Cytochrome P450 1A2

NameCytochrome P450 1A2
Synonyms1.14.14.1 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
    aromatase 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
caffeine oxidase activity
enzyme binding
demethylase activity
electron carrier activity
oxidoreductase activity
iron ion binding
heme binding
monooxygenase activity
Processes
    omega-hydroxylase P450 pathway
response to lipopolysaccharide
monocarboxylic acid metabolic process
oxidative deethylation
response to immobilization stress
oxidative demethylation
xenobiotic metabolic process
toxin biosynthetic process
arachidonic acid metabolic process
alkaloid metabolic process
small molecule metabolic process
drug metabolic process
cellular response to cadmium ion
response to estradiol
porphyrin-containing compound metabolic process
dibenzo-p-dioxin metabolic process
lung development
methylation
drug catabolic process
post-embryonic development
epoxygenase P450 pathway
heterocycle metabolic process
exogenous drug catabolic process
hydrogen peroxide biosynthetic process
oxidation-reduction process
steroid catabolic process
cellular respiration
monoterpenoid metabolic process
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.
Transmembrane Regions
GenBank Protein ID
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 IDNone
GenAtlas IDCYP1A2
HGNC IDHGNC:2596
Chromosome Location15
Locus15q24
References
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  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 ]

Related FRC

FRCD ID Name Exact Mass Structure




F03315



Methoxychlor


345.644




F03331



Naphthalene


128.174




F03394



2-Methylnaphthalene


142.201




F03460



Pyrene


202.256




F03555



Biphenyl


154.212




F03556



2-Chlorobiphenyl


188.654




F03558



4-Chlorobiphenyl


188.654




F03765



1-Methylnaphthalene


142.201




F03879



Ethanol


46.07




F03901



Acetochlor


269.769




F03929



Pendimethalin


281.312




F04019



Pirimicarb


238.291




F04050



Cypermethrin


416.298




F04158



Hydroxytriphenylstannane


367.035




F04332



Chlorfenapyr


407.615




F04875



4-Aminophenol


109.128




F05024



Acibenzolar-S-Methyl


210.269




F05680



Amitraz


293.414




F05039



Chloridazon


221.644




F05044



Clofentezine


303.146




F05048



Cyanazine


240.695




F05054



Dichloran


207.01




F05062



Ethalfluralin


333.267




F05064



Etoxazole


359.417




F05066



Fenamiphos


303.36




F05085



Enilconazole


297.179




F05089



Indoxacarb


527.837




F05095



Malathion


330.35




F05103



Methidathion


302.318




F05110



(E)-Monocrotophos


223.16




F05111



Myclobutanil


288.779




F05113



Niclosamide


327.117




F05115



Oxadiazon


345.22




F05121



Phosalone


367.799




F05127



Propiconazole


342.22




F05130



Pyraclostrobin


387.82




F05139



Tebufenozide


352.478




F05144



Thiabendazole


201.247




F05146



Thiazopyr


396.376




F05154



Vinclozolin


286.108




F05170



2-Naphthol


144.173




F05179



Butylparaben


194.23




F05394



Carboxin


235.301




F05400



Coumaphos


362.761




F05401



Cyazofamid


324.783




F05408



Diphenylamine


169.227




F05411



Diuron


233.092




F05418



Fludioxonil


248.189




F05421



Forchlorfenuron


247.682




F05422



Hexaconazole


314.21




F05426



Linuron


249.091




F05429



Oryzalin


346.358




F05433



Prallethrin


300.398




F05434



Profenofos


373.626




F05437



Pyrimethanil


199.257




F05440



Rimsulfuron


431.438




F05447



Triadimenol


295.767




F03312



Diazinon


304.35




F03378



Guthion


317.318




F03387



Parathion


291.258




F03442



Dimethoate


229.3




F02629



Mercuric chloride


271.492




F03962



Benomyl


290.323




F03972



Carbaril


201.225




F03981



Chlorpropham


213.661




F04047



Cyfluthrin


434.288




F04084



Butachlor


311.85




F04333



Chlorothalonil


265.902




F04749



Anidulafungin


1140.254




F04846



Fenthion


278.321




F04874



Aflatoxin B1


312.277




F05026



Ametryn


227.33




F05030



Benfluralin


335.283




F05031



Bensulide


397.503




F05032



Bifenazate


300.358




F05034



Boscalid


343.207




F05822



Buprofezin


305.44




F05043



Cinmethylin


274.404




F05051



Cyprodinil


225.295




F05058



Difenoconazole


406.263




F05068



Fenitrothion


277.24




F05071



Fluazinam


465.089




F05072



Flufenacet


363.331




F05079



Flutolanil


323.315




F05091



Iprodione


330.165




F05092



Isoxaben


332.4




F05094



Lactofen


461.774




F05104



Methoxyfenozide


368.477




F05112



Napropamide


271.36




F05114



Norflurazon


303.669




F05123



Prochloraz


376.662




F05124



Prometryn


241.357




F05125



Propargite


350.473




F05126



Propazine


229.712




F05136



Simazine


201.658




F05140



Tebufenpyrad


333.86




F05141



Tebupirimfos


318.372




F05143



Tetraconazole


372.145




F05168



1-Naphthol


144.173




F05171



1-Hydroxypyrene


220.271




F05388



Atrazine


215.685




F05391



Butralin


295.339




F05395



Chlorethoxyfos


335.985




F11483



Clodinafop-propargyl


349.742




F05399



Clopyralid


191.995




F05402



Cyclanilide


274.097




F05403



Cyproconazole


291.779




F05410



Dithiopyr


401.41




F05425



Isazofos


313.737




F05413



Ethofumesate


286.342




F05417



Fenbuconazole


336.823




F05419



Fluometuron


232.206




F05430



Picloram


241.452




F05435



Propyzamide


256.126




F05438



Quinoxyfen


308.133




F05439



Quintozene


295.321




F05444



Thidiazuron


220.25




F06003



Triflumizole


345.75




F05450



Trifluralin


335.283




F05451



Triticonazole


317.817