P02819 · OSTCN_MACFA
- ProteinOsteocalcin
- GeneBGLAP
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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. The carboxylated form binds strongly to apatite and calcium.
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.
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | extracellular region | |
Molecular Function | calcium ion binding | |
Molecular Function | hormone activity | |
Molecular Function | hydroxyapatite binding | |
Molecular Function | structural constituent of bone | |
Biological Process | biomineral tissue development | |
Biological Process | bone development | |
Biological Process | brain development | |
Biological Process | cellular response to insulin stimulus | |
Biological Process | cognition | |
Biological Process | glucose homeostasis | |
Biological Process | learning or memory | |
Biological Process | negative regulation of bone development | |
Biological Process | osteoblast differentiation | |
Biological Process | positive regulation of neurotransmitter secretion | |
Biological Process | regulation of bone mineralization | |
Biological Process | regulation of cellular response to insulin stimulus | |
Biological Process | regulation of testosterone biosynthetic process | |
Biological Process | response to vitamin K | |
Biological Process | type B pancreatic cell proliferation |
Keywords
- Molecular function
- Biological process
- Ligand
Names & Taxonomy
Protein names
- Recommended nameOsteocalcin
- Alternative names
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Cercopithecidae > Cercopithecinae > Macaca
Accessions
- Primary accessionP02819
Proteomes
Subcellular Location
PTM/Processing
Features
Showing features for chain, modified residue, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000148901 | 1-49 | Osteocalcin | |||
Sequence: YLYQWLGAPAPYPDPLEPKREVCELNPDCDELADHIGFQEAYRRFYGPV | ||||||
Modified residue | 9 | 4-hydroxyproline | ||||
Sequence: P | ||||||
Modified residue | 17 | 4-carboxyglutamate | ||||
Sequence: E | ||||||
Modified residue | 21 | 4-carboxyglutamate | ||||
Sequence: E | ||||||
Disulfide bond | 23↔29 | |||||
Sequence: CELNPDC | ||||||
Modified residue | 24 | 4-carboxyglutamate | ||||
Sequence: E |
Post-translational modification
Gamma-carboxyglutamate residues are formed by vitamin K dependent carboxylation by GGCX. These residues are essential for the binding of calcium (By similarity) (PubMed:6978733).
Decarboxylation promotes the hormone activity (By similarity).
Decarboxylation promotes the hormone activity (By similarity).
Keywords
- PTM
Interaction
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 1-47 | Gla | ||||
Sequence: YLYQWLGAPAPYPDPLEPKREVCELNPDCDELADHIGFQEAYRRFYG |
Sequence similarities
Belongs to the osteocalcin/matrix Gla protein family.