Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P05181 (CP2E1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 156. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cytochrome P450 2E1

EC=1.14.13.-
Alternative name(s):
4-nitrophenol 2-hydroxylase
EC=1.14.13.n7
CYPIIE1
Cytochrome P450-J

Cleaved into the following chain:

  1. Cytochrome P450 2E1, N-terminally processed
Gene names
Name:CYP2E1
Synonyms:CYP2E
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length493 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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.

Catalytic activity

4-nitrophenol + NADPH + O2 = 4-nitrocatechol + NADP+ + H2O. Ref.13

Cofactor

Heme group.

Subcellular location

Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.

Induction

By ethanol and isoniazid.

Sequence similarities

Belongs to the cytochrome P450 family.

Ontologies

Keywords
   Cellular componentEndoplasmic reticulum
Membrane
Microsome
   Coding sequence diversityPolymorphism
   LigandHeme
Iron
Metal-binding
NADP
   Molecular functionMonooxygenase
Oxidoreductase
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processdrug metabolic process

Inferred from direct assay PubMed 19219744. Source: BHF-UCL

heterocycle metabolic process

Inferred from direct assay PubMed 19651758. Source: BHF-UCL

monoterpenoid metabolic process

Inferred from direct assay PubMed 16401082. Source: BHF-UCL

oxidation-reduction process

Inferred from direct assay PubMed 16401082PubMed 19219744. Source: BHF-UCL

response to drug

Inferred from electronic annotation. Source: Ensembl

response to ethanol

Inferred from electronic annotation. Source: Ensembl

response to organonitrogen compound

Inferred from electronic annotation. Source: Ensembl

response to ozone

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

steroid metabolic process

Inferred from mutant phenotype PubMed 18356043. Source: BHF-UCL

triglyceride metabolic process

Inferred from electronic annotation. Source: Ensembl

xenobiotic metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentGolgi membrane

Inferred from electronic annotation. Source: Ensembl

endoplasmic reticulum membrane

Traceable author statement. Source: Reactome

intrinsic component of endoplasmic reticulum membrane

Inferred from electronic annotation. Source: Ensembl

mitochondrion

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionenzyme binding

Inferred from physical interaction PubMed 15680923. Source: BHF-UCL

heme binding

Inferred from direct assay Ref.14. Source: UniProtKB

iron ion binding

Inferred from electronic annotation. Source: InterPro

monooxygenase activity

Inferred from direct assay PubMed 19651758. Source: BHF-UCL

oxidoreductase activity

Inferred from direct assay PubMed 16401082PubMed 19219744. Source: BHF-UCL

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

Traceable author statement Ref.14. Source: UniProtKB

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

Inferred from electronic annotation. Source: Ensembl

oxygen binding

Traceable author statement Ref.2. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 493493Cytochrome P450 2E1
PRO_0000051751
Initiator methionine11Removed; alternate By similarity
Chain2 – 493492Cytochrome P450 2E1, N-terminally processed
PRO_0000421771

Regions

Region298 – 3036Substrate binding Probable

Sites

Metal binding4371Iron (heme axial ligand)

Natural variations

Natural variant761R → H in allele CYP2E1*2; reduced activity. Ref.15
Corresponds to variant rs72559710 [ dbSNP | Ensembl ].
VAR_008360
Natural variant1791V → I in allele CYP2E1*4. Ref.16 Ref.17
Corresponds to variant rs6413419 [ dbSNP | Ensembl ].
VAR_008361
Natural variant2191N → D. Ref.4
Corresponds to variant rs41299426 [ dbSNP | Ensembl ].
VAR_055382
Natural variant3661S → C. Ref.4
Corresponds to variant rs41299434 [ dbSNP | Ensembl ].
VAR_055383
Natural variant3891V → I in allele CYP2E1*3. Ref.15
Corresponds to variant rs55897648 [ dbSNP | Ensembl ].
VAR_008362
Natural variant4571H → L. Ref.4 Ref.17
Corresponds to variant rs28969387 [ dbSNP | Ensembl ].
VAR_024727

Experimental info

Sequence conflict21Missing AA sequence Ref.10
Sequence conflict231W → A AA sequence Ref.12
Sequence conflict321L → N AA sequence Ref.12
Sequence conflict711Y → C in AAH67433. Ref.7
Sequence conflict2351V → A in AAF13601. Ref.3
Sequence conflict3551H → R in AAH67433. Ref.7

Secondary structure

............................................................................... 493
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P05181 [UniParc].

Last modified April 1, 1988. Version 1.
Checksum: ED0399E32A005644

FASTA49356,849
        10         20         30         40         50         60 
MSALGVTVAL LVWAAFLLLV SMWRQVHSSW NLPPGPFPLP IIGNLFQLEL KNIPKSFTRL 

        70         80         90        100        110        120 
AQRFGPVFTL YVGSQRMVVM HGYKAVKEAL LDYKDEFSGR GDLPAFHAHR DRGIIFNNGP 

       130        140        150        160        170        180 
TWKDIRRFSL TTLRNYGMGK QGNESRIQRE AHFLLEALRK TQGQPFDPTF LIGCAPCNVI 

       190        200        210        220        230        240 
ADILFRKHFD YNDEKFLRLM YLFNENFHLL STPWLQLYNN FPSFLHYLPG SHRKVIKNVA 

       250        260        270        280        290        300 
EVKEYVSERV KEHHQSLDPN CPRDLTDCLL VEMEKEKHSA ERLYTMDGIT VTVADLFFAG 

       310        320        330        340        350        360 
TETTSTTLRY GLLILMKYPE IEEKLHEEID RVIGPSRIPA IKDRQEMPYM DAVVHEIQRF 

       370        380        390        400        410        420 
ITLVPSNLPH EATRDTIFRG YLIPKGTVVV PTLDSVLYDN QEFPDPEKFK PEHFLNENGK 

       430        440        450        460        470        480 
FKYSDYFKPF STGKRVCAGE GLARMELFLL LCAILQHFNL KPLVDPKDID LSPIHIGFGC 

       490 
IPPRYKLCVI PRS 

« Hide

References

« Hide 'large scale' references
[1]"Complementary DNA and protein sequences of ethanol-inducible rat and human cytochrome P-450s. Transcriptional and post-transcriptional regulation of the rat enzyme."
Song B.-J., Gelboin H.V., Park S.-S., Yang C.S., Gonzalez F.J.
J. Biol. Chem. 261:16689-16697(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Human ethanol-inducible P450IIE1: complete gene sequence, promoter characterization, chromosome mapping, and cDNA-directed expression."
Umeno M., McBride O.W., Yang C.S., Gelboin H.V., Gonzalez F.J.
Biochemistry 27:9006-9013(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Sequence of a new human cytochrome P450-2E1 cDNA and establishing the transgenic cell line."
Zhuge J., Qian Y., Xie H., Yu Y.
Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[4]NIEHS SNPs program
Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ASP-219; CYS-366 AND LEU-457.
[5]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., 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 A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[8]"Partial sequence of human brain cytochrome P450 2E1."
Yoo M., Shin S.W.
Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 32-493.
Tissue: Brain.
[9]"Rapid detection of a novel mutation in the human CYP2EI exon VIII by the PCR method."
Iwahashi K., Okuyama E., Nakamura K., Furukawa A., Ichikawa Y.
Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 387-432.
[10]"Purification and characterization of human liver cytochrome P-450-ALC."
Lasker J.M., Raucy J., Kubota S., Bloswick B.P., Black M., Lieber C.S.
Biochem. Biophys. Res. Commun. 148:232-238(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1-20.
Tissue: Liver.
[11]"Human liver cytochrome P-450 related to a rat acetone-inducible, nitrosamine-metabolizing cytochrome P-450: identification and isolation."
Robinson R.C., Shorr R.G., Varrichio A., Park S.S., Gelboin H.V., Miller H., Friedman F.K.
Pharmacology 39:137-144(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 3-20.
[12]"Expression of modified human cytochrome P450 2E1 in Escherichia coli, purification, and spectral and catalytic properties."
Gillam E.M., Guo Z., Guengerich F.P.
Arch. Biochem. Biophys. 312:59-66(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 23-42.
[13]"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."
Zerilli A., Ratanasavanh D., Lucas D., Goasduff T., Dreano Y., Menard C., Picart D., Berthou F.
Chem. Res. Toxicol. 10:1205-1212(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY.
[14]"Structures of human cytochrome P-450 2E1. Insights into the binding of inhibitors and both small molecular weight and fatty acid substrates."
Porubsky P.R., Meneely K.M., Scott E.E.
J. Biol. Chem. 283:33698-33707(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 32-493 IN COMPLEX WITH THE INHIBITORS INDAZOLE AND 4-METHYLPYRAZOLE AND HEME.
[15]"Genetic polymorphism of human CYP2E1: characterization of two variant alleles."
Hu Y., Oscarson M., Johansson I., Yue Q.Y., Dahl M.L., Tabone M., Arinco S., Albano E., Ingelman-Sundberg M.
Mol. Pharmacol. 51:370-376(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CYP2E1*2 HIS-76 AND CYP2E1*3 ILE-389.
[16]"Detection and characterization of novel polymorphisms in the CYP2E1 gene."
Fairbrother K.S., Grove J., de Waziers I., Steimel D.T., Day C.P., Crespi C.L., Daly A.K.
Pharmacogenetics 8:543-552(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CYP2E1*4 ILE-179.
[17]"Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population."
Solus J.F., Arietta B.J., Harris J.R., Sexton D.P., Steward J.Q., McMunn C., Ihrie P., Mehall J.M., Edwards T.L., Dawson E.P.
Pharmacogenomics 5:895-931(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ILE-179 AND LEU-457.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J02625 mRNA. Translation: AAA35743.1.
J02843 Genomic DNA. Translation: AAA52155.1.
AF182276 mRNA. Translation: AAF13601.1.
DQ515958 Genomic DNA. Translation: ABF47105.1.
AL161645 Genomic DNA. Translation: CAH70047.1.
CH471211 Genomic DNA. Translation: EAW61357.1.
BC067433 mRNA. Translation: AAH67433.1.
AF084225 mRNA. Translation: AAD13753.1.
D50111 Genomic DNA. Translation: BAA08796.1.
PIRA31949.
RefSeqNP_000764.1. NM_000773.3.
UniGeneHs.12907.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3E4EX-ray2.60A/B32-493[»]
3E6IX-ray2.20A/B32-493[»]
3GPHX-ray2.70A/B32-493[»]
3KOHX-ray2.90A/B32-493[»]
3LC4X-ray3.10A/B32-493[»]
3T3ZX-ray2.35A/B/C/D32-493[»]
ProteinModelPortalP05181.
SMRP05181. Positions 32-493.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107944. 17 interactions.
IntActP05181. 10 interactions.
STRING9606.ENSP00000252945.

Chemistry

BindingDBP05181.
ChEMBLCHEMBL5281.
DrugBankDB00316. Acetaminophen.
DB00356. Chlorzoxazone.
DB00568. Cinnarizine.
DB00636. Clofibrate.
DB00851. Dacarbazine.
DB00250. Dapsone.
DB00228. Enflurane.
DB00402. Eszopiclone.
DB00898. Ethanol.
DB00593. Ethosuximide.
DB01213. Fomepizole.
DB00143. Glutathione.
DB01159. Halothane.
DB01355. Hexobarbital.
DB00753. Isoflurane.
DB00951. Isoniazid.
DB00170. Menadione.
DB00532. Mephenytoin.
DB01028. Methoxyflurane.
DB00683. Midazolam.
DB01204. Mitoxantrone.
DB00184. Nicotine.
DB01115. Nifedipine.
DB00698. Nitrofurantoin.
DB01173. Orphenadrine.
DB00780. Phenelzine.
DB00908. Quinidine.
DB00118. S-Adenosylmethionine.
DB01236. Sevoflurane.
DB00277. Theophylline.
DB01124. Tolbutamide.

PTM databases

PhosphoSiteP05181.

Polymorphism databases

DMDM117250.

Proteomic databases

PaxDbP05181.
PeptideAtlasP05181.
PRIDEP05181.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000252945; ENSP00000252945; ENSG00000130649.
ENST00000463117; ENSP00000440689; ENSG00000130649.
GeneID1571.
KEGGhsa:1571.
UCSCuc001lnj.1. human.

Organism-specific databases

CTD1571.
GeneCardsGC10P135352.
HGNCHGNC:2631. CYP2E1.
HPAHPA009128.
HPA029564.
MIM124040. gene.
neXtProtNX_P05181.
PharmGKBPA129.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2124.
HOGENOMHOG000036992.
HOVERGENHBG015789.
InParanoidP05181.
KOK07415.
OMAGNESRIQ.
OrthoDBEOG7RBZ85.
PhylomeDBP05181.
TreeFamTF352043.

Enzyme and pathway databases

BioCycMetaCyc:HS05414-MONOMER.
ReactomeREACT_111217. Metabolism.
SABIO-RKP05181.

Gene expression databases

ArrayExpressP05181.
BgeeP05181.
CleanExHS_CYP2E1.
GenevestigatorP05181.

Family and domain databases

Gene3D1.10.630.10. 1 hit.
InterProIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
IPR008070. Cyt_P450_E_grp-I_CYP2E-like.
[Graphical view]
PfamPF00067. p450. 1 hit.
[Graphical view]
PRINTSPR00463. EP450I.
PR01687. EP450ICYP2E.
PR00385. P450.
SUPFAMSSF48264. SSF48264. 1 hit.
PROSITEPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP05181.
GeneWikiCYP2E1.
GenomeRNAi1571.
NextBio6461.
PROP05181.
SOURCESearch...

Entry information

Entry nameCP2E1_HUMAN
AccessionPrimary (citable) accession number: P05181
Secondary accession number(s): Q5VZD5, Q6NWT9, Q9UK47
Entry history
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: April 1, 1988
Last modified: April 16, 2014
This is version 156 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM