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   27-MAR-2024, entry version 195.
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
CC         [NADPH--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; 10090-ENSMUSP00000026552; -.
DR   PeptideAtlas; Q05421; -.
DR   ProteomicsDB; 283443; -.
DR   Antibodypedia; 2427; 765 antibodies from 39 providers.
DR   DNASU; 13106; -.
DR   Ensembl; ENSMUST00000026552.9; ENSMUSP00000026552.8; ENSMUSG00000025479.10.
DR   GeneID; 13106; -.
DR   KEGG; mmu:13106; -.
DR   UCSC; uc009kic.1; mouse.
DR   AGR; MGI:88607; -.
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; LMYGRRI; -.
DR   OrthoDB; 2900138at2759; -.
DR   PhylomeDB; Q05421; -.
DR   TreeFam; TF352043; -.
DR   BioCyc; MetaCyc:MONOMER-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; 3 hits in 79 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 cell types or tissues.
DR   ExpressionAtlas; Q05421; baseline and differential.
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; IBA:GO_Central.
DR   GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
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: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:0009617; P:response to bacterium; IEP:MGI.
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   CDD; cd20665; CYP2C-like; 1.
DR   Gene3D; 1.10.630.10; Cytochrome P450; 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   PANTHER; PTHR24300:SF356; CYTOCHROME P450 2E1; 1.
DR   PANTHER; PTHR24300; CYTOCHROME P450 508A4-RELATED; 1.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00463; EP450I.
DR   PRINTS; PR01687; EP450ICYP2E.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; Cytochrome P450; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
DR   Genevisible; Q05421; MM.
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
//