ID CP2E1_MACFA Reviewed; 449 AA.
AC P33266;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 24-JAN-2024, entry version 119.
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-MKJ1;
DE Flags: Fragment;
GN Name=CYP2E1; Synonyms=CYP2E;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=1282830; DOI=10.1016/0167-4781(92)90113-e;
RA Komori M., Kikuchi O., Sakuma T., Funaki J., Kitada M., Kamataki T.;
RT "Molecular cloning of monkey liver cytochrome P-450 cDNAs: similarity of
RT the primary sequences to human cytochromes P-450.";
RL Biochim. Biophys. Acta 1171:141-146(1992).
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 -!- INDUCTION: By ethanol.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; S55205; AAB24951.2; -; mRNA.
DR PIR; S28167; S28167.
DR AlphaFoldDB; P33266; -.
DR SMR; P33266; -.
DR STRING; 9541.ENSMFAP00000025829; -.
DR eggNOG; KOG0156; Eukaryota.
DR UniPathway; UPA00199; -.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC.
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:0006631; P:fatty acid metabolic process; IEA:UniProtKB-UniPathway.
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.
PE 2: Evidence at transcript 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..449
FT /note="Cytochrome P450 2E1"
FT /id="PRO_0000051752"
FT BINDING 254..259
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 393
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"
FT NON_TER 1
SQ SEQUENCE 449 AA; 51790 MW; 3C8099DB2D5DE9C4 CRC64;
LFQLELKNIP KSFTRLAQRF GPVFTLYVGS RRVVVVHGIK AVKEVLPGPQ GRVLGQRRHP
AFHAHRDRGI IFNNGPTWKD IRRFSLTTLR NYGMGKQGNE SRIQREAHFL LEALRKTQGQ
PFDPTFLIGC APCNVIADIL FRKRFDYNDE KFLRLMYLFN ENFQGLSCPW LQLYNNFPSL
LHYLPGSHRK VMKNVAEIKE YVSERVKEHH QSLDPNCPRD LTDCLLVEME KEKHSAERLY
TMDGITVTVA DLFFAGTETT STTLRYGLLI LMKYPEIEEK LHEEIDRVIG PSRIPAIKDR
QEMPYMHAVV HEIQRFITLV PSNLPHEATR DTIFRGYIIP KGTVIVPTLD SVLYHNQEFP
DPEKFKPEHL VDESGKFKYS DYFKPFSAGK RVCAGEGLAR MELFLLLSAI LQHFNLKPLV
DPKDIDISPV NIGFGCIPPR FKLCVIPRS
//
