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O95972 (BMP15_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 123. 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:
Bone morphogenetic protein 15

Short name=BMP-15
Alternative name(s):
Growth/differentiation factor 9B
Short name=GDF-9B
Gene names
Name:BMP15
Synonyms:GDF9B
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length392 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May be involved in follicular development. Oocyte-specific growth/differentiation factor that stimulates folliculogenesis and granulosa cell (GC) growth. Ref.5

Subunit structure

Homodimer. But, in contrast to other members of this family, cannot be disulfide-linked. Ref.5

Subcellular location

Secreted.

Involvement in disease

Ovarian dysgenesis 2 (ODG2) [MIM:300510]: A disorder characterized by lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism as a result of streak gonads.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7

Premature ovarian failure 4 (POF4) [MIM:300510]: An 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12

Miscellaneous

The mature protein migrates in two distinct mature proteins, P16 (16KDa) and P17 (17KDa).

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.6, 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 – 1818 Potential
Propeptide19 – 267249
PRO_0000033892
Chain268 – 392125Bone morphogenetic protein 15
PRO_0000033893

Amino acid modifications

Modified residue2681Pyrrolidone carboxylic acid; in P16 and P17
Modified residue2731Phosphoserine; in P16 Ref.5
Glycosylation871N-linked (GlcNAc...) Potential
Glycosylation1471N-linked (GlcNAc...) Potential
Glycosylation2371N-linked (GlcNAc...) Potential
Glycosylation2771O-linked (HexNAc...); in P17 Ref.5
Glycosylation3731N-linked (GlcNAc...) Potential
Disulfide bond291 ↔ 357 By similarity
Disulfide bond320 ↔ 389 By similarity
Disulfide bond324 ↔ 391 By similarity

Natural variations

Natural variant51S → R Polymorphism with no or minor deleterious effect observed. Ref.11
Corresponds to variant rs113099187 [ dbSNP | Ensembl ].
VAR_058974
Natural variant611R → Q in POF4. Ref.9
VAR_058975
Natural variant611R → W in POF4. Ref.9
VAR_058976
Natural variant681R → W in POF4; leads to marked reduction of mature protein production; does not generate a complete recovery of wild-type activity in granulosa cell line transfected with defective mutant and with equal amount of wild-type protein. Ref.10 Ref.11
Corresponds to variant rs104894763 [ dbSNP | Ensembl ].
VAR_058977
Natural variant761R → C in POF4. Ref.9
VAR_058978
Natural variant761R → H in POF4. Ref.9
VAR_058979
Natural variant1031N → S. Ref.1 Ref.9
Corresponds to variant rs41308602 [ dbSNP | Ensembl ].
VAR_058980
Natural variant1381R → H in POF4; leads to marked reduction of mature protein production; does not generate a complete recovery of wild-type activity in granulosa cell line transfected with defective mutant and with equal amount of wild-type protein. Ref.11
VAR_058981
Natural variant1481L → P in POF4; leads to marked reduction of mature protein production; does not generate a complete recovery of wild-type activity in granulosa cell line transfected with defective mutant and with equal amount of wild-type protein. Ref.8 Ref.11
Corresponds to variant rs114823607 [ dbSNP | Ensembl ].
VAR_058982
Natural variant1801A → F Requires 2 nucleotide substitutions. Ref.9
VAR_058983
Natural variant1801A → T in POF4; unknown pathological significance; no or minor deleterious effect detected. Ref.8 Ref.9 Ref.10 Ref.11
Corresponds to variant rs104894767 [ dbSNP | Ensembl ].
VAR_058984
Natural variant1961N → K in POF4. Ref.9
VAR_058985
Natural variant2001H → Y. Ref.12
Corresponds to variant rs202165852 [ dbSNP | Ensembl ].
VAR_066932
Natural variant2061R → H in POF4. Ref.9
VAR_058986
Natural variant2211W → R in POF4. Ref.9
VAR_058987
Natural variant2351Y → C in ODG2; dominant-negative effect; may cause relevant modifications in the conformation of the precursor protein possibly leading to altered processing and impaired activation of latent forms or to abnormal dimerization. Ref.7 Ref.10
VAR_021195
Natural variant2431I → V in POF4. Ref.9
VAR_058988
Natural variant2631L → LL No or minor deleterious effect detected. Ref.8 Ref.9 Ref.10 Ref.11
VAR_058989
Natural variant3291R → C in POF4. Ref.12
VAR_066933

Sequences

Sequence LengthMass (Da)Tools
O95972 [UniParc].

Last modified August 16, 2004. Version 2.
Checksum: A957275EF275A2E8

FASTA39245,055
        10         20         30         40         50         60 
MVLLSILRIL FLCELVLFME HRAQMAEGGQ SSIALLAEAP TLPLIEELLE ESPGEQPRKP 

        70         80         90        100        110        120 
RLLGHSLRYM LELYRRSADS HGHPRENRTI GATMVRLVKP LTNVARPHRG TWHIQILGFP 

       130        140        150        160        170        180 
LRPNRGLYQL VRATVVYRHH LQLTRFNLSC HVEPWVQKNP TNHFPSSEGD SSKPSLMSNA 

       190        200        210        220        230        240 
WKEMDITQLV QQRFWNNKGH RILRLRFMCQ QQKDSGGLEL WHGTSSLDIA FLLLYFNDTH 

       250        260        270        280        290        300 
KSIRKAKFLP RGMEEFMERE SLLRRTRQAD GISAEVTASS SKHSGPENNQ CSLHPFQISF 

       310        320        330        340        350        360 
RQLGWDHWII APPFYTPNYC KGTCLRVLRD GLNSPNHAII QNLINQLVDQ SVPRPSCVPY 

       370        380        390 
KYVPISVLMI EANGSILYKE YEGMIAESCT CR 

« Hide

References

« Hide 'large scale' references
[1]"The bone morphogenetic protein 15 gene is X-linked and expressed in oocytes."
Dube J.L., Wang P., Elvin J., Lyons K.M., Celeste A.J., Matzuk M.M.
Mol. Endocrinol. 12:1809-1817(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT SER-103.
[2]"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: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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].
[5]"Characterization of the post-translational modification of recombinant human BMP-15 mature protein."
Saito S., Yano K., Sharma S., McMahon H.E., Shimasaki S.
Protein Sci. 17:362-370(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PYROGLUTAMATE FORMATION AT GLN-268, PHOSPHORYLATION AT SER-273, GLYCOSYLATION AT THR-277, HOMODIMERIZATION.
[6]"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.
[7]"Hypergonadotropic ovarian failure associated with an inherited mutation of human bone morphogenetic protein-15 (BMP15) gene."
Di Pasquale E., Beck-Peccoz P., Persani L.
Am. J. Hum. Genet. 75:106-111(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ODG2 CYS-235, CHARACTERIZATION OF VARIANT ODG2 CYS-235.
[8]"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: VARIANTS POF4 PRO-148 AND THR-180, VARIANT LEU-263 INS.
[9]"Missense mutations in the BMP15 gene are associated with ovarian failure."
Dixit H., Rao L.K., Padmalatha V.V., Kanakavalli M., Deenadayal M., Gupta N., Chakrabarty B., Singh L.
Hum. Genet. 119:408-415(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS POF4 TRP-61; GLN-61; CYS-76; HIS-76; THR-180; LYS-196; HIS-206; ARG-221 AND VAL-243, VARIANTS SER-103; PHE-180 AND LEU-263 INS.
[10]"Identification of new variants of human BMP15 gene in a large cohort of women with premature ovarian failure."
Di Pasquale E., Rossetti R., Marozzi A., Bodega B., Borgato S., Cavallo L., Einaudi S., Radetti G., Russo G., Sacco M., Wasniewska M., Cole T., Beck-Peccoz P., Nelson L.M., Persani L.
J. Clin. Endocrinol. Metab. 91:1976-1979(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS POF4 TRP-68; THR-180 AND CYS-235, VARIANT LEU-263 INS.
[11]"BMP15 mutations associated with primary ovarian insufficiency cause a defective production of bioactive protein."
Rossetti R., Di Pasquale E., Marozzi A., Bione S., Toniolo D., Grammatico P., Nelson L.M., Beck-Peccoz P., Persani L.
Hum. Mutat. 30:804-810(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS POF4 TRP-68; HIS-138; PRO-148 AND THR-180, VARIANTS ARG-5 AND LEU-263 INS, CHARACTERIZATION OF VARIANTS POF4 TRP-68; HIS-138; PRO-148 AND THR-180, CHARACTERIZATION OF VARIANTS ARG-5 AND LEU-263 INS.
[12]"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-200, VARIANT POF4 CYS-329.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF082350, AF082349 Genomic DNA. Translation: AAC99768.1.
AJ132405 Genomic DNA. Translation: CAB43531.1.
AL359914 Genomic DNA. Translation: CAI41226.1.
BC069155 mRNA. Translation: AAH69155.1.
BC117264 mRNA. Translation: AAI17265.1.
BC117266 mRNA. Translation: AAI17267.1.
CCDSCCDS14334.1.
RefSeqNP_005439.2. NM_005448.2.
UniGeneHs.532692.

3D structure databases

ProteinModelPortalO95972.
SMRO95972. Positions 290-392.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000252677.

PTM databases

PhosphoSiteO95972.

Proteomic databases

PaxDbO95972.
PRIDEO95972.

Protocols and materials databases

DNASU9210.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000252677; ENSP00000252677; ENSG00000130385.
ENST00000598029; ENSP00000469070; ENSG00000269479.
GeneID9210.
KEGGhsa:9210.
UCSCuc011mnw.2. human.

Organism-specific databases

CTD9210.
GeneCardsGC0XP050670.
HGNCHGNC:1068. BMP15.
MIM300247. gene.
300510. phenotype.
neXtProtNX_O95972.
Orphanet243. 46,XX gonadal dysgenesis.
619. Primary ovarian failure.
PharmGKBPA25378.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG298347.
HOGENOMHOG000095242.
HOVERGENHBG004660.
InParanoidO95972.
KOK05498.
OMANQCSLHP.
OrthoDBEOG70W3DJ.
PhylomeDBO95972.
TreeFamTF316134.

Enzyme and pathway databases

SignaLinkO95972.

Gene expression databases

BgeeO95972.
CleanExHS_BMP15.
GenevestigatorO95972.

Family and domain databases

Gene3D2.10.90.10. 1 hit.
InterProIPR015923. BMP-15.
IPR029034. Cystine-knot_cytokine.
IPR002405. Inhibin_asu.
IPR001839. TGF-b_C.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view]
PANTHERPTHR11848. PTHR11848. 1 hit.
PTHR11848:SF22. PTHR11848:SF22. 1 hit.
PfamPF00019. TGF_beta. 1 hit.
[Graphical view]
PRINTSPR00669. INHIBINA.
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

GeneWikiBone_morphogenetic_protein_15.
GenomeRNAi9210.
NextBio34527.
PROO95972.
SOURCESearch...

Entry information

Entry nameBMP15_HUMAN
AccessionPrimary (citable) accession number: O95972
Secondary accession number(s): Q17RM6, Q5JST1, Q9UMS1
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: August 16, 2004
Last modified: July 9, 2014
This is version 123 of the entry and version 2 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 X

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