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FLASH GENE
Symbol ABCC4 contributors: mct/npt/pgu - updated : 18-09-2014
HGNC name ATP-binding cassette, sub-family C (CFTR/MRP), member 4
HGNC id 55
Location 13q32.1      Physical location : 95.672.083 - 95.953.687
Synonym name
  • cystic fibrosis transmembrane conductance regulator-like 1
  • canalicular multispecific organic anion transporter (ABC superfamily)
  • bA464I2.1 (ATP-binding cassette, sub-family C (CFTR/MRP), member 4)
  • multidrug resistance-associated protein 4
  • multispecific organic anion transporter B
  • MRP/cMOAT-related ABC transporter
  • Synonym symbol(s) CFTRL1, MRP4, MOATB, EST170205, MOAT-B
    EC.number 3.6.3.49
    DNA
    TYPE functioning gene
    STRUCTURE 281.60 kb     31 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    GPC6 13q32 glypican 6 DCT 13q32 dopachrome tautomerase (dopachrome delta-isomerase, tyrosine-related protein 2) TGDS 13q32.1 TDP-glucose 4,6-dehydratase ITR 13q32.1 intimal thickness-related receptor SOX21 13q31-q32 SRY (sex determining region Y)-box 21 LOC387941 13 LOC387941 LOC341583 13q32.1 similar to bromodomain containing 7; bromodomain protein; bromodomain-containing 7 LOC387942 13 LOC387942 ABCC4 13q31 ATP-binding cassette, sub-family C (CFTR/MRP), member 4 CLDN10 13q31-q34 claudin 10 DZIP1 13q32.1 claudin 10 DNAJC3 13q32 DnaJ (Hsp40) homolog, subfamily C, member 3 UGCGL2 13q32.1 UDP-glucose ceramide glucosyltransferase-like 2 HS6ST3 13 heparan sulfate 6-O-sulfotransferase 3 LOC283476 13q32.2 hypothetical protein LOC283476 LOC390420 13 similar to heat shock protein 84 - mouse LOC341592 13q32.2 similar to tubby like protein 3 GPR80 13q32.2 G protein-coupled receptor 80 MBNL2 13q31.1 muscleblind-like 2 (Drosophila) RAP2A 13q34 RAP2A, member of RAS oncogene family LOC121906 13q32.2 similar to Proteasome subunit alpha type 6 (Proteasome iota chain) (Macropain iota chain) (Multicatalytic endopeptidase complex iota chain) (27 kDa prosomal protein) (PROS-27) (p27K)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    31 - 5843 149.4 1325 - 2009 19073137
    21 - 3077 96.71 859 - 2009 19073137
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   highly Homo sapiens
    Endocrineadrenal gland   highly Homo sapiens
     pancreas   highly Homo sapiens
    Skin/Tegumentskin     Homo sapiens
    Urinarykidney   highly Homo sapiens
    Visualeyeretina    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier liningepidermis   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticerythrocyte Homo sapiens
    Blood/Hematopoieticplatelet Homo sapiens
    Cardiovascularendothelial cell Homo sapiens
    Lymphoid/Immunedendritic cell Homo sapiens
    cell lineage
    cell lines a PMEA (phosphometoxylmethyladenine resistant cell lines)
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two ATP binding, each containing highly conserved Walker motifs
  • two transmembrane (2TM) domains(2 x 6 segments)
  • conserved domain in cytoplasmic loop 3 of ABCC4 that is crucial in ensuring its proper plasma membrane localization
  • 12 putative membrane-spanning domains
  • a consensus class I PDZ-binding motif (PDZ-bm) at the C-terminal end 0)
  • HOMOLOGY
    Homologene
    FAMILY
  • ABC transporter superfamily
  • subfamily C of the ABC transporter superfamily
  • conjugate transporter subfamily
  • CATEGORY transport carrier
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic,granule
    text
  • renal proximal tubule apical membrane
  • localizes to the plasma membrane
  • basic FUNCTION
  • traffic ATPase, cellular detoxification monophosphate (nucleoside multispecific apical organic anion transporter)acting as a putative efflux pump for cAMP and cGMP in kidney proximal tubules
  • having a function in platelet mediator storage and playing a role in inhibition of platelet function by some anti-inflammatory drugs
  • important protein, significantly contributing to dendritic cells migration toward the draining lymph nodes, and therefore relevant for the initiation of an immune response and a possible target for immunotherapy
  • mediates the efflux of certain cyclic nucleotides, eicosanoids, conjugated steroids, and uric acid
  • confers resistance to nucleoside and nucleotide analogs as well as camptothecin derivatives
  • plays an important role in renal secretion of adefovir
  • responsible for the distribution of drugs and endogenous compounds in various tissues, such as the bone marrow, kidney, and brain
  • ATP-binding cassette transporter that actively effluxes endogenous and xenobiotic substrates out of cells
  • uniquely involved in retinal angiogenesis likely
  • acts as a component of the blood–brain barrier through its pump function
  • role for ABCC4 in the regulation of cAMP in cardiac myocytes and involvement of CFTR in beta-adrenergic stimulated contraction
  • functions as a nucleotide efflux transporter and thus plays a role in the regulation of intracellular cyclic nucleotide levels
  • plays potentially a key role in fibroblast migration
  • efflux transporter of cyclic nucleotides capable of regulating the intracellular cAMP/cGMP level
  • recognized as an ATP-dependent exporter of endogenous substances as well as an increasing variety of anionic chemotherapeutics
  • independent regulator of cyclic AMP (cAMP) levels particularly in vascular smooth muscle cells and in hematopoietic cells
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with SLC9A3R1 (implicated in ABCC4 internalization in non-polarized cells)
  • statistically positive correlation between ABCC4 mRNA and NR1I3, suggesting that NR1I3 may activate transcription of ABCC4 genes by its nuclear translocation
  • acts as a cAMP efflux pump to regulate intracellular cAMP levels and alter effector function, including activation of the cAMP-stimulated Cl(-) channel, CFTR
  • SNX27 is the interacting PDZ adaptor protein with a PDZ-binding motif of ABCC4
  • cell & other
    REGULATION
    inhibited by probenecid and dipyridamole
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in aggressive primary neuroblastoma correlated with MYCN oncogene amplification and significantly associated with poor clinical outcome
    tumoral     --over  
    and amplified in a PMEA (phosphomethoxylmethyladenine) resistant cell line
    tumoral     --over  
    highly expressed in lung cancer cell lines
    constitutional     --over  
    mRNA/protein levels were markedly increased in obstructive cholestasis
    constitutional       loss of function
    moderately increases the intracellular cyclic nucleotide level and stimulates fibroblast cell migration
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Mrp4-null mice had higher brain and cerebrospinal concentrations of the anticancer agent topotecan compared with wild-type mice
  • ABcc4-deficient mice displayed enhanced cardiac myocyte cAMP formation, contractility, and cardiac hypertrophy at 9 mo of age, an effect that was compensated transiently by increased phosphodiesterase expression at young age (