Expressed in early bell stage dental mesenchymal cells at 15.5 dpc (at protein level) (PubMed:24028588). Expressed in bell stage dental mesenchymal cells at 17.5 dpc (PubMed:29148101).
The carboxylated form is one of the main organic components of the bone matrix, which constitutes 1-2% of the total bone protein: it acts as a negative regulator of bone formation and is required to limit bone formation without impairing bone resorption or mineralization (PubMed:8684484). The carboxylated form binds strongly to apatite and calcium (PubMed:17693256).
The uncarboxylated form acts as a hormone secreted by osteoblasts, which regulates different cellular processes, such as energy metabolism, male fertility and brain development (PubMed:17693256, PubMed:20655470, PubMed:20655471, PubMed:21333348, PubMed:24074871). Regulates of energy metabolism by acting as a hormone favoring pancreatic beta-cell proliferation, insulin secretion and sensitivity and energy expenditure (PubMed:17693256, PubMed:20655470, PubMed:20655471). 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 (PubMed:21333348). 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) (PubMed:24074871, PubMed:28851741). Osteocalcin also crosses the placenta during pregnancy and maternal osteocalcin is required for fetal brain development (PubMed:24074871).
Gamma-carboxyglutamate residues are formed by vitamin K dependent carboxylation by GGCX (By similarity). These residues are essential for the binding of calcium (By similarity). Carboxylated in a Ptprv/Esp-dependent process (PubMed:17693256, PubMed:20655470, PubMed:20655471). Decarboxylation promotes the hormone activity (PubMed:17693256, PubMed:20655470, PubMed:20655471, PubMed:21333348, PubMed:24074871).
Belongs to the osteocalcin/matrix Gla protein family.
Bone.
Ocn, Bglap, Osteocalcin, OG1, Bone Gla protein, Gamma-carboxyglutamic acid-containing protein, BGP
Proteins
Cardiovascular
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