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: 14q22.2

Cellular Component: endoplasmic reticulum lumen; extracellular region; extracellular space; proteinaceous extracellular matrix

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

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

Disease: Microphthalmia, Syndromic 6; Orofacial Cleft 11