Cytochrome P450 1A2

NameCytochrome P450 1A2
Synonyms
  • 1.14.14.1
  • Cholesterol 25-hydroxylase
  • CYPIA2
  • Cytochrome P(3)450
  • Cytochrome P450 4
  • Cytochrome P450-P3
Gene NameCYP1A2
OrganismHuman
Amino acid sequence
>lcl|BSEQ0004778|Cytochrome P450 1A2
MALSQSVPFSATELLLASAIFCLVFWVLKGLRPRVPKGLKSPPEPWGWPLLGHVLTLGKN
PHLALSRMSQRYGDVLQIRIGSTPVLVLSRLDTIRQALVRQGDDFKGRPDLYTSTLITDG
QSLTFSTDSGPVWAARRRLAQNALNTFSIASDPASSSSCYLEEHVSKEAKALISRLQELM
AGPGHFDPYNQVVVSVANVIGAMCFGQHFPESSDEMLSLVKNTHEFVETASSGNPLDFFP
ILRYLPNPALQRFKAFNQRFLWFLQKTVQEHYQDFDKNSVRDITGALFKHSKKGPRASGN
LIPQEKIVNLVNDIFGAGFDTVTTAISWSLMYLVTKPEIQRKIQKELDTVIGRERRPRLS
DRPQLPYLEAFILETFRHSSFLPFTIPHSTTRDTTLNGFYIPKKCCVFVNQWQVNHDPEL
WEDPSEFRPERFLTADGTAINKPLSEKMMLFGMGKRRCIGEVLAKWEIFLFLAILLQQLE
FSVPPGVKVDLTPIYGLTMKHARCEHVQARRFSIN
Number of residues515
Molecular Weight58293.76
Theoretical pI9.43
GO Classification
Functions
  • oxidoreductase activity
  • iron ion binding
  • heme binding
  • monooxygenase activity
  • 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
  • enzyme binding
  • electron carrier activity
  • aromatase activity
  • caffeine oxidase activity
  • demethylase activity
Processes
  • dibenzo-p-dioxin metabolic process
  • response to lipopolysaccharide
  • drug catabolic process
  • response to immobilization stress
  • xenobiotic metabolic process
  • heterocycle metabolic process
  • arachidonic acid metabolic process
  • hydrogen peroxide biosynthetic process
  • drug metabolic process
  • cellular respiration
  • monoterpenoid metabolic process
  • porphyrin-containing compound metabolic process
  • omega-hydroxylase P450 pathway
  • methylation
  • oxidative deethylation
  • epoxygenase P450 pathway
  • oxidative demethylation
  • exogenous drug catabolic process
  • toxin biosynthetic process
  • steroid catabolic process
  • small molecule metabolic process
  • response to estradiol
  • monocarboxylic acid metabolic process
  • lung development
  • post-embryonic development
  • alkaloid metabolic process
  • oxidation-reduction process
  • cellular response to cadmium ion
  • regulation of gene expression
Components
  • endoplasmic reticulum membrane
  • intracellular membrane-bounded organelle
General FunctionOxidoreductase 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
Specific FunctionCytochromes 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.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDP05177
UniProtKB Entry NameCP1A2_HUMAN
Cellular LocationEndoplasmic reticulum membrane
Gene sequence
>lcl|BSEQ0011742|Cytochrome P450 1A2 (CYP1A2)
ATGGCATTGTCCCAGTCTGTTCCCTTCTCGGCCACAGAGCTTCTCCTGGCCTCTGCCATC
TTCTGCCTGGTATTCTGGGTGCTCAAGGGTTTGAGGCCTCGGGTCCCCAAAGGCCTGAAA
AGTCCACCAGAGCCATGGGGCTGGCCCTTGCTCGGGCATGTGCTGACCCTGGGGAAGAAC
CCGCACCTGGCACTGTCAAGGATGAGCCAGCGCTACGGGGACGTCCTGCAGATCCGCATT
GGCTCCACGCCCGTGCTGGTGCTGAGCCGCCTGGACACCATCCGGCAGGCCCTGGTGCGG
CAGGGCGACGATTTCAAGGGCCGGCCTGACCTCTACACCTCCACCCTCATCACTGATGGC
CAGAGCTTGACCTTCAGCACAGACTCTGGACCGGTGTGGGCTGCCCGCCGGCGCCTGGCC
CAGAATGCCCTCAACACCTTCTCCATCGCCTCTGACCCAGCTTCCTCATCCTCCTGCTAC
CTGGAGGAGCATGTGAGCAAGGAGGCTAAGGCCCTGATCAGCAGGTTGCAGGAGCTGATG
GCAGGGCCTGGGCACTTCGACCCTTACAATCAGGTGGTGGTGTCAGTGGCCAACGTCATT
GGTGCCATGTGCTTCGGACAGCACTTCCCTGAGAGTAGCGATGAGATGCTCAGCCTCGTG
AAGAACACTCATGAGTTCGTGGAGACTGCCTCCTCCGGGAACCCCCTGGACTTCTTCCCC
ATCCTTCGCTACCTGCCTAACCCTGCCCTGCAGAGGTTCAAGGCCTTCAACCAGAGGTTC
CTGTGGTTCCTGCAGAAAACAGTCCAGGAGCACTATCAGGACTTTGACAAGAACAGTGTC
CGGGACATCACGGGTGCCCTGTTCAAGCACAGCAAGAAGGGGCCTAGAGCCAGCGGCAAC
CTCATCCCACAGGAGAAGATTGTCAACCTTGTCAATGACATCTTTGGAGCAGGATTTGAC
ACAGTCACCACAGCCATCTCCTGGAGCCTCATGTACCTTGTGACCAAGCCTGAGATACAG
AGGAAGATCCAGAAGGAGCTGGACACTGTGATTGGCAGGGAGCGGCGGCCCCGGCTCTCT
GACAGACCCCAGCTGCCCTACTTGGAGGCCTTCATCCTGGAGACCTTCCGACACTCCTCC
TTCTTGCCCTTCACCATCCCCCACAGCACAACAAGGGACACAACGCTGAATGGCTTCTAC
ATCCCCAAGAAATGCTGTGTCTTCGTAAACCAGTGGCAGGTCAACCATGACCCAGAGCTG
TGGGAGGACCCCTCTGAGTTCCGGCCTGAGCGGTTCCTCACCGCCGATGGCACTGCCATT
AACAAGCCCTTGAGTGAGAAGATGATGCTGTTTGGCATGGGCAAGCGCCGGTGTATCGGG
GAAGTCCTGGCCAAGTGGGAGATCTTCCTCTTCCTGGCCATCCTGCTACAGCAACTGGAG
TTCAGCGTGCCGCCGGGCGTGAAAGTCGACCTGACCCCCATCTACGGGCTGACCATGAAG
CACGCCCGCTGTGAACATGTCCAGGCGCGGCTGCGCTTCTCCATCAATTGA
GenBank Gene IDZ00036
GeneCard IDNot Available
GenAtlas IDCYP1A2
HGNC IDHGNC:2596
Chromosome Location15
Locus15q24
References
  1. Jaiswal AK, Nebert DW, Gonzalez FJ: Human P3(450): cDNA and complete amino acid sequence. Nucleic Acids Res. 1986 Aug 26;14(16):6773-4. 3755823
  2. Quattrochi LC, Pendurthi UR, Okino ST, Potenza C, Tukey RH: Human cytochrome P-450 4 mRNA and gene: part of a multigene family that contains Alu sequences in its mRNA. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6731-5. 3462722
  3. Ikeya K, Jaiswal AK, Owens RA, Jones JE, Nebert DW, Kimura S: Human CYP1A2: sequence, gene structure, comparison with the mouse and rat orthologous gene, and differences in liver 1A2 mRNA expression. Mol Endocrinol. 1989 Sep;3(9):1399-408. 2575218
  4. Jaiswal AK, Nebert DW, McBride OW, Gonzalez FJ: Human P(3)450: cDNA and complete protein sequence, repetitive Alu sequences in the 3' nontranslated region, and localization of gene to chromosome 15. J Exp Pathol. 1987 Winter;3(1):1-17. 3681487
  5. Corchero J, Pimprale S, Kimura S, Gonzalez FJ: Organization of the CYP1A cluster on human chromosome 15: implications for gene regulation. Pharmacogenetics. 2001 Feb;11(1):1-6. 11207026
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  7. Wrighton SA, Campanile C, Thomas PE, Maines SL, Watkins PB, Parker G, Mendez-Picon G, Haniu M, Shively JE, Levin W, et al.: Identification of a human liver cytochrome P-450 homologous to the major isosafrole-inducible cytochrome P-450 in the rat. Mol Pharmacol. 1986 Apr;29(4):405-10. 3517618
  8. Quattrochi LC, Okino ST, Pendurthi UR, Tukey RH: Cloning and isolation of human cytochrome P-450 cDNAs homologous to dioxin-inducible rabbit mRNAs encoding P-450 4 and P-450 6. DNA. 1985 Oct;4(5):395-400. 3000715
  9. Zhou H, Josephy PD, Kim D, Guengerich FP: Functional characterization of four allelic variants of human cytochrome P450 1A2. Arch Biochem Biophys. 2004 Feb 1;422(1):23-30. 14725854
  10. Honda A, Miyazaki T, Ikegami T, Iwamoto J, Maeda T, Hirayama T, Saito Y, Teramoto T, Matsuzaki Y: Cholesterol 25-hydroxylation activity of CYP3A. J Lipid Res. 2011 Aug;52(8):1509-16. doi: 10.1194/jlr.M014084. Epub 2011 May 16. 21576599
  11. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  12. Sansen S, Yano JK, Reynald RL, Schoch GA, Griffin KJ, Stout CD, Johnson EF: Adaptations for the oxidation of polycyclic aromatic hydrocarbons exhibited by the structure of human P450 1A2. J Biol Chem. 2007 May 11;282(19):14348-55. Epub 2007 Feb 20. 17311915
  13. Huang JD, Guo WC, Lai MD, Guo YL, Lambert GH: Detection of a novel cytochrome P-450 1A2 polymorphism (F21L) in Chinese. Drug Metab Dispos. 1999 Jan;27(1):98-101. 9884316
  14. Chevalier D, Cauffiez C, Allorge D, Lo-Guidice JM, Lhermitte M, Lafitte JJ, Broly F: Five novel natural allelic variants-951A>C, 1042G>A (D348N), 1156A>T (I386F), 1217G>A (C406Y) and 1291C>T (C431Y)-of the human CYP1A2 gene in a French Caucasian population. Hum Mutat. 2001 Apr;17(4):355-6. 11295848
  15. Murayama N, Soyama A, Saito Y, Nakajima Y, Komamura K, Ueno K, Kamakura S, Kitakaze M, Kimura H, Goto Y, Saitoh O, Katoh M, Ohnuma T, Kawai M, Sugai K, Ohtsuki T, Suzuki C, Minami N, Ozawa S, Sawada J: Six novel nonsynonymous CYP1A2 gene polymorphisms: catalytic activities of the naturally occurring variant enzymes. J Pharmacol Exp Ther. 2004 Jan;308(1):300-6. Epub 2003 Oct 16. 14563787
  16. Solus JF, Arietta BJ, Harris JR, Sexton DP, Steward JQ, McMunn C, Ihrie P, Mehall JM, Edwards TL, Dawson EP: Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population. Pharmacogenomics. 2004 Oct;5(7):895-931. 15469410
  17. Soyama A, Saito Y, Hanioka N, Maekawa K, Komamura K, Kamakura S, Kitakaze M, Tomoike H, Ueno K, Goto Y, Kimura H, Katoh M, Sugai K, Saitoh O, Kawai M, Ohnuma T, Ohtsuki T, Suzuki C, Minami N, Kamatani N, Ozawa S, Sawada J: Single nucleotide polymorphisms and haplotypes of CYP1A2 in a Japanese population. Drug Metab Pharmacokinet. 2005 Feb;20(1):24-33. 15770072
  18. Jiang Z, Dalton TP, Jin L, Wang B, Tsuneoka Y, Shertzer HG, Deka R, Nebert DW: Toward the evaluation of function in genetic variability: characterizing human SNP frequencies and establishing BAC-transgenic mice carrying the human CYP1A1_CYP1A2 locus. Hum Mutat. 2005 Feb;25(2):196-206. 15643613
  19. Cornelis MC, El-Sohemy A, Kabagambe EK, Campos H: Coffee, CYP1A2 genotype, and risk of myocardial infarction. JAMA. 2006 Mar 8;295(10):1135-41. 16522833