Cytochrome P450, family 1, member A1

Cytochrome P450, family 1, subfamily A, polypeptide 1
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 4I8V
Identifiers
Symbols	CYP1A1 ; AHH; AHRR; CP11; CYP1; P1-450; P450-C; P450DX
External IDs	OMIM: 108330 MGI: 88588 HomoloGene: 68062 IUPHAR: 1318 ChEMBL: 2231 GeneCards: CYP1A1 Gene
EC number	1.14.14.1
Gene ontology Molecular function • iron ion binding • steroid hydroxylase activity • oxidoreductase activity • oxidoreductase activity, acting on diphenols and related substances as donors • flavonoid 3'-monooxygenase activity • oxygen binding • enzyme binding • heme binding • demethylase activity • aromatase activity • vitamin D 24-hydroxylase activity Cellular component • mitochondrion • endoplasmic reticulum membrane Biological process • response to hypoxia • porphyrin-containing compound metabolic process • xenobiotic metabolic process • aging • cell proliferation • amine metabolic process • response to wounding • response to virus • response to nematode • response to herbicide • embryo development ending in birth or egg hatching • coumarin metabolic process • flavonoid metabolic process • response to iron(III) ion • insecticide metabolic process • drug metabolic process • dibenzo-p-dioxin catabolic process • arachidonic acid metabolic process • epoxygenase P450 pathway • response to food • response to lipopolysaccharide • response to vitamin A • vitamin D metabolic process • response to drug • 9-cis-retinoic acid biosynthetic process • camera-type eye development • cellular lipid metabolic process • small molecule metabolic process • response to antibiotic • response to arsenic-containing substance • digestive tract development • hydrogen peroxide biosynthetic process • response to hyperoxia • oxidation-reduction process • maternal process involved in parturition • hepatocyte differentiation • demethylation • cellular response to organic cyclic compound • omega-hydroxylase P450 pathway • positive regulation of G1/S transition of mitotic cell cycle Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1543	13076
Ensembl	ENSG00000140465	ENSMUSG00000032315
UniProt	P04798	P00184
RefSeq (mRNA)	NM_000499	NM_001136059
RefSeq (protein)	NP_000490	NP_001129531
Location (UCSC)	Chr 15: 75.01 – 75.02 Mb	Chr 9: 57.7 – 57.7 Mb
PubMed search

Cytochrome P450, family 1, subfamily A, polypeptide 1 is a protein^[1] that in humans is encoded by the CYP1A1 gene.^[2] The protein is a member of the cytochrome P450 superfamily of enzymes.^[3]

Function

CYP1A1 is involved in phase I xenobiotic and drug metabolism (one substrate of it is theophylline). It is inhibited by fluoroquinolones and macrolides and induced by aromatic hydrocarbons.^[4]

CYP1A1 is also known as AHH (aryl hydrocarbon hydroxylase). It is involved in the metabolic activation of aromatic hydrocarbons (polycyclic aromatic hydrocarbons, PAH), for example, benzo(a)pyrene (BP), by transforming it to an epoxide. In this reaction, the oxidation of benzo[a]pyrene is catalysed by CYP1A1 to form BP-7,8-epoxide, which can be further oxidized by epoxide hydrolase (EH) to form BP-7,8-dihydrodiol. Finally CYP1A1 catalyses this intermediate to form BP-7,8-dihydrodiol-9,10-epoxide, which is the ultimate carcinogen.^[5]

However, an in vivo experiment with gene-deficient mice has found that the hydroxylation of benzo(a)pyrene by CYP1A1 can have an overall protective effect on the DNA, rather than contributing to potentially carcinogenic DNA modifications. This effect is likely due to the fact that CYP1A1 is highly active in the intestinal mucosa, and thus inhibits infiltration of ingested benzo(a)pyrene carcinogen into the systemic circulation.^[6]

Regulation

The expression of the CYP1A1 gene, along with that of CYP1A2/1B1 genes, is regulated by a heterodimeric transcription factor that consist of the aryl hydrocarbon receptor, a ligand activated transcription factor, and the aryl hydrocarbon receptor nuclear translocator.^[7] In the intestine, but not the liver, CYP1A1 expression moreover depends on TOLL-like receptor 2 (TLR2),^[8] which recognizes bacterial surface structures such as lipoteichoic acid.

Polymorphisms

Several polymorphisms have been identified in CYP1A1, some of which lead to more highly inducible AHH activity. CYP1A1 polymorphisms include:^{[9][10][11][12]}

• M1, T→C substitution at nucleotide 3801 in the 3'-non-coding region
• M2, A→G substitution at nucleotide 2455 leading to an amino acid change of isoleucine to valine at codon 462
• M3, T→C substitution at nucleotide 3205 in the 3'-non-coding region
• M4, C→A substitution at nucleotide 2453 leading to an amino acid change of threonine to asparagine at codon 461

The highly inducible forms of CYP1A1 are associated with an increased risk of lung cancer in smokers. (Reference = Kellerman et al., New Eng J Med 1973:289;934-937) Light smokers with the susceptible genotype CYP1A1 have a sevenfold higher risk of developing lung cancer compared to light smokers with the normal genotype.

References

Further reading