Bone Morphogenetic Protein-4 (BMP4) Human Active Protein

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]

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: extracellular space; proteinaceous extracellular matrix; 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; BMP signaling pathway; regulation of protein import into nucleus; positive regulation of endothelial cell differentiation; positive chemotaxis; erythrocyte differentiation; chondrocyte differentiation; mesonephros development; kidney development; endochondral ossification; regulation of odontogenesis of dentine-containing teeth; negative regulation of immature T cell proliferation in the thymus; positive regulation of cardiac muscle fiber development; specification of organ position; monocyte differentiation; neuron fate commitment; embryonic cranial skeleton morphogenesis; negative regulation of striated muscle development; branching morphogenesis of a tube; negative regulation of mitosis; positive regulation of epidermal cell differentiation; negative regulation of phosphorylation; positive regulation of endothelial cell proliferation; hemopoietic progenitor cell differentiation; positive regulation of transcription from RNA polymerase II promoter; steroid hormone mediated signaling; 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; smooth muscle development; negative regulation of cell proliferation; inner ear receptor cell differentiation; ureteric bud development; intermediate mesodermal cell differentiation; regulation of smooth muscle cell differentiation; dorsoventral neural tube patterning; positive regulation of BMP signaling pathway; 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; telencephalon development; blood vessel endothelial cell proliferation during sprouting angiogenesis; ureteric bud branching; pituitary gland development; regulation of cell fate commitment; neural tube closure; positive regulation of protein amino acid phosphorylation; positive regulation of neuron differentiation; negative regulation of myoblast differentiation; mesodermal cell fate determination; anterior/posterior axis specification

Disease: Orofacial Cleft 11; Microphthalmia, Syndromic 6