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Reviewed, UniProtKB/Swiss-Prot P05181 (CP2E1_HUMAN)

Last modified July 7, 2009. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Cytochrome P450 2E1
    EC=1.14.13.-
Alternative name(s):
    CYPIIE1
    4-nitrophenol 2-hydroxylase
    EC=1.14.13.n7
    P450-J
Gene names
Name: CYP2E1
Synonyms: CYP2E
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length493 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
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.

Cofactor

Heme group By similarity.

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 493493Cytochrome P450 2E1
PRO_0000051751

Sites

Metal binding4371Iron (heme axial ligand)

Amino acid modifications

Modified residue1291Phosphoserine By similarity

Natural variations

Natural variant761R → H in allele CYP2E1*2; reduced activity. Ref.13
VAR_008360
Natural variant1791V → I in allele CYP2E1*4. dbSNP rs6413419. Ref.14 Ref.15
VAR_008361
Natural variant2191N → D: dbSNP rs41299426.
VAR_055382
Natural variant3661S → C: dbSNP rs41299434.
VAR_055383
Natural variant3891V → I in allele CYP2E1*3. dbSNP rs55897648.
VAR_008362
Natural variant4571H → L: dbSNP rs28969387. Ref.15
VAR_024727

Experimental info

Sequence conflict21Missing AA sequence Ref.9
Sequence conflict231W → A AA sequence Ref.11
Sequence conflict321L → N AA sequence Ref.11
Sequence conflict2351V → A in AAF13601. Ref.3

Sequences

Sequence LengthMass (Da)Tools
P05181-1 [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: 3782137] [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: 3233219] [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: 15164054] [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]"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.
[8]"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.
[9]"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: 3675576] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1-20.
Tissue: Liver.
[10]"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: 2587619] [Abstract]
Cited for: PROTEIN SEQUENCE OF 3-20.
[11]"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: 8031147] [Abstract]
Cited for: PROTEIN SEQUENCE OF 23-42.
[12]"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: 9348445] [Abstract]
Cited for: CATALYTIC ACTIVITY.
[13]"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: 9058590] [Abstract]
Cited for: VARIANTS CYP2E1*2 HIS-76 AND CYP2E1*3 ILE-389.
[14]"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: 9918138] [Abstract]
Cited for: VARIANT CYP2E1*4 ILE-179.
[15]"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: 15469410] [Abstract]
Cited for: VARIANTS ILE-179 AND LEU-457.
+Additional computationally mapped references.

Cross-references

Sequence databases

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.
AF084225 mRNA. Translation: AAD13753.1.
D50111 Genomic DNA. Translation: BAA08796.1.
IPIIPI00007282.
PIRA31949.
RefSeqNP_000764.1.
UniGeneHs.12907

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
3E4EX-ray2.60A/B32-493[»]
3E6IX-ray2.20A/B32-493[»]
ModBaseSearch...

PTM databases

PhosphoSiteP05181.

Proteomic databases

PeptideAtlasP05181.
PRIDEP05181.

Genome annotation databases

EnsemblENSG00000130649. Homo sapiens. [Contig view]
GeneID1571.
KEGGhsa:1571.
UCSCuc001lnj.1. human.

Organism-specific databases

GeneCardsGC10P135229.
H-InvDBHIX0035318.
HGNCHGNC:2631. CYP2E1.
HPAHPA009128.
MIM124040. gene.
PharmGKBPA129.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP05181.
HOVERGENP05181.
OMAP05181. PTWKDIR.

Enzyme and pathway databases

BRENDA1.14.14.1. 247.
ReactomeREACT_13433. Biological oxidations.
REACT_649. Phase 1 functionalization.

Gene expression databases

ArrayExpressP05181.
BgeeP05181.
CleanExHS_CYP2E1.
GermOnlineENSG00000130649. Homo sapiens.

Family and domain databases

InterProIPR001128. Cyt_P450.
IPR017973. Cyt_P450_C.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
IPR008070. Cyt_P450_E_grp-I_CYP2E-like.
[Graphical view]
Gene3DG3DSA:1.10.630.10. Cyt_P450. 1 hit.
PANTHERPTHR19383. Cyt_P450. 1 hit.
PfamPF00067. p450. 1 hit.
[Graphical view]
PRINTSPR00463. EP450I.
PR01687. EP450ICYP2E.
PR00385. P450.
PROSITEPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

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.
NextBio6461.
SOURCESearch...

Entry information

Entry nameCP2E1_HUMAN
AccessionPrimary (citable) accession number: P05181
Secondary accession number(s): Q5VZD5, Q9UK47
Entry history
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: April 1, 1988
Last modified: July 7, 2009
This is version 109 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 10

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents