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Protein

Bone morphogenetic protein 15

Gene

BMP15

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Growth factor

Enzyme and pathway databases

BioCyciZFISH:ENSG00000130385-MONOMER.
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

HGNCiHGNC:1068. BMP15.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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 rs104894765dbSNPEnsembl.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 rs144392417dbSNPEnsembl.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 rs104894763dbSNPEnsembl.1
Natural variantiVAR_05897876R → C in POF4. 1 PublicationCorresponds to variant rs104894766dbSNPEnsembl.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 rs371418883dbSNPEnsembl.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 rs114823607dbSNPEnsembl.1
Natural variantiVAR_058984180A → T in POF4; unknown pathological significance; no or minor deleterious effect detected. 4 PublicationsCorresponds to variant rs104894767dbSNPEnsembl.1
Natural variantiVAR_058985196N → K in POF4. 1 Publication1
Natural variantiVAR_058986206R → H in POF4. 1 PublicationCorresponds to variant rs782516193dbSNPEnsembl.1
Natural variantiVAR_058987221W → R in POF4. 1 PublicationCorresponds to variant rs375284458dbSNPEnsembl.1
Natural variantiVAR_058988243I → V in POF4. 1 PublicationCorresponds to variant rs782379521dbSNPEnsembl.1
Natural variantiVAR_066933329R → C in POF4. 1 PublicationCorresponds to variant rs782375794dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation, Premature ovarian failure

Organism-specific databases

DisGeNETi9210.
MalaCardsiBMP15.
MIMi300510. phenotype.
OpenTargetsiENSG00000130385.
Orphaneti243. 46,XX gonadal dysgenesis.
619. 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...)Sequence analysis1
Glycosylationi147N-linked (GlcNAc...)Sequence analysis1
Glycosylationi237N-linked (GlcNAc...)Sequence analysis1
Modified residuei268Pyrrolidone carboxylic acid; in P16 and P171 Publication1
Modified residuei273Phosphoserine; in P161 Publication1
Glycosylationi277O-linked (HexNAc...); in P171 Publication1
Disulfide bondi291 ↔ 357By similarity
Disulfide bondi320 ↔ 389By similarity
Disulfide bondi324 ↔ 391By similarity
Glycosylationi373N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Pyrrolidone carboxylic acid

Proteomic databases

PaxDbiO95972.
PRIDEiO95972.

PTM databases

iPTMnetiO95972.
PhosphoSitePlusiO95972.

Expressioni

Gene expression databases

BgeeiENSG00000130385.
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.
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.
GeneTreeiENSGT00740000114888.
HOGENOMiHOG000095242.
HOVERGENiHBG004660.
InParanoidiO95972.
KOiK05498.
OMAiNQCSLHP.
OrthoDBiEOG091G09RN.
PhylomeDBiO95972.
TreeFamiTF316134.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR015923. BMP-15.
IPR029034. Cystine-knot_cytokine.
IPR002405. Inhibin_asu.
IPR001839. TGF-b_C.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view]
PANTHERiPTHR11848. PTHR11848. 1 hit.
PTHR11848:SF22. PTHR11848:SF22. 1 hit.
PfamiPF00019. TGF_beta. 1 hit.
[Graphical view]
PRINTSiPR00669. INHIBINA.
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.

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 rs113099187dbSNPEnsembl.1
Natural variantiVAR_05897561R → Q in POF4. 1 Publication1
Natural variantiVAR_05897661R → W in POF4. 1 PublicationCorresponds to variant rs144392417dbSNPEnsembl.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 rs104894763dbSNPEnsembl.1
Natural variantiVAR_05897876R → C in POF4. 1 PublicationCorresponds to variant rs104894766dbSNPEnsembl.1
Natural variantiVAR_05897976R → H in POF4. 1 Publication1
Natural variantiVAR_058980103N → S.2 PublicationsCorresponds to variant rs41308602dbSNPEnsembl.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 rs371418883dbSNPEnsembl.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 rs114823607dbSNPEnsembl.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 rs104894767dbSNPEnsembl.1
Natural variantiVAR_058985196N → K in POF4. 1 Publication1
Natural variantiVAR_066932200H → Y.1 PublicationCorresponds to variant rs202165852dbSNPEnsembl.1
Natural variantiVAR_058986206R → H in POF4. 1 PublicationCorresponds to variant rs782516193dbSNPEnsembl.1
Natural variantiVAR_058987221W → R in POF4. 1 PublicationCorresponds to variant rs375284458dbSNPEnsembl.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 rs104894765dbSNPEnsembl.1
Natural variantiVAR_058988243I → V in POF4. 1 PublicationCorresponds to variant rs782379521dbSNPEnsembl.1
Natural variantiVAR_058989263L → LL No or minor deleterious effect detected. 4 Publications1
Natural variantiVAR_066933329R → C in POF4. 1 PublicationCorresponds to variant rs782375794dbSNPEnsembl.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. Translation: CAI41226.1.
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.

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. Translation: CAI41226.1.
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.
STRINGi9606.ENSP00000252677.

PTM databases

iPTMnetiO95972.
PhosphoSitePlusiO95972.

Polymorphism and mutation databases

BioMutaiBMP15.

Proteomic databases

PaxDbiO95972.
PRIDEiO95972.

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.
GeneCardsiBMP15.
HGNCiHGNC:1068. BMP15.
MalaCardsiBMP15.
MIMi300247. gene.
300510. phenotype.
neXtProtiNX_O95972.
OpenTargetsiENSG00000130385.
Orphaneti243. 46,XX gonadal dysgenesis.
619. Primary ovarian failure.
PharmGKBiPA25378.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3900. Eukaryota.
ENOG410XT8Z. LUCA.
GeneTreeiENSGT00740000114888.
HOGENOMiHOG000095242.
HOVERGENiHBG004660.
InParanoidiO95972.
KOiK05498.
OMAiNQCSLHP.
OrthoDBiEOG091G09RN.
PhylomeDBiO95972.
TreeFamiTF316134.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000130385-MONOMER.
SignaLinkiO95972.
SIGNORiO95972.

Miscellaneous databases

GeneWikiiBone_morphogenetic_protein_15.
GenomeRNAii9210.
PROiO95972.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000130385.
CleanExiHS_BMP15.
GenevisibleiO95972. HS.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR015923. BMP-15.
IPR029034. Cystine-knot_cytokine.
IPR002405. Inhibin_asu.
IPR001839. TGF-b_C.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view]
PANTHERiPTHR11848. PTHR11848. 1 hit.
PTHR11848:SF22. PTHR11848:SF22. 1 hit.
PfamiPF00019. TGF_beta. 1 hit.
[Graphical view]
PRINTSiPR00669. INHIBINA.
SMARTiSM00204. TGFB. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiBMP15_HUMAN
AccessioniPrimary (citable) accession number: O95972
Secondary accession number(s): Q17RM6, Q5JST1, Q9UMS1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: August 16, 2004
Last modified: November 2, 2016
This is version 142 of the entry and version 2 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

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.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.