P12644 · BMP4_HUMAN
- ProteinBone morphogenetic protein 4
- GeneBMP4
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids408 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes, including neurogenesis, vascular development, angiogenesis and osteogenesis (PubMed:31363885).
Acts in concert with PTHLH/PTHRP to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction (By similarity).
Initiates the canonical BMP signaling cascade by associating with type I receptor BMPR1A and type II receptor BMPR2 (PubMed:25868050, PubMed:8006002).
Once all three components are bound together in a complex at the cell surface, BMPR2 phosphorylates and activates BMPR1A. In turn, BMPR1A propagates signal by phosphorylating SMAD1/5/8 that travel to the nucleus and act as activators and repressors of transcription of target genes (PubMed:25868050, PubMed:29212066).
Positively regulates the expression of odontogenic development regulator MSX1 via inducing the IPO7-mediated import of SMAD1 to the nucleus (By similarity).
Required for MSX1-mediated mesenchymal molar tooth bud development beyond the bud stage, via promoting Wnt signaling (By similarity).
Acts as a positive regulator of odontoblast differentiation during mesenchymal tooth germ formation, expression is repressed during the bell stage by MSX1-mediated inhibition of CTNNB1 signaling (By similarity).
Able to induce its own expression in dental mesenchymal cells and also in the neighboring dental epithelial cells via an MSX1-mediated pathway (By similarity).
Can also signal through non-canonical BMP pathways such as ERK/MAP kinase, PI3K/Akt, or SRC cascades (PubMed:31363885).
For example, induces SRC phosphorylation which, in turn, activates VEGFR2, leading to an angiogenic response (PubMed:31363885).
Acts in concert with PTHLH/PTHRP to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction (By similarity).
Initiates the canonical BMP signaling cascade by associating with type I receptor BMPR1A and type II receptor BMPR2 (PubMed:25868050, PubMed:8006002).
Once all three components are bound together in a complex at the cell surface, BMPR2 phosphorylates and activates BMPR1A. In turn, BMPR1A propagates signal by phosphorylating SMAD1/5/8 that travel to the nucleus and act as activators and repressors of transcription of target genes (PubMed:25868050, PubMed:29212066).
Positively regulates the expression of odontogenic development regulator MSX1 via inducing the IPO7-mediated import of SMAD1 to the nucleus (By similarity).
Required for MSX1-mediated mesenchymal molar tooth bud development beyond the bud stage, via promoting Wnt signaling (By similarity).
Acts as a positive regulator of odontoblast differentiation during mesenchymal tooth germ formation, expression is repressed during the bell stage by MSX1-mediated inhibition of CTNNB1 signaling (By similarity).
Able to induce its own expression in dental mesenchymal cells and also in the neighboring dental epithelial cells via an MSX1-mediated pathway (By similarity).
Can also signal through non-canonical BMP pathways such as ERK/MAP kinase, PI3K/Akt, or SRC cascades (PubMed:31363885).
For example, induces SRC phosphorylation which, in turn, activates VEGFR2, leading to an angiogenic response (PubMed:31363885).
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameBone morphogenetic protein 4
- Short namesBMP-4
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP12644
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Microphthalmia, syndromic, 6 (MCOPS6)
- Note
- 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 alsoMIM:607932
Natural variants in MCOPS6
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_043532 | 93 | E>G | in MCOPS6; dbSNP:rs121912765 |
Non-syndromic orofacial cleft 11 (OFC11)
- Note
- 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 alsoMIM:600625
Natural variants in OFC11
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_043531 | 91 | S>C | in OFC11; also found in renal hypodysplasia patients; dbSNP:rs121912767 | |
VAR_058315 | 162 | R>Q | in OFC11; dbSNP:rs770493925 | |
VAR_058317 | 287 | R>H | in OFC11; dbSNP:rs121912768 | |
VAR_058318 | 346 | A>V | in OFC11; dbSNP:rs121912766 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_043531 | 91 | in OFC11; also found in renal hypodysplasia patients; dbSNP:rs121912767 | |||
Sequence: S → C | ||||||
Natural variant | VAR_043532 | 93 | in MCOPS6; dbSNP:rs121912765 | |||
Sequence: E → G | ||||||
Natural variant | VAR_058314 | 102 | in dbSNP:rs202159001 | |||
Sequence: T → A | ||||||
Natural variant | VAR_043533 | 116 | in a renal hypodysplasia patient; dbSNP:rs750427266 | |||
Sequence: T → S | ||||||
Natural variant | VAR_043534 | 150 | in a renal hypodysplasia patient; dbSNP:rs767216159 | |||
Sequence: N → K | ||||||
Natural variant | VAR_016174 | 152 | in dbSNP:rs17563 | |||
Sequence: V → A | ||||||
Natural variant | VAR_058315 | 162 | in OFC11; dbSNP:rs770493925 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_058316 | 168 | ||||
Sequence: G → A | ||||||
Natural variant | VAR_043535 | 225 | in dbSNP:rs144556455 | |||
Sequence: T → A | ||||||
Natural variant | VAR_043536 | 226 | in dbSNP:rs140590144 | |||
Sequence: R → W | ||||||
Natural variant | VAR_058317 | 287 | in OFC11; dbSNP:rs121912768 | |||
Sequence: R → H | ||||||
Natural variant | VAR_058318 | 346 | in OFC11; dbSNP:rs121912766 | |||
Sequence: A → V | ||||||
Natural variant | VAR_043537 | 367 | in dbSNP:rs1320581580 | |||
Sequence: S → T |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 541 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for signal, propeptide, modified residue, glycosylation, chain, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-19 | |||||
Sequence: MIPGNRMLMVVLLCQVLLG | ||||||
Propeptide | PRO_0000033856 | 20-292 | ||||
Sequence: GASHASLIPETGKKKVAEIQGHAGGRRSGQSHELLRDFEATLLQMFGLRRRPQPSKSAVIPDYMRDLYRLQSGEEEEEQIHSTGLEYPERPASRANTVRSFHHEEHLENIPGTSENSAFRFLFNLSSIPENEVISSAELRLFREQVDQGPDWERGFHRINIYEVMKPPAEVVPGHLITRLLDTRLVHHNVTRWETFDVSPAVLRWTREKQPNYGLAIEVTHLHQTRTHQGQHVRISRSLPQGSGNWAQLRPLLVTFGHDGRGHALTRRRRAKR | ||||||
Modified residue | 91 | Phosphoserine; by FAM20C | ||||
Sequence: S | ||||||
Glycosylation | 143 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 208 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Chain | PRO_0000033857 | 293-408 | Bone morphogenetic protein 4 | |||
Sequence: SPKHHSQRARKKNKNCRRHSLYVDFSDVGWNDWIVAPPGYQAFYCHGDCPFPLADHLNSTNHAIVQTLVNSVNSSIPKACCVPTELSAISMLYLDEYDKVVLKNYQEMVVEGCGCR | ||||||
Disulfide bond | 308↔373 | |||||
Sequence: CRRHSLYVDFSDVGWNDWIVAPPGYQAFYCHGDCPFPLADHLNSTNHAIVQTLVNSVNSSIPKACC | ||||||
Disulfide bond | 337↔405 | |||||
Sequence: CHGDCPFPLADHLNSTNHAIVQTLVNSVNSSIPKACCVPTELSAISMLYLDEYDKVVLKNYQEMVVEGC | ||||||
Disulfide bond | 341↔407 | |||||
Sequence: CPFPLADHLNSTNHAIVQTLVNSVNSSIPKACCVPTELSAISMLYLDEYDKVVLKNYQEMVVEGCGC | ||||||
Glycosylation | 350 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 365 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 372 | Interchain | ||||
Sequence: C |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
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
Organism-specific databases
Interaction
Subunit
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).
Interacts with type I receptor BMPR1A (PubMed:8006002).
Interacts with type II receptor BMPR2 (PubMed:29212066).
Interacts with FSTL1; this interaction inhibits the activation of the BMP4/Smad1/5/8 signaling pathway (PubMed:29212066).
Interacts with SCUBE3 (PubMed:33308444).
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).
Interacts with type I receptor BMPR1A (PubMed:8006002).
Interacts with type II receptor BMPR2 (PubMed:29212066).
Interacts with FSTL1; this interaction inhibits the activation of the BMP4/Smad1/5/8 signaling pathway (PubMed:29212066).
Interacts with SCUBE3 (PubMed:33308444).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P12644 | BMPR1A P36894 | 2 | EBI-1998134, EBI-1029237 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 283-307 | Disordered | ||||
Sequence: ALTRRRRAKRSPKHHSQRARKKNKN |
Sequence similarities
Belongs to the TGF-beta family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length408
- Mass (Da)46,555
- Last updated1989-10-01 v1
- Checksum79B01179DBB98204
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M22490 EMBL· GenBank· DDBJ | AAA51835.1 EMBL· GenBank· DDBJ | mRNA | ||
U43842 EMBL· GenBank· DDBJ | AAC72278.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC020546 EMBL· GenBank· DDBJ | AAH20546.1 EMBL· GenBank· DDBJ | mRNA | ||
D30751 EMBL· GenBank· DDBJ | BAA06410.1 EMBL· GenBank· DDBJ | mRNA |