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O60383

- GDF9_HUMAN

UniProt

O60383 - GDF9_HUMAN

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Protein

Growth/differentiation factor 9

Gene
GDF9
Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. growth factor activity Source: ProtInc

GO - Biological processi

  1. female gamete generation Source: ProtInc
  2. negative regulation of cell growth Source: Ensembl
  3. oocyte growth Source: Ensembl
  4. positive regulation of cell proliferation Source: UniProtKB
  5. regulation of progesterone secretion Source: UniProtKB
  6. transforming growth factor beta receptor signaling pathway Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Growth factor

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
ProteomesiUP000005640: Chromosome 5

Organism-specific databases

HGNCiHGNC:4224. GDF9.

Subcellular locationi

Secreted By similarity

GO - Cellular componenti

  1. extracellular space Source: UniProtKB-KW
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

PharmGKBiPA28639.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424 Reviewed predictionAdd
BLAST
Propeptidei25 – 319295 Reviewed predictionPRO_0000033980Add
BLAST
Chaini320 – 454135Growth/differentiation factor 9PRO_0000033981Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi106 – 1061N-linked (GlcNAc...) Reviewed prediction
Glycosylationi163 – 1631N-linked (GlcNAc...) Reviewed prediction
Glycosylationi236 – 2361N-linked (GlcNAc...) Reviewed prediction
Glycosylationi255 – 2551N-linked (GlcNAc...) Reviewed prediction
Glycosylationi268 – 2681N-linked (GlcNAc...) Reviewed prediction
Modified residuei325 – 3251Phosphoserine; by CK Inferred
Glycosylationi338 – 3381N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi353 ↔ 419 By similarity
Disulfide bondi382 ↔ 451 By similarity
Disulfide bondi386 ↔ 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, Phosphoprotein

Proteomic databases

PaxDbiO60383.
PRIDEiO60383.

PTM databases

PhosphoSiteiO60383.

Expressioni

Tissue specificityi

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

Gene expression databases

ArrayExpressiO60383.
BgeeiO60383.
CleanExiHS_GDF9.
GenevestigatoriO60383.

Interactioni

Subunit structurei

Homodimer or heterodimer Reviewed prediction. But, in contrast to other members of this family, cannot be disulfide-linked By similarity.

Protein-protein interaction databases

BioGridi108930. 39 interactions.
IntActiO60383. 39 interactions.
MINTiMINT-1430245.
STRINGi9606.ENSP00000296875.

Structurei

3D structure databases

ProteinModelPortaliO60383.
SMRiO60383. Positions 353-454.

Family & Domainsi

Sequence similaritiesi

Belongs to the TGF-beta family.

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG261730.
HOGENOMiHOG000073526.
HOVERGENiHBG004660.
InParanoidiO60383.
KOiK05498.
OMAiDNWIVAP.
OrthoDBiEOG70W3DJ.
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. 1 hit.
PTHR11848:SF19. PTHR11848:SF19. 1 hit.
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

MARPNKFLLW FCCFAWLCFP ISLGSQASGG EAQIAASAEL ESGAMPWSLL    50
QHIDERDRAG LLPALFKVLS VGRGGSPRLQ PDSRALHYMK KLYKTYATKE 100
GIPKSNRSHL YNTVRLFTPC TRHKQAPGDQ VTGILPSVEL LFNLDRITTV 150
EHLLKSVLLY NINNSVSFSS AVKCVCNLMI KEPKSSSRTL GRAPYSFTFN 200
SQFEFGKKHK WIQIDVTSLL QPLVASNKRS IHMSINFTCM KDQLEHPSAQ 250
NGLFNMTLVS PSLILYLNDT SAQAYHSWYS LHYKRRPSQG PDQERSLSAY 300
PVGEEAAEDG RSSHHRHRRG QETVSSELKK PLGPASFNLS EYFRQFLLPQ 350
NECELHDFRL SFSQLKWDNW IVAPHRYNPR YCKGDCPRAV GHRYGSPVHT 400
MVQNIIYEKL DSSVPRPSCV PAKYSPLSVL TIEPDGSIAY KEYEDMIATK 450
CTCR 454
Length:454
Mass (Da):51,444
Last modified:August 1, 1998 - v1
Checksum:i94EA366E90CDBC27
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti57 – 571D → Y.1 Publication
Corresponds to variant rs138136756 [ dbSNP | Ensembl ].
VAR_066934
Natural varianti67 – 671K → E in some patients with premature ovarian failure. 1 Publication
VAR_058945
Natural varianti103 – 1031P → S.2 Publications
Corresponds to variant rs61754583 [ dbSNP | Ensembl ].
VAR_066935
Natural varianti121 – 1211T → I.1 Publication
Corresponds to variant rs149821575 [ dbSNP | Ensembl ].
VAR_066936
Natural varianti146 – 1461R → C.1 Publication
Corresponds to variant rs76349024 [ dbSNP | Ensembl ].
VAR_066937
Natural varianti186 – 1861S → Y in a patient with premature ovarian failure. 1 Publication
VAR_058946
Natural varianti216 – 2161V → M in two patients with premature ovarian failure. 1 Publication
VAR_058947
Natural varianti238 – 2381T → A in a patient with premature ovarian failure. 1 Publication
VAR_066938
Natural varianti374 – 3741P → L Rare variant found in mothers of dizygotic twins. 1 Publication
VAR_066939
Natural varianti428 – 4281S → T.1 Publication
Corresponds to variant rs118080183 [ dbSNP | Ensembl ].
VAR_066940
Natural varianti454 – 4541R → C.1 Publication
Corresponds to variant rs61754582 [ dbSNP | Ensembl ].
VAR_066941

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_005260.4.
UniGeneiHs.25022.
Hs.739230.
Hs.742490.

Genome annotation databases

EnsembliENST00000296875; ENSP00000296875; ENSG00000164404.
ENST00000378673; ENSP00000367942; ENSG00000164404.
GeneIDi2661.
KEGGihsa:2661.
UCSCiuc003kxz.1. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_005260.4.
UniGenei Hs.25022.
Hs.739230.
Hs.742490.

3D structure databases

ProteinModelPortali O60383.
SMRi O60383. Positions 353-454.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 108930. 39 interactions.
IntActi O60383. 39 interactions.
MINTi MINT-1430245.
STRINGi 9606.ENSP00000296875.

PTM databases

PhosphoSitei O60383.

Proteomic databases

PaxDbi O60383.
PRIDEi O60383.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000296875 ; ENSP00000296875 ; ENSG00000164404 .
ENST00000378673 ; ENSP00000367942 ; ENSG00000164404 .
GeneIDi 2661.
KEGGi hsa:2661.
UCSCi uc003kxz.1. human.

Organism-specific databases

CTDi 2661.
GeneCardsi GC05M132196.
HGNCi HGNC:4224. GDF9.
MIMi 601918. gene.
neXtProti NX_O60383.
PharmGKBi PA28639.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG261730.
HOGENOMi HOG000073526.
HOVERGENi HBG004660.
InParanoidi O60383.
KOi K05498.
OMAi DNWIVAP.
OrthoDBi EOG70W3DJ.
PhylomeDBi O60383.
TreeFami TF351788.

Miscellaneous databases

GeneWikii Growth_differentiation_factor-9.
GenomeRNAii 2661.
NextBioi 10504.
PROi O60383.
SOURCEi Search...

Gene expression databases

ArrayExpressi O60383.
Bgeei O60383.
CleanExi HS_GDF9.
Genevestigatori O60383.

Family and domain databases

Gene3Di 2.10.90.10. 1 hit.
InterProi IPR029034. Cystine-knot_cytokine.
IPR015617. Growth_differentiation_fac-9.
IPR001839. TGF-b_C.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view ]
PANTHERi PTHR11848. PTHR11848. 1 hit.
PTHR11848:SF19. PTHR11848:SF19. 1 hit.
Pfami PF00019. TGF_beta. 1 hit.
[Graphical view ]
SMARTi SM00204. TGFB. 1 hit.
[Graphical view ]
SUPFAMi SSF57501. SSF57501. 1 hit.
PROSITEi PS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "The DNA sequence and comparative analysis of human chromosome 5."
    Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.
    , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
    Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  2. "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].
  3. "Human growth differentiation factor 9 (GDF-9) and its novel homolog GDF-9B are expressed in oocytes during early folliculogenesis."
    Aaltonen J., Laitinen M.P., Vuojolainen K., Jaatinen R., Horelli-Kuitunen N., Seppae L., Louhio H., Tuuri T., Sjoeberg J., Buetzow R., Hovatta O., Dale L., Ritvos O.
    J. Clin. Endocrinol. Metab. 84:2744-2750(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  4. "Growth differentiation factor-9 inhibits 3'5'-adenosine monophosphate-stimulated steroidogenesis in human granulosa and theca cells."
    Yamamoto N., Christenson L.K., McAllister J.M., Strauss J.F. III
    J. Clin. Endocrinol. Metab. 87:2849-2856(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS REGULATOR OF PROGESTERONE RELEASE, TISSUE SPECIFICITY.
  5. Erratum
    Yamamoto N., Christenson L.K., McAllister J.M., Strauss J.F. III
    J. Clin. Endocrinol. Metab. 87:4495-4495(2002)
  6. "Phosphorylation of bone morphogenetic protein-15 and growth and differentiation factor-9 plays a critical role in determining agonistic or antagonistic functions."
    McMahon H.E., Sharma S., Shimasaki S.
    Endocrinology 149:812-817(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION.
  7. "Effects of growth differentiation factor 9 on cell cycle regulators and ERK42/44 in human granulosa cell proliferation."
    Huang Q., Cheung A.P., Zhang Y., Huang H.F., Auersperg N., Leung P.C.
    Am. J. Physiol. 296:E1344-E1353(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN GRANULOSA CELLS PROLIFERATION.
  8. "Golgi apparatus casein kinase phosphorylates bioactive Ser-6 of bone morphogenetic protein 15 and growth and differentiation factor 9."
    Tibaldi E., Arrigoni G., Martinez H.M., Inagaki K., Shimasaki S., Pinna L.A.
    FEBS Lett. 584:801-805(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-325 BY CK, IDENTIFICATION BY MASS SPECTROMETRY.
  9. "Growth differentiation factor 9 reverses activin A suppression of steroidogenic acute regulatory protein expression and progesterone production in human granulosa-lutein cells."
    Shi F.T., Cheung A.P., Klausen C., Huang H.F., Leung P.C.
    J. Clin. Endocrinol. Metab. 95:E172-E180(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS REGULATOR OF STAR EXPRESSION AND PROGESTERONE RELEASE.
  10. "Growth differentiating factor 9 (GDF9) and bone morphogenetic protein 15 both activate development of human primordial follicles in vitro, with seemingly more beneficial effects of GDF9."
    Kedem A., Fisch B., Garor R., Ben-Zaken A., Gizunterman T., Felz C., Ben-Haroush A., Kravarusic D., Abir R.
    J. Clin. Endocrinol. Metab. 96:E1246-E1254(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PRIMORDIAL FOLLICLE DEVELOPMENT.
  11. "Growth differentiation factor 9 (GDF9) suppresses follistatin and follistatin-like 3 production in human granulosa-lutein cells."
    Shi F.T., Cheung A.P., Huang H.F., Leung P.C.
    PLoS ONE 6:E22866-E22866(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  12. "The ratio of growth differentiation factor 9: bone morphogenetic protein 15 mRNA expression is tightly co-regulated and differs between species over a wide range of ovulation rates."
    Crawford J.L., McNatty K.P.
    Mol. Cell. Endocrinol. 348:339-343(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: SPECIES-SPECIFIC OVULATION RATE DETERMINATION.
  13. "Mutational screening of the coding region of growth differentiation factor 9 gene in Indian women with ovarian failure."
    Dixit H., Rao L.K., Padmalatha V., Kanakavalli M., Deenadayal M., Gupta N., Chakravarty B., Singh L.
    Menopause 12:749-754(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS GLU-67 AND MET-216.
  14. Cited for: VARIANT TYR-186.
  15. Cited for: VARIANTS SER-103; ILE-121; LEU-374 AND CYS-454, POSSIBLE INVOLVEMENT IN OVARIAN DISORDERS.
  16. "Growth differentiating factor-9 mutations may be associated with premature ovarian failure."
    Kovanci E., Rohozinski J., Simpson J.L., Heard M.J., Bishop C.E., Carson S.A.
    Fertil. Steril. 87:143-146(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT SER-103, POSSIBLE INVOLVEMENT IN PREMATURE OVARIAN FAILURE.
  17. "Analyses of GDF9 mutation in 100 Chinese women with premature ovarian failure."
    Zhao H., Qin Y., Kovanci E., Simpson J.L., Chen Z.J., Rajkovic A.
    Fertil. Steril. 88:1474-1476(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS CYS-146; ALA-238 AND THR-428.
  18. "Analyses of growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) mutation in Chinese women with premature ovarian failure."
    Wang B., Wen Q., Ni F., Zhou S., Wang J., Cao Y., Ma X.
    Clin. Endocrinol. (Oxf.) 72:135-136(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT TYR-57.

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: July 9, 2014
This is version 115 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 1 Publication, 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

External Data

Dasty 3

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