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FLASH GENE
Symbol ABCB4 contributors: mct - updated : 28-06-2015
HGNC name ATP-binding cassette, sub-family B (MDR/TAP), member 4
HGNC id 45
DNA
TYPE functioning gene
STRUCTURE 73.66 kb     28 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter (CAAT box)
cytosine-phosphate-guanine/HTF
Binding site   transcription factor
text structure
  • composed of GC-rich sequences and contains multiple putative SP1 binding sites
  • a highly conserved farnesoid X receptor (FXR) response element in the distal region of the MDR3 promoter, and transcription of MDR3 can be trans-activated by FXR
  • contains a CCAAT box with the sequence AGATCCAATGAC, which would be recognized by NFY.A, NFYB, NFYC
  • MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    28 - 3967 140.6 1279 - 2004 15258199
    28 splicing 3988 - 1286 - 2004 15258199
    an alternate in-frame splice site in the 3' coding region
    27 splicing 3826 - 1232 - 2004 15258199
    lacking an alternate in-frame exon
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveliver     Homo sapiens
    Endocrineadrenal gland    
     pancreas    
    Reproductivemale systemtestis   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestivehepatocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • ABC transporter, traffic ATPase with two ATP binding
  • two transmembrane (2TM) domains (2x6 segments), localized to the hepatocyte canalicular membrane
  • conjugated GlycoP
    HOMOLOGY
    intraspecies homolog to ABCB1
    Homologene
    FAMILY
  • ATP binding cassette superfamily
  • subfamily B (MDR/TAP)
  • CATEGORY transport carrier
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • involved in phosphatidylcholine translocation into the bile
  • critical trans-locator for phospholipids across canalicular membranes of hepatocytes
  • liver-specific membrane transporter of phosphatidylcholine, a major and exclusive component of bile
  • translocates phosphatidylcholine from the inner to the outer leaflet of the canalicular membrane
  • ABCB4 and ATP8B1 cooperate to protect hepatocytes from bile salts
  • might play a critical role in glucose homeostasis
  • plays an important role in protecting the liver from bile acids
  • may be involved in the transport of a broad array of drugs, because ABCB4 shows high amino acid homology to ABCB1 that plays an important role in transporting of various clinical drugs such as digoxin and paclitaxel
  • located in nonrafts, but not in rafts, is predominantly involved in the efflux of phospholipids and other substrates
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • NFYA, NFYB, NFYC can act as a transcriptional activator of ABCB4
  • interaction of ABCB4 with SLC9A3R1 through its PDZ-like motif plays a critical role in the regulation of ABCB4 expression and stability at the canalicular plasma membrane
  • cell & other
    REGULATION
    Other ABCB4 activity is regulated by phosphorylation, in particular, of N-terminal residues
    ASSOCIATED DISORDERS
    corresponding disease(s) PFIC3 , LPAC
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    cause intrahepatic cholestasis of pregnancy, with normal gamma-GT and may be associated with stillbirths and gallstone disease
    constitutional germinal mutation      
    splicing mutations cause intrahepatic cholestasis of pregnancy in women with high gamma-glutamyl transpeptidase (Tavian 2009)
    Susceptibility
  • to drug-induced cholestasis
  • to higher BMI and triglyceride and cholesterol levels
  • to to drug-induced cholestatic liver injury
  • Variant & Polymorphism SNP , other
  • polylmorphisms increasing drug-induced cholestasis (Lang 2007)
  • SNP C.504C > T associated with higher BMI and triglyceride and cholesterol levels (Acalovschi 2009)
  • g.-1584C>T and g.-1014A>G, may be associated with a susceptibility. to drug-induced cholestatic liver injury
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS