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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
Location 1q22      Physical location : 156.211.950 - 156.213.112
Synonym name
  • gamma-carboxyglutamic acid-containing protein
  • osteocalcin
  • bone Gla protein
  • Synonym symbol(s) BGLA, BGP, PMF1, OCN, OC
    DNA
    TYPE functioning gene
    STRUCTURE 1.17 kb     3 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   transcription factor
    text structure
  • in the proximal promoter a minimal C/T-rich motif, termed BGLAP-CxRE (connexin-response element) that binds Sp1 and Sp3 in a gap junction-dependent manner
  • . ATF6 increases BGLAP transcription via directly binding to BGLAP promoter
  • MAPPING cloned Y linked N status confirmed
    Map cen - D1S189 - D1S252 - D1S305 - D1S303 - BGLAP /D1S3737 - D1S2721 - D1S2624 - CRP - SPTA1 - APOA2 APOA2 - D1S194 qter
    Authors Raymond (99)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 1001 - 211 - 2000 10486212
    3 - 940 - 220 - 2000 10486212
    3 - 805 - 175 - 2000 10486212
    3 - 794 - 142 - 2000 10486212
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveintestinesmall intestine   
    Endocrineparathyroid    
    Skeletonappendicularpectoral girdleclavicle  
     axialskull   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Skeletonosteoblast Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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