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Identification
HMDB Protein ID HMDBP01544
Secondary Accession Numbers
  • 6840
  • HMDBP05554
Name Cytochrome P450 2E1
Synonyms
  1. 4-nitrophenol 2-hydroxylase
  2. CYPIIE1
  3. Cytochrome P450-J
Gene Name CYP2E1
Protein Type Unknown
Biological Properties
General Function Involved in monooxygenase 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.
Pathways
  • Acetaminophen Action Pathway
  • Acetaminophen Metabolism Pathway
  • Acetylsalicylic Acid Action Pathway
  • Antipyrine Action Pathway
  • Antrafenine Action Pathway
  • Arachidonic acid metabolism
  • Arachidonic Acid Metabolism
  • Bromfenac Action Pathway
  • Caffeine Metabolism
  • Carprofen Action Pathway
  • Celecoxib Action Pathway
  • Chemical carcinogenesis
  • Diclofenac Action Pathway
  • Diflunisal Action Pathway
  • Disulfiram Action Pathway
  • Drug metabolism - cytochrome P450
  • Ethanol Degradation
  • Etodolac Action Pathway
  • Etoricoxib Action Pathway
  • Felbamate Metabolism Pathway
  • Fenoprofen Action Pathway
  • Flurbiprofen Action Pathway
  • Ibuprofen Action Pathway
  • Indomethacin Action Pathway
  • Ketoprofen Action Pathway
  • Ketorolac Action Pathway
  • Leukotriene C4 Synthesis Deficiency
  • Linoleic acid metabolism
  • Lornoxicam Action Pathway
  • Lumiracoxib Action Pathway
  • Magnesium salicylate Action Pathway
  • Mefenamic Acid Action Pathway
  • Meloxicam Action Pathway
  • Metabolism of xenobiotics by cytochrome P450
  • Nabumetone Action Pathway
  • Naproxen Action Pathway
  • Nepafenac Action Pathway
  • Oxaprozin Action Pathway
  • Phenylbutazone Action Pathway
  • Phenytoin (Antiarrhythmic) Action Pathway
  • Piroxicam Action Pathway
  • Rofecoxib Action Pathway
  • Salicylate-sodium Action Pathway
  • Salicylic Acid Action Pathway
  • Salsalate Action Pathway
  • Sulindac Action Pathway
  • Suprofen Action Pathway
  • Tenoxicam Action Pathway
  • Tiaprofenic Acid Action Pathway
  • Tolmetin Action Pathway
  • Trisalicylate-choline Action Pathway
  • Valdecoxib Action Pathway
Reactions
4-Nitrophenol + NADPH + Oxygen → 4-Nitrocatechol + NADP + Water details
GO Classification
Biological Process
small molecule metabolic process
drug metabolic process
response to organic nitrogen
response to drug
response to ethanol
heterocycle metabolic process
monoterpenoid metabolic process
steroid metabolic process
xenobiotic metabolic process
response to ozone
triglyceride metabolic process
Cellular Component
endoplasmic reticulum membrane
mitochondrion
intrinsic to endoplasmic reticulum membrane
Golgi membrane
Function
ion binding
cation binding
metal ion binding
binding
catalytic activity
transition metal ion binding
electron carrier activity
iron ion binding
monooxygenase activity
heme binding
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
oxidoreductase activity
Molecular Function
electron carrier activity
oxygen binding
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NADH or NADPH 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
iron ion binding
heme binding
Process
metabolic process
oxidation reduction
Cellular Location
  1. Peripheral membrane protein
  2. Peripheral membrane protein
  3. Endoplasmic reticulum membrane
  4. Microsome membrane
Gene Properties
Chromosome Location 10
Locus 10q24.3-qter
SNPs CYP2E1
Gene Sequence
>1482 bp
ATGTCTGCCCTCGGAGTGACCGTGGCCCTGCTGGTGTGGGCGGCCTTCCTCCTGCTGGTG
TCCATGTGGAGGCAGGTGCACAGCAGCTGGAATCTGCCCCCAGGTCCTTTCCCGCTTCCC
ATCATCGGGAACCTCTTCCAGTTGGAATTGAAGAATATTCCCAAGTCCTTCACCCGGTTG
GCCCAGCGCTTCGGGCCGGTGTTCACGCTGTACGTGGGCTCGCAGCGCATGGTGGTGATG
CACGGCTACAAGGCGGTGAAGGAAGCGCTGCTGGACTACAAGGACGAGTTCTCGGGCAGA
GGCGACCTCCCCGCGTTCCATGCGCACAGGGACAGGGGAATCATTTTTAATAATGGACCT
ACCTGGAAGGACATCCGGCGGTTTTCCCTGACCACCCTCCGGAACTATGGGATGGGGAAA
CAGGGCAATGAGAGCCGGATCCAGAGGGAGGCCCACTTCCTGCTGGAAGCACTCAGGAAG
ACCCAAGGCCAGCCTTTCGACCCCACCTTCCTCATCGGCTGCGCGCCCTGCAACGTCATA
GCCGACATCCTCTTCCGCAAGCATTTTGACTACAATGATGAGAAGTTTCTAAGGCTGATG
TATTTGTTTAATGAGAACTTCCACCTACTCAGCACTCCCTGGCTCCAGCTTTACAATAAT
TTTCCCAGCTTTCTACACTACTTGCCTGGAAGCCACAGAAAAGTCATAAAAAATGTGGCT
GAAGTAAAAGAGTATGTGTCTGAAAGGGTGAAGGAGCACCATCAATCTCTGGACCCCAAC
TGTCCCCGGGACCTCACCGACTGCCTGCTCGTGGAAATGGAGAAGGAAAAGCACAGTGCA
GAGCGCTTGTACACAATGGACGGTATCACCGTGACTGTGGCCGACCTGTTCTTTGCGGGG
ACAGAGACCACCAGCACAACTCTGAGATATGGGCTCCTGATTCTCATGAAATACCCTGAG
ATCGAAGAGAAGCTCCATGAAGAAATTGACAGGGTGATTGGGCCAAGCCGAATCCCTGCC
ATCAAGGATAGGCAAGAGATGCCCTACATGGATGCTGTGGTGCATGAGATTCAGCGGTTC
ATCACCCTCGTGCCCTCCAACCTGCCCCATGAAGCAACCCGAGACACCATTTTCAGAGGA
TACCTCATCCCCAAGGGCACAGTCGTAGTGCCAACTCTGGACTCTGTTTTGTATGACAAC
CAAGAATTTCCTGATCCAGAAAAGTTTAAGCCAGAACACTTCCTGAATGAAAATGGAAAG
TTCAAGTACAGTGACTATTTCAAGCCATTTTCCACAGGAAAACGAGTGTGTGCTGGAGAA
GGCCTGGCTCGCATGGAGTTGTTTCTTTTGTTGTGTGCCATTTTGCAGCATTTTAATTTG
AAGCCTCTCGTTGACCCAAAGGATATCGACCTCAGCCCTATACATATTGGGTTTGGCTGT
ATCCCACCACGTTACAAACTCTGTGTCATTCCCCGCTCATGA
Protein Properties
Number of Residues 493
Molecular Weight 56848.42
Theoretical pI 8.104
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Cytochrome P450 2E1
MSALGVTVALLVWAAFLLLVSMWRQVHSSWNLPPGPFPLPIIGNLFQLELKNIPKSFTRL
AQRFGPVFTLYVGSQRMVVMHGYKAVKEALLDYKDEFSGRGDLPAFHAHRDRGIIFNNGP
TWKDIRRFSLTTLRNYGMGKQGNESRIQREAHFLLEALRKTQGQPFDPTFLIGCAPCNVI
ADILFRKHFDYNDEKFLRLMYLFNENFHLLSTPWLQLYNNFPSFLHYLPGSHRKVIKNVA
EVKEYVSERVKEHHQSLDPNCPRDLTDCLLVEMEKEKHSAERLYTMDGITVTVADLFFAG
TETTSTTLRYGLLILMKYPEIEEKLHEEIDRVIGPSRIPAIKDRQEMPYMDAVVHEIQRF
ITLVPSNLPHEATRDTIFRGYLIPKGTVVVPTLDSVLYDNQEFPDPEKFKPEHFLNENGK
FKYSDYFKPFSTGKRVCAGEGLARMELFLLLCAILQHFNLKPLVDPKDIDLSPIHIGFGC
IPPRYKLCVIPRS
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P05181
UniProtKB/Swiss-Prot Entry Name CP2E1_HUMAN
PDB IDs
GenBank Gene ID J02625
GeneCard ID CYP2E1
GenAtlas ID CYP2E1
HGNC ID HGNC:2631
References
General References
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  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. 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 ]
  10. 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 ]
  11. 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 ]