Bone Morphogenetic Protein-4 (BMP4) Human Active Protein

This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein regulates heart development and adipogenesis. Mutations in this gene are associated with orofacial cleft and microphthalmia in human patients. The encoded protein may also be involved in the pathology of multiple cardiovascular diseases and human cancers. [provided by RefSeq, Jul 2016]

BMP4: Induces cartilage and bone formation. Also act 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. Homodimer; disulfide-linked. 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. Interacts with SOSTDC1. Expressed in the lung and lower levels seen in the kidney. Present also in normal and neoplastic prostate tissues, and prostate cancer cell lines. Belongs to the TGF-beta family.

Protein type: Secreted; Secreted, signal peptide

Chromosomal Location of Human Ortholog: 14q22-q23

Cellular Component: proteinaceous extracellular matrix; extracellular space; extracellular region

Molecular Function: heparin binding; protein binding; growth factor activity; cytokine activity; transforming growth factor beta receptor binding; chemoattractant activity

Biological Process: negative regulation of MAP kinase activity; extracellular matrix organization and biogenesis; renal system process; macrophage differentiation; activation of MAPKK activity; positive regulation of apoptosis; positive regulation of transcription, DNA-dependent; negative regulation of chondrocyte differentiation; lymphoid progenitor cell differentiation; telencephalon regionalization; germ cell development; post-embryonic development; regulation of protein import into nucleus; BMP signaling pathway; positive regulation of endothelial cell differentiation; positive chemotaxis; erythrocyte differentiation; chondrocyte differentiation; mesonephros development; kidney development; regulation of odontogenesis of dentine-containing teeth; endochondral ossification; positive regulation of cardiac muscle fiber development; negative regulation of immature T cell proliferation in the thymus; specification of organ position; monocyte differentiation; neuron fate commitment; embryonic cranial skeleton morphogenesis; negative regulation of striated muscle development; branching morphogenesis of a tube; positive regulation of epidermal cell differentiation; negative regulation of mitosis; negative regulation of phosphorylation; hemopoietic progenitor cell differentiation; steroid hormone mediated signaling; positive regulation of endothelial cell proliferation; positive regulation of transcription from RNA polymerase II promoter; embryonic digit morphogenesis; negative regulation of transcription, DNA-dependent; alveolus development; positive regulation of epithelial cell proliferation; negative regulation of apoptosis; positive regulation of protein binding; positive regulation of smooth muscle cell proliferation; positive regulation of collagen biosynthetic process; cloacal septation; negative regulation of transcription from RNA polymerase II promoter; embryonic hindlimb morphogenesis; negative regulation of cell cycle; odontogenesis; negative regulation of cell proliferation; smooth muscle development; inner ear receptor cell differentiation; ureteric bud development; intermediate mesodermal cell differentiation; regulation of smooth muscle cell differentiation; positive regulation of BMP signaling pathway; dorsoventral neural tube patterning; negative regulation of epithelial cell proliferation; smoothened signaling pathway; common-partner SMAD protein phosphorylation; negative regulation of T cell differentiation in the thymus; positive regulation of bone mineralization; positive regulation of ossification; odontogenesis of dentine-containing teeth; osteoblast differentiation; positive regulation of osteoblast differentiation; blood vessel endothelial cell proliferation during sprouting angiogenesis; telencephalon development; pituitary gland development; ureteric bud branching; regulation of cell fate commitment; neural tube closure; positive regulation of protein amino acid phosphorylation; negative regulation of myoblast differentiation; positive regulation of neuron differentiation; mesodermal cell fate determination; anterior/posterior axis specification

Disease: Orofacial Cleft 11; Microphthalmia, Syndromic 6