Reviewed, UniProtKB/Swiss-Prot P05181 (CP2E1_HUMAN)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	493 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Polymorphism
Ligand	Heme Iron Metal-binding NADP
Molecular function	Monooxygenase Oxidoreductase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	drug metabolic process Inferred from direct assay. Source: UniProtKB oxidation reduction Inferred from direct assay. Source: UniProtKB
Cellular component	endoplasmic reticulum membrane Inferred from Experiment. Source: Reactome microsome Inferred from direct assay. Source: UniProtKB
Molecular function	aromatase activity Inferred from electronic annotation. Source: EC electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Inferred from electronic annotation. Source: InterPro oxygen binding Ref.2 Inferred from Experiment. Source: Reactome
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 493	493	Cytochrome P450 2E1		PRO_0000051751
Sites
	Metal binding	437	1	Iron (heme axial ligand)
Amino acid modifications
	Modified residue	129	1	Phosphoserine By similarity
Natural variations
	Natural variant	76	1	R → H in allele CYP2E1*2; reduced activity. Ref.13		VAR_008360
	Natural variant	179	1	V → I in allele CYP2E1*4. dbSNP rs6413419. Ref.14 Ref.15		VAR_008361
	Natural variant	219	1	N → D: dbSNP rs41299426.		VAR_055382
	Natural variant	366	1	S → C: dbSNP rs41299434.		VAR_055383
	Natural variant	389	1	V → I in allele CYP2E1*3. dbSNP rs55897648.		VAR_008362
	Natural variant	457	1	H → L: dbSNP rs28969387. Ref.15		VAR_024727
Experimental info
	Sequence conflict	2	1	Missing AA sequence Ref.9
	Sequence conflict	23	1	W → A AA sequence Ref.11
	Sequence conflict	32	1	L → N AA sequence Ref.11
	Sequence conflict	235	1	V → A in AAF13601. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P05181-1 [UniParc]. Last modified April 1, 1988. Version 1. Checksum: ED0399E32A005644	FASTA	493	56,849
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.

Web resources

Cytochrome P450 Allele Nomenclature Committee

CYP2E1 alleles

Wikipedia

CYP2E1 entry

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

IPI

IPI00007282.

PIR

A31949.

RefSeq

NP_000764.1.

UniGene

Hs.12907

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3E4E	X-ray	2.60	A/B	32-493	[»]
3E6I	X-ray	2.20	A/B	32-493	[»]

ModBase

Search...

PTM databases

PhosphoSite

P05181.

Proteomic databases

PeptideAtlas

P05181.

PRIDE

P05181.

Genome annotation databases

Ensembl

ENSG00000130649. Homo sapiens. [Contig view]

GeneID

1571.

KEGG

hsa:1571.

UCSC

uc001lnj.1. human.

Organism-specific databases

GeneCards

GC10P135229.

H-InvDB

HIX0035318.

HGNC

HGNC:2631. CYP2E1.

HPA

HPA009128.

MIM

124040. gene.

PharmGKB

PA129.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P05181.

HOVERGEN

P05181.

OMA

P05181. PTWKDIR.

Enzyme and pathway databases

BRENDA

1.14.14.1. 247.

Reactome

REACT_13433. Biological oxidations.
REACT_649. Phase 1 functionalization.

Gene expression databases

ArrayExpress

P05181.

Bgee

P05181.

CleanEx

HS_CYP2E1.

GermOnline

ENSG00000130649. Homo sapiens.

Family and domain databases

InterPro

IPR001128. 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]

Gene3D

G3DSA:1.10.630.10. Cyt_P450. 1 hit.

PANTHER

PTHR19383. Cyt_P450. 1 hit.

Pfam

PF00067. p450. 1 hit.
[Graphical view]

PRINTS

PR00463. EP450I.
PR01687. EP450ICYP2E.
PR00385. P450.

PROSITE

PS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00316. 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.

NextBio

6461.

SOURCE

Search...

Entry information

Entry name

CP2E1_HUMAN

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)