GeneID: 193


Common Name: CYP1A2 Type: Gene
Chromosome: 15 (NC_000015.10) Locus: NG_008431.2 (CYP1A1)
HUGO Symbol: CYP1A2 Full Name: cytochrome P450 family 1 subfamily A member 2
Exons: 14 Introns: 13

CYP1A2 is a member of the cytochrome P450 (CYP450) superfamily of heme-thiolate proteins that catalyze the oxidation of various endogenous and xenobiotic substrates in the metabolic pathway. It is mainly expressed in the liver and metabolizes about 20% of clinically used drugs. Its active site is surrounded by several aromatic residues, such that many of its substrates are small, lipophilic and planar molecules, including caffeine, clozapine, tinazidine, phenacetin, and zolmitriptan. It is subject to induction and inhibition by several compounds. For example, therapeutic drugs, such as enoxacin, furafylline, and zileuton mediate inhibition of CYP1A2, while environmental factors, such as polycyclic aromatic hydrocarbons in tobacco smoke and dietary agents in cruciferous vegetables, mediate its induction. The transcription of CYP1A2 is induced through AhR (arylhydrocarbon receptor) in the cytosol. Upon binding, AhR translocates to the nucleus where it dimerizes with ARNT (aryl hydrocarbon nuclear translocator), followed by binding to consensus regulatory sequences termed AhREs (Aryl hydrocarbon response elements), XREs (Xenobiotic response elements) or DREs (Dioxin response elements) in the promoter region of CYP1A2, thereby recruiting RNApol-II (possibly in co-operation with other proteins) to activate transcription. Polymoprhisms in this gene associated with variable plasma levels of deferasirox, and thus variable drug response, in a cohort of β-thalassaemia patients with transfusional iron overload.

Synonyms: CP12 , P3-450 , P450(PA)


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Publications / Origin

  1. Zhou H, Josephy PD, Kim D, Guengerich FP, Functional characterization of four allelic variants of human cytochrome P450 1A2., Arch. Biochem. Biophys. , 422(1), 23-30, 2004 PubMed
  2. Androutsopoulos VP, Tsatsakis AM, Spandidos DA, Cytochrome P450 CYP1A1: wider roles in cancer progression and prevention., BMC Cancer , 9(0), 187, 2009 PubMed
  3. Wang B, Zhou SF, Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development., Curr. Med. Chem. , 16(31), 4066-218, 2009 PubMed
  4. Cusato J, Allegra S, Massano D, De Francia S, Piga A, D'Avolio A, Influence of single-nucleotide polymorphisms on deferasirox C trough levels and effectiveness., Pharmacogenomics J. , 15(3), 263-71, 2015 PubMed
Created on 2016-10-25 17:50:04, Last reviewed on 2016-10-26 09:20:29 (Show full history)

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