The BMPR1A gene (BMPR1A stands for: Bone Morphogenetic Protein Receptor Type 1A) is a protein-coding gene located on chromosome 10q23.2. GO (Gene Ontology) annotations associated with this gene include protein homodimerization activity and protein kinase activity. An important paralog of this gene is BMPR1B.
BMPR1A gene
DefinitionThis section has been translated automatically.
General informationThis section has been translated automatically.
The BMPR1A gene encodes the bone morphogenetic receptor protein (BMP) of the same name (seeBone morphogenetic proteins below). Upon ligand binding, this protein forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. The type II receptors phosphorylate and activate type I receptors, which autophosphorylate, then bind and activate SMAD transcriptional regulators.
Bone morphogenetic proteins (BMPs) are multifunctional growth factors that belong to the superfamily of transforming growth factors (TGFs). The BMPs are a component of the TGF-beta signaling pathway, one of the basic signaling systems for communication between cells. The BMPs are also known as paracrine signaling molecules. To date, about 20 members of the BMP family have been identified and characterized.
The bone morphogenetic protein (BMP) receptors are a family of transmembrane serine/threonine kinases that include the type I receptors BMPR1A and BMPR1B and the type II receptor BMPR2. These receptors are also closely related to the activin receptors ACVR1 and ACVR2. The ligands of these receptors belong to the TGF-beta superfamily. TGF-beta and activins transmit their signals by forming heteromeric complexes with two different types of serine (threonine) kinase receptors: type I receptors of about 50-55 kD and type II receptors of about 70-80 kD. Type II receptors bind ligands in the absence of type I receptors, but require their respective type I receptors for signaling, whereas type I receptors require their respective type II receptors for ligand binding.
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Diseases associated with BMPR1A include various polyposis syndromes. Polyposis syndromes:
- familial juvenile polyposis syndrome, an autosomal dominant disorder characterized by hamartomatous polyps in the gastrointestinal tract associated with an increased risk of gastrointestinal malignancies. 45-60% of JPS cases are due to disease-causing variants (DCVs) in BMPR1a or SMAD4, with BMPR1a DCVs accounting for 17-38% of JPS cases (Papadopulos ME et al. 2023).
- Juvenile polyposis syndrome of childhood
LiteratureThis section has been translated automatically.
- Chen D et al. (2004) Bone morphogenetic proteins. Growth Factors 22:233-241.
- Koenig, B.B. et al. (1994) Characterization and cloning of a receptor for BMP-2 and BMP-4 from NIH 3T3 cells. Mol Cell Biol 14: 5961-5974
- Moustakas A et al. (2002) From mono- to oligo-Smads: the heart of the matter in TGFbeta signal transduction. Genes Dev 16: 67-871.
- Papadopulos ME et al. (2023) Genotype-phenotype correlation of BMPR1a disease causing variants in juvenile polyposis syndrome. Hered Cancer Clin Pract 21:12.
- Sampath TK et al. (2020) Discovery of bone morphogenetic proteins - A historical perspective. Bone. 140:115548.
- ten Dijke P et al. (1994) Identification of type I receptors for osteogenic protein-1 and bone morphogenetic protein-4. J Biol Chem 269: 16985-16988
- Urist MR (1965) Bone formation by autoinduction. Science 150: 893-899.