CP2E1_CANLF
ID CP2E1_CANLF Reviewed; 494 AA.
AC Q9MZY0; Q9MZY1;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 136.
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;
GN Name=CYP2E1;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT HIS-485.
RX PubMed=10901710;
RA Lankford S.M., Bai S.A., Goldstein J.A.;
RT "Cloning of canine cytochrome P450 2E1 cDNA: identification and
RT characterization of two variant alleles.";
RL Drug Metab. Dispos. 28:981-986(2000).
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 -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AF029978; AAF88144.1; -; mRNA.
DR EMBL; AF029979; AAF88145.1; -; mRNA.
DR RefSeq; NP_001003339.1; NM_001003339.1.
DR AlphaFoldDB; Q9MZY0; -.
DR SMR; Q9MZY0; -.
DR STRING; 9612.ENSCAFP00000034940; -.
DR PaxDb; Q9MZY0; -.
DR Ensembl; ENSCAFT00030048596; ENSCAFP00030042533; ENSCAFG00030026254.
DR Ensembl; ENSCAFT00040035095; ENSCAFP00040030554; ENSCAFG00040018971.
DR Ensembl; ENSCAFT00845048390; ENSCAFP00845037964; ENSCAFG00845027431.
DR GeneID; 415128; -.
DR KEGG; cfa:415128; -.
DR CTD; 1571; -.
DR VEuPathDB; HostDB:ENSCAFG00845027431; -.
DR eggNOG; KOG0156; Eukaryota.
DR GeneTree; ENSGT00940000161594; -.
DR HOGENOM; CLU_001570_22_3_1; -.
DR InParanoid; Q9MZY0; -.
DR OMA; AMKGDYG; -.
DR OrthoDB; 702827at2759; -.
DR TreeFam; TF352043; -.
DR Reactome; R-CFA-211981; Xenobiotics.
DR Reactome; R-CFA-211999; CYP2E1 reactions.
DR Reactome; R-CFA-9027307; Biosynthesis of maresin-like SPMs.
DR Reactome; R-CFA-9749641; Aspirin ADME.
DR Reactome; R-CFA-9753281; Paracetamol ADME.
DR SABIO-RK; Q9MZY0; -.
DR UniPathway; UPA00199; -.
DR Proteomes; UP000002254; Chromosome 28.
DR Bgee; ENSCAFG00000013311; Expressed in liver and 17 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
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; IEA:Ensembl.
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; IEA:Ensembl.
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; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0019373; P:epoxygenase P450 pathway; IBA:GO_Central.
DR GO; GO:0046483; P:heterocycle metabolic process; IEA:Ensembl.
DR GO; GO:0002933; P:lipid hydroxylation; IEA:Ensembl.
DR GO; GO:0016098; P:monoterpenoid metabolic process; IEA:Ensembl.
DR GO; GO:0006082; P:organic acid metabolic process; IBA:GO_Central.
DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
DR GO; GO:0008202; P:steroid metabolic process; IEA:Ensembl.
DR GO; GO:0006805; P:xenobiotic metabolic process; IBA:GO_Central.
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..494
FT /note="Cytochrome P450 2E1"
FT /id="PRO_0000289585"
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"
FT VARIANT 485
FT /note="Y -> H (in minor allele)"
FT /evidence="ECO:0000269|PubMed:10901710"
SQ SEQUENCE 494 AA; 56599 MW; F3F891371B65A36D CRC64;
MAALGITVAL LVWMATLMLI SIWKQIYSRW KLPPGPFPLP IIGNILQVDI KNVPKSLAKL
AEQYGPVFTL YLGSQRTVVL HGYKAVKEVL LDHKNDLSGR GEVFAFQSHK DRGITFNNGP
GWKDTRRLSL STLRDYGMGK RGNEERIQRE IPFLLEALRG TRGQPFDPTF LLGFAPFNVI
ADILFHKHFD YSDQTGLRIQ KLFNENFHLL STGWLQLYNI FPSYLHYLPG SHRKVLRNVA
ELKDYSLERV KEHQESLDPT CSRDFTDCLL QELQKERYGT EPWYTLDNIA VTVADLFFAG
TETTSTTLRY GLLILMKYPE VEEKLHEEID RVIGPSRVPA IKDRLEMPYM DAVVHEIQRF
IDLLPSNLPH VANQDTMFRG YVIPKGTVVI PTLDSVLFDK QEFPDPEKFK PEHFLNENGK
FKYSDYFKAF SAGKRVCVGE GLARMELFLF LSAILQHFNL KSLVDPKDID LSPCTIGFAK
IPPHYKLCVV PRSG
