UniProtKB - O60383 (GDF9_HUMAN)
Protein
Growth/differentiation factor 9
Gene
GDF9
Organism
Homo sapiens (Human)
Status
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
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.
GO - Molecular functioni
- cytokine activity Source: GO_Central
- growth factor activity Source: ProtInc
- type I activin receptor binding Source: GO_Central
GO - Biological processi
- BMP signaling pathway Source: GO_Central
- female gamete generation Source: ProtInc
- negative regulation of cell growth Source: Ensembl
- oocyte growth Source: Ensembl
- positive regulation of cell population proliferation Source: UniProtKB
- positive regulation of pathway-restricted SMAD protein phosphorylation Source: GO_Central
- regulation of progesterone secretion Source: UniProtKB
- SMAD protein signal transduction Source: GO_Central
- transforming growth factor beta receptor signaling pathway Source: ProtInc
Keywordsi
Molecular function | Cytokine, Growth factor |
Enzyme and pathway databases
PathwayCommonsi | O60383 |
Names & Taxonomyi
Protein namesi | Recommended name: Growth/differentiation factor 9Short name: GDF-9 |
Gene namesi | Name:GDF9 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:4224, GDF9 |
MIMi | 601918, gene |
neXtProti | NX_O60383 |
VEuPathDBi | HostDB:ENSG00000164404.8 |
Subcellular locationi
Extracellular region or secreted
- Secreted By similarity
Extracellular region or secreted
- extracellular space Source: GO_Central
Other locations
- cytoplasm Source: Ensembl
Keywords - Cellular componenti
SecretedPathology & Biotechi
Involvement in diseasei
Altered GDF9 function may be involved in ovarian disorders and contribute to the likelihood of dizygotic twinning.1 Publication
Premature ovarian failure 14 (POF14)7 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_066934 | 57 | D → Y in POF14; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs138136756Ensembl. | 1 | |
Natural variantiVAR_058945 | 67 | K → E in POF14; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_066935 | 103 | P → S in POF14; unknown pathological significance; also found at higher frequency in mothers of dizygotic twins than in controls. 2 PublicationsCorresponds to variant dbSNP:rs61754583Ensembl. | 1 | |
Natural variantiVAR_066937 | 146 | R → C in POF14; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs76349024Ensembl. | 1 | |
Natural variantiVAR_058946 | 186 | S → Y in POF14; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_058947 | 216 | V → M in POF14; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1205723048Ensembl. | 1 | |
Natural variantiVAR_066938 | 238 | T → A in POF14; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_066940 | 428 | S → T in POF14; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs118080183Ensembl. | 1 |
Keywords - Diseasei
Premature ovarian failureOrganism-specific databases
DisGeNETi | 2661 |
MalaCardsi | GDF9 |
MIMi | 618014, phenotype |
OpenTargetsi | ENSG00000164404 |
Orphaneti | 619, NON RARE IN EUROPE: Primary ovarian failure |
PharmGKBi | PA28639 |
Miscellaneous databases
Pharosi | O60383, Tbio |
Genetic variation databases
BioMutai | GDF9 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 24 | Sequence analysisAdd BLAST | 24 | |
PropeptideiPRO_0000033980 | 25 – 319 | Sequence analysisAdd BLAST | 295 | |
ChainiPRO_0000033981 | 320 – 454 | Growth/differentiation factor 9Add BLAST | 135 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 106 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 163 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 236 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 255 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 268 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 325 | Phosphoserine; by CK1 Publication | 1 | |
Glycosylationi | 338 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 353 ↔ 419 | By similarity | ||
Disulfide bondi | 382 ↔ 451 | By similarity | ||
Disulfide bondi | 386 ↔ 453 | By 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, PhosphoproteinProteomic databases
PaxDbi | O60383 |
PeptideAtlasi | O60383 |
PRIDEi | O60383 |
ProteomicsDBi | 49386 |
PTM databases
GlyGeni | O60383, 6 sites |
iPTMneti | O60383 |
PhosphoSitePlusi | O60383 |
Expressioni
Tissue specificityi
Expressed in ovarian granulosa cells. Present in oocytes of primary follicles (at protein level).2 Publications
Gene expression databases
Bgeei | ENSG00000164404, Expressed in oocyte and 117 other tissues |
ExpressionAtlasi | O60383, baseline and differential |
Genevisiblei | O60383, HS |
Organism-specific databases
HPAi | ENSG00000164404, Group enriched (epididymis, testis) |
Interactioni
Subunit structurei
Homodimer or heterodimer (Potential). But, in contrast to other members of this family, cannot be disulfide-linked (By similarity).
By similarityCuratedGO - Molecular functioni
- cytokine activity Source: GO_Central
- growth factor activity Source: ProtInc
- type I activin receptor binding Source: GO_Central
Protein-protein interaction databases
BioGRIDi | 108930, 53 interactors |
IntActi | O60383, 50 interactors |
MINTi | O60383 |
STRINGi | 9606.ENSP00000367942 |
Miscellaneous databases
RNActi | O60383, protein |
Family & Domainsi
Sequence similaritiesi
Belongs to the TGF-beta family.Curated
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG3900, Eukaryota |
GeneTreei | ENSGT00940000159784 |
InParanoidi | O60383 |
OMAi | LKLDHWI |
OrthoDBi | 724783at2759 |
PhylomeDBi | O60383 |
TreeFami | TF351788 |
Family and domain databases
Gene3Di | 2.10.90.10, 1 hit |
InterProi | View protein in InterPro IPR029034, Cystine-knot_cytokine IPR015617, Growth_differentiation_fac-9 IPR001839, TGF-b_C IPR015615, TGF-beta-rel IPR017948, TGFb_CS |
PANTHERi | PTHR11848, PTHR11848, 1 hit PTHR11848:SF19, PTHR11848:SF19, 1 hit |
Pfami | View protein in Pfam PF00019, TGF_beta, 1 hit |
SMARTi | View protein in SMART SM00204, TGFB, 1 hit |
SUPFAMi | SSF57501, SSF57501, 1 hit |
PROSITEi | View protein in PROSITE PS00250, TGF_BETA_1, 1 hit PS51362, TGF_BETA_2, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
O60383-1 [UniParc]FASTAAdd to basket
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
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketB4DXG3 | B4DXG3_HUMAN | Growth/differentiation factor 9 | GDF9 | 366 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_066934 | 57 | D → Y in POF14; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs138136756Ensembl. | 1 | |
Natural variantiVAR_058945 | 67 | K → E in POF14; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_066935 | 103 | P → S in POF14; unknown pathological significance; also found at higher frequency in mothers of dizygotic twins than in controls. 2 PublicationsCorresponds to variant dbSNP:rs61754583Ensembl. | 1 | |
Natural variantiVAR_066936 | 121 | T → I Found at higher frequency in mothers of dizygotic twins than in controls. 1 PublicationCorresponds to variant dbSNP:rs149821575Ensembl. | 1 | |
Natural variantiVAR_066937 | 146 | R → C in POF14; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs76349024Ensembl. | 1 | |
Natural variantiVAR_058946 | 186 | S → Y in POF14; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_058947 | 216 | V → M in POF14; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1205723048Ensembl. | 1 | |
Natural variantiVAR_066938 | 238 | T → A in POF14; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_066939 | 374 | P → L Found at higher frequency in mothers of dizygotic twins than in controls. 1 PublicationCorresponds to variant dbSNP:rs373477788Ensembl. | 1 | |
Natural variantiVAR_066940 | 428 | S → T in POF14; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs118080183Ensembl. | 1 | |
Natural variantiVAR_066941 | 454 | R → C Found at higher frequency in mothers of dizygotic twins than in controls. 1 PublicationCorresponds to variant dbSNP:rs61754582Ensembl. | 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 |
CCDSi | CCDS4162.1 |
RefSeqi | NP_001275753.1, NM_001288824.2 NP_005251.1, NM_005260.5 XP_011541610.1, XM_011543308.2 |
Genome annotation databases
Ensembli | ENST00000378673; ENSP00000367942; ENSG00000164404 |
GeneIDi | 2661 |
KEGGi | hsa:2661 |
UCSCi | uc003kxz.3, human |
Similar proteinsi
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 |
CCDSi | CCDS4162.1 |
RefSeqi | NP_001275753.1, NM_001288824.2 NP_005251.1, NM_005260.5 XP_011541610.1, XM_011543308.2 |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 108930, 53 interactors |
IntActi | O60383, 50 interactors |
MINTi | O60383 |
STRINGi | 9606.ENSP00000367942 |
PTM databases
GlyGeni | O60383, 6 sites |
iPTMneti | O60383 |
PhosphoSitePlusi | O60383 |
Genetic variation databases
BioMutai | GDF9 |
Proteomic databases
PaxDbi | O60383 |
PeptideAtlasi | O60383 |
PRIDEi | O60383 |
ProteomicsDBi | 49386 |
Protocols and materials databases
Antibodypediai | 26178, 555 antibodies |
Genome annotation databases
Ensembli | ENST00000378673; ENSP00000367942; ENSG00000164404 |
GeneIDi | 2661 |
KEGGi | hsa:2661 |
UCSCi | uc003kxz.3, human |
Organism-specific databases
CTDi | 2661 |
DisGeNETi | 2661 |
GeneCardsi | GDF9 |
HGNCi | HGNC:4224, GDF9 |
HPAi | ENSG00000164404, Group enriched (epididymis, testis) |
MalaCardsi | GDF9 |
MIMi | 601918, gene 618014, phenotype |
neXtProti | NX_O60383 |
OpenTargetsi | ENSG00000164404 |
Orphaneti | 619, NON RARE IN EUROPE: Primary ovarian failure |
PharmGKBi | PA28639 |
VEuPathDBi | HostDB:ENSG00000164404.8 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3900, Eukaryota |
GeneTreei | ENSGT00940000159784 |
InParanoidi | O60383 |
OMAi | LKLDHWI |
OrthoDBi | 724783at2759 |
PhylomeDBi | O60383 |
TreeFami | TF351788 |
Enzyme and pathway databases
PathwayCommonsi | O60383 |
Miscellaneous databases
BioGRID-ORCSi | 2661, 3 hits in 985 CRISPR screens |
ChiTaRSi | GDF9, human |
GeneWikii | Growth_differentiation_factor-9 |
GenomeRNAii | 2661 |
Pharosi | O60383, Tbio |
PROi | PR:O60383 |
RNActi | O60383, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000164404, Expressed in oocyte and 117 other tissues |
ExpressionAtlasi | O60383, baseline and differential |
Genevisiblei | O60383, HS |
Family and domain databases
Gene3Di | 2.10.90.10, 1 hit |
InterProi | View protein in InterPro IPR029034, Cystine-knot_cytokine IPR015617, Growth_differentiation_fac-9 IPR001839, TGF-b_C IPR015615, TGF-beta-rel IPR017948, TGFb_CS |
PANTHERi | PTHR11848, PTHR11848, 1 hit PTHR11848:SF19, PTHR11848:SF19, 1 hit |
Pfami | View protein in Pfam PF00019, TGF_beta, 1 hit |
SMARTi | View protein in SMART SM00204, TGFB, 1 hit |
SUPFAMi | SSF57501, SSF57501, 1 hit |
PROSITEi | View protein in PROSITE PS00250, TGF_BETA_1, 1 hit PS51362, TGF_BETA_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | GDF9_HUMAN | |
Accessioni | O60383Primary (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: | April 7, 2021 | |
This is version 163 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 5
Human chromosome 5: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families