CP2E1_RAT
ID CP2E1_RAT Reviewed; 493 AA.
AC P05182;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Cytochrome P450 2E1;
DE EC=1.14.14.1 {ECO:0000250|UniProtKB:P05181};
DE AltName: Full=4-nitrophenol 2-hydroxylase;
DE EC=1.14.13.n7 {ECO:0000250|UniProtKB:P05181};
DE AltName: Full=CYPIIE1;
DE AltName: Full=Cytochrome P450-J;
DE AltName: Full=Cytochrome P450RLM6;
GN Name=Cyp2e1 {ECO:0000303|PubMed:19401463, ECO:0000312|RGD:2475};
GN Synonyms=Cyp2e, Cyp2e-1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
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].
RC TISSUE=Liver;
RX PubMed=2832413; DOI=10.1016/s0021-9258(18)68880-5;
RA Umeno M., Song B.-J., Kozak C., Gelboin H.V., Gonzalez F.J.;
RT "The rat P450IIE1 gene: complete intron and exon sequence, chromosome
RT mapping, and correlation of developmental expression with specific 5'
RT cytosine demethylation.";
RL J. Biol. Chem. 263:4956-4962(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RA Yoo M., Shin S.W.;
RT "The complete coding sequence of the rat brain cytochrome P450 2E1.";
RL Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 [5]
RP PROTEIN SEQUENCE OF 2-35.
RC TISSUE=Liver;
RX PubMed=3308889; DOI=10.1016/s0021-9258(18)47940-9;
RA Favreau L.V., Malchoff D.M., Mole J.E., Schenkman J.B.;
RT "Responses to insulin by two forms of rat hepatic microsomal cytochrome P-
RT 450 that undergo major (RLM6) and minor (RLM5b) elevations in diabetes.";
RL J. Biol. Chem. 262:14319-14326(1987).
RN [6]
RP PROTEIN SEQUENCE OF 2-20.
RC TISSUE=Liver;
RX PubMed=2321956; DOI=10.1016/0003-9861(90)90245-t;
RA Imaoka S., Terano Y., Funae Y.;
RT "Changes in the amount of cytochrome P450s in rat hepatic microsomes with
RT starvation.";
RL Arch. Biochem. Biophys. 278:168-178(1990).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 100-463.
RX PubMed=1441586; DOI=10.3109/00498259209053125;
RA Richardson T.H., Schenkman J.B., Turcan R., Goldfarb P.S., Gibson G.G.;
RT "Molecular cloning of a cDNA for rat diabetes-inducible cytochrome
RT P450RLM6: hormonal regulation and similarity to the cytochrome P4502E1
RT gene.";
RL Xenobiotica 22:621-631(1992).
RN [8]
RP SUBCELLULAR LOCATION, TOPOLOGY, INTERACTION WITH HSP70, INTERACTION WITH
RP HSP90, AND MUTAGENESIS OF SER-129.
RX PubMed=19401463; DOI=10.1074/jbc.m109.007492;
RA Anandatheerthavarada H.K., Sepuri N.B., Avadhani N.G.;
RT "Mitochondrial targeting of cytochrome P450 proteins containing NH2-
RT terminal chimeric signals involves an unusual TOM20/TOM22 bypass
RT mechanism.";
RL J. Biol. Chem. 284:17352-17363(2009).
CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of
CC fatty acids. Mechanistically, uses molecular oxygen inserting one
CC oxygen atom into a substrate, and reducing the second into a water
CC molecule, with two electrons provided by NADPH via cytochrome P450
CC reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation
CC of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the
CC omega-1 position displaying the highest catalytic activity for
CC saturated fatty acids. May be involved in the oxidative metabolism of
CC xenobiotics. {ECO:0000250|UniProtKB:P05181}.
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:0000250|UniProtKB:P05181};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17150;
CC Evidence={ECO:0000250|UniProtKB:P05181};
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:0000250|UniProtKB:P05181};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50077;
CC Evidence={ECO:0000250|UniProtKB:P05181};
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:0000250|UniProtKB:P05181};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39788;
CC Evidence={ECO:0000250|UniProtKB:P05181};
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:0000250|UniProtKB:P05181};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50089;
CC Evidence={ECO:0000250|UniProtKB:P05181};
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:0000250|UniProtKB:P05181};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39752;
CC Evidence={ECO:0000250|UniProtKB:P05181};
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:0000250|UniProtKB:P05181};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50097;
CC Evidence={ECO:0000250|UniProtKB:P05181};
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:0000250|UniProtKB:P05181};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26206;
CC Evidence={ECO:0000250|UniProtKB:P05181};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: The omega-1 hydroxylase activity is stimulated by
CC cytochrome b5. {ECO:0000250|UniProtKB:P05181}.
CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism.
CC {ECO:0000250|UniProtKB:P05181}.
CC -!- SUBUNIT: Interacts with chaperones HSP70 and HSP90; this interaction is
CC required for initial targeting to mitochondria.
CC {ECO:0000269|PubMed:19401463}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000305|PubMed:19401463}; Peripheral membrane protein. Microsome
CC membrane {ECO:0000305|PubMed:19401463}; Peripheral membrane protein.
CC Mitochondrion inner membrane {ECO:0000305|PubMed:19401463}; Peripheral
CC membrane protein {ECO:0000305|PubMed:19401463}. Note=Post-
CC translationally targeted to mitochondria. TOMM70 is required for the
CC translocation across the mitochondrial outer membrane. After
CC translocation into the matrix, associates with the inner membrane as a
CC membrane extrinsic protein. {ECO:0000305|PubMed:19401463}.
CC -!- INDUCTION: By ethanol.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; J02627; AAA41060.1; -; mRNA.
DR EMBL; M20131; AAA41033.1; -; Genomic_DNA.
DR EMBL; AF061442; AAC15991.1; -; mRNA.
DR EMBL; BC081774; AAH81774.1; -; mRNA.
DR EMBL; S48325; AAB24151.1; -; mRNA.
DR PIR; A25341; A25341.
DR RefSeq; NP_113731.1; NM_031543.1.
DR AlphaFoldDB; P05182; -.
DR SMR; P05182; -.
DR BioGRID; 247159; 4.
DR IntAct; P05182; 2.
DR STRING; 10116.ENSRNOP00000016883; -.
DR BindingDB; P05182; -.
DR ChEMBL; CHEMBL5978; -.
DR iPTMnet; P05182; -.
DR PhosphoSitePlus; P05182; -.
DR PaxDb; P05182; -.
DR PRIDE; P05182; -.
DR GeneID; 25086; -.
DR KEGG; rno:25086; -.
DR UCSC; RGD:2475; rat.
DR CTD; 1571; -.
DR RGD; 2475; Cyp2e1.
DR VEuPathDB; HostDB:ENSRNOG00000012458; -.
DR eggNOG; KOG0156; Eukaryota.
DR HOGENOM; CLU_001570_22_3_1; -.
DR InParanoid; P05182; -.
DR OMA; AMKGDYG; -.
DR OrthoDB; 702827at2759; -.
DR PhylomeDB; P05182; -.
DR TreeFam; TF352043; -.
DR BRENDA; 1.14.14.1; 5301.
DR Reactome; R-RNO-211981; Xenobiotics.
DR Reactome; R-RNO-211999; CYP2E1 reactions.
DR Reactome; R-RNO-9027307; Biosynthesis of maresin-like SPMs.
DR Reactome; R-RNO-9749641; Aspirin ADME.
DR Reactome; R-RNO-9753281; Paracetamol ADME.
DR SABIO-RK; P05182; -.
DR UniPathway; UPA00199; -.
DR PRO; PR:P05182; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000012458; Expressed in liver and 17 other tissues.
DR ExpressionAtlas; P05182; baseline and differential.
DR Genevisible; P05182; RN.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IDA:RGD.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
DR GO; GO:0031227; C:intrinsic component of endoplasmic reticulum membrane; IDA:RGD.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0018601; F:4-nitrophenol 2-monooxygenase activity; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR GO; GO:0030544; F:Hsp70 protein binding; IDA:UniProtKB.
DR GO; GO:0051879; F:Hsp90 protein binding; IDA:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0120319; F:long-chain fatty acid omega-1 hydroxylase activity; ISO:RGD.
DR GO; GO:0004497; F:monooxygenase activity; ISO:RGD.
DR GO; GO:0016491; F:oxidoreductase activity; ISO:RGD.
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:0008395; F:steroid hydroxylase activity; IBA:GO_Central.
DR GO; GO:0018960; P:4-nitrophenol metabolic process; ISO:RGD.
DR GO; GO:0019373; P:epoxygenase P450 pathway; IBA:GO_Central.
DR GO; GO:0046483; P:heterocycle metabolic process; ISO:RGD.
DR GO; GO:0002933; P:lipid hydroxylation; ISO:RGD.
DR GO; GO:0001676; P:long-chain fatty acid metabolic process; ISO:RGD.
DR GO; GO:0016098; P:monoterpenoid metabolic process; ISO:RGD.
DR GO; GO:0006082; P:organic acid metabolic process; IBA:GO_Central.
DR GO; GO:0009617; P:response to bacterium; ISO:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0010243; P:response to organonitrogen compound; IEP:RGD.
DR GO; GO:0010193; P:response to ozone; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0008202; P:steroid metabolic process; ISO:RGD.
DR GO; GO:0006641; P:triglyceride metabolic process; IMP:RGD.
DR GO; GO:0006805; P:xenobiotic metabolic process; IMP:RGD.
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 Direct protein sequencing; Endoplasmic reticulum; Fatty acid metabolism;
KW Heme; Iron; Lipid metabolism; Membrane; Metal-binding; Microsome;
KW Mitochondrion; Mitochondrion inner membrane; Monooxygenase; NADP;
KW Oxidoreductase; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:2321956,
FT ECO:0000269|PubMed:3308889"
FT CHAIN 2..493
FT /note="Cytochrome P450 2E1"
FT /id="PRO_0000051758"
FT BINDING 298..303
FT /ligand="substrate"
FT /evidence="ECO:0000250"
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 MUTAGEN 129
FT /note="S->A: Reduces interaction with HSP70; impairs
FT interaction with HSP90."
FT /evidence="ECO:0000269|PubMed:19401463"
FT CONFLICT 25
FT /note="Q -> K (in Ref. 1; AAA41060)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 493 AA; 56627 MW; 7600B9D28AED5EDB CRC64;
MAVLGITIAL LVWVATLLVI SIWKQIYNSW NLPPGPFPLP ILGNIFQLDL KDIPKSFTKL
AKRFGPVFTL HLGSRRIVVL HGYKAVKEVL LNHKNEFSGR GDIPVFQEYK NKGIIFNNGP
TWKDVRRFSL SILRDWGMGK QGNEARIQRE AQFLVEELKK TKGQPFDPTF LIGCAPCNVI
ADILFNKRFD YNDKKCLRLM SLFNENFYLL STPWIQLYNN FADYLRYLPG SHRKIMKNVS
EIKQYTLEKA KEHLQSLDIN CARDVTDCLL IEMEKEKHSQ EPMYTMENVS VTLADLFFAG
TETTSTTLRY GLLILMKYPE IEEKLHEEID RVIGPSRVPA VRDRLDMPYM DAVVHEIQRF
INLVPSNLPH EATRDTVFQG YVIPKGTVVI PTLDSLLYDS HEFPDPEKFK PEHFLNENGK
FKYSDYFKAF SAGKRVCVGE GLARMELFLL LSAILQHFNL KSLVDPKDID LSPVTVGFGS
IPPQFKLCVI PRS
