8xs1

Structural highlights

Function

OSTCN_HUMAN Bone protein that constitutes 1-2% of the total bone protein, and which acts as a negative regulator of bone formation (PubMed:3019668, PubMed:6967872). Functions to limit bone formation without impairing bone resorption or mineralization (By similarity). It binds strongly to apatite and calcium (PubMed:6967872).[UniProtKB:P86546]^{[1] [2]} The uncarboxylated form acts as a hormone secreted by osteoblasts, which regulates different cellular processes, such as energy metabolism, male fertility and brain development. Regulates of energy metabolism by acting as a hormone favoring pancreatic beta-cell proliferation, insulin secretion and sensitivity and energy expenditure. Uncarboxylated osteocalcin hormone also promotes testosterone production in the testes: acts as a ligand for G protein-coupled receptor GPRC6A at the surface of Leydig cells, initiating a signaling response that promotes the expression of enzymes required for testosterone synthesis in a CREB-dependent manner. Also acts as a regulator of brain development: osteocalcin hormone crosses the blood-brain barrier and acts as a ligand for GPR158 on neurons, initiating a signaling response that prevents neuronal apoptosis in the hippocampus, favors the synthesis of all monoamine neurotransmitters and inhibits that of gamma-aminobutyric acid (GABA). Osteocalcin also crosses the placenta during pregnancy and maternal osteocalcin is required for fetal brain development.[UniProtKB:P86546]

References

1. ↑ Celeste AJ, Rosen V, Buecker JL, Kriz R, Wang EA, Wozney JM. Isolation of the human gene for bone gla protein utilizing mouse and rat cDNA clones. EMBO J. 1986 Aug;5(8):1885-90. PMID:3019668 doi:10.1002/j.1460-2075.1986.tb04440.x
2. ↑ Poser JW, Esch FS, Ling NC, Price PA. Isolation and sequence of the vitamin K-dependent protein from human bone. Undercarboxylation of the first glutamic acid residue. J Biol Chem. 1980 Sep 25;255(18):8685-91 PMID:6967872