Cytochrome P450 2E1

Details

Name
Cytochrome P450 2E1
Synonyms
  • 1.14.13.-
  • 4-nitrophenol 2-hydroxylase
  • CYP2E
  • CYPIIE1
  • Cytochrome P450-J
Gene Name
CYP2E1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0012460|Cytochrome P450 2E1
MSALGVTVALLVWAAFLLLVSMWRQVHSSWNLPPGPFPLPIIGNLFQLELKNIPKSFTRL
AQRFGPVFTLYVGSQRMVVMHGYKAVKEALLDYKDEFSGRGDLPAFHAHRDRGIIFNNGP
TWKDIRRFSLTTLRNYGMGKQGNESRIQREAHFLLEALRKTQGQPFDPTFLIGCAPCNVI
ADILFRKHFDYNDEKFLRLMYLFNENFHLLSTPWLQLYNNFPSFLHYLPGSHRKVIKNVA
EVKEYVSERVKEHHQSLDPNCPRDLTDCLLVEMEKEKHSAERLYTMDGITVTVADLFFAG
TETTSTTLRYGLLILMKYPEIEEKLHEEIDRVIGPSRIPAIKDRQEMPYMDAVVHEIQRF
ITLVPSNLPHEATRDTIFRGYLIPKGTVVVPTLDSVLYDNQEFPDPEKFKPEHFLNENGK
FKYSDYFKPFSTGKRVCAGEGLARMELFLLLCAILQHFNLKPLVDPKDIDLSPIHIGFGC
IPPRYKLCVIPRS
Number of residues
493
Molecular Weight
56848.42
Theoretical pI
8.22
GO Classification
Functions
arachidonic acid epoxygenase activity / enzyme binding / heme binding / iron ion binding / monooxygenase activity / oxidoreductase activity / oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen / 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 / oxygen binding / steroid hydroxylase activity
Processes
drug metabolic process / epoxygenase P450 pathway / exogenous drug catabolic process / heterocycle metabolic process / monoterpenoid metabolic process / oxidation-reduction process / response to ethanol / response to organonitrogen compound / response to ozone / small molecule metabolic process / steroid metabolic process / triglyceride metabolic process / xenobiotic metabolic process
Components
cytoplasm / endoplasmic reticulum membrane / Golgi membrane / intracellular membrane-bounded organelle / intrinsic component of endoplasmic reticulum membrane / mitochondrion
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Endoplasmic reticulum membrane
Gene sequence
>lcl|BSEQ0012461|Cytochrome P450 2E1 (CYP2E1)
ATGTCTGCCCTCGGAGTCACCGTGGCCCTGCTGGTGTGGGCGGCCTTCCTCCTGCTGGTG
TCCATGTGGAGGCAGGTGCACAGCAGCTGGAATCTGCCCCCAGGCCCTTTCCCGCTTCCC
ATCATCGGGAACCTCTTCCAGTTGGAATTGAAGAATATTCCCAAGTCCTTCACCCGGTTG
GCCCAGCGCTTCGGGCCGGTGTTCACGCTGTACGTGGGCTCGCAGCGCATGGTGGTGATG
CACGGCTACAAGGCGGTGAAGGAAGCGCTGCTGGACTACAAGGACGAGTTCTCGGGCAGA
GGCGACCTCCCCGCGTTCCATGCGCACAGGGACAGGGGAATCATTTTTAATAATGGACCT
ACCTGGAAGGACATCCGGCGGTTTTCCCTGACCACCCTCCGGAACTATGGGATGGGGAAA
CAGGGCAATGAGAGCCGGATCCAGAGGGAGGCCCACTTCCTGCTGGAAGCACTCAGGAAG
ACCCAAGGCCAGCCTTTCGACCCCACCTTCCTCATCGGCTGCGCGCCCTGCAACGTCATA
GCCGACATCCTCTTCCGCAAGCATTTTGACTACAATGATGAGAAGTTTCTAAGGCTGATG
TATTTGTTTAATGAGAACTTCCACCTACTCAGCACTCCCTGGCTCCAGCTTTACAATAAT
TTTCCCAGCTTTCTACACTACTTGCCTGGAAGCCACAGAAAAGTCATAAAAAATGTGGCT
GAAGTAAAAGAGTATGTGTCTGAAAGGGTGAAGGAGCACCATCAATCTCTGGACCCCAAC
TGTCCCCGGGACCTCACCGACTGCCTGCTCGTGGAAATGGAGAAGGAAAAGCACAGTGCA
GAGCGCTTGTACACAATGGACGGTATCACCGTGACTGTGGCCGACCTGTTCTTTGCGGGG
ACAGAGACCACCAGCACAACTCTGAGATATGGGCTCCTGATTCTCATGAAATACCCTGAG
ATCGAAGAGAAGCTCCATGAAGAAATTGACAGGGTGATTGGGCCAAGCCGAATCCCTGCC
ATCAAGGATAGGCAAGAGATGCCCTACATGGATGCTGTGGTGCATGAGATTCAGCGGTTC
ATCACCCTCGTGCCCTCCAACCTGCCCCATGAAGCAACCCGAGACACCATTTTCAGAGGA
TACCTCATCCCCAAGGGCACAGTCGTAGTGCCAACTCTGGACTCTGTTTTGTATGACAAC
CAAGAATTTCCTGATCCAGAAAAGTTTAAGCCAGAACACTTCCTGAATGAAAATGGAAAG
TTCAAGTACAGTGACTATTTCAAGCCATTTTCCACAGGAAAACGAGTGTGTGCTGGAGAA
GGCCTGGCTCGCATGGAGTTGTTTCTTTTGTTGTGTGCCATTTTGCAGCATTTTAATTTG
AAGCCTCTCGTTGACCCAAAGGATATCGACCTCAGCCCTATACATATTGGGTTTGGCTGT
ATCCCACCACGTTACAAACTCTGTGTCATTCCCCGCTCATGA
Chromosome Location
10
Locus
10q24.3-qter
External Identifiers
ResourceLink
UniProtKB IDP05181
UniProtKB Entry NameCP2E1_HUMAN
GenBank Protein ID181360
GenBank Gene IDJ02625
HGNC IDHGNC:2631
General References
  1. Song BJ, Gelboin HV, Park SS, Yang CS, Gonzalez FJ: Complementary DNA and protein sequences of ethanol-inducible rat and human cytochrome P-450s. Transcriptional and post-transcriptional regulation of the rat enzyme. J Biol Chem. 1986 Dec 15;261(35):16689-97. [PubMed:3782137]
  2. Umeno M, McBride OW, Yang CS, Gelboin HV, Gonzalez FJ: Human ethanol-inducible P450IIE1: complete gene sequence, promoter characterization, chromosome mapping, and cDNA-directed expression. Biochemistry. 1988 Dec 13;27(25):9006-13. [PubMed:3233219]
  3. Deloukas P, Earthrowl ME, Grafham DV, Rubenfield M, French L, Steward CA, Sims SK, Jones MC, Searle S, Scott C, Howe K, Hunt SE, Andrews TD, Gilbert JG, Swarbreck D, Ashurst JL, Taylor A, Battles J, Bird CP, Ainscough R, Almeida JP, Ashwell RI, Ambrose KD, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Bates K, Beasley H, Bray-Allen S, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Cahill P, Camire D, Carter NP, Chapman JC, Clark SY, Clarke G, Clee CM, Clegg S, Corby N, Coulson A, Dhami P, Dutta I, Dunn M, Faulkner L, Frankish A, Frankland JA, Garner P, Garnett J, Gribble S, Griffiths C, Grocock R, Gustafson E, Hammond S, Harley JL, Hart E, Heath PD, Ho TP, Hopkins B, Horne J, Howden PJ, Huckle E, Hynds C, Johnson C, Johnson D, Kana A, Kay M, Kimberley AM, Kershaw JK, Kokkinaki M, Laird GK, Lawlor S, Lee HM, Leongamornlert DA, Laird G, Lloyd C, Lloyd DM, Loveland J, Lovell J, McLaren S, McLay KE, McMurray A, Mashreghi-Mohammadi M, Matthews L, Milne S, Nickerson T, Nguyen M, Overton-Larty E, Palmer SA, Pearce AV, Peck AI, Pelan S, Phillimore B, Porter K, Rice CM, Rogosin A, Ross MT, Sarafidou T, Sehra HK, Shownkeen R, Skuce CD, Smith M, Standring L, Sycamore N, Tester J, Thorpe A, Torcasso W, Tracey A, Tromans A, Tsolas J, Wall M, Walsh J, Wang H, Weinstock K, West AP, Willey DL, Whitehead SL, Wilming L, Wray PW, Young L, Chen Y, Lovering RC, Moschonas NK, Siebert R, Fechtel K, Bentley D, Durbin R, Hubbard T, Doucette-Stamm L, Beck S, Smith DR, Rogers J: The DNA sequence and comparative analysis of human chromosome 10. Nature. 2004 May 27;429(6990):375-81. [PubMed:15164054]
  4. 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. [PubMed:15489334]
  5. Lasker JM, Raucy J, Kubota S, Bloswick BP, Black M, Lieber CS: Purification and characterization of human liver cytochrome P-450-ALC. Biochem Biophys Res Commun. 1987 Oct 14;148(1):232-8. [PubMed:3675576]
  6. Robinson RC, Shorr RG, Varrichio A, Park SS, Gelboin HV, Miller H, Friedman FK: Human liver cytochrome P-450 related to a rat acetone-inducible, nitrosamine-metabolizing cytochrome P-450: identification and isolation. Pharmacology. 1989;39(3):137-44. [PubMed:2587619]
  7. Gillam EM, Guo Z, Guengerich FP: Expression of modified human cytochrome P450 2E1 in Escherichia coli, purification, and spectral and catalytic properties. Arch Biochem Biophys. 1994 Jul;312(1):59-66. [PubMed:8031147]
  8. Zerilli A, Ratanasavanh D, Lucas D, Goasduff T, Dreano Y, Menard C, Picart D, Berthou F: Both cytochromes P450 2E1 and 3A are involved in the O-hydroxylation of p-nitrophenol, a catalytic activity known to be specific for P450 2E1. Chem Res Toxicol. 1997 Oct;10(10):1205-12. [PubMed:9348445]
  9. 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. [PubMed:24275569]
  10. Porubsky PR, Meneely KM, Scott EE: Structures of human cytochrome P-450 2E1. Insights into the binding of inhibitors and both small molecular weight and fatty acid substrates. J Biol Chem. 2008 Nov 28;283(48):33698-707. doi: 10.1074/jbc.M805999200. Epub 2008 Sep 24. [PubMed:18818195]
  11. Hu Y, Oscarson M, Johansson I, Yue QY, Dahl ML, Tabone M, Arinco S, Albano E, Ingelman-Sundberg M: Genetic polymorphism of human CYP2E1: characterization of two variant alleles. Mol Pharmacol. 1997 Mar;51(3):370-6. [PubMed:9058590]
  12. Fairbrother KS, Grove J, de Waziers I, Steimel DT, Day CP, Crespi CL, Daly AK: Detection and characterization of novel polymorphisms in the CYP2E1 gene. Pharmacogenetics. 1998 Dec;8(6):543-52. [PubMed:9918138]
  13. 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. [PubMed:15469410]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00184NicotineapprovedunknownsubstrateinhibitorinducerDetails
DB00228Enfluraneapproved, investigational, vet_approvedunknownsubstrateDetails
DB00356ChlorzoxazoneapprovedunknownsubstrateinhibitorDetails
DB00753Isofluraneapproved, vet_approvedunknownsubstrateDetails
DB00851Dacarbazineapproved, investigationalunknownsubstrateDetails
DB00898EthanolapprovedunknownsubstrateinducerDetails
DB01028Methoxyfluraneapproved, investigational, vet_approvedunknownsubstrateDetails
DB01159Halothaneapproved, vet_approvedunknownsubstrateDetails
DB01204Mitoxantroneapproved, investigationalunknownsubstrateDetails
DB01213Fomepizoleapproved, vet_approvedunknowninhibitorDetails
DB01236Sevofluraneapproved, vet_approvedunknownsubstrateDetails
DB00593EthosuximideapprovedunknownsubstrateDetails
DB01355HexobarbitalexperimentalunknownDetails
DB00118Ademetionineapproved, investigational, nutraceuticalunknowninhibitorDetails
DB00170Menadioneapproved, nutraceuticalunknownsubstrateDetails
DB00277TheophyllineapprovedunknownsubstrateDetails
DB00636Clofibrateapproved, investigationalunknowninducerDetails
DB00780PhenelzineapprovedunknowninducerDetails
DB00908Quinidineapproved, investigationalunknownsubstrateDetails
DB00951Isoniazidapproved, investigationalunknownsubstrateinhibitorinducerDetails
DB01115NifedipineapprovedunknowninhibitorDetails
DB01173OrphenadrineapprovedunknownDetails
DB00250Dapsoneapproved, investigationalunknownsubstrateDetails
DB04977PlitidepsininvestigationalunknownDetails
DB05708GTS-21investigationalunknownDetails
DB00316AcetaminophenapprovedunknownsubstrateDetails
DB00468QuinineapprovedunknownsubstrateDetails
DB01041Thalidomideapproved, investigational, withdrawnunknownsubstrateDetails
DB05109Trabectedinapproved, investigationalunknownsubstrateDetails
DB06728AnilineexperimentalunknownsubstrateDetails
DB00822DisulfiramapprovedunknowninhibitorDetails
DB01136Carvedilolapproved, investigationalunknownsubstrateDetails
DB00201CaffeineapprovedunknownsubstrateDetails
DB00818Propofolapproved, investigational, vet_approvedunknowninhibitorDetails
DB00969Alosetronapproved, withdrawnunknowninhibitorDetails
DB01223AminophyllineapprovedunknownsubstrateDetails
DB00321AmitriptylineapprovedunknownsubstrateinhibitorDetails
DB00972AzelastineapprovedunknowninhibitorDetails
DB04794Bifonazoleapproved, investigationalunknowninhibitorDetails
DB01558Bromazepamapproved, illicit, investigationalunknowninhibitorDetails
DB00835BrompheniramineapprovedunknownsubstrateDetails
DB01156BupropionapprovedunknownsubstrateDetails
DB00748CarbinoxamineapprovedunknownsubstrateDetails
DB00477Chlorpromazineapproved, investigational, vet_approvedunknowninhibitorDetails
DB00501Cimetidineapproved, investigationalunknowninhibitorDetails
DB00215CitalopramapprovedunknownsubstrateDetails
DB00882Clomifeneapproved, investigationalunknowninhibitorDetails
DB00257Clotrimazoleapproved, vet_approvedunknowninhibitorDetails
DB00363ClozapineapprovedunknowninhibitorDetails
DB01394ColchicineapprovedunknowninducerDetails
DB01151Desipramineapproved, investigationalunknowninhibitorDetails
DB01234Dexamethasoneapproved, investigational, vet_approvedunknowninducerDetails
DB01191Dexfenfluramineapproved, illicit, investigational, withdrawnunknowninhibitorDetails
DB00514DextromethorphanapprovedunknownsubstrateDetails
DB00586Diclofenacapproved, vet_approvedunknowninhibitorDetails
DB01127EconazoleapprovedunknowninhibitorDetails
DB00655EstroneapprovedunknownsubstrateDetails
DB00773EtoposideapprovedunknownsubstrateDetails
DB01628Etoricoxibapproved, investigationalunknowninhibitorDetails
DB00949FelbamateapprovedunknownsubstrateDetails
DB00623FluphenazineapprovedunknowninhibitorDetails
DB00690Flurazepamapproved, illicit, investigationalunknowninhibitorDetails
DB00176Fluvoxamineapproved, investigationalunknownsubstrateDetails
DB00158Folic Acidapproved, nutraceutical, vet_approvedunknownsubstrateDetails
DB01296Glucosamineapproved, investigationalunknownsubstrateDetails
DB09462Glycerinapproved, investigationalunknowninducerDetails
DB00458ImipramineapprovedunknowninhibitorDetails
DB00883Isosorbide dinitrateapproved, investigationalunknowninhibitorDetails
DB01167Itraconazoleapproved, investigationalunknowninhibitorDetails
DB01403Methotrimeprazineapproved, investigationalunknowninhibitorDetails
DB00371Meprobamateapproved, illicitunknownsubstrateDetails
DB00703MethazolamideapprovedunknowninhibitorDetails
DB01011Metyraponeapproved, investigationalunknowninhibitorDetails
DB00379Mexiletineapproved, investigationalunknownsubstrateDetails
DB01110Miconazoleapproved, investigational, vet_approvedunknowninhibitorDetails
DB06689Ethanolamine oleateapprovedunknownsubstrateDetails
DB00622Nicardipineapproved, investigationalunknownsubstrateDetails
DB02701Nicotinamideapproved, investigationalunknowninhibitorDetails
DB06712NilvadipineinvestigationalunknownsubstrateDetails
DB00540NortriptylineapprovedunknowninhibitorDetails
DB00904OndansetronapprovedunknownsubstrateDetails
DB00526Oxaliplatinapproved, investigationalunknownsubstrateDetails
DB03783PhenacetinwithdrawnunknownsubstrateDetails
DB01435Antipyrineapproved, investigationalunknownsubstrateDetails
DB01174Phenobarbitalapproved, investigationalunknownsubstrateinducerDetails
DB01085Pilocarpineapproved, investigationalunknownsubstrateDetails
DB01100PimozideapprovedunknowninhibitorDetails
DB01131ProguanilapprovedunknownsubstrateDetails
DB01045RifampicinapprovedunknowninducerDetails
DB00503Ritonavirapproved, investigationalunknowninhibitorDetails
DB01037Selegilineapproved, investigational, vet_approvedunknowninhibitorDetails
DB00203Sildenafilapproved, investigationalunknownsubstrateinhibitorDetails
DB00359Sulfadiazineapproved, investigational, vet_approvedunknownsubstrateDetails
DB00259SulfanilamideapprovedunknowninhibitorDetails
DB00675TamoxifenapprovedunknownsubstrateDetails
DB01079Tegaserodapproved, investigational, withdrawnunknowninhibitorDetails
DB01412TheobromineinvestigationalunknownsubstrateDetails
DB00763MethimazoleapprovedunknowninhibitorDetails
DB00599Thiopentalapproved, vet_approvedunknowninhibitorDetails
DB00679Thioridazineapproved, withdrawnunknowninhibitorDetails
DB00208TiclopidineapprovedunknowninhibitorDetails
DB01007TioconazoleapprovedunknowninhibitorDetails
DB00752Tranylcypromineapproved, investigationalunknowninhibitorDetails
DB00347TrimethadioneapprovedunknownsubstrateDetails
DB01586Ursodeoxycholic acidapproved, investigationalunknowninhibitorinducerDetails
DB00549Zafirlukastapproved, investigationalunknowninhibitorDetails
DB01198ZopicloneapprovedunknownsubstrateDetails
DB00617ParamethadioneapprovedunknownsubstrateDetails
DB04946IloperidoneapprovedunknownsubstrateDetails
DB00255Diethylstilbestrolapproved, investigationalunknowninhibitorDetails
DB00918Almotriptanapproved, investigationalunknownsubstrateDetails
DB06770Benzyl alcoholapprovedunknownsubstrateDetails
DB06774CapsaicinapprovedunknownsubstrateDetails
DB04920Clevidipineapproved, investigationalunknownsubstrateDetails
DB00633Dexmedetomidineapproved, vet_approvedunknownsubstrateDetails
DB06370IndisulaminvestigationalunknowninhibitorDetails
DB00109Enfuvirtideapproved, investigationalunknownsubstrateDetails
DB00041AldesleukinapprovedunknowninhibitorDetails
DB04858TirapazamineinvestigationalunknownsubstrateDetails
DB00428Streptozocinapproved, investigationalunknowninducerDetails
DB06637DalfampridineapprovedunknownsubstrateDetails
DB08868Fingolimodapproved, investigationalunknownsubstrateDetails
DB06201RufinamideapprovedunknowninhibitorDetails
DB01068Clonazepamapproved, illicitunknowninhibitorDetails
DB00829Diazepamapproved, illicit, investigational, vet_approvedunknowninhibitorDetails
DB01544Flunitrazepamapproved, illicitunknowninhibitorDetails
DB01595NitrazepamapprovedunknowninhibitorDetails
DB08846Ellagic AcidinvestigationalunknowninhibitorDetails
DB06595Midostaurinapproved, investigationalunknowninhibitorDetails
DB13174RheinexperimentalunknowninhibitorDetails
DB11994Diacereinapproved, investigationalunknowninhibitorDetails
DB11943Delafloxacinapproved, investigationalunknowninducerDetails
DB09120Zucapsaicinapproved, investigationalunknowninhibitorDetails
DB13941Piperaquineexperimental, investigationalunknowninducerDetails
DB09328Vayarinapproved, investigationalunknowninhibitorDetails
DB00486Nabiloneapproved, investigationalnoinhibitorDetails
DB04379N-Methyl-N-(Methylbenzyl)FormamideexperimentalunknownsubstrateDetails
DB01154Thiamylalapproved, vet_approvednosubstrateDetails
DB06654Safinamideapproved, investigationalunknowninhibitorDetails
DB09256Tegafurapproved, investigationalunknownsubstrateDetails
DB09288PropacetamolexperimentalnosubstrateDetails