CP2J2_HUMAN
ID CP2J2_HUMAN Reviewed; 502 AA.
AC P51589; B2RD33; Q8TF13;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 27-MAY-2002, sequence version 2.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=Cytochrome P450 2J2;
DE EC=1.14.14.- {ECO:0000269|PubMed:8631948};
DE AltName: Full=Albendazole monooxygenase (hydroxylating) {ECO:0000305};
DE EC=1.14.14.74 {ECO:0000269|PubMed:23959307};
DE AltName: Full=Albendazole monooxygenase (sulfoxide-forming) {ECO:0000305};
DE EC=1.14.14.73 {ECO:0000269|PubMed:19923256};
DE AltName: Full=Arachidonic acid epoxygenase {ECO:0000303|PubMed:8631948};
DE AltName: Full=CYPIIJ2;
DE AltName: Full=Hydroperoxy icosatetraenoate isomerase {ECO:0000303|PubMed:19737933};
DE EC=5.4.4.7 {ECO:0000269|PubMed:19737933};
GN Name=CYP2J2 {ECO:0000303|PubMed:19737933, ECO:0000312|HGNC:HGNC:2634};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 1-20, FUNCTION, CATALYTIC
RP ACTIVITY, PATHWAY, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RC TISSUE=Liver;
RX PubMed=8631948; DOI=10.1074/jbc.271.7.3460;
RA Wu S., Moomaw C.R., Tomer K.B., Falck J.R., Zeldin D.C.;
RT "Molecular cloning and expression of CYP2J2, a human cytochrome P450
RT arachidonic acid epoxygenase highly expressed in heart.";
RL J. Biol. Chem. 271:3460-3468(1996).
RN [2]
RP SEQUENCE REVISION TO 339 AND 378.
RA Wu S., Zeldin D.C., Moomaw C.R., Tomer K.B., Falck J.R.;
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=12386130; DOI=10.1124/dmd.30.11.1240;
RA Matsumoto S., Hirama T., Matsubara T., Nagata K., Yamazoe Y.;
RT "Involvement of CYP2J2 on the intestinal first-pass metabolism of
RT antihistamine drug, astemizole.";
RL Drug Metab. Dispos. 30:1240-1245(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ALA-143; CYS-158; ASN-192;
RP ASN-342 AND TYR-404, AND CHARACTERIZATION OF VARIANTS.
RX PubMed=11901223; DOI=10.1124/mol.61.4.840;
RA King L.M., Ma J., Srettabunjong S., Graves J., Bradbury J.A., Li L.,
RA Spiecker M., Liao J.K., Mohrenweiser H., Zeldin D.C.;
RT "Cloning of CYP2J2 gene and identification of functional polymorphisms.";
RL Mol. Pharmacol. 61:840-852(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-49.
RG NIEHS SNPs program;
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Corpus callosum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [8]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND TISSUE SPECIFICITY.
RX PubMed=19737933; DOI=10.1074/jbc.m109.025627;
RA Chawengsub Y., Gauthier K.M., Nithipatikom K., Hammock B.D., Falck J.R.,
RA Narsimhaswamy D., Campbell W.B.;
RT "Identification of 13-hydroxy-14,15-epoxyeicosatrienoic acid as an acid-
RT stable endothelium-derived hyperpolarizing factor in rabbit arteries.";
RL J. Biol. Chem. 284:31280-31290(2009).
RN [9]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=19923256; DOI=10.1124/dmd.109.030270;
RA Lee C.A., Neul D., Clouser-Roche A., Dalvie D., Wester M.R., Jiang Y.,
RA Jones J.P. III, Freiwald S., Zientek M., Totah R.A.;
RT "Identification of novel substrates for human cytochrome P450 2J2.";
RL Drug Metab. Dispos. 38:347-356(2010).
RN [10]
RP FUNCTION AS ALBENDAZOLE MONOOXYGENASE (HYDROXYLATION), AND CATALYTIC
RP ACTIVITY.
RX PubMed=23959307; DOI=10.1128/aac.00843-13;
RA Wu Z., Lee D., Joo J., Shin J.H., Kang W., Oh S., Lee D.Y., Lee S.J.,
RA Yea S.S., Lee H.S., Lee T., Liu K.H.;
RT "CYP2J2 and CYP2C19 are the major enzymes responsible for metabolism of
RT albendazole and fenbendazole in human liver microsomes and recombinant P450
RT assay systems.";
RL Antimicrob. Agents Chemother. 57:5448-5456(2013).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=19965576; DOI=10.1194/jlr.m003061;
RA Lucas D., Goulitquer S., Marienhagen J., Fer M., Dreano Y., Schwaneberg U.,
RA Amet Y., Corcos L.;
RT "Stereoselective epoxidation of the last double bond of polyunsaturated
RT fatty acids by human cytochromes P450.";
RL J. Lipid Res. 51:1125-1133(2010).
CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of
CC polyunsaturated fatty acids (PUFA) in the cardiovascular system
CC (PubMed:8631948, PubMed:19965576). Mechanistically, uses molecular
CC oxygen inserting one oxygen atom into a substrate, and reducing the
CC second into a water molecule, with two electrons provided by NADPH via
CC cytochrome P450 reductase (NADPH--hemoprotein reductase)
CC (PubMed:8631948, PubMed:19965576). Catalyzes the epoxidation of double
CC bonds of PUFA (PubMed:8631948, PubMed:19965576). Converts arachidonic
CC acid to four regioisomeric epoxyeicosatrienoic acids (EpETrE), likely
CC playing a major role in the epoxidation of endogenous cardiac
CC arachidonic acid pools (PubMed:8631948). In endothelial cells,
CC participates in eicosanoids metabolism by converting hydroperoxide
CC species into hydroxy epoxy metabolites. In combination with 15-
CC lipoxygenase metabolizes arachidonic acid and converts
CC hydroperoxyicosatetraenoates (HpETEs) into hydroxy epoxy
CC eicosatrienoates (HEETs), which are precursors of vasodilatory
CC trihydroxyicosatrienoic acids (THETAs). This hydroperoxide isomerase
CC activity is NADPH- and O2-independent (PubMed:19737933). Catalyzes the
CC monooxygenation of a various xenobiotics, such as danazol, amiodarone,
CC terfenadine, astemizole, thioridazine, tamoxifen, cyclosporin A and
CC nabumetone (PubMed:19923256). Catalyzes hydroxylation of the
CC anthelmintics albendazole and fenbendazole (PubMed:23959307). Catalyzes
CC the sulfoxidation of fenbedazole (PubMed:19923256).
CC {ECO:0000269|PubMed:19737933, ECO:0000269|PubMed:19923256,
CC ECO:0000269|PubMed:19965576, ECO:0000269|PubMed:23959307,
CC ECO:0000269|PubMed:8631948}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = 5,6-epoxy-(8Z,11Z,14Z)-eicosatrienoate +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49936, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:131992; Evidence={ECO:0000269|PubMed:8631948};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49937;
CC Evidence={ECO:0000305|PubMed:8631948};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = (8R,9S)-epoxy-(5Z,11Z,14Z)-eicosatrienoate +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49884, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:131975; Evidence={ECO:0000269|PubMed:8631948};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49885;
CC Evidence={ECO:0000305|PubMed:8631948};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = (8S,9R)-epoxy-(5Z,11Z,14Z)-eicosatrienoate +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49928, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:131974; Evidence={ECO:0000269|PubMed:8631948};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49929;
CC Evidence={ECO:0000305|PubMed:8631948};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = (11R,12S)-epoxy-(5Z,8Z,14Z)-eicosatrienoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49880, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:131970; Evidence={ECO:0000269|PubMed:8631948};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49881;
CC Evidence={ECO:0000305|PubMed:8631948};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = (11S,12R)-epoxy-(5Z,8Z,14Z)-eicosatrienoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49876, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:131969; Evidence={ECO:0000269|PubMed:8631948};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49877;
CC Evidence={ECO:0000305|PubMed:8631948};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = (14R,15S)-epoxy-(5Z,8Z,11Z)-eicosatrienoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49860, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:131965; Evidence={ECO:0000269|PubMed:19965576,
CC ECO:0000269|PubMed:8631948};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49861;
CC Evidence={ECO:0000305|PubMed:8631948};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = (14S,15R)-epoxy-(5Z,8Z,11Z)-eicosatrienoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49856, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:131964; Evidence={ECO:0000269|PubMed:19965576,
CC ECO:0000269|PubMed:8631948};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49857;
CC Evidence={ECO:0000305|PubMed:8631948};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate = (13S)-
CC hydroxy-(14S,15S)-epoxy-(5Z,8Z,11Z)-eicosatrienoate;
CC Xref=Rhea:RHEA:53400, ChEBI:CHEBI:57446, ChEBI:CHEBI:137320;
CC Evidence={ECO:0000269|PubMed:19737933};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53401;
CC Evidence={ECO:0000305|PubMed:19737933};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate = (13R)-
CC hydroxy-(14S,15S)-epoxy-(5Z,8Z,11Z)-eicosatrienoate;
CC Xref=Rhea:RHEA:37959, ChEBI:CHEBI:57446, ChEBI:CHEBI:75235;
CC EC=5.4.4.7; Evidence={ECO:0000269|PubMed:19737933};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37960;
CC Evidence={ECO:0000305|PubMed:19737933};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = (17R,18S)-epoxy-(5Z,8Z,11Z,14Z)-
CC eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:39779, 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:76634; Evidence={ECO:0000269|PubMed:19965576};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39780;
CC Evidence={ECO:0000305|PubMed:19965576};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = (17S,18R)-epoxy-(5Z,8Z,11Z,14Z)-
CC eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:39783, 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:76635; Evidence={ECO:0000269|PubMed:19965576};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39784;
CC Evidence={ECO:0000305|PubMed:19965576};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 + reduced
CC [NADPH--hemoprotein reductase] = (19R,20S)-epoxy-(4Z,7Z,10Z,13Z,16Z)-
CC docosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:52120, 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:136410; Evidence={ECO:0000269|PubMed:19965576};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52121;
CC Evidence={ECO:0000305|PubMed:19965576};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 + reduced
CC [NADPH--hemoprotein reductase] = (19S,20R)-epoxy-(4Z,7Z,10Z,13Z,16Z)-
CC docosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:52124, 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:136411; Evidence={ECO:0000269|PubMed:19965576};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52125;
CC Evidence={ECO:0000305|PubMed:19965576};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=albendazole + O2 + reduced [NADPH--hemoprotein reductase] =
CC H(+) + H2O + hydroxyalbendazole + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:56288, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16664, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:140182; EC=1.14.14.74;
CC Evidence={ECO:0000269|PubMed:23959307};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:56289;
CC Evidence={ECO:0000305|PubMed:23959307};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=albendazole + O2 + reduced [NADPH--hemoprotein reductase] =
CC albendazole S-oxide + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:55924, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16664, ChEBI:CHEBI:16959, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.73;
CC Evidence={ECO:0000269|PubMed:19923256};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55925;
CC Evidence={ECO:0000305|PubMed:19923256};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=fenbendazole + O2 + reduced [NADPH--hemoprotein reductase] =
CC fenbendazole S-oxide + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:55928, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:35812, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:77092; Evidence={ECO:0000269|PubMed:23959307};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55929;
CC Evidence={ECO:0000305|PubMed:23959307};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC -!- PATHWAY: Lipid metabolism; arachidonate metabolism.
CC {ECO:0000269|PubMed:19737933, ECO:0000269|PubMed:19965576,
CC ECO:0000269|PubMed:8631948}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
CC membrane protein. Microsome membrane {ECO:0000269|PubMed:8631948};
CC Peripheral membrane protein.
CC -!- TISSUE SPECIFICITY: Highly expressed in heart, present at lower levels
CC in liver, kidney and skeletal muscle (at protein level).
CC {ECO:0000269|PubMed:8631948}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=PharmVar Pharmacogen Variation Consortium;
CC Note=CYP2J2 alleles;
CC URL="https://www.pharmvar.org/gene/CYP2J2";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/cyp2j2/";
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DR EMBL; U37143; AAC50370.2; -; mRNA.
DR EMBL; AB080265; BAB85489.1; -; mRNA.
DR EMBL; AF272142; AAM44456.1; -; Genomic_DNA.
DR EMBL; AY426985; AAQ93356.1; -; Genomic_DNA.
DR EMBL; AK315387; BAG37780.1; -; mRNA.
DR EMBL; BC032594; AAH32594.1; -; mRNA.
DR CCDS; CCDS613.1; -.
DR RefSeq; NP_000766.2; NM_000775.3.
DR AlphaFoldDB; P51589; -.
DR SMR; P51589; -.
DR BioGRID; 107946; 30.
DR IntAct; P51589; 4.
DR STRING; 9606.ENSP00000360247; -.
DR BindingDB; P51589; -.
DR ChEMBL; CHEMBL3491; -.
DR DrugBank; DB01118; Amiodarone.
DR DrugBank; DB06605; Apixaban.
DR DrugBank; DB00637; Astemizole.
DR DrugBank; DB00169; Cholecalciferol.
DR DrugBank; DB04855; Dronedarone.
DR DrugBank; DB09148; Florbetaben (18F).
DR DrugBank; DB08918; Levomilnacipran.
DR DrugBank; DB04725; Licofelone.
DR DrugBank; DB05316; Pimavanserin.
DR DrugBank; DB12016; Ponesimod.
DR DrugBank; DB08931; Riociguat.
DR DrugBank; DB15305; Risdiplam.
DR DrugBank; DB06228; Rivaroxaban.
DR DrugBank; DB00342; Terfenadine.
DR DrugBank; DB09030; Vorapaxar.
DR DrugCentral; P51589; -.
DR GuidetoPHARMACOLOGY; 1332; -.
DR SwissLipids; SLP:000001594; -.
DR iPTMnet; P51589; -.
DR PhosphoSitePlus; P51589; -.
DR BioMuta; CYP2J2; -.
DR DMDM; 21264413; -.
DR EPD; P51589; -.
DR jPOST; P51589; -.
DR MassIVE; P51589; -.
DR MaxQB; P51589; -.
DR PaxDb; P51589; -.
DR PeptideAtlas; P51589; -.
DR PRIDE; P51589; -.
DR ProteomicsDB; 56341; -.
DR Antibodypedia; 33278; 386 antibodies from 31 providers.
DR DNASU; 1573; -.
DR Ensembl; ENST00000371204.4; ENSP00000360247.3; ENSG00000134716.11.
DR GeneID; 1573; -.
DR KEGG; hsa:1573; -.
DR MANE-Select; ENST00000371204.4; ENSP00000360247.3; NM_000775.4; NP_000766.2.
DR UCSC; uc001czq.4; human.
DR CTD; 1573; -.
DR DisGeNET; 1573; -.
DR GeneCards; CYP2J2; -.
DR HGNC; HGNC:2634; CYP2J2.
DR HPA; ENSG00000134716; Group enriched (heart muscle, intestine, liver).
DR MIM; 601258; gene.
DR neXtProt; NX_P51589; -.
DR OpenTargets; ENSG00000134716; -.
DR PharmGKB; PA27112; -.
DR VEuPathDB; HostDB:ENSG00000134716; -.
DR eggNOG; KOG0156; Eukaryota.
DR GeneTree; ENSGT00940000155417; -.
DR HOGENOM; CLU_001570_22_0_1; -.
DR InParanoid; P51589; -.
DR OMA; AEPRDFI; -.
DR OrthoDB; 702827at2759; -.
DR PhylomeDB; P51589; -.
DR TreeFam; TF352043; -.
DR BioCyc; MetaCyc:HS05902-MON; -.
DR BRENDA; 1.14.14.24; 2681.
DR BRENDA; 1.14.14.73; 2681.
DR BRENDA; 1.14.14.74; 2681.
DR BRENDA; 1.14.14.75; 2681.
DR PathwayCommons; P51589; -.
DR Reactome; R-HSA-211935; Fatty acids.
DR Reactome; R-HSA-211981; Xenobiotics.
DR Reactome; R-HSA-2142670; Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET).
DR SignaLink; P51589; -.
DR UniPathway; UPA00383; -.
DR BioGRID-ORCS; 1573; 6 hits in 1067 CRISPR screens.
DR ChiTaRS; CYP2J2; human.
DR GeneWiki; CYP2J2; -.
DR GenomeRNAi; 1573; -.
DR Pharos; P51589; Tchem.
DR PRO; PR:P51589; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P51589; protein.
DR Bgee; ENSG00000134716; Expressed in jejunal mucosa and 166 other tissues.
DR ExpressionAtlas; P51589; baseline and differential.
DR Genevisible; P51589; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0008405; F:arachidonic acid 11,12-epoxygenase activity; IDA:BHF-UCL.
DR GO; GO:0008404; F:arachidonic acid 14,15-epoxygenase activity; IDA:BHF-UCL.
DR GO; GO:0106301; F:arachidonic acid 5,6-epoxygenase activity; IEA:RHEA.
DR GO; GO:0008392; F:arachidonic acid epoxygenase activity; IDA:UniProtKB.
DR GO; GO:0020037; F:heme binding; IBA:GO_Central.
DR GO; GO:0106255; F:hydroperoxy icosatetraenoate isomerase activity; IEA:UniProtKB-EC.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016853; F:isomerase activity; IDA:UniProtKB.
DR GO; GO:0071614; F:linoleic acid epoxygenase activity; IDA:BHF-UCL.
DR GO; GO:0004497; F:monooxygenase activity; TAS:Reactome.
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:0019373; P:epoxygenase P450 pathway; IDA:UniProtKB.
DR GO; GO:0006631; P:fatty acid metabolic process; TAS:Reactome.
DR GO; GO:0006690; P:icosanoid metabolic process; IDA:UniProtKB.
DR GO; GO:0043651; P:linoleic acid metabolic process; IDA:BHF-UCL.
DR GO; GO:0006082; P:organic acid metabolic process; IBA:GO_Central.
DR GO; GO:0008016; P:regulation of heart contraction; TAS:ProtInc.
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; IPR008071; Cyt_P450_E_grp-I_CYP2J-like.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR01688; EP450ICYP2J.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Endoplasmic reticulum; Fatty acid metabolism;
KW Heme; Iron; Isomerase; Lipid metabolism; Membrane; Metal-binding;
KW Microsome; Monooxygenase; Oxidoreductase; Reference proteome.
FT CHAIN 1..502
FT /note="Cytochrome P450 2J2"
FT /id="PRO_0000051769"
FT BINDING 448
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 49
FT /note="R -> S (in dbSNP:rs11572190)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_029159"
FT VARIANT 113
FT /note="V -> M (in dbSNP:rs11572242)"
FT /id="VAR_029160"
FT VARIANT 124
FT /note="N -> S (in dbSNP:rs2228113)"
FT /id="VAR_022084"
FT VARIANT 143
FT /note="T -> A (in allele CYP2J2*2; significantly reduced
FT metabolism of both arachidonic acid and linoleic acid;
FT dbSNP:rs55753213)"
FT /evidence="ECO:0000269|PubMed:11901223"
FT /id="VAR_014317"
FT VARIANT 158
FT /note="R -> C (in allele CYP2J2*3; significantly reduced
FT metabolism of both arachidonic acid and linoleic acid;
FT dbSNP:rs56307989)"
FT /evidence="ECO:0000269|PubMed:11901223"
FT /id="VAR_014318"
FT VARIANT 192
FT /note="I -> N (in allele CYP2J2*4; significantly reduced
FT metabolism of arachidonic acid only; dbSNP:rs66515830)"
FT /evidence="ECO:0000269|PubMed:11901223"
FT /id="VAR_014319"
FT VARIANT 342
FT /note="D -> N (in allele CYP2J2*5; no change in activity;
FT dbSNP:rs56053398)"
FT /evidence="ECO:0000269|PubMed:11901223"
FT /id="VAR_014320"
FT VARIANT 404
FT /note="N -> Y (in allele CYP2J2*6; significantly reduced
FT metabolism of both arachidonic acid and linoleic acid;
FT dbSNP:rs72547598)"
FT /evidence="ECO:0000269|PubMed:11901223"
FT /id="VAR_014321"
FT CONFLICT 264
FT /note="K -> E (in Ref. 6; BAG37780)"
FT /evidence="ECO:0000305"
FT CONFLICT 318
FT /note="T -> A (in Ref. 6; BAG37780)"
FT /evidence="ECO:0000305"
FT CONFLICT 339
FT /note="A -> V (in Ref. 3; BAB85489)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 502 AA; 57611 MW; B5F006581E249EC0 CRC64;
MLAAMGSLAA ALWAVVHPRT LLLGTVAFLL AADFLKRRRP KNYPPGPWRL PFLGNFFLVD
FEQSHLEVQL FVKKYGNLFS LELGDISAVL ITGLPLIKEA LIHMDQNFGN RPVTPMREHI
FKKNGLIMSS GQAWKEQRRF TLTALRNFGL GKKSLEERIQ EEAQHLTEAI KEENGQPFDP
HFKINNAVSN IICSITFGER FEYQDSWFQQ LLKLLDEVTY LEASKTCQLY NVFPWIMKFL
PGPHQTLFSN WKKLKLFVSH MIDKHRKDWN PAETRDFIDA YLKEMSKHTG NPTSSFHEEN
LICSTLDLFF AGTETTSTTL RWALLYMALY PEIQEKVQAE IDRVIGQGQQ PSTAARESMP
YTNAVIHEVQ RMGNIIPLNV PREVTVDTTL AGYHLPKGTM ILTNLTALHR DPTEWATPDT
FNPDHFLENG QFKKREAFMP FSIGKRACLG EQLARTELFI FFTSLMQKFT FRPPNNEKLS
LKFRMGITIS PVSHRLCAVP QV
