P05181 (CP2E1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	493 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
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. Ref.12
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 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 Reference proteome
Gene Ontology (GO)
Biological_process	drug 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 response to drug Inferred from electronic annotation. Source: Compara response to ethanol Inferred from electronic annotation. Source: Compara response to organic nitrogen Inferred from electronic annotation. Source: Compara response to ozone Inferred from electronic annotation. Source: Compara 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: Compara xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular_component	Golgi membrane Inferred from electronic annotation. Source: Compara endoplasmic reticulum membrane Traceable author statement. Source: Reactome intrinsic to endoplasmic reticulum membrane Inferred from electronic annotation. Source: Compara mitochondrion Inferred from electronic annotation. Source: Compara
Molecular_function	electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Inferred from direct assay Ref.13. Source: UniProtKB iron ion binding Inferred from electronic annotation. Source: InterPro 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.13. 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: Compara oxygen binding Traceable author statement Ref.2. Source: ProtInc
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

Initiator methionine

1

1

Removed; alternate By similarity

Chain

2 – 493

492

Cytochrome P450 2E1, N-terminally processed

PRO_0000421771

Regions

Region

298 – 303

6

Substrate binding Probable

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.14

VAR_008360

Natural variant

179

1

V → I in allele CYP2E1*4. Ref.15 Ref.16
Corresponds to variant rs6413419 [ dbSNP | Ensembl ].

VAR_008361

Natural variant

219

1

N → D. Ref.4
Corresponds to variant rs41299426 [ dbSNP | Ensembl ].

VAR_055382

Natural variant

366

1

S → C. Ref.4
Corresponds to variant rs41299434 [ dbSNP | Ensembl ].

VAR_055383

Natural variant

389

1

V → I in allele CYP2E1*3. Ref.14
Corresponds to variant rs55897648 [ dbSNP | Ensembl ].

VAR_008362

Natural variant

457

1

H → L. Ref.4 Ref.16
Corresponds to variant rs28969387 [ dbSNP | Ensembl ].

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

Secondary structure

1

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493

Helix Strand Turn

Details...

Turn

40 – 42

3

Helix

45 – 47

3

Helix

50 – 52

3

Helix

53 – 64

12

Beta strand

66 – 72

7

Beta strand

75 – 80

6

Helix

83 – 91

9

Turn

94 – 97

4

Helix

104 – 109

6

Beta strand

112 – 114

3

Helix

122 – 135

14

Helix

142 – 159

18

Turn

160 – 163

4

Helix

169 – 172

4

Helix

174 – 185

12

Helix

194 – 209

16

Helix

213 – 220

8

Helix

222 – 225

4

Beta strand

228 – 230

3

Helix

231 – 255

25

Beta strand

259 – 261

3

Helix

265 – 274

10

Beta strand

275 – 278

4

Beta strand

279 – 281

3

Helix

286 – 317

32

Helix

319 – 332

14

Turn

333 – 336

4

Helix

341 – 346

6

Helix

348 – 361

14

Beta strand

376 – 378

3

Beta strand

381 – 383

3

Beta strand

388 – 391

4

Helix

394 – 397

4

Turn

400 – 402

3

Beta strand

403 – 405

3

Helix

411 – 414

4

Beta strand

419 – 421

3

Helix

433 – 435

3

Helix

440 – 457

18

Beta strand

458 – 464

7

Turn

466 – 468

3

Beta strand

474 – 481

8

Beta strand

487 – 491

5

Sequences

	Sequence		Length	Mass (Da)
	P05181 [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] [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. , 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. , 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY.
[13]	"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.
[14]	"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.
[15]	"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.
[16]	"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.

Web resources

Cytochrome P450 Allele Nomenclature Committee

CYP2E1 alleles

Wikipedia

CYP2E1 entry

NIEHS-SNPs

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.
AF084225 mRNA. Translation: AAD13753.1.
D50111 Genomic DNA. Translation: BAA08796.1.

IPI

IPI00007282.

PIR

A31949.

RefSeq

NP_000764.1. NM_000773.3.

UniGene

Hs.12907.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]
3GPH	X-ray	2.70	A/B	32-493	[»]
3KOH	X-ray	2.90	A/B	32-493	[»]
3LC4	X-ray	3.10	A/B	32-493	[»]
3T3Z	X-ray	2.35	A/B/C/D	32-493	[»]

ProteinModelPortal

P05181.

ModBase

Search...

Protein-protein interaction databases

IntAct

P05181. 10 interactions.

STRING

9606.ENSP00000252945.

PTM databases

PhosphoSite

P05181.

Polymorphism databases

DMDM

117250.

Proteomic databases

PaxDb

P05181.

PeptideAtlas

P05181.

PRIDE

P05181.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000252945; ENSP00000252945; ENSG00000130649.
ENST00000463117; ENSP00000440689; ENSG00000130649.

GeneID

1571.

KEGG

hsa:1571.

UCSC

uc001lnj.1. human.

Organism-specific databases

CTD

1571.

GeneCards

GC10P135352.

HGNC

HGNC:2631. CYP2E1.

HPA

HPA009128.
HPA029564.

MIM

124040. gene.

neXtProt

NX_P05181.

PharmGKB

PA129.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2124.

HOGENOM

HOG000036992.

HOVERGEN

HBG015789.

InParanoid

P05181.

KO

K07415.

OMA

RNYGMGK.

OrthoDB

EOG48WC22.

PhylomeDB

P05181.

Enzyme and pathway databases

BioCyc

MetaCyc:HS05414-MONOMER.

Reactome

REACT_111217. Metabolism.

SABIO-RK

P05181.

Gene expression databases

ArrayExpress

P05181.

Bgee

P05181.

CleanEx

HS_CYP2E1.

Genevestigator

P05181.

GermOnline

ENSG00000130649. Homo sapiens.

Family and domain databases

Gene3D

1.10.630.10. 1 hit.

InterPro

IPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
IPR008070. Cyt_P450_E_grp-I_CYP2E-like.
[Graphical view]

Pfam

PF00067. p450. 1 hit.
[Graphical view]

PRINTS

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

SUPFAM

SSF48264. Cytochrome_P450. 1 hit.

PROSITE

PS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P05181.

ChEMBL

CHEMBL5281.

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.

EvolutionaryTrace

P05181.

GenomeRNAi

1571.

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:	May 1, 2013
This is version 147 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.