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O60383 (GDF9_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 115. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Growth/differentiation factor 9

Short name=GDF-9
Gene names
Name:GDF9
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length454 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.4 Ref.7 Ref.9 Ref.10 Ref.11

Subunit structure

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

Subcellular location

Secreted By similarity.

Tissue specificity

Expressed in ovarian granulosa cells. Present in oocytes of primary follicles (at protein level). Ref.3 Ref.4

Post-translational modification

Phosphorylated; phosphorylation is critical for GDF9 function. In vitro, can be phosphorylated by CK at Ser-325. Ref.6 Ref.8

Involvement in disease

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.

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 Ref.12, mRNA expression levels of GDF9 and BMP15 are tightly coregulated within each species and influence species-specific ovulation-rates.

Sequence similarities

Belongs to the TGF-beta family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Potential
Propeptide25 – 319295 Potential
PRO_0000033980
Chain320 – 454135Growth/differentiation factor 9
PRO_0000033981

Amino acid modifications

Modified residue3251Phosphoserine; by CK Probable
Glycosylation1061N-linked (GlcNAc...) Potential
Glycosylation1631N-linked (GlcNAc...) Potential
Glycosylation2361N-linked (GlcNAc...) Potential
Glycosylation2551N-linked (GlcNAc...) Potential
Glycosylation2681N-linked (GlcNAc...) Potential
Glycosylation3381N-linked (GlcNAc...) Potential
Disulfide bond353 ↔ 419 By similarity
Disulfide bond382 ↔ 451 By similarity
Disulfide bond386 ↔ 453 By similarity

Natural variations

Natural variant571D → Y. Ref.18
Corresponds to variant rs138136756 [ dbSNP | Ensembl ].
VAR_066934
Natural variant671K → E in some patients with premature ovarian failure. Ref.13
VAR_058945
Natural variant1031P → S. Ref.15 Ref.16
Corresponds to variant rs61754583 [ dbSNP | Ensembl ].
VAR_066935
Natural variant1211T → I. Ref.15
Corresponds to variant rs149821575 [ dbSNP | Ensembl ].
VAR_066936
Natural variant1461R → C. Ref.17
Corresponds to variant rs76349024 [ dbSNP | Ensembl ].
VAR_066937
Natural variant1861S → Y in a patient with premature ovarian failure. Ref.14
VAR_058946
Natural variant2161V → M in two patients with premature ovarian failure. Ref.13
VAR_058947
Natural variant2381T → A in a patient with premature ovarian failure. Ref.17
VAR_066938
Natural variant3741P → L Rare variant found in mothers of dizygotic twins. Ref.15
VAR_066939
Natural variant4281S → T. Ref.17
Corresponds to variant rs118080183 [ dbSNP | Ensembl ].
VAR_066940
Natural variant4541R → C. Ref.15
Corresponds to variant rs61754582 [ dbSNP | Ensembl ].
VAR_066941

Sequences

Sequence LengthMass (Da)Tools
O60383 [UniParc].

Last modified August 1, 1998. Version 1.
Checksum: 94EA366E90CDBC27

FASTA45451,444
        10         20         30         40         50         60 
MARPNKFLLW FCCFAWLCFP ISLGSQASGG EAQIAASAEL ESGAMPWSLL QHIDERDRAG 

        70         80         90        100        110        120 
LLPALFKVLS VGRGGSPRLQ PDSRALHYMK KLYKTYATKE GIPKSNRSHL YNTVRLFTPC 

       130        140        150        160        170        180 
TRHKQAPGDQ VTGILPSVEL LFNLDRITTV EHLLKSVLLY NINNSVSFSS AVKCVCNLMI 

       190        200        210        220        230        240 
KEPKSSSRTL GRAPYSFTFN SQFEFGKKHK WIQIDVTSLL QPLVASNKRS IHMSINFTCM 

       250        260        270        280        290        300 
KDQLEHPSAQ NGLFNMTLVS PSLILYLNDT SAQAYHSWYS LHYKRRPSQG PDQERSLSAY 

       310        320        330        340        350        360 
PVGEEAAEDG RSSHHRHRRG QETVSSELKK PLGPASFNLS EYFRQFLLPQ NECELHDFRL 

       370        380        390        400        410        420 
SFSQLKWDNW IVAPHRYNPR YCKGDCPRAV GHRYGSPVHT MVQNIIYEKL DSSVPRPSCV 

       430        440        450 
PAKYSPLSVL TIEPDGSIAY KEYEDMIATK CTCR 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Mutations and sequence variants in GDF9 and BMP15 in patients with premature ovarian failure."
Laissue P., Christin-Maitre S., Touraine P., Kuttenn F., Ritvos O., Aittomaki K., Bourcigaux N., Jacquesson L., Bouchard P., Frydman R., Dewailly D., Reyss A.-C., Jeffery L., Bachelot A., Massin N., Fellous M., Veitia R.A.
Eur. J. Endocrinol. 154:739-744(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TYR-186.
[15]"Novel variants in growth differentiation factor 9 in mothers of dizygotic twins."
Palmer J.S., Zhao Z.Z., Hoekstra C., Hayward N.K., Webb P.M., Whiteman D.C., Martin N.G., Boomsma D.I., Duffy D.L., Montgomery G.W.
J. Clin. Endocrinol. Metab. 91:4713-4716(2006) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS4162.1.
RefSeqNP_001275753.1. NM_001288824.2.
NP_005251.1. NM_005260.4.
UniGeneHs.25022.
Hs.739230.
Hs.742490.

3D structure databases

ProteinModelPortalO60383.
SMRO60383. Positions 353-454.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108930. 39 interactions.
IntActO60383. 39 interactions.
MINTMINT-1430245.
STRING9606.ENSP00000296875.

PTM databases

PhosphoSiteO60383.

Proteomic databases

PaxDbO60383.
PRIDEO60383.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000296875; ENSP00000296875; ENSG00000164404.
ENST00000378673; ENSP00000367942; ENSG00000164404.
GeneID2661.
KEGGhsa:2661.
UCSCuc003kxz.1. human.

Organism-specific databases

CTD2661.
GeneCardsGC05M132196.
HGNCHGNC:4224. GDF9.
MIM601918. gene.
neXtProtNX_O60383.
PharmGKBPA28639.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG261730.
HOGENOMHOG000073526.
HOVERGENHBG004660.
InParanoidO60383.
KOK05498.
OMADNWIVAP.
OrthoDBEOG70W3DJ.
PhylomeDBO60383.
TreeFamTF351788.

Gene expression databases

ArrayExpressO60383.
BgeeO60383.
CleanExHS_GDF9.
GenevestigatorO60383.

Family and domain databases

Gene3D2.10.90.10. 1 hit.
InterProIPR029034. Cystine-knot_cytokine.
IPR015617. Growth_differentiation_fac-9.
IPR001839. TGF-b_C.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view]
PANTHERPTHR11848. PTHR11848. 1 hit.
PTHR11848:SF19. PTHR11848:SF19. 1 hit.
PfamPF00019. TGF_beta. 1 hit.
[Graphical view]
SMARTSM00204. TGFB. 1 hit.
[Graphical view]
SUPFAMSSF57501. SSF57501. 1 hit.
PROSITEPS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiGrowth_differentiation_factor-9.
GenomeRNAi2661.
NextBio10504.
PROO60383.
SOURCESearch...

Entry information

Entry nameGDF9_HUMAN
AccessionPrimary (citable) accession number: O60383
Secondary accession number(s): Q4VAW5
Entry history
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 statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM