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Protein

Bone morphogenetic protein 4

Gene

BMP4

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

Functioni

Induces cartilage and bone formation. Also acts in mesoderm induction, tooth development, limb formation and fracture repair. Acts in concert with PTHLH/PTHRP to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction (By similarity).By similarity

GO - Molecular functioni

  • BMP receptor binding Source: MGI
  • chemoattractant activity Source: UniProtKB
  • co-receptor binding Source: BHF-UCL
  • cytokine activity Source: MGI
  • growth factor activity Source: UniProtKB-KW
  • heparin binding Source: Ensembl
  • transforming growth factor beta receptor binding Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionCytokine, Developmental protein, Growth factor
Biological processChondrogenesis, Differentiation, Osteogenesis

Enzyme and pathway databases

ReactomeiR-HSA-2129379 Molecules associated with elastic fibres
R-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
SignaLinkiP12644
SIGNORiP12644

Names & Taxonomyi

Protein namesi
Recommended name:
Bone morphogenetic protein 4
Short name:
BMP-4
Alternative name(s):
Bone morphogenetic protein 2B
Short name:
BMP-2B
Gene namesi
Name:BMP4
Synonyms:BMP2B, DVR4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000125378.15
HGNCiHGNC:1071 BMP4
MIMi112262 gene
neXtProtiNX_P12644

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

Extracellular matrix, Secreted

Pathology & Biotechi

Involvement in diseasei

Microphthalmia, syndromic, 6 (MCOPS6)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by microphthalmia/anophthalmia associated with facial, genital, skeletal, neurologic and endocrine anomalies. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities.
See also OMIM:607932
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04353293E → G in MCOPS6. 1 PublicationCorresponds to variant dbSNP:rs121912765EnsemblClinVar.1
Non-syndromic orofacial cleft 11 (OFC11)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum.
See also OMIM:600625
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04353191S → C in OFC11; also found in renal hypodysplasia patients. 3 PublicationsCorresponds to variant dbSNP:rs121912767EnsemblClinVar.1
Natural variantiVAR_058315162R → Q in OFC11. 1 PublicationCorresponds to variant dbSNP:rs770493925Ensembl.1
Natural variantiVAR_058317287R → H in OFC11. 1 PublicationCorresponds to variant dbSNP:rs121912768EnsemblClinVar.1
Natural variantiVAR_058318346A → V in OFC11. 1 PublicationCorresponds to variant dbSNP:rs121912766EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Microphthalmia

Organism-specific databases

DisGeNETi652
GeneReviewsiBMP4
MalaCardsiBMP4
MIMi600625 phenotype
607932 phenotype
OpenTargetsiENSG00000125378
Orphaneti199306 Cleft lip/palate
139471 Microphthalmia with brain and digit anomalies
93100 Renal agenesis, unilateral
PharmGKBiPA25381

Chemistry databases

ChEMBLiCHEMBL5350

Polymorphism and mutation databases

BioMutaiBMP4
DMDMi115073

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
PropeptideiPRO_000003385620 – 292Add BLAST273
ChainiPRO_0000033857293 – 408Bone morphogenetic protein 4Add BLAST116

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei91Phosphoserine; by FAM20C1 Publication1
Glycosylationi143N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi208N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi308 ↔ 373By similarity
Disulfide bondi337 ↔ 405By similarity
Disulfide bondi341 ↔ 407By similarity
Glycosylationi350N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi365N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi372InterchainBy similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP12644
PeptideAtlasiP12644
PRIDEiP12644
ProteomicsDBi52861

PTM databases

iPTMnetiP12644
PhosphoSitePlusiP12644

Expressioni

Tissue specificityi

Expressed in the lung and lower levels seen in the kidney. Present also in normal and neoplastic prostate tissues, and prostate cancer cell lines.

Gene expression databases

BgeeiENSG00000125378 Expressed in 144 organ(s), highest expression level in pigmented layer of retina
CleanExiHS_BMP4
ExpressionAtlasiP12644 baseline and differential
GenevisibleiP12644 HS

Organism-specific databases

HPAiCAB006863
HPA066235

Interactioni

Subunit structurei

Homodimer; disulfide-linked (By similarity). Interacts with GREM2. Part of a complex consisting of TWSG1 and CHRD. Interacts with the serine proteases, HTRA1 and HTRA3; the interaction with either inhibits BMP4-mediated signaling. The HTRA protease activity is required for this inhibition (By similarity). Interacts with SOSTDC1. Interacts with FBN1 (via N-terminal domain) and FBN2 (PubMed:18339631).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BMPR1AP368942EBI-1998134,EBI-1029237

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107120, 14 interactors
CORUMiP12644
DIPiDIP-5795N
ELMiP12644
IntActiP12644, 11 interactors
MINTiP12644
STRINGi9606.ENSP00000245451

Chemistry databases

BindingDBiP12644

Structurei

3D structure databases

ProteinModelPortaliP12644
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the TGF-beta family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3900 Eukaryota
ENOG410XT8Z LUCA
GeneTreeiENSGT00760000118883
HOGENOMiHOG000249478
HOVERGENiHBG004860
InParanoidiP12644
KOiK04662
OMAiQGFHRIN
OrthoDBiEOG091G0K7Z
PhylomeDBiP12644
TreeFamiTF351789

Family and domain databases

Gene3Di2.10.90.10, 1 hit
InterProiView protein in InterPro
IPR029034 Cystine-knot_cytokine
IPR001839 TGF-b_C
IPR001111 TGF-b_propeptide
IPR015615 TGF-beta-rel
IPR017948 TGFb_CS
PANTHERiPTHR11848 PTHR11848, 1 hit
PfamiView protein in Pfam
PF00019 TGF_beta, 1 hit
PF00688 TGFb_propeptide, 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

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All

P12644-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MIPGNRMLMV VLLCQVLLGG ASHASLIPET GKKKVAEIQG HAGGRRSGQS
60 70 80 90 100
HELLRDFEAT LLQMFGLRRR PQPSKSAVIP DYMRDLYRLQ SGEEEEEQIH
110 120 130 140 150
STGLEYPERP ASRANTVRSF HHEEHLENIP GTSENSAFRF LFNLSSIPEN
160 170 180 190 200
EVISSAELRL FREQVDQGPD WERGFHRINI YEVMKPPAEV VPGHLITRLL
210 220 230 240 250
DTRLVHHNVT RWETFDVSPA VLRWTREKQP NYGLAIEVTH LHQTRTHQGQ
260 270 280 290 300
HVRISRSLPQ GSGNWAQLRP LLVTFGHDGR GHALTRRRRA KRSPKHHSQR
310 320 330 340 350
ARKKNKNCRR HSLYVDFSDV GWNDWIVAPP GYQAFYCHGD CPFPLADHLN
360 370 380 390 400
STNHAIVQTL VNSVNSSIPK ACCVPTELSA ISMLYLDEYD KVVLKNYQEM

VVEGCGCR
Length:408
Mass (Da):46,555
Last modified:October 1, 1989 - v1
Checksum:i79B01179DBB98204
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YLW3H0YLW3_HUMAN
Bone morphogenetic protein 4
BMP4
271Annotation score:
H0YM53H0YM53_HUMAN
Bone morphogenetic protein 4
BMP4
110Annotation score:
H0YMP9H0YMP9_HUMAN
Bone morphogenetic protein 4
BMP4
104Annotation score:
V9GYF1V9GYF1_HUMAN
Bone morphogenetic protein 4
BMP4
29Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04353191S → C in OFC11; also found in renal hypodysplasia patients. 3 PublicationsCorresponds to variant dbSNP:rs121912767EnsemblClinVar.1
Natural variantiVAR_04353293E → G in MCOPS6. 1 PublicationCorresponds to variant dbSNP:rs121912765EnsemblClinVar.1
Natural variantiVAR_058314102T → A1 PublicationCorresponds to variant dbSNP:rs202159001EnsemblClinVar.1
Natural variantiVAR_043533116T → S in a renal hypodysplasia patient. 1 PublicationCorresponds to variant dbSNP:rs750427266Ensembl.1
Natural variantiVAR_043534150N → K in a renal hypodysplasia patient. 1 PublicationCorresponds to variant dbSNP:rs767216159Ensembl.1
Natural variantiVAR_016174152V → A4 PublicationsCorresponds to variant dbSNP:rs17563EnsemblClinVar.1
Natural variantiVAR_058315162R → Q in OFC11. 1 PublicationCorresponds to variant dbSNP:rs770493925Ensembl.1
Natural variantiVAR_058316168G → A1 Publication1
Natural variantiVAR_043535225T → A1 PublicationCorresponds to variant dbSNP:rs144556455Ensembl.1
Natural variantiVAR_043536226R → W1 PublicationCorresponds to variant dbSNP:rs140590144EnsemblClinVar.1
Natural variantiVAR_058317287R → H in OFC11. 1 PublicationCorresponds to variant dbSNP:rs121912768EnsemblClinVar.1
Natural variantiVAR_058318346A → V in OFC11. 1 PublicationCorresponds to variant dbSNP:rs121912766EnsemblClinVar.1
Natural variantiVAR_043537367S → T1 PublicationCorresponds to variant dbSNP:rs1320581580Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M22490 mRNA Translation: AAA51835.1
U43842 Genomic DNA Translation: AAC72278.1
BC020546 mRNA Translation: AAH20546.1
D30751 mRNA Translation: BAA06410.1
CCDSiCCDS9715.1
PIRiC37278 BMHU4
RefSeqiNP_001193.2, NM_001202.5
NP_001334843.1, NM_001347914.1
NP_001334845.1, NM_001347916.1
NP_570911.2, NM_130850.4
NP_570912.2, NM_130851.3
UniGeneiHs.68879

Genome annotation databases

EnsembliENST00000245451; ENSP00000245451; ENSG00000125378
ENST00000417573; ENSP00000394165; ENSG00000125378
ENST00000558984; ENSP00000454134; ENSG00000125378
ENST00000559087; ENSP00000453485; ENSG00000125378
GeneIDi652
KEGGihsa:652

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Wikipedia

Bone morphogenetic protein 4 entry

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M22490 mRNA Translation: AAA51835.1
U43842 Genomic DNA Translation: AAC72278.1
BC020546 mRNA Translation: AAH20546.1
D30751 mRNA Translation: BAA06410.1
CCDSiCCDS9715.1
PIRiC37278 BMHU4
RefSeqiNP_001193.2, NM_001202.5
NP_001334843.1, NM_001347914.1
NP_001334845.1, NM_001347916.1
NP_570911.2, NM_130850.4
NP_570912.2, NM_130851.3
UniGeneiHs.68879

3D structure databases

ProteinModelPortaliP12644
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107120, 14 interactors
CORUMiP12644
DIPiDIP-5795N
ELMiP12644
IntActiP12644, 11 interactors
MINTiP12644
STRINGi9606.ENSP00000245451

Chemistry databases

BindingDBiP12644
ChEMBLiCHEMBL5350

PTM databases

iPTMnetiP12644
PhosphoSitePlusiP12644

Polymorphism and mutation databases

BioMutaiBMP4
DMDMi115073

Proteomic databases

PaxDbiP12644
PeptideAtlasiP12644
PRIDEiP12644
ProteomicsDBi52861

Protocols and materials databases

DNASUi652
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000245451; ENSP00000245451; ENSG00000125378
ENST00000417573; ENSP00000394165; ENSG00000125378
ENST00000558984; ENSP00000454134; ENSG00000125378
ENST00000559087; ENSP00000453485; ENSG00000125378
GeneIDi652
KEGGihsa:652

Organism-specific databases

CTDi652
DisGeNETi652
EuPathDBiHostDB:ENSG00000125378.15
GeneCardsiBMP4
GeneReviewsiBMP4
HGNCiHGNC:1071 BMP4
HPAiCAB006863
HPA066235
MalaCardsiBMP4
MIMi112262 gene
600625 phenotype
607932 phenotype
neXtProtiNX_P12644
OpenTargetsiENSG00000125378
Orphaneti199306 Cleft lip/palate
139471 Microphthalmia with brain and digit anomalies
93100 Renal agenesis, unilateral
PharmGKBiPA25381
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3900 Eukaryota
ENOG410XT8Z LUCA
GeneTreeiENSGT00760000118883
HOGENOMiHOG000249478
HOVERGENiHBG004860
InParanoidiP12644
KOiK04662
OMAiQGFHRIN
OrthoDBiEOG091G0K7Z
PhylomeDBiP12644
TreeFamiTF351789

Enzyme and pathway databases

ReactomeiR-HSA-2129379 Molecules associated with elastic fibres
R-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
SignaLinkiP12644
SIGNORiP12644

Miscellaneous databases

ChiTaRSiBMP4 human
GeneWikiiBone_morphogenetic_protein_4
GenomeRNAii652
PROiPR:P12644
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000125378 Expressed in 144 organ(s), highest expression level in pigmented layer of retina
CleanExiHS_BMP4
ExpressionAtlasiP12644 baseline and differential
GenevisibleiP12644 HS

Family and domain databases

Gene3Di2.10.90.10, 1 hit
InterProiView protein in InterPro
IPR029034 Cystine-knot_cytokine
IPR001839 TGF-b_C
IPR001111 TGF-b_propeptide
IPR015615 TGF-beta-rel
IPR017948 TGFb_CS
PANTHERiPTHR11848 PTHR11848, 1 hit
PfamiView protein in Pfam
PF00019 TGF_beta, 1 hit
PF00688 TGFb_propeptide, 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 nameiBMP4_HUMAN
AccessioniPrimary (citable) accession number: P12644
Secondary accession number(s): Q9UM80
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: October 1, 1989
Last modified: November 7, 2018
This is version 206 of the entry and version 1 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 14
    Human chromosome 14: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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