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FLASH GENE
Symbol BGLAP contributors: mct - updated : 19-10-2013
HGNC name bone gamma-carboxyglutamate (gla) protein (osteocalcin)
HGNC id 1043
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
three GLA residues
HOMOLOGY
Homologene
FAMILY osteocalcin/matrix gla-protein family
CATEGORY structural protein
SUBCELLULAR LOCALIZATION extracellular
    intracellular
intracellular,cytoplasm,organelle,membrane
intracellular,cytoplasm,organelle,endoplasmic reticulum
intracellular,cytoplasm,organelle,Golgi
basic FUNCTION
  • constituant of the total bone protein
  • possible link between adipose tissue and BGLAP in the regulation of metabolism
  • cross-talks with vascular system and contributes to vascular remodeling
  • plays important roles in mineralization and calcium ion homeostasis
  • non-collagenous, vitamin K-dependent protein secreted in the late stage of osteoblasts differentiation
  • acts as a regulator of bone mineralization, and regulates osteoblast and osteoclast activity
  • it is presumable that BGLAP also acts on blood vessels by inducing angiogenesis and pathological mineralization
  • bone matrix protein that regulates hydroxyapatite size and shape through its vitamin-K-dependent, gamma-carboxylated form
  • important regulator of energy metabolism
  • attenuatespotentially ER stress and rescues impaired insulin sensitivity in insulin resistance via the NFKB signaling pathway
  • noncollagenous protein found in bone matrix and involved in mineralization and calcium ion homeostasis, that is one of the major bone morphogenetic markers
  • modulates reproductive function in humans
  • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    text cellular growth and mineralization
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding, other,
  • it binds strongly to apatite and calcium
  • protein
  • GPRC6A is a candidate for mediating the response to BGLAP in the bone-pancreas endocrine loop regulating insulin signaling
  • unphosphorylated HSPB1 has an inhibitory effect on BGLAP synthesis, but has a stimulatory effect on mineralization, in osteoblasts
  • SP7 could act via the non-canonical Sp1/Sp3-binding element to regulate BGLAP transcription
  • TP53 can bind to the human osteocalcin promoter (may directly target the BGLAP and positively affect its gene expression)
  • BMP2 induces osteoblast differentiation through RUNX2-dependent ATF6 expression, which directly regulates BGLAP transcription
  • ATF4 activates BGLAP in osteoblasts and indian hedgehog (IHH) in chondrocytes
  • transforms adventitial fibroblasts to myofibroblasts through stimulating AGT release and subsequent activation of PKCD/TLR4/reactive oxygen species/cyclooxygenase-2 signaling cascade
  • NACA acts as a transcriptional coactivator of the Osteocalcin gene
  • regulates beta-cell replication in a cyclin D1-dependent manner by signaling through the GPRC6A receptor expressed in these cells
  • KDM6B plays important roles in osteoblast differentiation and regulates the expressions of IBSP and BGLAP via transcription factors RUNX2 and SP7
  • ROCK1 negatively regulates BMP4-stimulated BGLAP synthesis via the MAPK14 pathway in osteoblasts
  • RBM3 has a role in enhancing the transcription of ALPP and BGLAP genes
  • cell & other
    REGULATION
    Other regulated by AP1 related protein and CBFA1 transcription factor
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism other Hind III polymorphism putatively influencing bone density and osteoblast growth
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    diabetetype 2 
    may offer novel opportunities for treatment of obesity and diabetes
    obesity  
    may offer novel opportunities for treatment of obesity and diabetes
    ANIMAL & CELL MODELS
  • Osteocalcin-deficient mice exhibit increased levels of luteinizing hormone (LH), a pituitary hormone that regulates sex steroid synthesis in the testes