CYP1A2 cytochrome P450, family 1, subfamily A, polypeptide 2 [Homo sapiens (human)] - Gene

Summary

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Official Symbol: CYP1A2provided by HGNC
Official Full Name: cytochrome P450, family 1, subfamily A, polypeptide 2provided by HGNC
Primary source: HGNC:2596
See related: Ensembl:ENSG00000140505; HPRD:00489; MIM:124060; Vega:OTTHUMG00000172901
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CP12; P3-450; P450(PA)
Summary: This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The protein encoded by this gene localizes to the endoplasmic reticulum and its expression is induced by some polycyclic aromatic hydrocarbons (PAHs), some of which are found in cigarette smoke. The enzyme's endogenous substrate is unknown; however, it is able to metabolize some PAHs to carcinogenic intermediates. Other xenobiotic substrates for this enzyme include caffeine, aflatoxin B1, and acetaminophen. The transcript from this gene contains four Alu sequences flanked by direct repeats in the 3' untranslated region. [provided by RefSeq, Jul 2008]

Genomic context

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Location :: 15q24.1

Sequence :: Chromosome: 15; NC_000015.9 (75041184..75048941)

See CYP1A2 in Epigenomics, MapViewer

Chromosome 15 - NC_000015.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

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Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

3-Pyridyl substituted aliphatic cycles as CYP11B2 inhibitors: aromaticity abolishment of the core significantly increased selectivity over CYP1A2
Title: 3-Pyridyl substituted aliphatic cycles as CYP11B2 inhibitors: aromaticity abolishment of the core significantly increased selectivity over CYP1A2.
Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM
Title: Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM.
Human cytochrome P450 (CYP) 1A1 and 1A2 enzymes were found to be responsible for the aristolochic acid I reductive activation to form AAI-DNA adducts, while its structurally related analogue, CYP1B1 is almost without such activity.
Title: Theoretical investigation of differences in nitroreduction of aristolochic acid I by cytochromes P450 1A1, 1A2 and 1B1.
Several CYP1A2 haplotypes containing the -2467delT variant were associated with lower lung cancer risk, however, they did not correlate with significant changes in CYP1A2 metabolic activity toward caffeine.
Title: Haplotypes in the 5'-untranslated region of the CYP1A2 gene are inversely associated with lung cancer risk but do not correlate with caffeine metabolism.
In non-smokers, the CYP1A2 variants were associated with higher caffeine intake.
Title: Caffeine intake and CYP1A2 variants associated with high caffeine intake protect non-smokers from hypertension.
Scutellarin might have a weak inhibitory effect on the activity of CYP1A2 in rats.
Title: Scutellarin inhibits cytochrome P450 isoenzyme 1A2 (CYP1A2) in rats.
In this study of individuals of South Asian and European ancestry, variability in CYP1A2 activity can be explained by diet, lifestyle and genetic factors.
Title: Influence of environmental and genetic factors on CYP1A2 activity in individuals of South Asian and European ancestry.
genetic association studies in a Costa Rican population: Previous associations observed between an SNP in CYP1A2 (rs2470893) and caffeine/coffee consumption in European populations are also observed in an ethnically distinct Costa Rican population.
Title: Associations between polymorphisms in the AHR and CYP1A1-CYP1A2 gene regions and habitual caffeine consumption.
results demonstrate that CYP1A2 variant C of -163A/C, even independent of smoking exposure, may increase lung cancer risk, whereas variant delT of -2467 T/delT interacts with cigarette smoking to modify lung cancer risk in males
Title: Role of CYP1A2 polymorphisms on lung cancer risk in a prospective study.
Estimated hepatic CYP1A2 abundance values were 52, 64, 79, 90, and 94 pmol/mg microsomal protein for subjects smoking 0, 1-5, 6-10, 11-20, and >20 cigarettes/day respectively.
Title: Prediction of drug clearance in a smoking population: modeling the impact of variable cigarette consumption on the induction of CYP1A2.

Submit: New GeneRIF Correction See all (162)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM.

Genome-wide association study identifies eight loci associated with blood pressure.

Genome-wide meta-analysis identifies regions on 7p21 (AHR) and 15q24 (CYP1A2) as determinants of habitual caffeine consumption.

Sequence variants at CYP1A1-CYP1A2 and AHR associate with coffee consumption.

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_000752.1			BIND	PubMed	CYP1A2 interacts with Caffeine.
NP_000752.1			BIND	PubMed	CYP1A2 interacts with Meperidine.
NP_000752.1			BIND	PubMed	CYP1A2 interacts with OXY.
NP_000752.1			BIND	PubMed	CYP1A2 interacts with 17beta-estradiol.
NP_000752.1			BIND	PubMed	CYP1A2 interacts with Phenacetin.
P05177	P16435	POR	HPRD	PubMed
BioGRID:107924	BioGRID:107908	CYB5A	BioGRID	PubMed	Reconstituted Complex
BioGRID:107924	BioGRID:111443	POR	BioGRID	PubMed	Reconstituted Complex

Pathways from BioSystems

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Aflatoxin B1 metabolism, organism-specific biosystem (from WikiPathways)
Aflatoxin B1 metabolism, organism-specific biosystem'''Aflatoxins''' are naturally occurring [[wikipedia:mycotoxin|mycotoxin]]s that are produced by many species of ''[[wikipedia:Aspergillus|Aspergillus]]'', a [[wikipedia:fungus|fungus]], most notably...
AhR pathway, organism-specific biosystem (from WikiPathways)
AhR pathway, organism-specific biosystem
AhR pathway
Arachidonic acid metabolism, organism-specific biosystem (from REACTOME)
Arachidonic acid metabolism, organism-specific biosystemEicosanoids, oxygenated, 20-carbon fatty acids, are autocrine and paracrine signaling molecules that modulate physiological processes including pain, fever, inflammation, blood clot formation, smooth...
Aromatic amines can be N-hydroxylated or N-dealkylated by CYP1A2, organism-specific biosystem (from REACTOME)
Aromatic amines can be N-hydroxylated or N-dealkylated by CYP1A2, organism-specific biosystemCYP1A2 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. It is most active in catalyzing N-hydroxylation or N-dealkylation reactions.
Arylamine metabolism, organism-specific biosystem (from WikiPathways)
Arylamine metabolism, organism-specific biosystem
Arylamine metabolism
Biological oxidations, organism-specific biosystem (from REACTOME)
Biological oxidations, organism-specific biosystemAll organisms are constantly exposed to foreign chemicals every day. These can be man-made (drugs, industrial chemicals) or natural (alkaloids, toxins from plants and animals). Uptake is usually via ...
Caffeine metabolism, organism-specific biosystem (from KEGG)
Caffeine metabolism, organism-specific biosystem
Caffeine metabolism
Caffeine metabolism, conserved biosystem (from KEGG)
Caffeine metabolism, conserved biosystem
Caffeine metabolism
Chemical carcinogenesis, organism-specific biosystem (from KEGG)
Chemical carcinogenesis, organism-specific biosystemIt has been estimated that exposure to environmental chemical carcinogens may contribute significantly to the causation of a sizable fraction, perhaps a majority, of human cancers. Human carcinogens ...
Chemical carcinogenesis, conserved biosystem (from KEGG)
Chemical carcinogenesis, conserved biosystemIt has been estimated that exposure to environmental chemical carcinogens may contribute significantly to the causation of a sizable fraction, perhaps a majority, of human cancers. Human carcinogens ...
Cytochrome P450 - arranged by substrate type, organism-specific biosystem (from REACTOME)
Cytochrome P450 - arranged by substrate type, organism-specific biosystemThe P450 isozyme system is the major phase 1 biotransforming system in man, accounting for more than 90% of drug biotransformations. This system has huge catalytic versatility and a broad substrate s...
Drug metabolism - cytochrome P450, organism-specific biosystem (from KEGG)
Drug metabolism - cytochrome P450, organism-specific biosystem
Drug metabolism - cytochrome P450
Drug metabolism - cytochrome P450, conserved biosystem (from KEGG)
Drug metabolism - cytochrome P450, conserved biosystem
Drug metabolism - cytochrome P450
Estrogen metabolism, organism-specific biosystem (from WikiPathways)
Estrogen metabolism, organism-specific biosystem
Estrogen metabolism
Fatty Acid Omega Oxidation, organism-specific biosystem (from WikiPathways)
Fatty Acid Omega Oxidation, organism-specific biosystem
Fatty Acid Omega Oxidation
Linoleic acid metabolism, organism-specific biosystem (from KEGG)
Linoleic acid metabolism, organism-specific biosystem
Linoleic acid metabolism
Linoleic acid metabolism, conserved biosystem (from KEGG)
Linoleic acid metabolism, conserved biosystem
Linoleic acid metabolism
Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Metabolism of lipids and lipoproteins, organism-specific biosystem (from REACTOME)
Metabolism of lipids and lipoproteins, organism-specific biosystemLipids are hydrophobic but otherwise chemically diverse molecules that play a wide variety of roles in human biology. They include ketone bodies, fatty acids, triacylglycerols, phospholipids and sphi...
Metabolism of xenobiotics by cytochrome P450, organism-specific biosystem (from KEGG)
Metabolism of xenobiotics by cytochrome P450, organism-specific biosystem
Metabolism of xenobiotics by cytochrome P450
Metabolism of xenobiotics by cytochrome P450, conserved biosystem (from KEGG)
Metabolism of xenobiotics by cytochrome P450, conserved biosystem
Metabolism of xenobiotics by cytochrome P450
Methylation, organism-specific biosystem (from REACTOME)
Methylation, organism-specific biosystemMethylation is a common but minor pathway of Phase II conjugation compared to glucuronidation or sulfonation. The cofactor used in methylation conjugation is S-adenosylmethionine (SAM). SAM is the ...
Nuclear receptors in lipid metabolism and toxicity, organism-specific biosystem (from WikiPathways)
Nuclear receptors in lipid metabolism and toxicity, organism-specific biosystemNuclear receptors are transcription factors that are activated upon binding to its ligands. Initially, they had been classified as classic endocrine nuclear hormone receptors and orphan receptors. Ho...
Phase 1 - Functionalization of compounds, organism-specific biosystem (from REACTOME)
Phase 1 - Functionalization of compounds, organism-specific biosystemPhase 1 of metabolism is concerned with functionalization, that is the introduction or exposure of functional groups on the chemical structure of a compound. This provides a 'handle' for phase 2 conj...
Phase II conjugation, organism-specific biosystem (from REACTOME)
Phase II conjugation, organism-specific biosystemPhase II of biotransformation is concerned with conjugation, that is using groups from cofactors to react with functional groups present or introduced from phase I on the compound. The enzymes involv...
Retinol metabolism, organism-specific biosystem (from KEGG)
Retinol metabolism, organism-specific biosystem
Retinol metabolism
Retinol metabolism, conserved biosystem (from KEGG)
Retinol metabolism, conserved biosystem
Retinol metabolism
Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE), organism-specific biosystem (from REACTOME)
Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE), organism-specific biosystemSimilar to the lipoxygenases, cytochrome P450 (CYP) enzymes catalyse the hydroxylation and epoxygenation of arachidonic acid. However, whereas lipoxygenases use an active non-heme iron to abstract h...
Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET), organism-specific biosystem (from REACTOME)
Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET), organism-specific biosystemThe epoxidation of arachidonic acid by cytochrome P450s (CYPs) results in the formation of unique bioactive lipid mediators termed epoxyeicosatrienoic acids (EETs). Each double bond has been shown t...
Tamoxifen metabolism, organism-specific biosystem (from WikiPathways)
Tamoxifen metabolism, organism-specific biosystem
Tamoxifen metabolism
Tryptophan metabolism, organism-specific biosystem (from KEGG)
Tryptophan metabolism, organism-specific biosystem
Tryptophan metabolism
Tryptophan metabolism, organism-specific biosystem (from WikiPathways)
Tryptophan metabolism, organism-specific biosystem
Tryptophan metabolism
Tryptophan metabolism, conserved biosystem (from KEGG)
Tryptophan metabolism, conserved biosystem
Tryptophan metabolism
Xenobiotics, organism-specific biosystem (from REACTOME)
Xenobiotics, organism-specific biosystemOf the 50 microsomal CYPs, 15 act on xenobiotics. They all possess wide substrate specificity to cater for most foreign compounds that find their way into the body.
cytochrome P450, organism-specific biosystem (from WikiPathways)
cytochrome P450, organism-specific biosystemOxidation of a substrate by Cytochrome P450. Adapted from Niesink et al., Chapter 3, p. 47-48.
melatonin degradation I, organism-specific biosystem (from BIOCYC)
melatonin degradation I, organism-specific biosystemGeneral Background The indoleamine : N-ACETYL-5-METHOXY-TRYPTAMINE is a vertebrate hormone secreted by the pineal gland. It is involved in regulation of circadian and seasonal rhythms. : N-ACETYL-...
melatonin degradation I, conserved biosystem (from BIOCYC)
melatonin degradation I, conserved biosystemGeneral Background The indoleamine |FRAME: N-ACETYL-5-METHOXY-TRYPTAMINE| is a vertebrate hormone secreted by the pineal gland. It is involved in regulation of circadian and seasonal rhythms. |FRA...
metapathway biotransformation, organism-specific biosystem (from WikiPathways)
metapathway biotransformation, organism-specific biosystem
metapathway biotransformation
superpathway of melatonin degradation, conserved biosystem (from BIOCYC)
superpathway of melatonin degradation, conserved biosystemThe indoleamine |FRAME: N-ACETYL-5-METHOXY-TRYPTAMINE| is a vertebrate hormone secreted by the pineal gland. It is involved in regulation of circadian and seasonal rhythms. |FRAME: N-ACETYL-5-METHO...
superpathway of melatonin degradation, organism-specific biosystem (from BIOCYC)
superpathway of melatonin degradation, organism-specific biosystem
superpathway of melatonin degradation

General gene information

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Markers

PMC156606P1 (e-PCR)
- UniSTS:271408

D8S2279 (e-PCR)
- UniSTS:473907

RH80030 (e-PCR)
- UniSTS:87680

SGC35304 (e-PCR)
- UniSTS:24464

GDB:631802 (e-PCR)
- UniSTS:158429

STS-M31667 (e-PCR)
- UniSTS:14563

G10504 (e-PCR)
- UniSTS:18407

Genotypes

See CYP1A2 SNP Geneview Report
See CYP1A2 SNP Genotype Report
See CYP1A2 SNP Variation Viewer Report

Homology

Homologs of the CYP1A2 gene: The CYP1A2 gene is conserved in chimpanzee, dog, cow, mouse, rat, A.thaliana, and rice.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
aromatase activity	IEA Inferred from Electronic Annotation more info
caffeine oxidase activity	IDA Inferred from Direct Assay more info	PubMed
demethylase activity	IDA Inferred from Direct Assay more info	PubMed
electron carrier activity	TAS Traceable Author Statement more info	PubMed
enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
heme binding	IDA Inferred from Direct Assay more info	PubMed
iron ion binding	IEA Inferred from Electronic Annotation more info
monooxygenase activity	IDA Inferred from Direct Assay more info	PubMed
oxidoreductase activity	IDA Inferred from Direct Assay more info	PubMed
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
alkaloid metabolic process	IDA Inferred from Direct Assay more info	PubMed
arachidonic acid metabolic process	TAS Traceable Author Statement more info
cellular respiration	IEA Inferred from Electronic Annotation more info
cellular response to cadmium ion	IEA Inferred from Electronic Annotation more info
dibenzo-p-dioxin metabolic process	IEA Inferred from Electronic Annotation more info
drug catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
drug metabolic process	IDA Inferred from Direct Assay more info	PubMed
epoxygenase P450 pathway	TAS Traceable Author Statement more info
exogenous drug catabolic process	IDA Inferred from Direct Assay more info	PubMed
heterocycle metabolic process	IDA Inferred from Direct Assay more info	PubMed
hydrogen peroxide biosynthetic process	IEA Inferred from Electronic Annotation more info
lung development	IEA Inferred from Electronic Annotation more info
methylation	TAS Traceable Author Statement more info
monocarboxylic acid metabolic process	IDA Inferred from Direct Assay more info	PubMed
monoterpenoid metabolic process	IDA Inferred from Direct Assay more info	PubMed
omega-hydroxylase P450 pathway	TAS Traceable Author Statement more info
oxidation-reduction process	IDA Inferred from Direct Assay more info	PubMed
oxidative deethylation	IDA Inferred from Direct Assay more info	PubMed
oxidative demethylation	IDA Inferred from Direct Assay more info	PubMed
porphyrin-containing compound metabolic process	IEA Inferred from Electronic Annotation more info
post-embryonic development	IEA Inferred from Electronic Annotation more info
regulation of gene expression	IEA Inferred from Electronic Annotation more info
response to estradiol stimulus	IEA Inferred from Electronic Annotation more info
response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
response to stress	IEA Inferred from Electronic Annotation more info
small molecule metabolic process	TAS Traceable Author Statement more info
steroid catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
toxin biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
xenobiotic metabolic process	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
endoplasmic reticulum membrane	TAS Traceable Author Statement more info
intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: cytochrome P450 1A2

Names: cytochrome P450 1A2; CYPIA2; P450 form 4; cytochrome P450 4; cytochrome P(3)450; cytochrome P450-P3; dioxin-inducible P3-450; microsomal monooxygenase; xenobiotic monooxygenase; aryl hydrocarbon hydroxylase; flavoprotein-linked monooxygenase; cytochrome P450, subfamily I (aromatic compound-inducible), polypeptide 2

NP_000752.2

EC 1.14.14.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008431.1 RefSeqGene

Range

31302..39059

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000761.3 → NP_000752.2 cytochrome P450 1A2

Status: REVIEWED

Source sequence(s)

AC091230, BC067424, M55053

Consensus CDS

CCDS32293.1

UniProtKB/Swiss-Prot

P05177

Related

ENSP00000342007, OTTHUMP00000249691, ENST00000343932, OTTHUMT00000421263

Conserved Domains (2) summary

pfam00067
Location:42 – 494
Blast Score: 768

p450; Cytochrome P450

cl12078
Location:14 – 503
Blast Score: 570

CypX; Cytochrome P450 [Secondary metabolites biosynthesis, transport, and catabolism]

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000015.9 Reference GRCh37.p10 Primary Assembly

Range

75041184..75048941

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000147.1 Alternate HuRef

Range

51838984..51846743

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018926.1 Alternate CHM1_1.0

Range

55092226..55099982

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01060501.1 (3721..11480)	None
genomic	AC091230.23 (117367..125125)	None
genomic	AF253322.1	AAK25728.1
genomic	AMYH01006794.1 (223773..231529)	None
genomic	CH471136.2	EAW99313.1
genomic	DQ022432.1	AAY26399.1
genomic	L00389.1	AAA35738.1
genomic	M31664.1	AAA52163.1
genomic	M31667.1	AAA52163.1
mRNA	AF182274.1	AAF13599.1
mRNA	BC067424.1	AAH67424.1
mRNA	BC067425.1	AAH67425.1
mRNA	BC067426.1	AAH67426.1
mRNA	BC067427.1	AAH67427.1
mRNA	BC067428.1	AAH67428.1
mRNA	BC067429.1	AAH67429.1
mRNA	M12078.1	AAA52154.1
mRNA	M55053.1	AAA52146.1
mRNA	Z00036.1	CAA77335.1