Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Bone morphogenetic protein 15

Gene

BMP15

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

May be involved in follicular development. Oocyte-specific growth/differentiation factor that stimulates folliculogenesis and granulosa cell (GC) growth.1 Publication

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 PubMed:21970812, mRNA expression levels of GDF9 and BMP15 are tightly coregulated within each species and influence species-specific ovulation-rates.

GO - Molecular functioni

  • cytokine activity Source: GO_Central
  • growth factor activity Source: UniProtKB-KW
  • transforming growth factor beta receptor binding Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionCytokine, Growth factor

Enzyme and pathway databases

ReactomeiR-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275 Post-translational protein phosphorylation
SignaLinkiO95972
SIGNORiO95972

Names & Taxonomyi

Protein namesi
Recommended name:
Bone morphogenetic protein 15
Short name:
BMP-15
Alternative name(s):
Growth/differentiation factor 9B
Short name:
GDF-9B
Gene namesi
Name:BMP15
Synonyms:GDF9B
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000130385.5
HGNCiHGNC:1068 BMP15
MIMi300247 gene
neXtProtiNX_O95972

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Ovarian dysgenesis 2 (ODG2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism as a result of streak gonads.
See also OMIM:300510
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_021195235Y → 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. 2 PublicationsCorresponds to variant dbSNP:rs104894765EnsemblClinVar.1
Premature ovarian failure 4 (POF4)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:300510
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05897561R → Q in POF4. 1 Publication1
Natural variantiVAR_05897661R → W in POF4. 1 PublicationCorresponds to variant dbSNP:rs144392417Ensembl.1
Natural variantiVAR_05897768R → 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. 2 PublicationsCorresponds to variant dbSNP:rs104894763EnsemblClinVar.1
Natural variantiVAR_05897876R → C in POF4. 1 PublicationCorresponds to variant dbSNP:rs104894766EnsemblClinVar.1
Natural variantiVAR_05897976R → H in POF4. 1 Publication1
Natural variantiVAR_058981138R → 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. 1 PublicationCorresponds to variant dbSNP:rs371418883Ensembl.1
Natural variantiVAR_058982148L → 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. 2 PublicationsCorresponds to variant dbSNP:rs114823607EnsemblClinVar.1
Natural variantiVAR_058984180A → T in POF4; unknown pathological significance; no or minor deleterious effect detected. 4 PublicationsCorresponds to variant dbSNP:rs104894767EnsemblClinVar.1
Natural variantiVAR_058985196N → K in POF4. 1 Publication1
Natural variantiVAR_058986206R → H in POF4. 1 PublicationCorresponds to variant dbSNP:rs782516193Ensembl.1
Natural variantiVAR_058987221W → R in POF4. 1 PublicationCorresponds to variant dbSNP:rs375284458Ensembl.1
Natural variantiVAR_058988243I → V in POF4. 1 PublicationCorresponds to variant dbSNP:rs782379521Ensembl.1
Natural variantiVAR_066933329R → C in POF4. 1 PublicationCorresponds to variant dbSNP:rs782375794Ensembl.1

Keywords - Diseasei

Disease mutation, Premature ovarian failure

Organism-specific databases

DisGeNETi9210
MalaCardsiBMP15
MIMi300510 phenotype
OpenTargetsiENSG00000130385
Orphaneti243 46,XX gonadal dysgenesis
619 NON RARE IN EUROPE: Primary ovarian failure
PharmGKBiPA25378

Polymorphism and mutation databases

BioMutaiBMP15

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
PropeptideiPRO_000003389219 – 267Add BLAST249
ChainiPRO_0000033893268 – 392Bone morphogenetic protein 15Add BLAST125

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi87N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi147N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi237N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei268Pyrrolidone carboxylic acid; in P16 and P171 Publication1
Modified residuei273Phosphoserine; in P161 Publication1
Glycosylationi277O-linked (HexNAc...) threonine; in P171 Publication1
Disulfide bondi291 ↔ 357By similarity
Disulfide bondi320 ↔ 389By similarity
Disulfide bondi324 ↔ 391By similarity
Glycosylationi373N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Pyrrolidone carboxylic acid

Proteomic databases

PaxDbiO95972
PeptideAtlasiO95972
PRIDEiO95972
ProteomicsDBi51155

PTM databases

iPTMnetiO95972
PhosphoSitePlusiO95972

Expressioni

Gene expression databases

BgeeiENSG00000130385 Expressed in 9 organ(s), highest expression level in secondary oocyte
CleanExiHS_BMP15
GenevisibleiO95972 HS

Interactioni

Subunit structurei

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114644, 4 interactors
IntActiO95972, 1 interactor
STRINGi9606.ENSP00000252677

Structurei

3D structure databases

ProteinModelPortaliO95972
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the TGF-beta family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3900 Eukaryota
ENOG410XT8Z LUCA
GeneTreeiENSGT00910000143982
HOGENOMiHOG000095242
HOVERGENiHBG004660
InParanoidiO95972
KOiK05498
OMAiLYTPNYC
OrthoDBiEOG091G09RN
PhylomeDBiO95972
TreeFamiTF316134

Family and domain databases

Gene3Di2.10.90.10, 1 hit
InterProiView protein in InterPro
IPR015923 BMP-15
IPR029034 Cystine-knot_cytokine
IPR001839 TGF-b_C
IPR015615 TGF-beta-rel
IPR017948 TGFb_CS
PANTHERiPTHR11848 PTHR11848, 1 hit
PTHR11848:SF22 PTHR11848:SF22, 1 hit
PfamiView protein in Pfam
PF00019 TGF_beta, 1 hit
SMARTiView protein in SMART
SM00204 TGFB, 1 hit
SUPFAMiSSF57501 SSF57501, 1 hit
PROSITEiView protein in PROSITE
PS00250 TGF_BETA_1, 1 hit
PS51362 TGF_BETA_2, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O95972-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MVLLSILRIL FLCELVLFME HRAQMAEGGQ SSIALLAEAP TLPLIEELLE
60 70 80 90 100
ESPGEQPRKP RLLGHSLRYM LELYRRSADS HGHPRENRTI GATMVRLVKP
110 120 130 140 150
LTNVARPHRG TWHIQILGFP LRPNRGLYQL VRATVVYRHH LQLTRFNLSC
160 170 180 190 200
HVEPWVQKNP TNHFPSSEGD SSKPSLMSNA WKEMDITQLV QQRFWNNKGH
210 220 230 240 250
RILRLRFMCQ QQKDSGGLEL WHGTSSLDIA FLLLYFNDTH KSIRKAKFLP
260 270 280 290 300
RGMEEFMERE SLLRRTRQAD GISAEVTASS SKHSGPENNQ CSLHPFQISF
310 320 330 340 350
RQLGWDHWII APPFYTPNYC KGTCLRVLRD GLNSPNHAII QNLINQLVDQ
360 370 380 390
SVPRPSCVPY KYVPISVLMI EANGSILYKE YEGMIAESCT CR
Length:392
Mass (Da):45,055
Last modified:August 16, 2004 - v2
Checksum:iA957275EF275A2E8
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0589745S → R Polymorphism; no or minor deleterious effect observed. 1 PublicationCorresponds to variant dbSNP:rs113099187EnsemblClinVar.1
Natural variantiVAR_05897561R → Q in POF4. 1 Publication1
Natural variantiVAR_05897661R → W in POF4. 1 PublicationCorresponds to variant dbSNP:rs144392417Ensembl.1
Natural variantiVAR_05897768R → 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. 2 PublicationsCorresponds to variant dbSNP:rs104894763EnsemblClinVar.1
Natural variantiVAR_05897876R → C in POF4. 1 PublicationCorresponds to variant dbSNP:rs104894766EnsemblClinVar.1
Natural variantiVAR_05897976R → H in POF4. 1 Publication1
Natural variantiVAR_058980103N → S2 PublicationsCorresponds to variant dbSNP:rs41308602EnsemblClinVar.1
Natural variantiVAR_058981138R → 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. 1 PublicationCorresponds to variant dbSNP:rs371418883Ensembl.1
Natural variantiVAR_058982148L → 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. 2 PublicationsCorresponds to variant dbSNP:rs114823607EnsemblClinVar.1
Natural variantiVAR_058983180A → F Requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_058984180A → T in POF4; unknown pathological significance; no or minor deleterious effect detected. 4 PublicationsCorresponds to variant dbSNP:rs104894767EnsemblClinVar.1
Natural variantiVAR_058985196N → K in POF4. 1 Publication1
Natural variantiVAR_066932200H → Y1 PublicationCorresponds to variant dbSNP:rs202165852EnsemblClinVar.1
Natural variantiVAR_058986206R → H in POF4. 1 PublicationCorresponds to variant dbSNP:rs782516193Ensembl.1
Natural variantiVAR_058987221W → R in POF4. 1 PublicationCorresponds to variant dbSNP:rs375284458Ensembl.1
Natural variantiVAR_021195235Y → 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. 2 PublicationsCorresponds to variant dbSNP:rs104894765EnsemblClinVar.1
Natural variantiVAR_058988243I → V in POF4. 1 PublicationCorresponds to variant dbSNP:rs782379521Ensembl.1
Natural variantiVAR_058989263L → LL No or minor deleterious effect detected. 4 Publications1
Natural variantiVAR_066933329R → C in POF4. 1 PublicationCorresponds to variant dbSNP:rs782375794Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF082350, AF082349 Genomic DNA Translation: AAC99768.1
AJ132405 Genomic DNA Translation: CAB43531.1
AL359914 Genomic DNA No translation available.
BC069155 mRNA Translation: AAH69155.1
BC117264 mRNA Translation: AAI17265.1
BC117266 mRNA Translation: AAI17267.1
CCDSiCCDS14334.1
RefSeqiNP_005439.2, NM_005448.2
UniGeneiHs.532692

Genome annotation databases

EnsembliENST00000252677; ENSP00000252677; ENSG00000130385
GeneIDi9210
KEGGihsa:9210
UCSCiuc011mnw.3 human

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF082350, AF082349 Genomic DNA Translation: AAC99768.1
AJ132405 Genomic DNA Translation: CAB43531.1
AL359914 Genomic DNA No translation available.
BC069155 mRNA Translation: AAH69155.1
BC117264 mRNA Translation: AAI17265.1
BC117266 mRNA Translation: AAI17267.1
CCDSiCCDS14334.1
RefSeqiNP_005439.2, NM_005448.2
UniGeneiHs.532692

3D structure databases

ProteinModelPortaliO95972
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114644, 4 interactors
IntActiO95972, 1 interactor
STRINGi9606.ENSP00000252677

PTM databases

iPTMnetiO95972
PhosphoSitePlusiO95972

Polymorphism and mutation databases

BioMutaiBMP15

Proteomic databases

PaxDbiO95972
PeptideAtlasiO95972
PRIDEiO95972
ProteomicsDBi51155

Protocols and materials databases

DNASUi9210
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000252677; ENSP00000252677; ENSG00000130385
GeneIDi9210
KEGGihsa:9210
UCSCiuc011mnw.3 human

Organism-specific databases

CTDi9210
DisGeNETi9210
EuPathDBiHostDB:ENSG00000130385.5
GeneCardsiBMP15
HGNCiHGNC:1068 BMP15
MalaCardsiBMP15
MIMi300247 gene
300510 phenotype
neXtProtiNX_O95972
OpenTargetsiENSG00000130385
Orphaneti243 46,XX gonadal dysgenesis
619 NON RARE IN EUROPE: Primary ovarian failure
PharmGKBiPA25378
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3900 Eukaryota
ENOG410XT8Z LUCA
GeneTreeiENSGT00910000143982
HOGENOMiHOG000095242
HOVERGENiHBG004660
InParanoidiO95972
KOiK05498
OMAiLYTPNYC
OrthoDBiEOG091G09RN
PhylomeDBiO95972
TreeFamiTF316134

Enzyme and pathway databases

ReactomeiR-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275 Post-translational protein phosphorylation
SignaLinkiO95972
SIGNORiO95972

Miscellaneous databases

GeneWikiiBone_morphogenetic_protein_15
GenomeRNAii9210
PROiPR:O95972
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000130385 Expressed in 9 organ(s), highest expression level in secondary oocyte
CleanExiHS_BMP15
GenevisibleiO95972 HS

Family and domain databases

Gene3Di2.10.90.10, 1 hit
InterProiView protein in InterPro
IPR015923 BMP-15
IPR029034 Cystine-knot_cytokine
IPR001839 TGF-b_C
IPR015615 TGF-beta-rel
IPR017948 TGFb_CS
PANTHERiPTHR11848 PTHR11848, 1 hit
PTHR11848:SF22 PTHR11848:SF22, 1 hit
PfamiView protein in Pfam
PF00019 TGF_beta, 1 hit
SMARTiView protein in SMART
SM00204 TGFB, 1 hit
SUPFAMiSSF57501 SSF57501, 1 hit
PROSITEiView protein in PROSITE
PS00250 TGF_BETA_1, 1 hit
PS51362 TGF_BETA_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiBMP15_HUMAN
AccessioniPrimary (citable) accession number: O95972
Secondary accession number(s): Q17RM6, Q5JST1, Q9UMS1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: August 16, 2004
Last modified: November 7, 2018
This is version 154 of the entry and version 2 of the sequence. See 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again