BMP4 bone morphogenetic protein 4 [Homo sapiens] - Gene

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Summary

Official Symbol: BMP4provided by HGNC
Official Full Name: bone morphogenetic protein 4provided by HGNC
Primary source: HGNC:1071
See related: Ensembl:ENSG00000125378; HPRD:00207; MIM:112262; Vega:OTTHUMG00000140303
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ZYME; BMP2B; OFC11; BMP2B1; MCOPS6
Summary: The protein encoded by this gene is a member of the bone morphogenetic protein family which is part of the transforming growth factor-beta superfamily. The superfamily includes large families of growth and differentiation factors. Bone morphogenetic proteins were originally identified by an ability of demineralized bone extract to induce endochondral osteogenesis in vivo in an extraskeletal site. This particular family member plays an important role in the onset of endochondral bone formation in humans, and a reduction in expression has been associated with a variety of bone diseases, including the heritable disorder Fibrodysplasia Ossificans Progressiva. Alternative splicing in the 5' untranslated region of this gene has been described and three variants are described, all encoding an identical protein. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 14q22-q23

Sequence :: Chromosome: 14; NC_000014.8 (54416454..54423554, complement)

See BMP4 in Epigenomics, MapViewer

Chromosome 14 - NC_000014.8 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

down-regulation of Kruppel-like factor-4 (KLF4) by microRNA-143/145 is critical for modulation of vascular smooth muscle cell phenotype by transforming growth factor-beta and bone morphogenetic protein 4.
Title: down-regulation of Kruppel-like factor-4 (KLF4) by microRNA-143/145 is critical for modulation of vascular smooth muscle cell phenotype by transforming growth factor-beta and bone morphogenetic protein 4.
Novel mutations in the BMP4 gene and a specific haplotype TGGGCTT appear to contribute to the risk of developing ossification of the posterior longitudinal ligament.
Title: A new haplotype in BMP4 implicated in ossification of the posterior longitudinal ligament (OPLL) in a Chinese population.
components of the common cellular transcriptional response to BMP4 and BMP7
Title: Analysis of BMP4 and BMP7 signaling in breast cancer cells unveils time-dependent transcription patterns and highlights a common synexpression group of genes.
BMP4 causes endothelial cells (ECs) apoptosis through activation of caspase-3 in a ROS/p38MAPK/JNK-dependent signaling cascade.
Title: Bone morphogenic protein-4 induces endothelial cell apoptosis through oxidative stress-dependent p38MAPK and JNK pathway.
Characterize bone morphogenetic protein 4 as a cellular regulator of mitral valve interstitial cell activation in myxomatous mitral valve prolapse.
Title: Human myxomatous mitral valve prolapse: role of bone morphogenetic protein 4 in valvular interstitial cell activation.
Bone morphogenetic protein 4 promotes vascular smooth muscle contractility by activating microRNA-21 (miR-21), which down-regulates expression of family of dedicator of cytokinesis (DOCK) proteins.
Title: Bone morphogenetic protein 4 promotes vascular smooth muscle contractility by activating microRNA-21 (miR-21), which down-regulates expression of family of dedicator of cytokinesis (DOCK) proteins.
Activin, BMP and FGF pathways cooperate to promote endoderm and pancreatic lineage cell differentiation from human embryonic stem cells.
Title: Activin, BMP and FGF pathways cooperate to promote endoderm and pancreatic lineage cell differentiation from human embryonic stem cells.
Serum BMP-4 levels are inversely associated with surrogate markers of arterial stiffness and carotid atherosclerosis in patients with Type 2 diabetes
Title: Serum BMP-4 levels in relation to arterial stiffness and carotid atherosclerosis in patients with Type 2 diabetes.
these data show that BMP-4 and BMP-7 are associated with granulosa cell survival via several non-Smad specific pathways: BMP-4 via the PI3K/PDK-1/PKC and BMP-7 via the PI3K/PDK-1/Akt.
Title: Bone morphogenetic protein (BMP)-4 and BMP-7 suppress granulosa cell apoptosis via different pathways: BMP-4 via PI3K/PDK-1/Akt and BMP-7 via PI3K/PDK-1/PKC.
BMP4 acts in part by activating HMGA2 making this architectural transcription factor one of the major downstream players.
Title: BMP4 increases expression of HMGA2 in mesenchymal stem cells.

Submit: New GeneRIF Correction See all (156)

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Phenotypes

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Genome-wide association study reveals genetic risk underlying Parkinson's disease.

Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer.

Products	Interactant	Other Gene	Source	Pubs	Description
NP_001193.1	NP_001193.1	BMP4	BIND	PubMed	BMP4 forms homo-dimer. This interaction was modeled on a demonstrated interaction using BMP4 from an unspecified species.
NP_001193.1	NP_001194.1	BMPR1B	BIND	PubMed	BMP4 interacts with BMPR1B (BR). This interaction was modeled on a demonstrated interaction between BMP4 from an unspecified species and BMPR1B from an unspecified species.
NP_001193.1		CHRD	BIND	PubMed	BMP4 interacts with an unspecified isoform of CHRD (Chd). This interaction was modeled on a demonstrated interaction between BMP4 from an unspecified species and CHRD from an unspecified species.
P12644	P21810	BGN	HPRD	PubMed
P12644	P12644	BMP4	HPRD	PubMed
P12644	P34820	BMP8B	HPRD	PubMed
P12644	Q8N8U9	BMPER	HPRD	PubMed
P12644	P36894	BMPR1A	HPRD	PubMed
P12644	O00238	BMPR1B	HPRD	PubMed
P12644	Q13873	BMPR2	HPRD	PubMed
P12644	Q9BU40	CHRDL1	HPRD	PubMed
P12644	Q6WN34	CHRDL2	HPRD	PubMed
P12644	Q9H772	GREM2	HPRD	PubMed
P12644	Q92743	HTRA1	HPRD	PubMed
P12644	Q13253	NOG	HPRD	PubMed
P12644	Q6X4U4	SOSTDC1	HPRD	PubMed
P12644	Signal-transducing adaptor protein-2	STAP2	HPRD	PubMed
P12644	O95405	ZFYVE9	HPRD	PubMed
BioGRID:107120	BioGRID:107125	BMPR1A	BioGRID	PubMed	Reconstituted Complex
BioGRID:107120	BioGRID:107126	BMPR1B	BioGRID	PubMed	Reconstituted Complex
BioGRID:107120	BioGRID:107127	BMPR2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107120	BioGRID:117428	SOSTDC1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107120	BioGRID:121338	TWSG1	BioGRID	PubMed	Reconstituted Complex
BioGRID:107120	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

Function	Evidence Code	Pubs
BMP receptor binding	IDA Inferred from Direct Assay more info	PubMed
chemoattractant activity	IDA Inferred from Direct Assay more info	PubMed
cytokine activity	IDA Inferred from Direct Assay more info	PubMed
growth factor activity	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
BMP signaling pathway	IDA Inferred from Direct Assay more info	PubMed
BMP signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
BMP signaling pathway involved in heart induction	IMP Inferred from Mutant Phenotype more info
BMP signaling pathway involved in nephric duct formation	IDA Inferred from Direct Assay more info	PubMed
BMP signaling pathway involved in renal system segmentation	ISS Inferred from Sequence or Structural Similarity more info
BMP signaling pathway involved in ureter morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
SMAD protein signal transduction	IDA Inferred from Direct Assay more info	PubMed
activation of MAPKK activity	IDA Inferred from Direct Assay more info	PubMed
blood vessel endothelial cell proliferation involved in sprouting angiogenesis	IDA Inferred from Direct Assay more info	PubMed
branching involved in ureteric bud morphogenesis	IDA Inferred from Direct Assay more info	PubMed
branching morphogenesis of a tube	IDA Inferred from Direct Assay more info	PubMed
bronchus development	IDA Inferred from Direct Assay more info	PubMed
bud dilation involved in lung branching	IDA Inferred from Direct Assay more info	PubMed
cardiac septum development	TAS Traceable Author Statement more info	PubMed
chondrocyte differentiation	ISS Inferred from Sequence or Structural Similarity more info
deltoid tuberosity development	ISS Inferred from Sequence or Structural Similarity more info
endocardial cushion development	TAS Traceable Author Statement more info	PubMed
endochondral ossification	ISS Inferred from Sequence or Structural Similarity more info
epithelial cell proliferation involved in lung morphogenesis	IDA Inferred from Direct Assay more info	PubMed
epithelial tube branching involved in lung morphogenesis	IDA Inferred from Direct Assay more info	PubMed
glomerular capillary formation	ISS Inferred from Sequence or Structural Similarity more info
growth	IEA Inferred from Electronic Annotation more info
hemopoietic progenitor cell differentiation	IDA Inferred from Direct Assay more info	PubMed
intermediate mesodermal cell differentiation	IDA Inferred from Direct Assay more info	PubMed
kidney development	IMP Inferred from Mutant Phenotype more info	PubMed
lung alveolus development	IDA Inferred from Direct Assay more info	PubMed
lung morphogenesis	IDA Inferred from Direct Assay more info	PubMed
lymphoid progenitor cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
macrophage differentiation	IDA Inferred from Direct Assay more info
mesenchymal to epithelial transition involved in metanephros morphogenesis	IDA Inferred from Direct Assay more info	PubMed
mesonephros development	IEP Inferred from Expression Pattern more info	PubMed
metanephric collecting duct development	ISS Inferred from Sequence or Structural Similarity more info
monocyte differentiation	IDA Inferred from Direct Assay more info
negative regulation of MAP kinase activity	IDA Inferred from Direct Assay more info	PubMed
negative regulation of T cell differentiation in thymus	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
negative regulation of branch elongation involved in ureteric bud branching by BMP signaling pathway	IDA Inferred from Direct Assay more info	PubMed
negative regulation of branching involved in ureteric bud morphogenesis	IDA Inferred from Direct Assay more info	PubMed
negative regulation of cell cycle	IDA Inferred from Direct Assay more info	PubMed
negative regulation of cell death	IDA Inferred from Direct Assay more info	PubMed
negative regulation of cell proliferation	IDA Inferred from Direct Assay more info	PubMed
negative regulation of cell proliferation involved in heart morphogenesis	IMP Inferred from Mutant Phenotype more info
negative regulation of glomerular mesangial cell proliferation	IDA Inferred from Direct Assay more info	PubMed
negative regulation of glomerulus development	IDA Inferred from Direct Assay more info	PubMed
negative regulation of immature T cell proliferation in thymus	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of mesenchymal cell proliferation involved in ureter development	IDA Inferred from Direct Assay more info	PubMed
negative regulation of metanephric S-shaped body morphogenesis	IDA Inferred from Direct Assay more info	PubMed
negative regulation of metanephric comma-shaped body morphogenesis	IDA Inferred from Direct Assay more info	PubMed
negative regulation of mitosis	IDA Inferred from Direct Assay more info	PubMed
negative regulation of myoblast differentiation	IDA Inferred from Direct Assay more info	PubMed
negative regulation of phosphorylation	IDA Inferred from Direct Assay more info	PubMed
negative regulation of striated muscle tissue development	IDA Inferred from Direct Assay more info	PubMed
negative regulation of thymocyte apoptosis	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of transcription from RNA polymerase II promoter	IDA Inferred from Direct Assay more info	PubMed
negative regulation of transcription, DNA-dependent	IDA Inferred from Direct Assay more info	PubMed
odontogenesis	IGI Inferred from Genetic Interaction more info	PubMed
osteoblast differentiation	IDA Inferred from Direct Assay more info	PubMed
positive chemotaxis	IDA Inferred from Direct Assay more info	PubMed
positive regulation of BMP signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of SMAD protein import into nucleus	IDA Inferred from Direct Assay more info	PubMed
positive regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
positive regulation of bone mineralization	IDA Inferred from Direct Assay more info	PubMed
positive regulation of branching involved in lung morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of cardiac muscle fiber development	IMP Inferred from Mutant Phenotype more info
positive regulation of cartilage development	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cell death	IDA Inferred from Direct Assay more info	PubMed
positive regulation of collagen biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
positive regulation of endothelial cell migration	IDA Inferred from Direct Assay more info	PubMed
positive regulation of endothelial cell proliferation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of kidney development	IDA Inferred from Direct Assay more info	PubMed
positive regulation of ossification	IDA Inferred from Direct Assay more info	PubMed
positive regulation of osteoblast differentiation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of pathway-restricted SMAD protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of pathway-restricted SMAD protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of smooth muscle cell proliferation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription from RNA polymerase II promoter	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription, DNA-dependent	IDA Inferred from Direct Assay more info	PubMed
post-embryonic development	IDA Inferred from Direct Assay more info	PubMed
protein localization to nucleus	IDA Inferred from Direct Assay more info	PubMed
pulmonary artery endothelial tube morphogenesis	IDA Inferred from Direct Assay more info	PubMed
regulation of pathway-restricted SMAD protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
renal system development	IEP Inferred from Expression Pattern more info	PubMed
secondary heart field specification	IMP Inferred from Mutant Phenotype more info
smooth muscle tissue development	ISS Inferred from Sequence or Structural Similarity more info
smoothened signaling pathway	IEP Inferred from Expression Pattern more info	PubMed
specification of ureteric bud anterior/posterior symmetry by BMP signaling pathway	IDA Inferred from Direct Assay more info	PubMed
steroid hormone mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
telencephalon development	IDA Inferred from Direct Assay more info	PubMed
tendon cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
trachea development	IDA Inferred from Direct Assay more info	PubMed
ureter epithelial cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
ureter smooth muscle cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
ureteric bud development	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
extracellular region	ISS Inferred from Sequence or Structural Similarity more info
extracellular space	ISS Inferred from Sequence or Structural Similarity more info
proteinaceous extracellular matrix	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: bone morphogenetic protein 4

Names: bone morphogenetic protein 4; BMP-4; BMP-2B; bone morphogenetic protein 2B

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009215.1 RefSeqGene

Range

5001..12101

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001202.3 → NP_001193.2 bone morphogenetic protein 4 preproprotein

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript. Variants 1, 2 and 3 encode the same protein.

Source sequence(s)

BQ083000, BU683974, BX161385, M22490

Consensus CDS

CCDS9715.1

UniProtKB/Swiss-Prot

P12644

UniProtKB/TrEMBL

Q53XC5

Related

ENSP00000245451, OTTHUMP00000178992, ENST00000245451, OTTHUMT00000276894

Conserved Domains (2) summary

pfam00688
Location:36 – 275
Blast Score: 576

TGFb_propeptide; TGF-beta propeptide

cl02510
Location:308 – 408
Blast Score: 475

TGF_beta; Transforming growth factor beta like domain
NM_130850.2 → NP_570911.2 bone morphogenetic protein 4 preproprotein

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, compared to variant 1. Variants 1, 2 and 3 encode the same protein.

Source sequence(s)

BC020546, BQ083000, BU683974, BX161385

Consensus CDS

CCDS9715.1

UniProtKB/Swiss-Prot

P12644

UniProtKB/TrEMBL

Q53XC5

Related

ENSP00000453485, OTTHUMP00000247950, ENST00000559087, OTTHUMT00000417538

Conserved Domains (2) summary

pfam00688
Location:36 – 275
Blast Score: 576

TGFb_propeptide; TGF-beta propeptide

cl02510
Location:308 – 408
Blast Score: 475

TGF_beta; Transforming growth factor beta like domain
NM_130851.2 → NP_570912.2 bone morphogenetic protein 4 preproprotein

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR, compared to variants 1 and 2. Variants 1, 2 and 3 encode the same protein.

Source sequence(s)

AL138479, BU683974, BX161385

Consensus CDS

CCDS9715.1

UniProtKB/Swiss-Prot

P12644

UniProtKB/TrEMBL

Q53XC5

Related

ENSP00000394165, ENST00000417573

Conserved Domains (2) summary

pfam00688
Location:36 – 275
Blast Score: 576

TGFb_propeptide; TGF-beta propeptide

cl02510
Location:308 – 408
Blast Score: 475

TGF_beta; Transforming growth factor beta like domain

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000014.8 Reference GRCh37.p5 Primary Assembly

Range

54416454..54423554, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000146.1 Alternate HuRef

Range

34579652..34586754, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AF035427.1	None
genomic	AF035428.1	None
genomic	AF210053.1	None
genomic	AL138479.4 (79028..79159)	None
genomic	CH471061.1	EAW80628.1
		EAW80629.1
		EAW80630.1
		EAW80631.1
genomic	EU518936.1	ACB21039.1
genomic	HB975907.1	CBE74713.1
genomic	U43842.1	AAC72278.1
mRNA	BC020546.2	AAH20546.1
mRNA	BQ083000.1	None
mRNA	BU683974.1	None
mRNA	BX161385.1	CAD61876.1
mRNA	BX161438.1	CAD61909.1
mRNA	D30751.1	BAA06410.1
mRNA	M22490.1	AAA51835.1
other-genetic	EU176183.1	ABW03634.1
other-genetic	HQ447921.1	ADQ32405.1