Human Gene CYP1A2 (ENST00000343932.5) from GENCODE V44
Description: Homo sapiens cytochrome P450 family 1 subfamily A member 2 (CYP1A2), mRNA. (from RefSeq NM_000761) RefSeq Summary (NM_000761): 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]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. Gencode Transcript: ENST00000343932.5 Gencode Gene: ENSG00000140505.7 Transcript (Including UTRs) Position: hg38 chr15:74,748,845-74,756,607 Size: 7,763 Total Exon Count: 7 Strand: + Coding Region Position: hg38 chr15:74,749,739-74,755,088 Size: 5,350 Coding Exon Count: 6
ID:CP1A2_HUMAN DESCRIPTION: RecName: Full=Cytochrome P450 1A2; EC=1.14.14.1; AltName: Full=CYPIA2; AltName: Full=Cytochrome P(3)450; AltName: Full=Cytochrome P450 4; AltName: Full=Cytochrome P450-P3; FUNCTION: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O- deethylation of phenacetin. CATALYTIC ACTIVITY: RH + reduced flavoprotein + O(2) = ROH + oxidized flavoprotein + H(2)O. COFACTOR: Heme group. BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=4 uM for 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole; KM=21 uM for 2-amino-3-methylimidazo[4,5-f]quinoline; KM=26 uM for 2-amino-2,4-dimethylimidazo[4,5-f]quinoline; KM=27 uM for 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline; KM=71 uM for 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine; KM=25 uM for phenacetin; SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein. TISSUE SPECIFICITY: Liver. INDUCTION: By nicotine, omeprazole, phenobarbital, primidone and rifampicin. POLYMORPHISM: The CYP1A2*1F allele which is quite common (40 to 50%) is due to a substitution of a base in the non-coding region of the CYP1A2 gene and has the effect of decreasing the enzyme inducibility. Individuals who are homozygous for the CYP1A2*1F allele are 'slow' caffeine metabolizers. Thus for these individual increased intake of caffeine seems to be associated with a concomitant increase in the risk of non-fatal myocardial infraction (MI). SIMILARITY: Belongs to the cytochrome P450 family. WEB RESOURCE: Name=Cytochrome P450 Allele Nomenclature Committee; Note=CYP1A2 alleles; URL="http://www.cypalleles.ki.se/cyp1a2.htm"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/cyp1a2/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P05177
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0004497 monooxygenase activity GO:0005506 iron ion binding GO:0009055 electron carrier activity GO:0016491 oxidoreductase activity GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen GO:0016712 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 GO:0019899 enzyme binding GO:0020037 heme binding GO:0032451 demethylase activity GO:0034875 caffeine oxidase activity GO:0046872 metal ion binding GO:0070330 aromatase activity
Biological Process: GO:0006629 lipid metabolic process GO:0006706 steroid catabolic process GO:0006725 cellular aromatic compound metabolic process GO:0006778 porphyrin-containing compound metabolic process GO:0006805 xenobiotic metabolic process GO:0008202 steroid metabolic process GO:0009403 toxin biosynthetic process GO:0009404 toxin metabolic process GO:0009791 post-embryonic development GO:0009820 alkaloid metabolic process GO:0010033 response to organic substance GO:0010468 regulation of gene expression GO:0014070 response to organic cyclic compound GO:0016098 monoterpenoid metabolic process GO:0017144 drug metabolic process GO:0018894 dibenzo-p-dioxin metabolic process GO:0019373 epoxygenase P450 pathway GO:0022900 electron transport chain GO:0030324 lung development GO:0032259 methylation GO:0032355 response to estradiol GO:0032496 response to lipopolysaccharide GO:0032787 monocarboxylic acid metabolic process GO:0035902 response to immobilization stress GO:0042493 response to drug GO:0042737 drug catabolic process GO:0042738 exogenous drug catabolic process GO:0042759 long-chain fatty acid biosynthetic process GO:0045333 cellular respiration GO:0046483 heterocycle metabolic process GO:0050665 hydrogen peroxide biosynthetic process GO:0055114 oxidation-reduction process GO:0070989 oxidative demethylation GO:0071276 cellular response to cadmium ion GO:0071280 cellular response to copper ion GO:0071615 oxidative deethylation GO:0097267 omega-hydroxylase P450 pathway
BC067424 - Homo sapiens cytochrome P450, family 1, subfamily A, polypeptide 2, mRNA (cDNA clone MGC:79250 IMAGE:7002123), complete cds. BC067425 - Homo sapiens cytochrome P450, family 1, subfamily A, polypeptide 2, mRNA (cDNA clone MGC:79251 IMAGE:7002124), complete cds. BC067426 - Homo sapiens cytochrome P450, family 1, subfamily A, polypeptide 2, mRNA (cDNA clone MGC:79252 IMAGE:7002125), complete cds. BC067427 - Homo sapiens cytochrome P450, family 1, subfamily A, polypeptide 2, mRNA (cDNA clone MGC:79253 IMAGE:7002126), complete cds. BC067428 - Homo sapiens cytochrome P450, family 1, subfamily A, polypeptide 2, mRNA (cDNA clone MGC:79254 IMAGE:7002128), complete cds. BC067429 - Homo sapiens cytochrome P450, family 1, subfamily A, polypeptide 2, mRNA (cDNA clone MGC:79255 IMAGE:7002129), complete cds. JD348683 - Sequence 329707 from Patent EP1572962. KJ891013 - Synthetic construct Homo sapiens clone ccsbBroadEn_00407 CYP1A2 gene, encodes complete protein. KR711984 - Synthetic construct Homo sapiens clone CCSBHm_00034488 CYP1A2 (CYP1A2) mRNA, encodes complete protein. KR711985 - Synthetic construct Homo sapiens clone CCSBHm_00034489 CYP1A2 (CYP1A2) mRNA, encodes complete protein. KR711986 - Synthetic construct Homo sapiens clone CCSBHm_00034490 CYP1A2 (CYP1A2) mRNA, encodes complete protein. AF182274 - Homo sapiens cytochrome P450-1A2 (CYP1A2) mRNA, complete cds. M55053 - Human cytochrome P-3-450 mRNA, complete cds. Z00036 - Human mRNA for cytochrome P-3-450. JD317141 - Sequence 298165 from Patent EP1572962. E10852 - cDNA encoding human cytochrome P450. E11498 - cDNA encoding human cytochrome P-4501A2. M12078 - Human cytochrome P-450 4 mRNA, partial cds. JD174048 - Sequence 155072 from Patent EP1572962. JD081183 - Sequence 62207 from Patent EP1572962. JD229647 - Sequence 210671 from Patent EP1572962. JD564622 - Sequence 545646 from Patent EP1572962. JD442903 - Sequence 423927 from Patent EP1572962. JD092576 - Sequence 73600 from Patent EP1572962. JD559820 - Sequence 540844 from Patent EP1572962. JD539036 - Sequence 520060 from Patent EP1572962. JD434841 - Sequence 415865 from Patent EP1572962. JD514424 - Sequence 495448 from Patent EP1572962. JD371262 - Sequence 352286 from Patent EP1572962. JD337553 - Sequence 318577 from Patent EP1572962. JD463079 - Sequence 444103 from Patent EP1572962. JD533808 - Sequence 514832 from Patent EP1572962. JD095255 - Sequence 76279 from Patent EP1572962. JD514007 - Sequence 495031 from Patent EP1572962. JD120918 - Sequence 101942 from Patent EP1572962. JD452111 - Sequence 433135 from Patent EP1572962. JD101224 - Sequence 82248 from Patent EP1572962. JD342662 - Sequence 323686 from Patent EP1572962. JD435406 - Sequence 416430 from Patent EP1572962. JD308108 - Sequence 289132 from Patent EP1572962. JD165355 - Sequence 146379 from Patent EP1572962. JD561125 - Sequence 542149 from Patent EP1572962. JD213646 - Sequence 194670 from Patent EP1572962. JD554450 - Sequence 535474 from Patent EP1572962. JD379576 - Sequence 360600 from Patent EP1572962. JD079913 - Sequence 60937 from Patent EP1572962. JD356574 - Sequence 337598 from Patent EP1572962. JD506279 - Sequence 487303 from Patent EP1572962. JD374339 - Sequence 355363 from Patent EP1572962. JD223650 - Sequence 204674 from Patent EP1572962. JD177625 - Sequence 158649 from Patent EP1572962. JD357418 - Sequence 338442 from Patent EP1572962. JD063902 - Sequence 44926 from Patent EP1572962. JD448603 - Sequence 429627 from Patent EP1572962. JD352436 - Sequence 333460 from Patent EP1572962. JD524667 - Sequence 505691 from Patent EP1572962. JD514399 - Sequence 495423 from Patent EP1572962. JD337490 - Sequence 318514 from Patent EP1572962. JD321924 - Sequence 302948 from Patent EP1572962. JD323930 - Sequence 304954 from Patent EP1572962. JD189363 - Sequence 170387 from Patent EP1572962. JD242687 - Sequence 223711 from Patent EP1572962. JD330957 - Sequence 311981 from Patent EP1572962. JD550518 - Sequence 531542 from Patent EP1572962. JD488088 - Sequence 469112 from Patent EP1572962. JD513927 - Sequence 494951 from Patent EP1572962. JD069745 - Sequence 50769 from Patent EP1572962. JD397056 - Sequence 378080 from Patent EP1572962. JD414851 - Sequence 395875 from Patent EP1572962. JD311828 - Sequence 292852 from Patent EP1572962. JD081630 - Sequence 62654 from Patent EP1572962. JD040242 - Sequence 21266 from Patent EP1572962. JD078434 - Sequence 59458 from Patent EP1572962. JD438034 - Sequence 419058 from Patent EP1572962. JD369127 - Sequence 350151 from Patent EP1572962. JD254408 - Sequence 235432 from Patent EP1572962. JD133304 - Sequence 114328 from Patent EP1572962. JD153399 - Sequence 134423 from Patent EP1572962. JD161873 - Sequence 142897 from Patent EP1572962. JD547993 - Sequence 529017 from Patent EP1572962. JD541263 - Sequence 522287 from Patent EP1572962. JD374564 - Sequence 355588 from Patent EP1572962. JD489238 - Sequence 470262 from Patent EP1572962. JD081033 - Sequence 62057 from Patent EP1572962. JD379672 - Sequence 360696 from Patent EP1572962. JD311796 - Sequence 292820 from Patent EP1572962. JD313747 - Sequence 294771 from Patent EP1572962. JD356645 - Sequence 337669 from Patent EP1572962. JD238889 - Sequence 219913 from Patent EP1572962. JD125305 - Sequence 106329 from Patent EP1572962. JD253310 - Sequence 234334 from Patent EP1572962. JD126500 - Sequence 107524 from Patent EP1572962. JD536738 - Sequence 517762 from Patent EP1572962. JD397687 - Sequence 378711 from Patent EP1572962. JD364786 - Sequence 345810 from Patent EP1572962. JD417384 - Sequence 398408 from Patent EP1572962.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa00232 - Caffeine metabolism hsa00380 - Tryptophan metabolism hsa00591 - Linoleic acid metabolism hsa00830 - Retinol metabolism hsa00980 - Metabolism of xenobiotics by cytochrome P450 hsa00982 - Drug metabolism - cytochrome P450 hsa01100 - Metabolic pathways
BioCyc Knowledge Library PWY-6398 - melatonin degradation I PWY-6402 - superpathway of melatonin degradation PWY66-401 - superpathway of L-tryptophan utilization
BioCarta from NCI Cancer Genome Anatomy Project h_nuclearRsPathway - Nuclear Receptors in Lipid Metabolism and Toxicity h_AcetaminophenPathway - Mechanism of Acetaminophen Activity and Toxicity
Reactome (by CSHL, EBI, and GO)
Protein P05177 (Reactome details) participates in the following event(s):
R-HSA-76373 N-hydroxylation of 4-aminobiphenyl R-HSA-76386 CYP1A2 S-demethylates 6MMP R-HSA-76426 N-atom dealkylation of caffeine R-HSA-5423678 CYP1A2 hydroxylates AFB1 to AFM1 R-HSA-2161814 Arachidonic acid is hydroxylated to 19-HETE by CYP(2) R-HSA-2161890 Arachidonic acid is epoxidated to 5,6-EET by CYP(4) R-HSA-2161940 Arachidonic acid is hydroxylated to 20-HETE by CYP(3) R-HSA-2161899 Arachidonic acid is epoxidated to 8,9/11,12/14,15-EET by CYP(5) R-HSA-2161795 Arachidonic acid is hydroxylated to 16/17/18-HETE by CYP(1) R-HSA-156526 CYP1A2,3A4,3A5,2A13 oxidise AFB1 to AFXBO R-HSA-5423672 CYP1A2, 3A4 oxidise AFB1 to AFNBO R-HSA-9027043 CYPs hydroxylate DHA to 14(R)-HDHA R-HSA-9037761 CYP1, CYP2 hydroxylate (N)PD1 to 22-OH-(N)PD1 R-HSA-211957 Aromatic amines can be N-hydroxylated or N-dealkylated by CYP1A2 R-HSA-156581 Methylation R-HSA-5423646 Aflatoxin activation and detoxification R-HSA-2142816 Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE) R-HSA-2142670 Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET) R-HSA-9027307 Biosynthesis of maresin-like SPMs R-HSA-9018681 Biosynthesis of protectins R-HSA-211981 Xenobiotics R-HSA-156580 Phase II - Conjugation of compounds R-HSA-211859 Biological oxidations R-HSA-2142753 Arachidonic acid metabolism R-HSA-9018682 Biosynthesis of maresins R-HSA-9018677 Biosynthesis of DHA-derived SPMs R-HSA-211897 Cytochrome P450 - arranged by substrate type R-HSA-1430728 Metabolism R-HSA-8978868 Fatty acid metabolism R-HSA-9018678 Biosynthesis of specialized proresolving mediators (SPMs) R-HSA-211945 Phase I - Functionalization of compounds R-HSA-556833 Metabolism of lipids