHRHRRG QETVSSELKK PLGPASFNLS EYFRQFLLPQ
360 370 380 390 400
NECELHDFRL SFSQLKWDNW IVAPHRYNPR YCKGDCPRAV GHRYGSPVHT
410 420 430 440 450
MVQNIIYEKL DSSVPRPSCV PAKYSPLSVL TIEPDGSIAY KEYEDMIATK

CTCR
Length:454
Mass (Da):51,444
Last modified:August 1, 1998 - v1
Checksum:i94EA366E90CDBC27
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06693457D → Y.1 PublicationCorresponds to variant rs138136756dbSNPEnsembl.1
Natural variantiVAR_05894567K → E in some patients with premature ovarian failure. 1 Publication1
Natural variantiVAR_066935103P → S.2 PublicationsCorresponds to variant rs61754583dbSNPEnsembl.1
Natural variantiVAR_066936121T → I.1 PublicationCorresponds to variant rs149821575dbSNPEnsembl.1
Natural variantiVAR_066937146R → C.1 PublicationCorresponds to variant rs76349024dbSNPEnsembl.1
Natural variantiVAR_058946186S → Y in a patient with premature ovarian failure. 1 Publication1
Natural variantiVAR_058947216V → M in two patients with premature ovarian failure. 1 Publication1
Natural variantiVAR_066938238T → A in a patient with premature ovarian failure. 1 Publication1
Natural variantiVAR_066939374P → L Rare variant found in mothers of dizygotic twins. 1 PublicationCorresponds to variant rs373477788dbSNPEnsembl.1
Natural variantiVAR_066940428S → T.1 PublicationCorresponds to variant rs118080183dbSNPEnsembl.1
Natural variantiVAR_066941454R → C.1 PublicationCorresponds to variant rs61754582dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC004500 Genomic DNA. Translation: AAC08450.1.
BC096228 mRNA. Translation: AAH96228.1.
BC096229 mRNA. Translation: AAH96229.1.
BC096230 mRNA. Translation: AAH96230.1.
BC096231 mRNA. Translation: AAH96231.1.
CCDSiCCDS4162.1.
RefSeqiNP_001275753.1. NM_001288824.2.
NP_005251.1. NM_005260.5.
XP_011541610.1. XM_011543308.2.
UniGeneiHs.25022.
Hs.739230.
Hs.742490.

Genome annotation databases

EnsembliENST00000378673; ENSP00000367942; ENSG00000164404.
GeneIDi2661.
KEGGihsa:2661.
UCSCiuc003kxz.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC004500 Genomic DNA. Translation: AAC08450.1.
BC096228 mRNA. Translation: AAH96228.1.
BC096229 mRNA. Translation: AAH96229.1.
BC096230 mRNA. Translation: AAH96230.1.
BC096231 mRNA. Translation: AAH96231.1.
CCDSiCCDS4162.1.
RefSeqiNP_001275753.1. NM_001288824.2.
NP_005251.1. NM_005260.5.
XP_011541610.1. XM_011543308.2.
UniGeneiHs.25022.
Hs.739230.
Hs.742490.

3D structure databases

ProteinModelPortaliO60383.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108930. 49 interactors.
IntActiO60383. 39 interactors.
MINTiMINT-1430245.
STRINGi9606.ENSP00000296875.

PTM databases

iPTMnetiO60383.
PhosphoSitePlusiO60383.

Polymorphism and mutation databases

BioMutaiGDF9.

Proteomic databases

PaxDbiO60383.
PeptideAtlasiO60383.
PRIDEiO60383.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000378673; ENSP00000367942; ENSG00000164404.
GeneIDi2661.
KEGGihsa:2661.
UCSCiuc003kxz.3. human.

Organism-specific databases

CTDi2661.
DisGeNETi2661.
GeneCardsiGDF9.
HGNCiHGNC:4224. GDF9.
HPAiHPA069146.
MIMi601918. gene.
neXtProtiNX_O60383.
OpenTargetsiENSG00000164404.
Orphaneti619. Primary ovarian failure.
PharmGKBiPA28639.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3900. Eukaryota.
ENOG410XT8Z. LUCA.
GeneTreeiENSGT00740000114888.
HOGENOMiHOG000073526.
HOVERGENiHBG004660.
InParanoidiO60383.
KOiK05498.
OMAiSQLKWDN.
OrthoDBiEOG091G09RN.
PhylomeDBiO60383.
TreeFamiTF351788.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000164404-MONOMER.

Miscellaneous databases

ChiTaRSiGDF9. human.
GeneWikiiGrowth_differentiation_factor-9.
GenomeRNAii2661.
PROiO60383.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000164404.
CleanExiHS_GDF9.
ExpressionAtlasiO60383. baseline and differential.
GenevisibleiO60383. HS.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR015617. Growth_differentiation_fac-9.
IPR001839. TGF-b_C.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view]
PANTHERiPTHR11848. PTHR11848. 3 hits.
PTHR11848:SF19. PTHR11848:SF19. 3 hits.
PfamiPF00019. TGF_beta. 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...

Entry informationi

Entry nameiGDF9_HUMAN
AccessioniPrimary (citable) accession number: O60383
Secondary accession number(s): Q4VAW5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: August 1, 1998
Last modified: November 2, 2016
This is version 133 of the entry and version 1 of the sequence. [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

Miscellaneous

Ovarian physiology and fertility are controlled by endocrine and paracrine signals. These act in a species-dependent manner and determine the ovulation quota in different mammalian species. While humans, and mammals such as the cow or red deer, normally ovulate only one egg per cycle, other mammals such as mouse and pig can ovulate in excess of ten per cycle. The mechanisms that regulate the species-specific differences in the number of follicles that go onto ovulate during each reproductive cycle are poorly understood. According to PubMed:21970812, mRNA expression levels of GDF9 and BMP15 are tightly coregulated within each species and influence species-specific ovulation-rates.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: 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. SIMILARITY comments
    Index of protein domains and families

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 one 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.