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FLASH GENE
Symbol CYP3A4 contributors: mct - updated : 27/04/2010
HGNC name cytochrome P450, family 3, subfamily A, polypeptide 4
HGNC id 2637
Location 7q22.1      Physical location : 99.354.603 - 99.381.808
Synonym name
  • P450-III, steroid inducible
  • cytochrome P450, subfamily IIIA (niphedipine oxidase), polypeptide 3
  • albendazole sulfoxidase
  • quinine 3-monooxygenase
  • albendazole monooxygenase
  • glucocorticoid-inducible P450
  • taurochenodeoxycholate 6-alpha-hydroxylase
  • cytochrome P450, subfamily IIIA (niphedipine oxidase), polypeptide 4
  • nifedipine oxidase
  • Synonym symbol(s) CP34, P450C3, P450PCN1, CYP3A3, HLP, CP33, CYP3A, NF-25, MGC126680
    EC.number 1.14.13.32, 1.14.13.67, 1.14.13.97
    DNA
    TYPE functioning gene
    SPECIAL FEATURE component of a cluster
    STRUCTURE 27.21 kb     13 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   HRE
    text structure
  • variant CYP3A4V in the 5' of promoter, high frequence in African-American people
  • NR1I2 responsive elements in the 5' upstream regulatory region of gene
  • MAPPING cloned Y linked N status confirmed
    Physical map
    ARPC1A 7q22.1-q31.33 actin related protein 2/3 complex, subunit 1A, 41kDa ARPC1B 7q22.1-q31.33 actin related protein 2/3 complex, subunit 1B, 41kDa PDAP1 7q11.21 PDGFA associated protein 1 G10 7q11.21 PDGFA associated protein 1 CPSF4 7q22.1 cleavage and polyadenylation specific factor 4, 30kDa KIAA0632 7q22.1 cleavage and polyadenylation specific factor 4, 30kDa ATP5J2 7q21.3-q22 ATP synthase, H+ transporting, mitochondrial F0 complex, subunit f, isoform 2 LOC285989 7q22.1 hypothetical protein LOC285989 ZNF394 7q22.1 zinc finger protein 394 ZFP95 7q22 zinc finger protein 95 homolog (mouse) DKFZp727G131 7q22.1 hypothetical protein DKFZp727G131 VIK 7q22.1 vav-1 interacting Kruppel-like protein ZNF498 7q22.1 zinc finger protein 498 CYP3A5 7q21.3-q22.1 cytochrome P450, family 3, subfamily A, polypeptide 5 CYP3A5P1 7q21.3-q22.1 cytochrome P450, family 3, subfamily A, polypeptide 5 pseudogene 1 CYP3A7 7q21.3-q22.1 cytochrome P450, family 3, subfamily A, polypeptide 7 CYP3A5P2 7q21.3-q22.1 cytochrome P450, family 3, subfamily A, polypeptide 5 pseudogene 2 CYP3A4 7q21.3-q22.1 cytochrome P450, family 3, subfamily A, polypeptide 4 CYP3A43 7q21.1 cytochrome P450, family 3, subfamily A, polypeptide 43 TRIM4 7q22-q31.1 tripartite motif-containing 4 AZGP1 7q22.1 alpha-2-glycoprotein 1, zinc LOC392078 7 hypothetical gene supported by BC022382 ZNF36 7q21.3-q22.1 zinc finger protein 36 (KOX 18) ZNF38 7q21-q22 zinc finger protein 38 ZNF3 7q22.1 zinc finger protein 3 (A8-51) COPS6 7q22.1 zinc finger protein 3 (A8-51) MCM7 7q21.3-q22.1 MCM7 minichromosome maintenance deficient 7 (S. cerevisiae) AP4M1 7q22.1 adaptor-related protein complex 4, mu 1 subunit TAF6 7q11 TAF6 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 80kDa MGC40499 7q22.1 hypothetical protein MGC40499 LOC255374 7q22.1 similar to hypothetical protein MGC49416 LOC392079 7 similar to ribosomal protein L7
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    21 - 2768 57.3 503 - 1986 3460094
    - - 2010 58 504 - -
    also called CYP3A3 variant
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   predominantly Homo sapiens
    Reproductivemale systemprostate   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal 33-AAs domain embedded in the ER membrane with the bulk of its structure in the cytosol
  • conjugated HemoP
    mono polymer monomer
    HOMOLOGY
    interspecies homolog to C.elegans t10b9.10
    Homologene
    FAMILY
  • cytochrome P450 family
  • subfamily IIIA
  • multigenic cytochrome P450 superfamily of mixed-function monooxygenases
  • CATEGORY enzyme , transport
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,inner
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic,microsome
    basic FUNCTION
  • heme-thiolate monooxygenases, involved in an NADPH-dependent electron transport pathway
  • vitamin D 25-hydroxylase for vitamin D2 in hepatic microsomes and hydroxylates both 1alpha(OH)D2 and 1alpha(OH)D3
  • involved in the metabolism of more than 50 p100 of drugs and other xenobiotics
  • its induction represents an important detoxification mechanism
  • endoplasmic reticulum (ER)-anchored hemoprotein engaged in the oxidative biotransformation of various endo- and xenobiotics
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS electron transport
    PATHWAY
    metabolism drug , lipid/lipoprotein
    signaling
    drug including acetaminophen, codeine, cyclosporin A, diazepam, erythromycin
    a component
    INTERACTION
    DNA
    RNA
    small molecule cofactor, nucleotide,
  • NADPH, heme
  • protein
  • flavoprotein P450 oxidoreductase (POR)
  • transcriptional target of SMARCA4
  • cell & other
    REGULATION
    induced by induced to high levels in liver and other tissues by various foreign compounds, including drugs,
    pesticides, and carcinogens.
    glucocorticoids and some pharmacological agents
    VDR, transactivating CYP3A4 in the intestine by secondary bile acids
    NR1I2
    inhibited by Ketamine (Ketamine may inhibit CYP3A4 expression possibly through reducing calcium mobilization and mitochondrial ATP synthesis and consequently disturbing cytoskeleton remodeling)
    repressed by binding of nuclear receptors (NR2F1, NR2F2, THRA, THRB) competing for response element in the promoter
    Other phosphorylation of CYP3A4 Ser478, Thr264, and Ser420 AAs by cytosolic kinases is important both for its ubiquitination and proteasomal degradation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    related resource Human Cytochrome P450 (CYP) Allele Nomenclature Committee
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in lung cancer
    Susceptibility
  • to prostate cancer
  • to treatment-related leukemia
  • Variant & Polymorphism other
  • polymorphism CYP3A4V potentially increased susceptibility to prostate cancer
  • CYP3A4-W genotype may be at increased risk for treatment-related leukemia
  • CYP3A4-W genotype may increase production of potentially DNA-damaging reactive intermediates and may decrease production of the epipodophyllotoxin catechol metabolite, which is the precursor of the potentially DNA-damaging quinone
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS