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O60383

- GDF9_HUMAN

UniProt

O60383 - GDF9_HUMAN

Protein

Growth/differentiation factor 9

Gene

GDF9

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 116 (01 Oct 2014)
      Sequence version 1 (01 Aug 1998)
      Previous versions | rss
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    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

    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

    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.1 Publication

    Organism-specific databases

    PharmGKBiPA28639.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2424Sequence AnalysisAdd
    BLAST
    Propeptidei25 – 319295Sequence AnalysisPRO_0000033980Add
    BLAST
    Chaini320 – 454135Growth/differentiation factor 9PRO_0000033981Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi106 – 1061N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi163 – 1631N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi236 – 2361N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi255 – 2551N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi268 – 2681N-linked (GlcNAc...)Sequence Analysis
    Modified residuei325 – 3251Phosphoserine; by CK2 Publications
    Glycosylationi338 – 3381N-linked (GlcNAc...)Sequence Analysis
    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.
    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 Potential. But, in contrast to other members of this family, cannot be disulfide-linked By similarity.By similarityCurated

    Protein-protein interaction databases

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

    Structurei

    3D structure databases

    ProteinModelPortaliO60383.
    SMRiO60383. Positions 353-454.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the TGF-beta family.Curated

    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

    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: October 1, 2014
    This is version 116 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

    External Data

    Dasty 3