Recombinant Human Bone morphogenetic protein 6 (BMP6), partial

Function

Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes including cartilage and bone formation (PubMed:31019025). Also plays an important role in the regulation of HAMP/hepcidin expression and iron metabolism by acting as a ligand for hemojuvelin/HJV (PubMed:26582087). Also acts to promote expression of HAMP, potentially via the interaction with its receptor BMPR1A/ALK3 (PubMed:30097509, PubMed:31800957). Initiates the canonical BMP signaling cascade by associating with type I receptor ACVR1 and type II receptor ACVR2B (PubMed:18070108). In turn, ACVR1 propagates signal by phosphorylating SMAD1/5/8 that travel to the nucleus and act as activators and repressors of transcription of target. Can also signal through non-canonical pathway such as TAZ-Hippo signaling cascade to modulate VEGF signaling by regulating VEGFR2 expression (PubMed:33021694)

Subcellular Location

Secreted

Disease Association

Iron overload (IO) : A disorder of iron homeostasis with incomplete and age-dependent penetrance. It is characterized by adult onset of increased hepatic and systemic iron levels, increased serum ferritin, normal or high transferrin saturation, and inappropriately low or normal levels of hepcidin. The severity of the phenotype depends on age, sex, as well as additional genetic or acquired factors including alcohol consumption and increased body weight. [Disease susceptibility is associated with variants affecting the gene represented in this entry]

Subunit

Interacts with SOSTDC1 (By similarity). Interacts (when glycosylated) with type I receptor ACVR1; the interaction may induce HAMP expression (PubMed:18070108, PubMed:31800957). Interacts with type II receptor ACVR2B (PubMed:18070108). Interacts with Hemojuvelin/HJV (By similarity). Interacts with ERFE; the interaction inhibits BMP-induced transcription of HAMP (PubMed:30097509, PubMed:31800957). Interacts with BMPR1A/ALK3 (PubMed:31800957). Forms heterodimers with BMP2 in vitro; the heterodimer then binds to its receptor BMPR1A /ALK3 and may induce HAMP expression (PubMed:31800957)

• Celeste A.J. et al. Identification of transforming growth factor beta family members present in bone-inductive protein purified from bovine bone. — Proc. Natl. Acad. Sci. U.S.A. (1990)
• Mungall A.J. et al. The DNA sequence and analysis of human chromosome 6. — Nature (2003)
• Pulkkinen H.H. et al. BMP6/TAZ-Hippo signaling modulates angiogenesis and endothelial cell response to VEGF. — Angiogenesis (2021)
• Sjoeblom T. et al. The consensus coding sequences of human breast and colorectal cancers. — Science (2006)
• Arezes J. et al. Erythroferrone inhibits the induction of hepcidin by BMP6. — Blood (2018)
• Wang C.Y. et al. Erythroferrone lowers hepcidin by sequestering BMP2/6 heterodimer from binding to the BMP type I receptor ALK3. — Blood (2020)
• Allendorph G.P. et al. BMP-3 and BMP-6 structures illuminate the nature of binding specificity with receptors. — Biochemistry (2007)
• Saremba S. et al. Type I receptor binding of bone morphogenetic protein 6 is dependent on N-glycosylation of the ligand. — FEBS J. (2008)