Bone morphogenetic protein 15

Bone morphogenetic protein 15
Identifiers
Symbols	BMP15 ; GDF9B; ODG2; POF4
External IDs	OMIM: 300247 MGI: 1316745 HomoloGene: 3977 GeneCards: BMP15 Gene
Gene ontology Molecular function • cytokine activity • transforming growth factor beta receptor binding • growth factor activity Cellular component • extracellular space • cytoplasm Biological process • ovarian follicle development • female gamete generation • positive regulation of pathway-restricted SMAD protein phosphorylation • BMP signaling pathway • regulation of apoptotic process • regulation of MAPK cascade • cell development • granulosa cell development • SMAD protein signal transduction Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	9210	12155
Ensembl	ENSG00000130385	ENSMUSG00000023279
UniProt	O95972	Q9Z0L4
RefSeq (mRNA)	NM_005448	NM_009757
RefSeq (protein)	NP_005439	NP_033887
Location (UCSC)	Chr X: 50.91 – 50.92 Mb	Chr X: 6.31 – 6.32 Mb
PubMed search

Bone morphogenetic protein 15 is a protein that in humans is encoded by the BMP15 gene.^[1][2] It's mainly involved in folliculogenesis.^[3]

Structure and expression

The protein encoded by this gene is a member of the TGF-β superfamily. It is a paracrine signaling molecule involved in oocyte and follicular development. Using Northern blot analysis, BMP15 has been shown to be exclusively expressed in the ovaries. It is thought that this protein may be involved in oocyte maturation and follicular development as a homodimer or by forming heterodimers with a related protein, Gdf9.^[2]

Functions

The functions of BMP15 include:^[3]

• Promotion of growth and maturation of ovarian follicles, starting from the primary gonadotrophin-independent phases of folliculogenesis.
• Regulation of the sensitivity of granulosa cells to follicle-stimulating hormone (FSH) action, contributing to the determination of the number of eggs that are ovulated.
• Prevention of granulosa cell apoptosis.
• Promotion of developmental competence of oocytes.

Defects in BMP15 are associated with primary ovarian insufficiency. BMP15may represent a biomarker of ovarian response to ovarian stimulation or oocyte quality.^[3]

References

1. Dube JL, Wang P, Elvin J, Lyons KM, Celeste AJ, Matzuk MM (Feb 1999). "The bone morphogenetic protein 15 gene is X-linked and expressed in oocytes". Mol Endocrinol 12 (12): 1809–17. doi:10.1210/me.12.12.1809. PMID 9849956.
2. "Entrez Gene: BMP15 bone morphogenetic protein 15".
3. Persani, L.; Rossetti, R.; Di Pasquale, E.; Cacciatore, C.; Fabre, S. (2014). "The fundamental role of bone morphogenetic protein 15 in ovarian function and its involvement in female fertility disorders". Human Reproduction Update 20 (6): 869–883. doi:10.1093/humupd/dmu036. ISSN 1355-4786.

Further reading

• Aaltonen J, Laitinen MP, Vuojolainen K; et al. (1999). "Human growth differentiation factor 9 (GDF-9) and its novel homolog GDF-9B are expressed in oocytes during early folliculogenesis.". J. Clin. Endocrinol. Metab. 84 (8): 2744–50. doi:10.1210/jc.84.8.2744. PMID 10443672.
• Galloway SM, McNatty KP, Cambridge LM; et al. (2000). "Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner.". Nat. Genet. 25 (3): 279–83. doi:10.1038/77033. PMID 10888873.
• Otsuka F, Yao Z, Lee T; et al. (2001). "Bone morphogenetic protein-15. Identification of target cells and biological functions.". J. Biol. Chem. 275 (50): 39523–8. doi:10.1074/jbc.M007428200. PMID 10998422.
• Otsuka F, Moore RK, Iemura S; et al. (2002). "Follistatin inhibits the function of the oocyte-derived factor BMP-15.". Biochem. Biophys. Res. Commun. 289 (5): 961–6. doi:10.1006/bbrc.2001.6103. PMID 11741284.
• Moore RK, Otsuka F, Shimasaki S (2003). "Molecular basis of bone morphogenetic protein-15 signaling in granulosa cells.". J. Biol. Chem. 278 (1): 304–10. doi:10.1074/jbc.M207362200. PMID 12419820.
• Liao WX, Moore RK, Otsuka F, Shimasaki S (2003). "Effect of intracellular interactions on the processing and secretion of bone morphogenetic protein-15 (BMP-15) and growth and differentiation factor-9. Implication of the aberrant ovarian phenotype of BMP-15 mutant sheep.". J. Biol. Chem. 278 (6): 3713–9. doi:10.1074/jbc.M210598200. PMID 12446716.
• Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Liao WX, Moore RK, Shimasaki S (2004). "Functional and molecular characterization of naturally occurring mutations in the oocyte-secreted factors bone morphogenetic protein-15 and growth and differentiation factor-9.". J. Biol. Chem. 279 (17): 17391–6. doi:10.1074/jbc.M401050200. PMID 14970198.
• Di Pasquale E, Beck-Peccoz P, Persani L (2004). "Hypergonadotropic ovarian failure associated with an inherited mutation of human bone morphogenetic protein-15 (BMP15) gene.". Am. J. Hum. Genet. 75 (1): 106–11. doi:10.1086/422103. PMC 1181993. PMID 15136966.
• Gerhard DS, Wagner L, Feingold EA; et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Ross MT, Grafham DV, Coffey AJ; et al. (2005). "The DNA sequence of the human X chromosome.". Nature 434 (7031): 325–37. doi:10.1038/nature03440. PMC 2665286. PMID 15772651.
• Hashimoto O, Moore RK, Shimasaki S (2005). "Posttranslational processing of mouse and human BMP-15: potential implication in the determination of ovulation quota.". Proc. Natl. Acad. Sci. U.S.A. 102 (15): 5426–31. doi:10.1073/pnas.0409533102. PMC 556231. PMID 15809424.
• Dixit H, Rao LK, Padmalatha VV; et al. (2006). "Missense mutations in the BMP15 gene are associated with ovarian failure.". Hum. Genet. 119 (4): 408–15. doi:10.1007/s00439-006-0150-0. PMID 16508750.
• Laissue P, Christin-Maitre S, Touraine P; et al. (2006). "Mutations and sequence variants in GDF9 and BMP15 in patients with premature ovarian failure.". Eur. J. Endocrinol. 154 (5): 739–44. doi:10.1530/eje.1.02135. PMID 16645022.
• Chand AL, Ponnampalam AP, Harris SE; et al. (2006). "Mutational analysis of BMP15 and GDF9 as candidate genes for premature ovarian failure.". Fertil. Steril. 86 (4): 1009–12. doi:10.1016/j.fertnstert.2006.02.107. PMID 17027369.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.