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FLASH GENE
Symbol ABCG8 contributors: mct - updated : 03-11-2015
HGNC name ATP-binding cassette, sub-family G (WHITE), member 8 (sterolin 2)
HGNC id 13887
Corresponding disease
STSL sitosterolemia
Location 2p21      Physical location : 44.066.102 - 44.105.604
Synonym name sterolin 2
Synonym symbol(s) MGC142217, GBD4, STSL
DNA
TYPE functioning gene
SPECIAL FEATURE head to head, opposite orientation
text clone head to head and opposite orientation with ABCG5
STRUCTURE 51.23 kb     13 Exon(s)
10 Kb 5' upstream gene genomic sequence study
text structure common promoter and regulatory sequences with ABCG5
MAPPING cloned Y linked N status provisional
Map see ABCG5
RNA
TRANSCRIPTS type messenger
text
  • several isoforms
  • expression of ABCG5 and ABCG8 mRNAs is tightly co-regulated due to the sharing of a short intergenic promoter that separates their initiation codons by only 374 base pairs (PMID: 22715101)
    • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    13 - 2740 - 651 - 2006 16893193
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon   Homo sapiens
     liver     Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialabsorptive excretorydigestive epithelium (mucosa)  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestiveenterocyte Homo sapiens
    Digestivehepatocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal ATP binding motifs (Walker A and B)
  • an ABC-transporter signature motif (C motif)
  • six transmembrane (TM6) segments at the C terminus
    • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies homolog to Drosophila white
    intraspecies homolog to ABCG1
    Homologene
    FAMILY ATP binding cassette superfamily
    CATEGORY transport carrier
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    text
  • consistent with their function, ABCG5 and ABCG8 are located on the apical membrane of enterocytes and hepatocytes
    • basic FUNCTION
  • selective regulator of dietary cholesterol absorption, also promoting biliary excretion of sterols
  • sterol transporters may be playing a role in mediating apical cholesterol efflux in the gallbladder epithelium
  • required to modulate biliary cholesterol secretion in response to the non-cholesterol steroids cholate and diosgenin
  • bile acids may promote an active conformation of purified ABCG5/G8 either by global stabilization of the transporter or by binding to a specific site on ABCG5/G8
  • complex G5G8 mitigates the impact of a high fat diet on hepatic lipid accumulation and glucose intolerance
  • sterol transporters ABCA1, ABCG5, and ABCG8 may play a role in the pathogenesis of cholesterol-related gallbladder diseases (CAGD)
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS digestion , active transport
    PATHWAY
    metabolism
    signaling
    a component
  • heterodimerizing with ABCB6, to promote sterol excretion into bile
  • ABCG5 and ABCG8 form a complex (G5G8) that opposes the absorption of plant sterols but is also expressed in liver where it promotes the excretion of cholesterol into bile
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • MDR2 (ABCD4) required for G5G8-mediated biliary sterol secretion in mouse
  • NPC2 is a positive regulator of biliary cholesterol secretion via stimulation of ABCG5/G8-mediated cholesterol transport
  • SYVN1 and RNF5 may be negative regulators of disease-associated transporter ABCG5/ABCG8
    • cell & other
    REGULATION
    induced by high cholesterol diet in mice and LXR (liver orphan nuclear receptor) agonist
    ASSOCIATED DISORDERS
    corresponding disease(s) STSL
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    increased ABCA1, ABCG5, and ABCG8 expression in cholesterol-related gallbladder diseases (CAGD)
    Susceptibility
  • to gallstone disease
  • to myocardial infarction (MI) versus gallstone disease
    • Variant & Polymorphism other
  • variant D19H associated to gallstone disease
  • genetic variation in ABCG5/8, which associates with decreased levels of plasma LDL cholesterol protects against MI, but increases the risk of symptomatic gallstone disease
    • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Abcg5/g8 deficiency in mice fed a chow diet markedly raises TG levels by impairing TG catabolism and by increasing liver and intestinal TG secretion
  • overexpression of ABCG5 and ABCG8 in mice retards diet-induced atherosclerosis because of reduced circulating and hepatic cholesterol