CP2E1_RABIT
ID CP2E1_RABIT Reviewed; 493 AA.
AC P08682;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 2.
DT 03-AUG-2022, entry version 140.
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 isozyme 3A;
DE Short=Cytochrome P450 LM3A;
DE AltName: Full=Cytochrome P450-ALC;
GN Name=CYP2E1; Synonyms=CYP2E;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3366772; DOI=10.1016/s0021-9258(18)68622-3;
RA Khani S.C., Porter T.D., Fujita V.S., Coon M.J.;
RT "Organization and differential expression of two highly similar genes in
RT the rabbit alcohol-inducible cytochrome P-450 subfamily.";
RL J. Biol. Chem. 263:7170-7175(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 22-493.
RX PubMed=3027695; DOI=10.1073/pnas.84.3.638;
RA Khani S.C., Zaphiropoulos P.G., Fujita V.S., Porter T.D., Koop D.R.,
RA Coon M.J.;
RT "cDNA and derived amino acid sequence of ethanol-inducible rabbit liver
RT cytochrome P-450 isozyme 3a (P-450ALC).";
RL Proc. Natl. Acad. Sci. U.S.A. 84:638-642(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 7-493.
RX PubMed=2831965; DOI=10.1021/bi00401a014;
RA Imai Y., Komori M., Sato R.;
RT "Comparison of primary structures deduced from cDNA nucleotide sequences
RT for various forms of liver microsomal cytochrome P-450 from phenobarbital-
RT treated rabbits.";
RL Biochemistry 27:80-88(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-59.
RX PubMed=2827660; DOI=10.1016/0006-291x(88)90479-2;
RA Khani S.C., Porter T.D., Coon M.J.;
RT "Isolation and partial characterization of the gene for cytochrome P-450 3a
RT (P-450ALC) and a second closely related gene.";
RL Biochem. Biophys. Res. Commun. 150:10-17(1988).
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; M21363; AAA31222.1; -; Genomic_DNA.
DR EMBL; M21351; AAA31222.1; JOINED; Genomic_DNA.
DR EMBL; M21349; AAA31222.1; JOINED; Genomic_DNA.
DR EMBL; M21350; AAA31222.1; JOINED; Genomic_DNA.
DR EMBL; M21358; AAA31222.1; JOINED; Genomic_DNA.
DR EMBL; M21359; AAA31222.1; JOINED; Genomic_DNA.
DR EMBL; M21360; AAA31222.1; JOINED; Genomic_DNA.
DR EMBL; M21361; AAA31222.1; JOINED; Genomic_DNA.
DR EMBL; M15061; AAA31213.1; -; mRNA.
DR EMBL; M19235; AAA31219.1; -; mRNA.
DR EMBL; M18770; AAA31176.1; -; Genomic_DNA.
DR PIR; A27750; A26579.
DR RefSeq; XP_002718818.1; XM_002718772.3.
DR AlphaFoldDB; P08682; -.
DR SMR; P08682; -.
DR BioGRID; 1178429; 3.
DR STRING; 9986.ENSOCUP00000006677; -.
DR PRIDE; P08682; -.
DR GeneID; 100342572; -.
DR KEGG; ocu:100342572; -.
DR eggNOG; KOG0156; Eukaryota.
DR InParanoid; P08682; -.
DR OrthoDB; 702827at2759; -.
DR UniPathway; UPA00199; -.
DR Proteomes; UP000001811; 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 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 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..493
FT /note="Cytochrome P450 2E1"
FT /id="PRO_0000051757"
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"
SQ SEQUENCE 493 AA; 56945 MW; 91F6F24233D6BC29 CRC64;
MAVLGITVAL LGWMVILLFI SVWKQIHSSW NLPPGPFPLP IIGNLLQLDL KDIPKSFGRL
AERFGPVFTV YLGSRRVVVL HGYKAVREML LNHKNEFSGR GEIPAFREFK DKGIIFNNGP
TWKDTRRFSL TTLRDYGMGK QGNEDRIQKE AHFLLEELRK TQGQPFDPTF VIGCTPFNVI
AKILFNDRFD YKDKQALRLM SLFNENFYLL STPWLQVYNN FSNYLQYMPG SHRKVIKNVS
EIKEYTLARV KEHHKSLDPS CPRDFIDSLL IEMEKDKHST EPLYTLENIA VTVADMFFAG
TETTSTTLRY GLLILLKHPE IEEKLHEEID RVIGPSRMPS VRDRVQMPYM DAVVHEIQRF
IDLVPSNLPH EATRDTTFQG YVIPKGTVVI PTLDSLLYDK QEFPDPEKFK PEHFLNEEGK
FKYSDYFKPF SAGKRVCVGE GLARMELFLL LSAILQHFNL KPLVDPEDID LRNITVGFGR
VPPRYKLCVI PRS
