CP2E1_HUMAN
ID CP2E1_HUMAN Reviewed; 493 AA.
AC P05181; Q5VZD5; Q6NWT9; Q9UK47;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1988, sequence version 1.
DT 03-AUG-2022, entry version 216.
DE RecName: Full=Cytochrome P450 2E1 {ECO:0000303|PubMed:8031147};
DE EC=1.14.14.1 {ECO:0000269|PubMed:10553002, ECO:0000269|PubMed:18577768};
DE AltName: Full=4-nitrophenol 2-hydroxylase;
DE EC=1.14.13.n7 {ECO:0000269|PubMed:9348445};
DE AltName: Full=CYPIIE1;
DE AltName: Full=Cytochrome P450-J;
GN Name=CYP2E1 {ECO:0000303|PubMed:10553002, ECO:0000312|HGNC:HGNC:2631};
GN Synonyms=CYP2E;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3782137; DOI=10.1016/s0021-9258(18)66620-7;
RA Song B.-J., Gelboin H.V., Park S.-S., Yang C.S., Gonzalez F.J.;
RT "Complementary DNA and protein sequences of ethanol-inducible rat and human
RT cytochrome P-450s. Transcriptional and post-transcriptional regulation of
RT the rat enzyme.";
RL J. Biol. Chem. 261:16689-16697(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3233219; DOI=10.1021/bi00425a019;
RA Umeno M., McBride O.W., Yang C.S., Gelboin H.V., Gonzalez F.J.;
RT "Human ethanol-inducible P450IIE1: complete gene sequence, promoter
RT characterization, chromosome mapping, and cDNA-directed expression.";
RL Biochemistry 27:9006-9013(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA Zhuge J., Qian Y., Xie H., Yu Y.;
RT "Sequence of a new human cytochrome P450-2E1 cDNA and establishing the
RT transgenic cell line.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ASP-219; CYS-366 AND
RP LEU-457.
RG NIEHS SNPs program;
RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 32-493.
RC TISSUE=Brain;
RA Yoo M., Shin S.W.;
RT "Partial sequence of human brain cytochrome P450 2E1.";
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 387-432.
RA Iwahashi K., Okuyama E., Nakamura K., Furukawa A., Ichikawa Y.;
RT "Rapid detection of a novel mutation in the human CYP2EI exon VIII by the
RT PCR method.";
RL Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP PROTEIN SEQUENCE OF 1-20.
RC TISSUE=Liver;
RX PubMed=3675576; DOI=10.1016/0006-291x(87)91100-4;
RA Lasker J.M., Raucy J., Kubota S., Bloswick B.P., Black M., Lieber C.S.;
RT "Purification and characterization of human liver cytochrome P-450-ALC.";
RL Biochem. Biophys. Res. Commun. 148:232-238(1987).
RN [11]
RP PROTEIN SEQUENCE OF 3-20.
RX PubMed=2587619; DOI=10.1159/000138590;
RA Robinson R.C., Shorr R.G., Varrichio A., Park S.S., Gelboin H.V.,
RA Miller H., Friedman F.K.;
RT "Human liver cytochrome P-450 related to a rat acetone-inducible,
RT nitrosamine-metabolizing cytochrome P-450: identification and isolation.";
RL Pharmacology 39:137-144(1989).
RN [12]
RP PROTEIN SEQUENCE OF 23-42.
RX PubMed=8031147; DOI=10.1006/abbi.1994.1280;
RA Gillam E.M., Guo Z., Guengerich F.P.;
RT "Expression of modified human cytochrome P450 2E1 in Escherichia coli,
RT purification, and spectral and catalytic properties.";
RL Arch. Biochem. Biophys. 312:59-66(1994).
RN [13]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=9348445; DOI=10.1021/tx970048z;
RA Zerilli A., Ratanasavanh D., Lucas D., Goasduff T., Dreano Y., Menard C.,
RA Picart D., Berthou F.;
RT "Both cytochromes P450 2E1 and 3A are involved in the O-hydroxylation of p-
RT nitrophenol, a catalytic activity known to be specific for P450 2E1.";
RL Chem. Res. Toxicol. 10:1205-1212(1997).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND ACTIVITY REGULATION.
RX PubMed=10553002;
RA Adas F., Salauen J.P., Berthou F., Picart D., Simon B., Amet Y.;
RT "Requirement for omega and (omega;-1)-hydroxylations of fatty acids by
RT human cytochromes P450 2E1 and 4A11.";
RL J. Lipid Res. 40:1990-1997(1999).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=18577768; DOI=10.1194/jlr.m800199-jlr200;
RA Fer M., Corcos L., Dreano Y., Plee-Gautier E., Salaun J.P., Berthou F.,
RA Amet Y.;
RT "Cytochromes P450 from family 4 are the main omega hydroxylating enzymes in
RT humans: CYP4F3B is the prominent player in PUFA metabolism.";
RL J. Lipid Res. 49:2379-2389(2008).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 32-493 IN COMPLEX WITH THE
RP INHIBITORS INDAZOLE AND 4-METHYLPYRAZOLE AND HEME.
RX PubMed=18818195; DOI=10.1074/jbc.m805999200;
RA Porubsky P.R., Meneely K.M., Scott E.E.;
RT "Structures of human cytochrome P-450 2E1. Insights into the binding of
RT inhibitors and both small molecular weight and fatty acid substrates.";
RL J. Biol. Chem. 283:33698-33707(2008).
RN [18]
RP VARIANTS CYP2E1*2 HIS-76 AND CYP2E1*3 ILE-389.
RX PubMed=9058590;
RA Hu Y., Oscarson M., Johansson I., Yue Q.Y., Dahl M.L., Tabone M.,
RA Arinco S., Albano E., Ingelman-Sundberg M.;
RT "Genetic polymorphism of human CYP2E1: characterization of two variant
RT alleles.";
RL Mol. Pharmacol. 51:370-376(1997).
RN [19]
RP VARIANT CYP2E1*4 ILE-179.
RX PubMed=9918138; DOI=10.1097/00008571-199812000-00011;
RA Fairbrother K.S., Grove J., de Waziers I., Steimel D.T., Day C.P.,
RA Crespi C.L., Daly A.K.;
RT "Detection and characterization of novel polymorphisms in the CYP2E1
RT gene.";
RL Pharmacogenetics 8:543-552(1998).
RN [20]
RP VARIANTS ILE-179 AND LEU-457.
RX PubMed=15469410; DOI=10.1517/14622416.5.7.895;
RA Solus J.F., Arietta B.J., Harris J.R., Sexton D.P., Steward J.Q.,
RA McMunn C., Ihrie P., Mehall J.M., Edwards T.L., Dawson E.P.;
RT "Genetic variation in eleven phase I drug metabolism genes in an ethnically
RT diverse population.";
RL Pharmacogenomics 5:895-931(2004).
CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of
CC fatty acids (PubMed:10553002, PubMed:18577768). Mechanistically, uses
CC molecular oxygen inserting one oxygen atom into a substrate, and
CC reducing the second into a water molecule, with two electrons provided
CC by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase)
CC (PubMed:10553002, PubMed:18577768). Catalyzes the hydroxylation of
CC carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the
CC omega-1 position displaying the highest catalytic activity for
CC saturated fatty acids (PubMed:10553002, PubMed:18577768). May be
CC involved in the oxidative metabolism of xenobiotics (Probable).
CC {ECO:0000269|PubMed:10553002, ECO:0000269|PubMed:18577768,
CC ECO:0000305|PubMed:9348445}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an organic molecule + O2 + reduced [NADPH--hemoprotein
CC reductase] = an alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:17149, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:30879, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:142491; EC=1.14.14.1;
CC Evidence={ECO:0000269|PubMed:10553002, ECO:0000269|PubMed:18577768};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17150;
CC Evidence={ECO:0000305|PubMed:10553002, ECO:0000305|PubMed:18577768};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z)-eicosatrienoate + O2 + reduced [NADPH--hemoprotein
CC reductase] = 19-hydroxy-(5Z,8Z,11Z)-eicosatrienoate + H(+) + H2O +
CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:50076,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:78043, ChEBI:CHEBI:132024;
CC Evidence={ECO:0000269|PubMed:18577768};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50077;
CC Evidence={ECO:0000305|PubMed:18577768};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = 19-hydroxy-(5Z,8Z,11Z,14Z,17Z)-
CC eicosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:39787, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58562,
CC ChEBI:CHEBI:76636; Evidence={ECO:0000269|PubMed:18577768};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39788;
CC Evidence={ECO:0000305|PubMed:18577768};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 + reduced
CC [NADPH--hemoprotein reductase] = 21-hydroxy-(4Z,7Z,10Z,13Z,16Z,19Z)-
CC docosahexaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:50088, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:77016,
CC ChEBI:CHEBI:132025; Evidence={ECO:0000269|PubMed:18577768};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50089;
CC Evidence={ECO:0000305|PubMed:18577768};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dodecanoate + O2 + reduced [NADPH--hemoprotein reductase] =
CC 11-hydroxydodecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:39751, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:18262, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:76628; Evidence={ECO:0000269|PubMed:10553002};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39752;
CC Evidence={ECO:0000305|PubMed:10553002};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + reduced [NADPH--hemoprotein reductase] + tetradecanoate =
CC 13-hydroxytetradecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:50096, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:30807, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:132031; Evidence={ECO:0000269|PubMed:10553002};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50097;
CC Evidence={ECO:0000305|PubMed:10553002};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-nitrophenol + H(+) + NADPH + O2 = 4-nitrocatechol + H2O +
CC NADP(+); Xref=Rhea:RHEA:26205, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57730, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:57917, ChEBI:CHEBI:58349; EC=1.14.13.n7;
CC Evidence={ECO:0000269|PubMed:9348445};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC -!- ACTIVITY REGULATION: The omega-1 hydroxylase activity is stimulated by
CC cytochrome b5. {ECO:0000269|PubMed:10553002}.
CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism.
CC {ECO:0000269|PubMed:10553002, ECO:0000269|PubMed:18577768}.
CC -!- SUBUNIT: Interacts with chaperones HSP70 and HSP90; this interaction is
CC required for initial targeting to mitochondria.
CC {ECO:0000250|UniProtKB:P05182}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P05182}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P05182}. Microsome membrane
CC {ECO:0000250|UniProtKB:P05182}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P05182}. Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:P05182}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P05182}. Note=Post-translationally targeted to
CC mitochondria. TOMM70 is required for the translocation across the
CC mitochondrial outer membrane. After translocation into the matrix,
CC associates with the inner membrane as a membrane extrinsic protein.
CC {ECO:0000250|UniProtKB:P05182}.
CC -!- INDUCTION: By ethanol and isoniazid.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=PharmVar Pharmacogen Variation Consortium;
CC Note=CYP2E1 alleles;
CC URL="https://www.pharmvar.org/gene/CYP2E1";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=CYP2E1 entry;
CC URL="https://en.wikipedia.org/wiki/CYP2E1";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/cyp2e1/";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; J02625; AAA35743.1; -; mRNA.
DR EMBL; J02843; AAA52155.1; -; Genomic_DNA.
DR EMBL; AF182276; AAF13601.1; -; mRNA.
DR EMBL; DQ515958; ABF47105.1; -; Genomic_DNA.
DR EMBL; AL161645; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471211; EAW61357.1; -; Genomic_DNA.
DR EMBL; BC067433; AAH67433.1; -; mRNA.
DR EMBL; AF084225; AAD13753.1; -; mRNA.
DR EMBL; D50111; BAA08796.1; -; Genomic_DNA.
DR CCDS; CCDS7686.1; -.
DR PIR; A31949; A31949.
DR RefSeq; NP_000764.1; NM_000773.3.
DR PDB; 3E4E; X-ray; 2.60 A; A/B=32-493.
DR PDB; 3E6I; X-ray; 2.20 A; A/B=32-493.
DR PDB; 3GPH; X-ray; 2.70 A; A/B=32-493.
DR PDB; 3KOH; X-ray; 2.90 A; A/B=32-493.
DR PDB; 3LC4; X-ray; 3.10 A; A/B=32-493.
DR PDB; 3T3Z; X-ray; 2.35 A; A/B/C/D=32-493.
DR PDBsum; 3E4E; -.
DR PDBsum; 3E6I; -.
DR PDBsum; 3GPH; -.
DR PDBsum; 3KOH; -.
DR PDBsum; 3LC4; -.
DR PDBsum; 3T3Z; -.
DR AlphaFoldDB; P05181; -.
DR SMR; P05181; -.
DR BioGRID; 107944; 20.
DR IntAct; P05181; 12.
DR STRING; 9606.ENSP00000440689; -.
DR BindingDB; P05181; -.
DR ChEMBL; CHEMBL5281; -.
DR DrugBank; DB13963; 1,2-dichlorobenzene.
DR DrugBank; DB00316; Acetaminophen.
DR DrugBank; DB00118; Ademetionine.
DR DrugBank; DB00041; Aldesleukin.
DR DrugBank; DB00918; Almotriptan.
DR DrugBank; DB00969; Alosetron.
DR DrugBank; DB01223; Aminophylline.
DR DrugBank; DB06728; Aniline.
DR DrugBank; DB01435; Antipyrine.
DR DrugBank; DB00972; Azelastine.
DR DrugBank; DB01086; Benzocaine.
DR DrugBank; DB06770; Benzyl alcohol.
DR DrugBank; DB04794; Bifonazole.
DR DrugBank; DB01558; Bromazepam.
DR DrugBank; DB01156; Bupropion.
DR DrugBank; DB00201; Caffeine.
DR DrugBank; DB06774; Capsaicin.
DR DrugBank; DB01136; Carvedilol.
DR DrugBank; DB06119; Cenobamate.
DR DrugBank; DB00477; Chlorpromazine.
DR DrugBank; DB00356; Chlorzoxazone.
DR DrugBank; DB00501; Cimetidine.
DR DrugBank; DB12499; Clascoterone.
DR DrugBank; DB04920; Clevidipine.
DR DrugBank; DB00636; Clofibrate.
DR DrugBank; DB01068; Clonazepam.
DR DrugBank; DB00257; Clotrimazole.
DR DrugBank; DB01394; Colchicine.
DR DrugBank; DB00851; Dacarbazine.
DR DrugBank; DB06637; Dalfampridine.
DR DrugBank; DB00250; Dapsone.
DR DrugBank; DB11943; Delafloxacin.
DR DrugBank; DB01189; Desflurane.
DR DrugBank; DB01151; Desipramine.
DR DrugBank; DB01234; Dexamethasone.
DR DrugBank; DB14649; Dexamethasone acetate.
DR DrugBank; DB01191; Dexfenfluramine.
DR DrugBank; DB04856; Dexloxiglumide.
DR DrugBank; DB00633; Dexmedetomidine.
DR DrugBank; DB11994; Diacerein.
DR DrugBank; DB00829; Diazepam.
DR DrugBank; DB14046; Dichlorobenzene.
DR DrugBank; DB00586; Diclofenac.
DR DrugBank; DB00255; Diethylstilbestrol.
DR DrugBank; DB08995; Diosmin.
DR DrugBank; DB00822; Disulfiram.
DR DrugBank; DB02520; Ditiocarb.
DR DrugBank; DB00869; Dorzolamide.
DR DrugBank; DB01127; Econazole.
DR DrugBank; DB08846; Ellagic acid.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB00109; Enfuvirtide.
DR DrugBank; DB00655; Estrone.
DR DrugBank; DB00330; Ethambutol.
DR DrugBank; DB00898; Ethanol.
DR DrugBank; DB00593; Ethosuximide.
DR DrugBank; DB00773; Etoposide.
DR DrugBank; DB01628; Etoricoxib.
DR DrugBank; DB12466; Favipiravir.
DR DrugBank; DB00949; Felbamate.
DR DrugBank; DB08868; Fingolimod.
DR DrugBank; DB01544; Flunitrazepam.
DR DrugBank; DB00623; Fluphenazine.
DR DrugBank; DB00690; Flurazepam.
DR DrugBank; DB01213; Fomepizole.
DR DrugBank; DB09462; Glycerin.
DR DrugBank; DB05708; GTS-21.
DR DrugBank; DB01159; Halothane.
DR DrugBank; DB04946; Iloperidone.
DR DrugBank; DB00458; Imipramine.
DR DrugBank; DB06370; Indisulam.
DR DrugBank; DB00753; Isoflurane.
DR DrugBank; DB00951; Isoniazid.
DR DrugBank; DB00883; Isosorbide dinitrate.
DR DrugBank; DB01167; Itraconazole.
DR DrugBank; DB00602; Ivermectin.
DR DrugBank; DB06448; Lonafarnib.
DR DrugBank; DB00170; Menadione.
DR DrugBank; DB00763; Methimazole.
DR DrugBank; DB01403; Methotrimeprazine.
DR DrugBank; DB01028; Methoxyflurane.
DR DrugBank; DB01011; Metyrapone.
DR DrugBank; DB00379; Mexiletine.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB06595; Midostaurin.
DR DrugBank; DB01204; Mitoxantrone.
DR DrugBank; DB01844; N,N-dimethylformamide.
DR DrugBank; DB04379; N-Methyl-N-(Methylbenzyl)Formamide.
DR DrugBank; DB00486; Nabilone.
DR DrugBank; DB00627; Niacin.
DR DrugBank; DB00622; Nicardipine.
DR DrugBank; DB02701; Nicotinamide.
DR DrugBank; DB00184; Nicotine.
DR DrugBank; DB01115; Nifedipine.
DR DrugBank; DB06712; Nilvadipine.
DR DrugBank; DB01595; Nitrazepam.
DR DrugBank; DB00540; Nortriptyline.
DR DrugBank; DB00904; Ondansetron.
DR DrugBank; DB01173; Orphenadrine.
DR DrugBank; DB11837; Osilodrostat.
DR DrugBank; DB00617; Paramethadione.
DR DrugBank; DB03783; Phenacetin.
DR DrugBank; DB00780; Phenelzine.
DR DrugBank; DB01174; Phenobarbital.
DR DrugBank; DB00252; Phenytoin.
DR DrugBank; DB13941; Piperaquine.
DR DrugBank; DB04951; Pirfenidone.
DR DrugBank; DB04977; Plitidepsin.
DR DrugBank; DB00794; Primidone.
DR DrugBank; DB09288; Propacetamol.
DR DrugBank; DB00818; Propofol.
DR DrugBank; DB04216; Quercetin.
DR DrugBank; DB00908; Quinidine.
DR DrugBank; DB00468; Quinine.
DR DrugBank; DB13174; Rhein.
DR DrugBank; DB01045; Rifampicin.
DR DrugBank; DB08864; Rilpivirine.
DR DrugBank; DB14840; Ripretinib.
DR DrugBank; DB00412; Rosiglitazone.
DR DrugBank; DB06201; Rufinamide.
DR DrugBank; DB11689; Selumetinib.
DR DrugBank; DB01104; Sertraline.
DR DrugBank; DB01236; Sevoflurane.
DR DrugBank; DB00203; Sildenafil.
DR DrugBank; DB00428; Streptozocin.
DR DrugBank; DB00675; Tamoxifen.
DR DrugBank; DB09256; Tegafur.
DR DrugBank; DB01079; Tegaserod.
DR DrugBank; DB01412; Theobromine.
DR DrugBank; DB00277; Theophylline.
DR DrugBank; DB01154; Thiamylal.
DR DrugBank; DB00679; Thioridazine.
DR DrugBank; DB00208; Ticlopidine.
DR DrugBank; DB01007; Tioconazole.
DR DrugBank; DB04858; Tirapazamine.
DR DrugBank; DB05109; Trabectedin.
DR DrugBank; DB00347; Trimethadione.
DR DrugBank; DB13609; Umifenovir.
DR DrugBank; DB09328; Vayarin.
DR DrugBank; DB00661; Verapamil.
DR DrugBank; DB09120; Zucapsaicin.
DR DrugCentral; P05181; -.
DR GuidetoPHARMACOLOGY; 1330; -.
DR SwissLipids; SLP:000001596; -.
DR iPTMnet; P05181; -.
DR PhosphoSitePlus; P05181; -.
DR BioMuta; CYP2E1; -.
DR DMDM; 117250; -.
DR MassIVE; P05181; -.
DR PaxDb; P05181; -.
DR PeptideAtlas; P05181; -.
DR PRIDE; P05181; -.
DR ProteomicsDB; 51820; -.
DR Antibodypedia; 2427; 659 antibodies from 39 providers.
DR DNASU; 1571; -.
DR Ensembl; ENST00000252945.8; ENSP00000252945.3; ENSG00000130649.10.
DR Ensembl; ENST00000463117.6; ENSP00000440689.1; ENSG00000130649.10.
DR GeneID; 1571; -.
DR KEGG; hsa:1571; -.
DR MANE-Select; ENST00000252945.8; ENSP00000252945.3; NM_000773.4; NP_000764.1.
DR UCSC; uc001lnj.1; human.
DR CTD; 1571; -.
DR DisGeNET; 1571; -.
DR GeneCards; CYP2E1; -.
DR HGNC; HGNC:2631; CYP2E1.
DR HPA; ENSG00000130649; Tissue enriched (liver).
DR MIM; 124040; gene.
DR neXtProt; NX_P05181; -.
DR OpenTargets; ENSG00000130649; -.
DR PharmGKB; PA129; -.
DR VEuPathDB; HostDB:ENSG00000130649; -.
DR eggNOG; KOG0156; Eukaryota.
DR GeneTree; ENSGT00940000161594; -.
DR HOGENOM; CLU_001570_22_3_1; -.
DR InParanoid; P05181; -.
DR OMA; AMKGDYG; -.
DR OrthoDB; 702827at2759; -.
DR PhylomeDB; P05181; -.
DR TreeFam; TF352043; -.
DR BioCyc; MetaCyc:HS05414-MON; -.
DR PathwayCommons; P05181; -.
DR Reactome; R-HSA-211981; Xenobiotics.
DR Reactome; R-HSA-211999; CYP2E1 reactions.
DR Reactome; R-HSA-9027307; Biosynthesis of maresin-like SPMs.
DR Reactome; R-HSA-9749641; Aspirin ADME.
DR Reactome; R-HSA-9753281; Paracetamol ADME.
DR SABIO-RK; P05181; -.
DR SignaLink; P05181; -.
DR SIGNOR; P05181; -.
DR UniPathway; UPA00199; -.
DR BioGRID-ORCS; 1571; 7 hits in 1064 CRISPR screens.
DR ChiTaRS; CYP2E1; human.
DR EvolutionaryTrace; P05181; -.
DR GeneWiki; CYP2E1; -.
DR GenomeRNAi; 1571; -.
DR Pharos; P05181; Tchem.
DR PRO; PR:P05181; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P05181; protein.
DR Bgee; ENSG00000130649; Expressed in right lobe of liver and 149 other tissues.
DR ExpressionAtlas; P05181; baseline and differential.
DR Genevisible; P05181; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0000139; C:Golgi membrane; IEA:Ensembl.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0031227; C:intrinsic component of endoplasmic reticulum membrane; IEA:Ensembl.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0018601; F:4-nitrophenol 2-monooxygenase activity; IDA:UniProtKB.
DR GO; GO:0008392; F:arachidonic acid epoxygenase activity; IBA:GO_Central.
DR GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC.
DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR GO; GO:0020037; F:heme binding; IDA:UniProtKB.
DR GO; GO:0030544; F:Hsp70 protein binding; ISS:UniProtKB.
DR GO; GO:0051879; F:Hsp90 protein binding; ISS:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0120319; F:long-chain fatty acid omega-1 hydroxylase activity; IDA:UniProtKB.
DR GO; GO:0004497; F:monooxygenase activity; IDA:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IDA:BHF-UCL.
DR GO; GO:0016709; F: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; TAS:UniProtKB.
DR GO; GO:0016712; F: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; IBA:GO_Central.
DR GO; GO:0019825; F:oxygen binding; TAS:ProtInc.
DR GO; GO:0008395; F:steroid hydroxylase activity; IBA:GO_Central.
DR GO; GO:0018960; P:4-nitrophenol metabolic process; IDA:UniProtKB.
DR GO; GO:0018910; P:benzene metabolic process; TAS:Reactome.
DR GO; GO:0018885; P:carbon tetrachloride metabolic process; TAS:Reactome.
DR GO; GO:0019373; P:epoxygenase P450 pathway; IBA:GO_Central.
DR GO; GO:0042197; P:halogenated hydrocarbon metabolic process; TAS:Reactome.
DR GO; GO:0046483; P:heterocycle metabolic process; IDA:BHF-UCL.
DR GO; GO:0002933; P:lipid hydroxylation; IDA:UniProtKB.
DR GO; GO:0042759; P:long-chain fatty acid biosynthetic process; TAS:Reactome.
DR GO; GO:0001676; P:long-chain fatty acid metabolic process; IDA:UniProtKB.
DR GO; GO:0016098; P:monoterpenoid metabolic process; IDA:BHF-UCL.
DR GO; GO:0006082; P:organic acid metabolic process; IBA:GO_Central.
DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0010243; P:response to organonitrogen compound; IEA:Ensembl.
DR GO; GO:0010193; P:response to ozone; IEA:Ensembl.
DR GO; GO:0008202; P:steroid metabolic process; IMP:BHF-UCL.
DR GO; GO:0006641; P:triglyceride metabolic process; IEA:Ensembl.
DR GO; GO:0006805; P:xenobiotic metabolic process; IDA:BHF-UCL.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR008070; Cyt_P450_E_grp-I_CYP2E-like.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR01687; EP450ICYP2E.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Endoplasmic reticulum;
KW Fatty acid metabolism; Heme; Iron; Lipid metabolism; Membrane;
KW Metal-binding; Microsome; Mitochondrion; Mitochondrion inner membrane;
KW Monooxygenase; NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..493
FT /note="Cytochrome P450 2E1"
FT /id="PRO_0000051751"
FT BINDING 298..303
FT /ligand="substrate"
FT /evidence="ECO:0000305"
FT BINDING 437
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT VARIANT 76
FT /note="R -> H (in allele CYP2E1*2; reduced activity;
FT dbSNP:rs72559710)"
FT /evidence="ECO:0000269|PubMed:9058590"
FT /id="VAR_008360"
FT VARIANT 179
FT /note="V -> I (in allele CYP2E1*4; dbSNP:rs6413419)"
FT /evidence="ECO:0000269|PubMed:15469410,
FT ECO:0000269|PubMed:9918138"
FT /id="VAR_008361"
FT VARIANT 219
FT /note="N -> D (in dbSNP:rs41299426)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_055382"
FT VARIANT 366
FT /note="S -> C (in dbSNP:rs41299434)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_055383"
FT VARIANT 389
FT /note="V -> I (in allele CYP2E1*3; dbSNP:rs55897648)"
FT /evidence="ECO:0000269|PubMed:9058590"
FT /id="VAR_008362"
FT VARIANT 457
FT /note="H -> L (in dbSNP:rs28969387)"
FT /evidence="ECO:0000269|PubMed:15469410, ECO:0000269|Ref.4"
FT /id="VAR_024727"
FT CONFLICT 2
FT /note="Missing (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 23
FT /note="W -> A (in Ref. 12; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 32
FT /note="L -> N (in Ref. 12; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 71
FT /note="Y -> C (in Ref. 7; AAH67433)"
FT /evidence="ECO:0000305"
FT CONFLICT 235
FT /note="V -> A (in Ref. 3; AAF13601)"
FT /evidence="ECO:0000305"
FT CONFLICT 355
FT /note="H -> R (in Ref. 7; AAH67433)"
FT /evidence="ECO:0000305"
FT TURN 40..42
FT /evidence="ECO:0007829|PDB:3E6I"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:3E6I"
FT HELIX 50..52
FT /evidence="ECO:0007829|PDB:3T3Z"
FT HELIX 53..64
FT /evidence="ECO:0007829|PDB:3E6I"
FT STRAND 66..72
FT /evidence="ECO:0007829|PDB:3E6I"
FT STRAND 75..80
FT /evidence="ECO:0007829|PDB:3E6I"
FT HELIX 83..91
FT /evidence="ECO:0007829|PDB:3E6I"
FT TURN 94..97
FT /evidence="ECO:0007829|PDB:3E6I"
FT HELIX 104..109
FT /evidence="ECO:0007829|PDB:3E6I"
FT STRAND 112..114
FT /evidence="ECO:0007829|PDB:3E6I"
FT HELIX 122..135
FT /evidence="ECO:0007829|PDB:3E6I"
FT HELIX 142..159
FT /evidence="ECO:0007829|PDB:3E6I"
FT TURN 160..163
FT /evidence="ECO:0007829|PDB:3E6I"
FT HELIX 169..172
FT /evidence="ECO:0007829|PDB:3E6I"
FT HELIX 174..185
FT /evidence="ECO:0007829|PDB:3E6I"
FT HELIX 194..209
FT /evidence="ECO:0007829|PDB:3E6I"
FT HELIX 213..220
FT /evidence="ECO:0007829|PDB:3E6I"
FT HELIX 222..225
FT /evidence="ECO:0007829|PDB:3E6I"
FT STRAND 228..230
FT /evidence="ECO:0007829|PDB:3T3Z"
FT HELIX 231..255
FT /evidence="ECO:0007829|PDB:3E6I"
FT STRAND 259..261
FT /evidence="ECO:0007829|PDB:3KOH"
FT HELIX 265..274
FT /evidence="ECO:0007829|PDB:3E6I"
FT STRAND 275..278
FT /evidence="ECO:0007829|PDB:3E6I"
FT STRAND 279..281
FT /evidence="ECO:0007829|PDB:3T3Z"
FT HELIX 286..317
FT /evidence="ECO:0007829|PDB:3E6I"
FT HELIX 319..332
FT /evidence="ECO:0007829|PDB:3E6I"
FT TURN 333..336
FT /evidence="ECO:0007829|PDB:3E6I"
FT HELIX 341..346
FT /evidence="ECO:0007829|PDB:3E6I"
FT HELIX 348..361
FT /evidence="ECO:0007829|PDB:3E6I"
FT STRAND 376..378
FT /evidence="ECO:0007829|PDB:3E6I"
FT STRAND 381..383
FT /evidence="ECO:0007829|PDB:3E6I"
FT STRAND 388..391
FT /evidence="ECO:0007829|PDB:3E6I"
FT HELIX 394..397
FT /evidence="ECO:0007829|PDB:3E6I"
FT TURN 400..402
FT /evidence="ECO:0007829|PDB:3E6I"
FT STRAND 403..405
FT /evidence="ECO:0007829|PDB:3E6I"
FT HELIX 411..414
FT /evidence="ECO:0007829|PDB:3E6I"
FT STRAND 419..421
FT /evidence="ECO:0007829|PDB:3E6I"
FT HELIX 433..435
FT /evidence="ECO:0007829|PDB:3LC4"
FT HELIX 440..457
FT /evidence="ECO:0007829|PDB:3E6I"
FT STRAND 458..464
FT /evidence="ECO:0007829|PDB:3E6I"
FT TURN 466..468
FT /evidence="ECO:0007829|PDB:3E6I"
FT STRAND 474..481
FT /evidence="ECO:0007829|PDB:3E6I"
FT STRAND 487..491
FT /evidence="ECO:0007829|PDB:3E6I"
SQ SEQUENCE 493 AA; 56849 MW; ED0399E32A005644 CRC64;
MSALGVTVAL LVWAAFLLLV SMWRQVHSSW NLPPGPFPLP IIGNLFQLEL KNIPKSFTRL
AQRFGPVFTL YVGSQRMVVM HGYKAVKEAL LDYKDEFSGR GDLPAFHAHR DRGIIFNNGP
TWKDIRRFSL TTLRNYGMGK QGNESRIQRE AHFLLEALRK TQGQPFDPTF LIGCAPCNVI
ADILFRKHFD YNDEKFLRLM YLFNENFHLL STPWLQLYNN FPSFLHYLPG SHRKVIKNVA
EVKEYVSERV KEHHQSLDPN CPRDLTDCLL VEMEKEKHSA ERLYTMDGIT VTVADLFFAG
TETTSTTLRY GLLILMKYPE IEEKLHEEID RVIGPSRIPA IKDRQEMPYM DAVVHEIQRF
ITLVPSNLPH EATRDTIFRG YLIPKGTVVV PTLDSVLYDN QEFPDPEKFK PEHFLNENGK
FKYSDYFKPF STGKRVCAGE GLARMELFLL LCAILQHFNL KPLVDPKDID LSPIHIGFGC
IPPRYKLCVI PRS
