CP2E1_MOUSE
ID CP2E1_MOUSE Reviewed; 493 AA.
AC Q05421; Q9Z198;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 186.
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-ALC;
DE AltName: Full=Cytochrome P450-J;
GN Name=Cyp2e1; Synonyms=Cyp2e, Cyp2e-1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6S; TISSUE=Liver;
RX PubMed=8344939; DOI=10.1016/s0021-9258(19)85459-5;
RA Davis J.F., Felder M.R.;
RT "Mouse ethanol-inducible cytochrome P-450 (P450IIE1). Characterization of
RT cDNA clones and testosterone induction in kidney tissue.";
RL J. Biol. Chem. 268:16584-16589(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Liver;
RX PubMed=1536649; DOI=10.1042/bj2810689;
RA Freeman J.E., Stirling D., Russel A.L., Wolf C.R.;
RT "cDNA sequence, deduced amino acid sequence, predicted gene structure and
RT chemical regulation of mouse Cyp2e1.";
RL Biochem. J. 281:689-695(1992).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 455-493.
RC TISSUE=Liver;
RX PubMed=6851839;
RA Ivanov P.L., Ryskov A.P., Kramerov D.A., Georgiev G.P.;
RT "Primary structure of the repeating element B2 and of the adjoining
RT sequences in cloned mRNA actively transcribing in mouse liver cells.";
RL Dokl. Akad. Nauk SSSR 269:227-230(1983).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 455-493.
RX PubMed=6194512; DOI=10.1093/nar/11.18.6541;
RA Ryskov A.P., Ivanov P.L., Kramerov D.A., Georgiev G.P.;
RT "Mouse ubiquitous B2 repeat in polysomal and cytoplasmic poly(A)+RNAs:
RT unidirectional orientation and 3'-end localization.";
RL Nucleic Acids Res. 11:6541-6558(1983).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 455-493.
RA Ryskov A.P., Ivanov P.L., Kramerov D.A., Georgiev G.P.;
RT "Universal orientation and 3' terminal localization of repetitive sequences
RT of the B2 family in mRNA.";
RL Mol. Biol. (Mosk.) 18:74-83(1984).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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:0000250|UniProtKB:P05182}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P05182}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P05182}. Microsome membrane
CC {ECO:0000250|UniProtKB:P05182}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P05182}. Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:P05182}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P05182}. Note=Post-translationally targeted to
CC mitochondria. TOMM70 is required for the translocation across the
CC mitochondrial outer membrane. After translocation into the matrix,
CC associates with the inner membrane as a membrane extrinsic protein.
CC {ECO:0000250|UniProtKB:P05182}.
CC -!- TISSUE SPECIFICITY: Highest level in the liver and to a lesser extent
CC in the kidney, with a higher level in the male kidney than in the
CC female.
CC -!- DEVELOPMENTAL STAGE: Detectable in the female liver on day 1 and
CC reaches steady state levels on days 16-20.
CC -!- INDUCTION: By ethanol and acetone in the liver and by testosterone in
CC the kidney and adrenal tissues.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; L11650; AAA39879.1; -; mRNA.
DR EMBL; X62595; CAA44481.1; -; mRNA.
DR EMBL; BC013451; AAH13451.1; -; mRNA.
DR EMBL; M54877; AAA37275.1; -; mRNA.
DR EMBL; X01026; CAA25510.1; ALT_SEQ; mRNA.
DR CCDS; CCDS21985.1; -.
DR PIR; A47350; A47350.
DR PIR; S19657; A21231.
DR RefSeq; NP_067257.1; NM_021282.2.
DR AlphaFoldDB; Q05421; -.
DR SMR; Q05421; -.
DR BioGRID; 199023; 7.
DR STRING; 10090.ENSMUSP00000026552; -.
DR iPTMnet; Q05421; -.
DR PhosphoSitePlus; Q05421; -.
DR SwissPalm; Q05421; -.
DR jPOST; Q05421; -.
DR MaxQB; Q05421; -.
DR PaxDb; Q05421; -.
DR PeptideAtlas; Q05421; -.
DR PRIDE; Q05421; -.
DR ProteomicsDB; 283443; -.
DR Antibodypedia; 2427; 659 antibodies from 39 providers.
DR DNASU; 13106; -.
DR Ensembl; ENSMUST00000026552; ENSMUSP00000026552; ENSMUSG00000025479.
DR GeneID; 13106; -.
DR KEGG; mmu:13106; -.
DR UCSC; uc009kic.1; mouse.
DR CTD; 1571; -.
DR MGI; MGI:88607; Cyp2e1.
DR VEuPathDB; HostDB:ENSMUSG00000025479; -.
DR eggNOG; KOG0156; Eukaryota.
DR GeneTree; ENSGT00940000161594; -.
DR HOGENOM; CLU_001570_22_3_1; -.
DR InParanoid; Q05421; -.
DR OMA; AMKGDYG; -.
DR OrthoDB; 702827at2759; -.
DR PhylomeDB; Q05421; -.
DR TreeFam; TF352043; -.
DR BioCyc; MetaCyc:MON-12920; -.
DR Reactome; R-MMU-211981; Xenobiotics.
DR Reactome; R-MMU-211999; CYP2E1 reactions.
DR Reactome; R-MMU-9027307; Biosynthesis of maresin-like SPMs.
DR Reactome; R-MMU-9749641; Aspirin ADME.
DR Reactome; R-MMU-9753281; Paracetamol ADME.
DR UniPathway; UPA00199; -.
DR BioGRID-ORCS; 13106; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Cyp2e1; mouse.
DR PRO; PR:Q05421; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q05421; protein.
DR Bgee; ENSMUSG00000025479; Expressed in left lobe of liver and 104 other tissues.
DR ExpressionAtlas; Q05421; baseline and differential.
DR Genevisible; Q05421; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0000139; C:Golgi membrane; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0031227; C:intrinsic component of endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0018601; F:4-nitrophenol 2-monooxygenase activity; ISO:MGI.
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:MGI.
DR GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR GO; GO:0030544; F:Hsp70 protein binding; ISS:UniProtKB.
DR GO; GO:0051879; F:Hsp90 protein binding; ISS: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:MGI.
DR GO; GO:0004497; F:monooxygenase activity; IDA:MGI.
DR GO; GO:0016491; F:oxidoreductase activity; ISO:MGI.
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:MGI.
DR GO; GO:0019373; P:epoxygenase P450 pathway; IBA:GO_Central.
DR GO; GO:0046483; P:heterocycle metabolic process; ISO:MGI.
DR GO; GO:0002933; P:lipid hydroxylation; ISO:MGI.
DR GO; GO:0001676; P:long-chain fatty acid metabolic process; ISO:MGI.
DR GO; GO:0016098; P:monoterpenoid metabolic process; ISO:MGI.
DR GO; GO:0006082; P:organic acid metabolic process; IBA:GO_Central.
DR GO; GO:0009617; P:response to bacterium; IEP:MGI.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0010243; P:response to organonitrogen compound; IEA:Ensembl.
DR GO; GO:0010193; P:response to ozone; IEA:Ensembl.
DR GO; GO:0008202; P:steroid metabolic process; ISO:MGI.
DR GO; GO:0006641; P:triglyceride metabolic process; ISO:MGI.
DR GO; GO:0006805; P:xenobiotic metabolic process; ISO:MGI.
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 Endoplasmic reticulum; Fatty acid metabolism; Heme; Iron; Lipid metabolism;
KW Membrane; Metal-binding; Microsome; Mitochondrion;
KW Mitochondrion inner membrane; Monooxygenase; NADP; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..493
FT /note="Cytochrome P450 2E1"
FT /id="PRO_0000051755"
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 /evidence="ECO:0000250"
SQ SEQUENCE 493 AA; 56805 MW; 4031AB016DA56A9C CRC64;
MAVLGITVAL LVWIATLLLV SIWKQIYRSW NLPPGPFPIP FFGNIFQLDL KDIPKSLTKL
AKRFGPVFTL HLGQRRIVVL HGYKAVKEVL LNHKNEFSGR GDIPVFQEYK NKGIIFNNGP
TWKDVRRFSL SILRDWGMGK QGNEARIQRE AHFLVEELKK TKGQPFDPTF LIGCAPCNVI
ADILFNKRFD YDDKKCLELM SLFNENFYLL STPWIQAYNY FSDYLQYLPG SHRKVMKNVS
EIRQYTLGKA KEHLKSLDIN CPRDVTDCLL IEMEKEKHSQ EPMYTMENIS VTLADLFFAG
TETTSTTLRY GLLILMKYPE IEEKLHEEID RVIGPSRAPA VRDRMNMPYM DAVVHEIQRF
INLVPSNLPH EATRDTVFRG YVIPKGTVVI PTLDSLLFDN YEFPDPETFK PEHFLNENGK
FKYSDYFKAF SAGKRVCVGE GLARMELFLL LSAILQHFNL KSLVDPKDID LSPVTIGFGS
IPREFKLCVI PRS
