CP4F2_HUMAN
ID CP4F2_HUMAN Reviewed; 520 AA.
AC P78329; A0A024R7K3; A8K425; B4DV75; Q16677; Q6NWT4; Q6NWT6; Q9NNZ0; Q9UIU8;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=Cytochrome P450 4F2 {ECO:0000303|PubMed:20861217};
DE EC=1.14.14.1 {ECO:0000269|PubMed:10660572, ECO:0000269|PubMed:11997390, ECO:0000269|PubMed:24138531, ECO:0000269|PubMed:8026587};
DE AltName: Full=20-hydroxyeicosatetraenoic acid synthase {ECO:0000303|PubMed:10660572};
DE Short=20-HETE synthase {ECO:0000303|PubMed:10660572};
DE AltName: Full=Arachidonic acid omega-hydroxylase {ECO:0000303|PubMed:10660572};
DE AltName: Full=CYPIVF2;
DE AltName: Full=Cytochrome P450-LTB-omega;
DE AltName: Full=Docosahexaenoic acid omega-hydroxylase;
DE EC=1.14.14.79 {ECO:0000269|PubMed:18577768};
DE AltName: Full=Leukotriene-B(4) 20-monooxygenase 1;
DE AltName: Full=Leukotriene-B(4) omega-hydroxylase 1 {ECO:0000305};
DE EC=1.14.14.94 {ECO:0000269|PubMed:8026587, ECO:0000269|PubMed:9799565};
DE AltName: Full=Phylloquinone omega-hydroxylase CYP4F2 {ECO:0000305};
DE EC=1.14.14.78 {ECO:0000269|PubMed:24138531};
DE Flags: Precursor;
GN Name=CYP4F2 {ECO:0000303|PubMed:10492403, ECO:0000312|HGNC:HGNC:2645};
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] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Liver;
RX PubMed=8026587; DOI=10.1016/0014-5793(94)00587-7;
RA Kikuta Y., Kusunose E., Kondo T., Yamamoto S., Kinoshita H., Kusunose M.;
RT "Cloning and expression of a novel form of leukotriene B4 omega-hydroxylase
RT from human liver.";
RL FEBS Lett. 348:70-74(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RX PubMed=10492403; DOI=10.1089/104454999315006;
RA Kikuta Y., Miyauchi Y., Kusunose E., Kusunose M.;
RT "Expression and molecular cloning of human liver leukotriene B4 omega-
RT hydroxylase (CYP4F2) gene.";
RL DNA Cell Biol. 18:723-730(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RA Chen L., Hardwick J.P.;
RT "The human liver CYP4F2 cDNA sequence and expression in baculovirus-
RT infected insect cells.";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP VAL-185.
RC TISSUE=Kidney, and Small intestine;
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 [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS TYR-7; GLY-12; VAL-185;
RP MET-433 AND MET-519.
RG SeattleSNPs variation discovery resource;
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS GLY-12 AND
RP MET-433.
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 [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-175.
RC TISSUE=Liver;
RX PubMed=10860554; DOI=10.1006/abbi.2000.1836;
RA Zhang X., Chen L., Hardwick J.P.;
RT "Promoter activity and regulation of the CYP4F2 leukotriene B4 omega
RT hydroxylase gene by peroxisomal proliferators and retinoic acid in HepG2
RT cells.";
RL Arch. Biochem. Biophys. 378:364-376(2000).
RN [10]
RP PROTEIN SEQUENCE OF 5-21, FUNCTION, CATALYTIC ACTIVITY, AND VARIANT GLY-12.
RX PubMed=9799565; DOI=10.1006/abbi.1998.0880;
RA Jin R., Koop D.R., Raucy J.L., Lasker J.M.;
RT "Role of human CYP4F2 in hepatic catabolism of the proinflammatory agent
RT leukotriene B4.";
RL Arch. Biochem. Biophys. 359:89-98(1998).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RX PubMed=10833273; DOI=10.1093/oxfordjournals.jbchem.a022696;
RA Kikuta Y., Kusunose E., Kusunose M.;
RT "Characterization of human liver leukotriene B(4) omega-hydroxylase P450
RT (CYP4F2).";
RL J. Biochem. 127:1047-1052(2000).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=10660572; DOI=10.1074/jbc.275.6.4118;
RA Lasker J.M., Chen W.B., Wolf I., Bloswick B.P., Wilson P.D., Powell P.K.;
RT "Formation of 20-hydroxyeicosatetraenoic acid, a vasoactive and natriuretic
RT eicosanoid, in human kidney. Role of CYP4F2 and CYP4A11.";
RL J. Biol. Chem. 275:4118-4126(2000).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=11997390; DOI=10.1074/jbc.m201466200;
RA Sontag T.J., Parker R.S.;
RT "Cytochrome P450 omega-hydroxylase pathway of tocopherol catabolism. Novel
RT mechanism of regulation of vitamin E status.";
RL J. Biol. Chem. 277:25290-25296(2002).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15145985; DOI=10.1194/jlr.m300463-jlr200;
RA Le Quere V., Plee-Gautier E., Potin P., Madec S., Salauen J.P.;
RT "Human CYP4F3s are the main catalysts in the oxidation of fatty acid
RT epoxides.";
RL J. Lipid Res. 45:1446-1458(2004).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=16547005; DOI=10.1074/jbc.m513481200;
RA Sanders R.J., Ofman R., Duran M., Kemp S., Wanders R.J.;
RT "Omega-oxidation of very long-chain fatty acids in human liver microsomes.
RT Implications for X-linked adrenoleukodystrophy.";
RL J. Biol. Chem. 281:13180-13187(2006).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, AND CHARACTERIZATION OF VARIANT MET-433.
RX PubMed=17341693; DOI=10.1152/physiolgenomics.00003.2007;
RA Stec D.E., Roman R.J., Flasch A., Rieder M.J.;
RT "Functional polymorphism in human CYP4F2 decreases 20-HETE production.";
RL Physiol. Genomics 30:74-81(2007).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=18182499; DOI=10.1096/fj.07-099150;
RA Sanders R.J., Ofman R., Dacremont G., Wanders R.J., Kemp S.;
RT "Characterization of the human omega-oxidation pathway for omega-hydroxy-
RT very-long-chain fatty acids.";
RL FASEB J. 22:2064-2071(2008).
RN [18]
RP FUNCTION, AND CHARACTERIZATION OF VARIANT MET-433.
RX PubMed=18574070; DOI=10.1161/hypertensionaha.108.114199;
RA Fava C., Montagnana M., Almgren P., Rosberg L., Lippi G., Hedblad B.,
RA Engstrom G., Berglund G., Minuz P., Melander O.;
RT "The V433M variant of the CYP4F2 is associated with ischemic stroke in male
RT Swedes beyond its effect on blood pressure.";
RL Hypertension 52:373-380(2008).
RN [19]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=18065749; DOI=10.1194/jlr.m700450-jlr200;
RA Dhar M., Sepkovic D.W., Hirani V., Magnusson R.P., Lasker J.M.;
RT "Omega oxidation of 3-hydroxy fatty acids by the human CYP4F gene subfamily
RT enzyme CYP4F11.";
RL J. Lipid Res. 49:612-624(2008).
RN [20]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=18577768; DOI=10.1194/jlr.m800199-jlr200;
RA Fer M., Corcos L., Dreano Y., Plee-Gautier E., Salaun J.P., Berthou F.,
RA Amet Y.;
RT "Cytochromes P450 from family 4 are the main omega hydroxylating enzymes in
RT humans: CYP4F3B is the prominent player in PUFA metabolism.";
RL J. Lipid Res. 49:2379-2389(2008).
RN [21]
RP SUBCELLULAR LOCATION.
RX PubMed=20861217; DOI=10.3945/jn.110.128579;
RA Bardowell S.A., Stec D.E., Parker R.S.;
RT "Common variants of cytochrome P450 4F2 exhibit altered vitamin E-{omega}-
RT hydroxylase specific activity.";
RL J. Nutr. 140:1901-1906(2010).
RN [22]
RP FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, IDENTIFICATION BY MASS SPECTROMETRY, AND PATHWAY.
RX PubMed=24138531; DOI=10.1021/bi401208m;
RA Edson K.Z., Prasad B., Unadkat J.D., Suhara Y., Okano T., Guengerich F.P.,
RA Rettie A.E.;
RT "Cytochrome P450-dependent catabolism of vitamin K: omega-hydroxylation
RT catalyzed by human CYP4F2 and CYP4F11.";
RL Biochemistry 52:8276-8285(2013).
RN [23]
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 [24]
RP INVOLVEMENT IN CMRES, AND CHARACTERIZATION OF VARIANT MET-433.
RX PubMed=18250228; DOI=10.1182/blood-2007-11-122010;
RA Caldwell M.D., Awad T., Johnson J.A., Gage B.F., Falkowski M., Gardina P.,
RA Hubbard J., Turpaz Y., Langaee T.Y., Eby C., King C.R., Brower A.,
RA Schmelzer J.R., Glurich I., Vidaillet H.J., Yale S.H., Qi Zhang K.,
RA Berg R.L., Burmester J.K.;
RT "CYP4F2 genetic variant alters required warfarin dose.";
RL Blood 111:4106-4112(2008).
RN [25]
RP INVOLVEMENT IN CMRES, AND CHARACTERIZATION OF VARIANT MET-433.
RX PubMed=19270263; DOI=10.1182/blood-2008-09-176222;
RA Perez-Andreu V., Roldan V., Anton A.I., Garcia-Barbera N., Corral J.,
RA Vicente V., Gonzalez-Conejero R.;
RT "Pharmacogenetic relevance of CYP4F2 V433M polymorphism on acenocoumarol
RT therapy.";
RL Blood 113:4977-4979(2009).
RN [26]
RP FUNCTION, SUBCELLULAR LOCATION, INVOLVEMENT IN CMRES, AND CHARACTERIZATION
RP OF VARIANT MET-433.
RX PubMed=19297519; DOI=10.1124/mol.109.054833;
RA McDonald M.G., Rieder M.J., Nakano M., Hsia C.K., Rettie A.E.;
RT "CYP4F2 is a vitamin K1 oxidase: An explanation for altered warfarin dose
RT in carriers of the V433M variant.";
RL Mol. Pharmacol. 75:1337-1346(2009).
RN [27]
RP INVOLVEMENT IN CMRES, AND CHARACTERIZATION OF VARIANT MET-433.
RX PubMed=19207028; DOI=10.2217/14622416.10.2.261;
RA Borgiani P., Ciccacci C., Forte V., Sirianni E., Novelli L., Bramanti P.,
RA Novelli G.;
RT "CYP4F2 genetic variant (rs2108622) significantly contributes to warfarin
RT dosing variability in the Italian population.";
RL Pharmacogenomics 10:261-266(2009).
RN [28]
RP INVOLVEMENT IN CMRES, AND CHARACTERIZATION OF VARIANT MET-433.
RX PubMed=20555338; DOI=10.1038/jhg.2010.73;
RA Ross K.A., Bigham A.W., Edwards M., Gozdzik A., Suarez-Kurtz G.,
RA Parra E.J.;
RT "Worldwide allele frequency distribution of four polymorphisms associated
RT with warfarin dose requirements.";
RL J. Hum. Genet. 55:582-589(2010).
RN [29]
RP INVOLVEMENT IN CMRES, AND CHARACTERIZATION OF VARIANT MET-433.
RX PubMed=23132553; DOI=10.1038/clpt.2012.184;
RA Danese E., Montagnana M., Johnson J.A., Rettie A.E., Zambon C.F.,
RA Lubitz S.A., Suarez-Kurtz G., Cavallari L.H., Zhao L., Huang M.,
RA Nakamura Y., Mushiroda T., Kringen M.K., Borgiani P., Ciccacci C., Au N.T.,
RA Langaee T., Siguret V., Loriot M.A., Sagreiya H., Altman R.B., Shahin M.H.,
RA Scott S.A., Khalifa S.I., Chowbay B., Suriapranata I.M., Teichert M.,
RA Stricker B.H., Taljaard M., Botton M.R., Zhang J.E., Pirmohamed M.,
RA Zhang X., Carlquist J.F., Horne B.D., Lee M.T., Pengo V., Guidi G.C.,
RA Minuz P., Fava C.;
RT "Impact of the CYP4F2 p.V433M polymorphism on coumarin dose requirement:
RT systematic review and meta-analysis.";
RL Clin. Pharmacol. Ther. 92:746-756(2012).
CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of
CC various endogenous substrates, including fatty acids, eicosanoids and
CC vitamins (PubMed:18577768, PubMed:10833273, PubMed:10660572,
CC PubMed:11997390, PubMed:17341693, PubMed:18574070). Mechanistically,
CC uses molecular oxygen inserting one oxygen atom into a substrate, and
CC reducing the second into a water molecule, with two electrons provided
CC by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein
CC reductase). Catalyzes predominantly the oxidation of the terminal
CC carbon (omega-oxidation) of long- and very long-chain fatty acids.
CC Displays high omega-hydroxylase activity toward polyunsaturated fatty
CC acids (PUFAs) (PubMed:18577768). Participates in the conversion of
CC arachidonic acid to omega-hydroxyeicosatetraenoic acid (20-HETE), a
CC signaling molecule acting both as vasoconstrictive and natriuretic with
CC overall effect on arterial blood pressure (PubMed:10660572,
CC PubMed:17341693, PubMed:18574070). Plays a role in the oxidative
CC inactivation of eicosanoids, including both pro-inflammatory and anti-
CC inflammatory mediators such as leukotriene B4 (LTB4), lipoxin A4
CC (LXA4), and several HETEs (PubMed:8026587, PubMed:9799565,
CC PubMed:10833273, PubMed:10660572, PubMed:17341693, PubMed:18574070,
CC PubMed:18577768). Catalyzes omega-hydroxylation of 3-hydroxy fatty
CC acids (PubMed:18065749). Converts monoepoxides of linoleic acid
CC leukotoxin and isoleukotoxin to omega-hydroxylated metabolites
CC (PubMed:15145985). Contributes to the degradation of very long-chain
CC fatty acids (VLCFAs) by catalyzing successive omega-oxidations and
CC chain shortening (PubMed:16547005, PubMed:18182499). Plays an important
CC role in vitamin metabolism by chain shortening. Catalyzes omega-
CC hydroxylation of the phytyl chain of tocopherols (forms of vitamin E),
CC with preference for gamma-tocopherols over alpha-tocopherols, thus
CC promoting retention of alpha-tocopherols in tissues (PubMed:11997390).
CC Omega-hydroxylates and inactivates phylloquinone (vitamin K1), and
CC menaquinone-4 (MK-4, a form of vitamin K2), both acting as cofactors in
CC blood coagulation (PubMed:19297519, PubMed:24138531).
CC {ECO:0000269|PubMed:10660572, ECO:0000269|PubMed:10833273,
CC ECO:0000269|PubMed:11997390, ECO:0000269|PubMed:15145985,
CC ECO:0000269|PubMed:16547005, ECO:0000269|PubMed:17341693,
CC ECO:0000269|PubMed:18065749, ECO:0000269|PubMed:18182499,
CC ECO:0000269|PubMed:18574070, ECO:0000269|PubMed:18577768,
CC ECO:0000269|PubMed:19297519, ECO:0000269|PubMed:24138531,
CC ECO:0000269|PubMed:8026587, ECO:0000269|PubMed:9799565}.
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:0000269|PubMed:10660572, ECO:0000269|PubMed:11997390,
CC ECO:0000269|PubMed:24138531, ECO:0000269|PubMed:8026587};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17150;
CC Evidence={ECO:0000305|PubMed:10660572, ECO:0000305|PubMed:11997390,
CC ECO:0000305|PubMed:24138531, ECO:0000305|PubMed:8026587};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = 20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:39755, 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:76624; Evidence={ECO:0000269|PubMed:10660572,
CC ECO:0000269|PubMed:17341693, ECO:0000269|PubMed:18577768,
CC ECO:0000269|PubMed:24138531};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39756;
CC Evidence={ECO:0000305|PubMed:18577768};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z)-eicosatrienoate + O2 + reduced [NADPH--hemoprotein
CC reductase] = 20-hydroxy-(5Z,8Z,11Z)-eicosatrienoate + H(+) + H2O +
CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:50164,
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:132026;
CC Evidence={ECO:0000269|PubMed:18577768};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50165;
CC Evidence={ECO:0000305|PubMed:18577768};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = 20-hydroxy-(5Z,8Z,11Z,14Z,17Z)-
CC eicosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:39791, 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:76639; Evidence={ECO:0000269|PubMed:18577768};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39792;
CC Evidence={ECO:0000305|PubMed:18577768};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 + reduced
CC [NADPH--hemoprotein reductase] = 22-hydroxy-(4Z,7Z,10Z,13Z,16Z,19Z)-
CC docosahexaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:40155, 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:77015,
CC ChEBI:CHEBI:77016; EC=1.14.14.79;
CC Evidence={ECO:0000269|PubMed:18577768};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40156;
CC Evidence={ECO:0000305|PubMed:18577768};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = 20-hydroxy-8,9-epoxy-(5Z,11Z,14Z)-
CC eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:53572, 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:84025,
CC ChEBI:CHEBI:137474; Evidence={ECO:0000269|PubMed:15145985};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53573;
CC Evidence={ECO:0000305|PubMed:15145985};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9S,10R)-epoxy-octadecanoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = 18-hydroxy-(9S,10R)-epoxy-octadecanoate +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:53552, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:137458,
CC ChEBI:CHEBI:137461; Evidence={ECO:0000269|PubMed:15145985};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53553;
CC Evidence={ECO:0000305|PubMed:15145985};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9R,10S)-epoxy-octadecanoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = 18-hydroxy-(9R,10S)-epoxy-octadecanoate +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:53556, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:137459,
CC ChEBI:CHEBI:137460; Evidence={ECO:0000269|PubMed:15145985};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53557;
CC Evidence={ECO:0000305|PubMed:15145985};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=12,13-epoxy-(9Z)-octadecenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = 18-hydroxy-12,13-epoxy-(9Z)-octadecenoate +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:53568, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:84026,
CC ChEBI:CHEBI:137469; Evidence={ECO:0000269|PubMed:15145985};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53569;
CC Evidence={ECO:0000305|PubMed:15145985};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=9,10-epoxy-(12Z)-octadecenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = 18-hydroxy-9,10-epoxy-(12Z)-octadecenoate +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:53564, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:84023,
CC ChEBI:CHEBI:137467; Evidence={ECO:0000269|PubMed:15145985};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53565;
CC Evidence={ECO:0000305|PubMed:15145985};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=8-hydroxy-(5Z,9E,11Z,14Z)-eicosatetraenoate + O2 + reduced
CC [NADPH--hemoprotein reductase] = 8,20-dihydroxy-(5Z,9E,11Z,14Z)-
CC eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:48660, 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:90716,
CC ChEBI:CHEBI:90717; Evidence={ECO:0000269|PubMed:10833273};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48661;
CC Evidence={ECO:0000305|PubMed:10833273};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=12-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + O2 + reduced
CC [NADPH--hemoprotein reductase] = 12,20-dihydroxy-(5Z,8Z,10E,14Z)-
CC eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:48664, 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:90718,
CC ChEBI:CHEBI:90719; Evidence={ECO:0000269|PubMed:10833273};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48665;
CC Evidence={ECO:0000305|PubMed:10833273};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=12-hydroxyoctadecanoate + O2 + reduced [NADPH--hemoprotein
CC reductase] = 12,18-dihydroxyoctadecanoate + H(+) + H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:49376, Rhea:RHEA-
CC 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:84201, ChEBI:CHEBI:91294;
CC Evidence={ECO:0000269|PubMed:10833273};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49377;
CC Evidence={ECO:0000305|PubMed:10833273};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=docosanoate + O2 + reduced [NADPH--hemoprotein reductase] =
CC 22-hydroxydocosanoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:40079, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:23858, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:76304; Evidence={ECO:0000269|PubMed:16547005};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40080;
CC Evidence={ECO:0000305|PubMed:16547005};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=22-hydroxydocosanoate + O2 + reduced [NADPH--hemoprotein
CC reductase] = 22-oxodocosanoate + H(+) + 2 H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:39055, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:76298, ChEBI:CHEBI:76304;
CC Evidence={ECO:0000269|PubMed:18182499};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39056;
CC Evidence={ECO:0000305|PubMed:18182499};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=22-oxodocosanoate + O2 + reduced [NADPH--hemoprotein
CC reductase] = docosanedioate + 2 H(+) + H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:39043, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:76298, ChEBI:CHEBI:76299;
CC Evidence={ECO:0000269|PubMed:18182499};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39044;
CC Evidence={ECO:0000305|PubMed:18182499};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + reduced [NADPH--hemoprotein reductase] + tetracosanoate =
CC 24-hydroxytetracosanoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:39719, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:31014, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:76610; Evidence={ECO:0000269|PubMed:16547005};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39720;
CC Evidence={ECO:0000305|PubMed:16547005};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexacosanoate + O2 + reduced [NADPH--hemoprotein reductase] =
CC 26-hydroxyhexacosanoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:40083, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:31013, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:76305; Evidence={ECO:0000269|PubMed:16547005};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40084;
CC Evidence={ECO:0000305|PubMed:16547005};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=26-hydroxyhexacosanoate + O2 + reduced [NADPH--hemoprotein
CC reductase] = 26-oxohexacosanoate + H(+) + 2 H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:39059, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:76305, ChEBI:CHEBI:76311;
CC Evidence={ECO:0000269|PubMed:16547005};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39060;
CC Evidence={ECO:0000305|PubMed:16547005};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=26-oxohexacosanoate + O2 + reduced [NADPH--hemoprotein
CC reductase] = 2 H(+) + H2O + hexacosanedioate + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:39047, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:76311, ChEBI:CHEBI:76312;
CC Evidence={ECO:0000269|PubMed:16547005, ECO:0000269|PubMed:18182499};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39048;
CC Evidence={ECO:0000305|PubMed:16547005, ECO:0000305|PubMed:18182499};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-hydroxyoctadecanoate + O2 + reduced [NADPH--hemoprotein
CC reductase] = 3,18-dihydroxyoctadecanoate + H(+) + H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:39735, Rhea:RHEA-
CC 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:76614, ChEBI:CHEBI:76615;
CC Evidence={ECO:0000269|PubMed:18065749};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39736;
CC Evidence={ECO:0000305|PubMed:18065749};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-hydroxyhexadecanoate + O2 + reduced [NADPH--hemoprotein
CC reductase] = 3,16-dihydroxyhexadecanoate + H(+) + H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:39731, Rhea:RHEA-
CC 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:63904, ChEBI:CHEBI:76613;
CC Evidence={ECO:0000269|PubMed:18065749};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39732;
CC Evidence={ECO:0000305|PubMed:18065749};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=leukotriene B4 + O2 + reduced [NADPH--hemoprotein reductase] =
CC 20-hydroxy-leukotriene B4 + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:22176, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57460, ChEBI:CHEBI:57461, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.94;
CC Evidence={ECO:0000269|PubMed:10833273, ECO:0000269|PubMed:8026587,
CC ECO:0000269|PubMed:9799565};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22177;
CC Evidence={ECO:0000305|PubMed:8026587};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=6-trans-leukotriene B4 + O2 + reduced [NADPH--hemoprotein
CC reductase] = 20-hydroxy-6-trans-leukotriene B4 + H(+) + H2O +
CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:48676,
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:90723, ChEBI:CHEBI:90732;
CC Evidence={ECO:0000269|PubMed:10833273};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48677;
CC Evidence={ECO:0000305|PubMed:10833273};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=lipoxin A4 + O2 + reduced [NADPH--hemoprotein reductase] = 20-
CC hydroxy-lipoxin A4 + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:48648, 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:67026,
CC ChEBI:CHEBI:90707; Evidence={ECO:0000269|PubMed:10833273};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48649;
CC Evidence={ECO:0000305|PubMed:10833273};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=menaquinone-4 + O2 + reduced [NADPH--hemoprotein reductase] =
CC H(+) + H2O + omega-hydroxymenaquinone-4 + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:41520, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:78277, ChEBI:CHEBI:78278; EC=1.14.14.78;
CC Evidence={ECO:0000269|PubMed:24138531};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41521;
CC Evidence={ECO:0000305|PubMed:24138531};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + phylloquinone + reduced [NADPH--hemoprotein reductase] =
CC H(+) + H2O + omega-hydroxyphylloquinone + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:41516, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:18067, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:78276; EC=1.14.14.78;
CC Evidence={ECO:0000269|PubMed:24138531};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41517;
CC Evidence={ECO:0000305|PubMed:24138531};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(+)-alpha-tocopherol + O2 + reduced [NADPH--hemoprotein
CC reductase] = 13-hydroxy-alpha-tocopherol + H(+) + H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:45108, Rhea:RHEA-
CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:18145,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:84962;
CC Evidence={ECO:0000269|PubMed:11997390};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45109;
CC Evidence={ECO:0000305|PubMed:11997390};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=gamma-tocopherol + H(+) + NADPH + O2 = 13-hydroxy-gamma-
CC tocopherol + H2O + NADP(+); Xref=Rhea:RHEA:45112, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:18185,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:84963;
CC Evidence={ECO:0000269|PubMed:11997390};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45113;
CC Evidence={ECO:0000305|PubMed:11997390};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P24464};
CC -!- ACTIVITY REGULATION: Inhibited by dietary sesamin.
CC {ECO:0000269|PubMed:11997390}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.5 uM for docosanoate {ECO:0000269|PubMed:16547005};
CC KM=1.1 uM for tetracosanoate {ECO:0000269|PubMed:16547005};
CC KM=1.9 uM for hexacosanoate {ECO:0000269|PubMed:16547005};
CC KM=75.2 uM for 12-hydroxyoctadecanoate {ECO:0000269|PubMed:10833273};
CC KM=19 uM for 8-HETE {ECO:0000269|PubMed:10833273};
CC KM=42.3 uM for 12-HETE {ECO:0000269|PubMed:10833273};
CC KM=37.6 uM for 22-hydroxydocosanoate {ECO:0000269|PubMed:18182499};
CC KM=8.8 uM for 26-hydroxyhexacosanoate {ECO:0000269|PubMed:18182499};
CC KM=26.1 uM for 9(10)-epoxyoctadecanoate
CC {ECO:0000269|PubMed:15145985};
CC KM=163.1 uM for 9(10)-epoxy-(12Z)-octadecenoate
CC {ECO:0000269|PubMed:15145985};
CC KM=135 uM for 12(13)-epoxy-(9Z)-octadecenoate
CC {ECO:0000269|PubMed:15145985};
CC KM=60 uM for leukotriene B4 {ECO:0000269|PubMed:10833273};
CC KM=55.6 uM for 6-trans-leukotriene B4 {ECO:0000269|PubMed:10833273};
CC KM=58.2 uM for lipoxin A4 {ECO:0000269|PubMed:10833273};
CC KM=1.7 uM for menaquinone-4 (MK-4) {ECO:0000269|PubMed:24138531};
CC KM=21 uM for alpha-tocopherol {ECO:0000269|PubMed:11997390};
CC KM=37 uM for gamma-tocopherol {ECO:0000269|PubMed:11997390};
CC Vmax=1.6 pmol/min/pmol enzyme toward docosanoate
CC {ECO:0000269|PubMed:16547005};
CC Vmax=1.6 pmol/min/pmol enzyme toward tetracosanoate
CC {ECO:0000269|PubMed:16547005};
CC Vmax=0.9 pmol/min/pmol enzyme toward hexacosanoate
CC {ECO:0000269|PubMed:16547005};
CC Vmax=7 nmol/min/nmol enzyme toward 12-hydroxyoctadecanoate
CC {ECO:0000269|PubMed:10833273};
CC Vmax=4 nmol/min/nmol enzyme toward 8-HETE
CC {ECO:0000269|PubMed:10833273};
CC Vmax=2.9 nmol/min/nmol enzyme toward 12-HETE
CC {ECO:0000269|PubMed:10833273};
CC Vmax=1.6 pmol/min/pmol enzyme toward 22-hydroxydocosanoate
CC {ECO:0000269|PubMed:18182499};
CC Vmax=0.7 pmol/min/pmol enzyme toward 26-hydroxyhexacosanoate
CC {ECO:0000269|PubMed:18182499};
CC Vmax=7.9 nmol/min/nmol enzyme toward 9(10)-epoxyoctadecanoate
CC {ECO:0000269|PubMed:15145985};
CC Vmax=10.6 nmol/min/nmol enzyme toward 9(10)-epoxy-(12Z)-octadecenoate
CC {ECO:0000269|PubMed:15145985};
CC Vmax=0.84 nmol/min/nmol enzyme toward 12(13)-epoxy-(9Z)-octadecenoate
CC {ECO:0000269|PubMed:15145985};
CC Vmax=2.7 nmol/min/nmol enzyme toward leukotriene B4
CC {ECO:0000269|PubMed:10833273};
CC Vmax=11.9 nmol/min/nmol enzyme toward 6-trans-leukotriene B4
CC {ECO:0000269|PubMed:10833273};
CC Vmax=5.5 nmol/min/nmol enzyme toward lipoxin A4
CC {ECO:0000269|PubMed:10833273};
CC Vmax=0.16 nmol/min/nmol enzyme toward alpha-tocopherol
CC {ECO:0000269|PubMed:11997390};
CC Vmax=1.99 nmol/min/nmol enzyme toward gamma-tocopherol
CC {ECO:0000269|PubMed:11997390};
CC Note=kcat is 0.067 min(-1) with menaquinone-4 (MK-4) as substrate
CC (PubMed:24138531). The omega-hydroxylation of VLCFAs follows dual-
CC enzyme Michaelis-Menten kinetics, suggesting simultaneous binding of
CC two substrate molecules. The high affinity Michaelis-Menten constants
CC are shown (PubMed:16547005). {ECO:0000269|PubMed:16547005,
CC ECO:0000269|PubMed:24138531};
CC -!- PATHWAY: Lipid metabolism; arachidonate metabolism.
CC {ECO:0000269|PubMed:10833273}.
CC -!- PATHWAY: Lipid metabolism; leukotriene B4 degradation.
CC {ECO:0000269|PubMed:10833273}.
CC -!- PATHWAY: Cofactor degradation; phylloquinone degradation.
CC {ECO:0000269|PubMed:24138531}.
CC -!- INTERACTION:
CC P78329; Q13520: AQP6; NbExp=3; IntAct=EBI-1752413, EBI-13059134;
CC P78329; Q7Z7G2: CPLX4; NbExp=3; IntAct=EBI-1752413, EBI-18013275;
CC P78329; O43889-2: CREB3; NbExp=3; IntAct=EBI-1752413, EBI-625022;
CC P78329; Q96BA8: CREB3L1; NbExp=3; IntAct=EBI-1752413, EBI-6942903;
CC P78329; Q96KC8: DNAJC1; NbExp=3; IntAct=EBI-1752413, EBI-296550;
CC P78329; Q15125: EBP; NbExp=3; IntAct=EBI-1752413, EBI-3915253;
CC P78329; Q9GZR5: ELOVL4; NbExp=3; IntAct=EBI-1752413, EBI-18535450;
CC P78329; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-1752413, EBI-781551;
CC P78329; Q96KR6: FAM210B; NbExp=3; IntAct=EBI-1752413, EBI-18938272;
CC P78329; P48165: GJA8; NbExp=3; IntAct=EBI-1752413, EBI-17458373;
CC P78329; Q7Z5P4: HSD17B13; NbExp=3; IntAct=EBI-1752413, EBI-18053395;
CC P78329; Q8N5M9: JAGN1; NbExp=3; IntAct=EBI-1752413, EBI-10266796;
CC P78329; O95214: LEPROTL1; NbExp=3; IntAct=EBI-1752413, EBI-750776;
CC P78329; Q15546: MMD; NbExp=3; IntAct=EBI-1752413, EBI-17873222;
CC P78329; Q9H2K0: MTIF3; NbExp=3; IntAct=EBI-1752413, EBI-3923617;
CC P78329; P15941-11: MUC1; NbExp=3; IntAct=EBI-1752413, EBI-17263240;
CC P78329; P16333: NCK1; NbExp=2; IntAct=EBI-1752413, EBI-389883;
CC P78329; O15173: PGRMC2; NbExp=3; IntAct=EBI-1752413, EBI-1050125;
CC P78329; Q53GL0: PLEKHO1; NbExp=3; IntAct=EBI-1752413, EBI-949945;
CC P78329; Q9BRK0: REEP2; NbExp=3; IntAct=EBI-1752413, EBI-11337973;
CC P78329; Q9H6H4: REEP4; NbExp=3; IntAct=EBI-1752413, EBI-7545592;
CC P78329; Q86VR2: RETREG3; NbExp=3; IntAct=EBI-1752413, EBI-10192441;
CC P78329; Q03395: ROM1; NbExp=3; IntAct=EBI-1752413, EBI-9395257;
CC P78329; Q9NY72: SCN3B; NbExp=3; IntAct=EBI-1752413, EBI-17247926;
CC P78329; Q9NX18: SDHAF2; NbExp=3; IntAct=EBI-1752413, EBI-713250;
CC P78329; Q3KNW5: SLC10A6; NbExp=3; IntAct=EBI-1752413, EBI-18159983;
CC P78329; Q8NDX2-2: SLC17A8; NbExp=3; IntAct=EBI-1752413, EBI-17249797;
CC P78329; Q9BZV2: SLC19A3; NbExp=3; IntAct=EBI-1752413, EBI-3923779;
CC P78329; Q96QE2: SLC2A13; NbExp=3; IntAct=EBI-1752413, EBI-18082698;
CC P78329; Q9NPE6: SPAG4; NbExp=3; IntAct=EBI-1752413, EBI-10819434;
CC P78329; Q8WY91: THAP4; NbExp=3; IntAct=EBI-1752413, EBI-726691;
CC P78329; Q96MV1: TLCD4; NbExp=3; IntAct=EBI-1752413, EBI-12947623;
CC P78329; Q96DZ7: TM4SF19; NbExp=3; IntAct=EBI-1752413, EBI-6448756;
CC P78329; Q9NW97: TMEM51; NbExp=3; IntAct=EBI-1752413, EBI-726044;
CC P78329; Q9Y320: TMX2; NbExp=3; IntAct=EBI-1752413, EBI-6447886;
CC P78329; Q12999: TSPAN31; NbExp=3; IntAct=EBI-1752413, EBI-17678331;
CC P78329; Q7KZS0: UBE2I; NbExp=3; IntAct=EBI-1752413, EBI-10180829;
CC P78329; Q96MV8: ZDHHC15; NbExp=3; IntAct=EBI-1752413, EBI-12837904;
CC -!- SUBCELLULAR LOCATION: Microsome membrane {ECO:0000269|PubMed:19297519,
CC ECO:0000269|PubMed:24138531, ECO:0000269|PubMed:8026587}; Peripheral
CC membrane protein {ECO:0000305}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:20861217}; Peripheral membrane protein
CC {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P78329-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P78329-2; Sequence=VSP_055578, VSP_055579, VSP_055580;
CC -!- TISSUE SPECIFICITY: Liver. Also present in kidney: specifically
CC expressed in the S2 and S3 segments of proximal tubules in cortex and
CC outer medulla (PubMed:10660572). {ECO:0000269|PubMed:10492403,
CC ECO:0000269|PubMed:10660572}.
CC -!- DISEASE: Coumarin resistance (CMRES) [MIM:122700]: A condition
CC characterized by partial or complete resistance to warfarin or other 4-
CC hydroxycoumarin derivatives. These drugs are used as anti-coagulants
CC for the prevention of thromboembolic diseases in subjects with deep
CC vein thrombosis, atrial fibrillation, or mechanical heart valve
CC replacement. {ECO:0000269|PubMed:18250228, ECO:0000269|PubMed:19207028,
CC ECO:0000269|PubMed:19270263, ECO:0000269|PubMed:19297519,
CC ECO:0000269|PubMed:20555338, ECO:0000269|PubMed:23132553,
CC ECO:0000269|PubMed:24138531}. Note=Disease susceptibility may be
CC associated with variants affecting the gene represented in this entry.
CC The variant Met-433 is associated with coumarin (the brand name of
CC warfarin) resistance by increasing coumarin maintenance dose in
CC patients on this anti-coagulant therapy. This is probably due to
CC decreased activity of the phylloquinone omega-hydroxylase activity,
CC leading to an increase in hepatic vitamin K levels that warfarin must
CC antagonize (PubMed:24138531). {ECO:0000269|PubMed:24138531}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/cyp4f2/";
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DR EMBL; D26480; BAA05490.1; -; mRNA.
DR EMBL; AB015306; BAA75823.1; -; Genomic_DNA.
DR EMBL; U02388; AAC50052.2; -; mRNA.
DR EMBL; AK290790; BAF83479.1; -; mRNA.
DR EMBL; AK300961; BAG62587.1; -; mRNA.
DR EMBL; AF467894; AAL67578.1; -; Genomic_DNA.
DR EMBL; AC005336; AAC27730.1; -; Genomic_DNA.
DR EMBL; AC004791; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471106; EAW84509.1; -; Genomic_DNA.
DR EMBL; CH471106; EAW84510.1; -; Genomic_DNA.
DR EMBL; BC067437; AAH67437.1; -; mRNA.
DR EMBL; BC067439; AAH67439.1; -; mRNA.
DR EMBL; BC067440; AAH67440.1; -; mRNA.
DR EMBL; AF221943; AAF86378.1; -; Genomic_DNA.
DR CCDS; CCDS12336.1; -. [P78329-1]
DR PIR; S45702; S45702.
DR RefSeq; NP_001073.3; NM_001082.4. [P78329-1]
DR AlphaFoldDB; P78329; -.
DR SMR; P78329; -.
DR BioGRID; 114099; 38.
DR IntAct; P78329; 44.
DR STRING; 9606.ENSP00000221700; -.
DR BindingDB; P78329; -.
DR ChEMBL; CHEMBL3379; -.
DR DrugBank; DB14003; alpha-Tocopherol acetate.
DR DrugBank; DB12151; Brincidofovir.
DR DrugBank; DB08868; Fingolimod.
DR DrugBank; DB09148; Florbetaben (18F).
DR DrugBank; DB01026; Ketoconazole.
DR DrugBank; DB09568; Omega-3-carboxylic acids.
DR DrugBank; DB01022; Phylloquinone.
DR DrugBank; DB11635; Tocofersolan.
DR DrugBank; DB11251; Tocopherol.
DR GuidetoPHARMACOLOGY; 1344; -.
DR SwissLipids; SLP:000000421; -.
DR iPTMnet; P78329; -.
DR PhosphoSitePlus; P78329; -.
DR BioMuta; CYP4F2; -.
DR DMDM; 6166044; -.
DR jPOST; P78329; -.
DR MassIVE; P78329; -.
DR MaxQB; P78329; -.
DR PaxDb; P78329; -.
DR PeptideAtlas; P78329; -.
DR PRIDE; P78329; -.
DR ProteomicsDB; 5249; -.
DR ProteomicsDB; 57568; -. [P78329-1]
DR Antibodypedia; 2706; 151 antibodies from 26 providers.
DR DNASU; 8529; -.
DR Ensembl; ENST00000221700.11; ENSP00000221700.3; ENSG00000186115.13. [P78329-1]
DR GeneID; 8529; -.
DR KEGG; hsa:8529; -.
DR MANE-Select; ENST00000221700.11; ENSP00000221700.3; NM_001082.5; NP_001073.3.
DR UCSC; uc002nbs.2; human. [P78329-1]
DR CTD; 8529; -.
DR DisGeNET; 8529; -.
DR GeneCards; CYP4F2; -.
DR HGNC; HGNC:2645; CYP4F2.
DR HPA; ENSG00000186115; Tissue enhanced (intestine, kidney, liver).
DR MIM; 122700; phenotype.
DR MIM; 604426; gene.
DR neXtProt; NX_P78329; -.
DR OpenTargets; ENSG00000186115; -.
DR Orphanet; 413674; Prediction of toxicity or dose selection of vitamin K antagonists.
DR PharmGKB; PA27121; -.
DR VEuPathDB; HostDB:ENSG00000186115; -.
DR eggNOG; KOG0157; Eukaryota.
DR GeneTree; ENSGT00940000154646; -.
DR HOGENOM; CLU_001570_5_1_1; -.
DR InParanoid; P78329; -.
DR OMA; IVHECNR; -.
DR OrthoDB; 1247045at2759; -.
DR PhylomeDB; P78329; -.
DR TreeFam; TF105088; -.
DR BioCyc; MetaCyc:HS02675-MON; -.
DR BRENDA; 1.14.14.94; 2681.
DR PathwayCommons; P78329; -.
DR Reactome; R-HSA-211935; Fatty acids.
DR Reactome; R-HSA-211958; Miscellaneous substrates.
DR Reactome; R-HSA-211979; Eicosanoids.
DR Reactome; R-HSA-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX).
DR Reactome; R-HSA-2142816; Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).
DR SignaLink; P78329; -.
DR UniPathway; UPA00383; -.
DR UniPathway; UPA00883; -.
DR UniPathway; UPA01054; -.
DR BioGRID-ORCS; 8529; 35 hits in 1060 CRISPR screens.
DR ChiTaRS; CYP4F2; human.
DR GeneWiki; CYP4F2; -.
DR GenomeRNAi; 8529; -.
DR Pharos; P78329; Tchem.
DR PRO; PR:P78329; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P78329; protein.
DR Bgee; ENSG00000186115; Expressed in jejunal mucosa and 111 other tissues.
DR ExpressionAtlas; P78329; baseline and differential.
DR Genevisible; P78329; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:UniProtKB.
DR GO; GO:0097259; F:20-aldehyde-leukotriene B4 20-monooxygenase activity; TAS:Reactome.
DR GO; GO:0097258; F:20-hydroxy-leukotriene B4 omega oxidase activity; TAS:Reactome.
DR GO; GO:0018685; F:alkane 1-monooxygenase activity; IDA:BHF-UCL.
DR GO; GO:0052871; F:alpha-tocopherol omega-hydroxylase activity; IDA:UniProtKB.
DR GO; GO:0008392; F:arachidonic acid epoxygenase activity; IDA:UniProtKB.
DR GO; GO:0008391; F:arachidonic acid monooxygenase activity; IBA:GO_Central.
DR GO; GO:0052869; F:arachidonic acid omega-hydroxylase activity; IDA:UniProtKB.
DR GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC.
DR GO; GO:0102207; F:docosanoate omega-hydroxylase activity; IEA:RHEA.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0050051; F:leukotriene-B4 20-monooxygenase activity; IDA:UniProtKB.
DR GO; GO:0102033; F:long-chain fatty acid omega-hydroxylase activity; IDA:UniProtKB.
DR GO; GO:0004497; F:monooxygenase activity; TAS:Reactome.
DR GO; GO:0016709; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen; IDA:UniProtKB.
DR GO; GO:0052872; F:tocotrienol omega-hydroxylase activity; IDA:UniProtKB.
DR GO; GO:0019369; P:arachidonic acid metabolic process; IDA:UniProtKB.
DR GO; GO:0007596; P:blood coagulation; TAS:UniProtKB.
DR GO; GO:0019373; P:epoxygenase P450 pathway; IDA:UniProtKB.
DR GO; GO:0010430; P:fatty acid omega-oxidation; IDA:UniProtKB.
DR GO; GO:0006690; P:icosanoid metabolic process; TAS:Reactome.
DR GO; GO:0036101; P:leukotriene B4 catabolic process; IDA:UniProtKB.
DR GO; GO:0006691; P:leukotriene metabolic process; TAS:Reactome.
DR GO; GO:0001676; P:long-chain fatty acid metabolic process; IDA:BHF-UCL.
DR GO; GO:0042361; P:menaquinone catabolic process; IDA:UniProtKB.
DR GO; GO:0032304; P:negative regulation of icosanoid secretion; IMP:UniProtKB.
DR GO; GO:0097267; P:omega-hydroxylase P450 pathway; IDA:UniProtKB.
DR GO; GO:0042376; P:phylloquinone catabolic process; IDA:UniProtKB.
DR GO; GO:0032305; P:positive regulation of icosanoid secretion; IMP:UniProtKB.
DR GO; GO:0003095; P:pressure natriuresis; IEP:UniProtKB.
DR GO; GO:0008217; P:regulation of blood pressure; IMP:UniProtKB.
DR GO; GO:0003091; P:renal water homeostasis; IEP:UniProtKB.
DR GO; GO:0055078; P:sodium ion homeostasis; IEP:UniProtKB.
DR GO; GO:0000038; P:very long-chain fatty acid metabolic process; IDA:BHF-UCL.
DR GO; GO:0042360; P:vitamin E metabolic process; IDA:UniProtKB.
DR GO; GO:0042377; P:vitamin K catabolic process; IDA:UniProtKB.
DR GO; GO:0006805; P:xenobiotic metabolic process; IMP:UniProtKB.
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; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Direct protein sequencing; Endoplasmic reticulum;
KW Fatty acid metabolism; Heme; Iron; Lipid metabolism; Membrane;
KW Metal-binding; Microsome; Monooxygenase; Oxidoreductase;
KW Reference proteome.
FT PROPEP 1..4
FT /evidence="ECO:0000269|PubMed:9799565"
FT /id="PRO_0000430581"
FT CHAIN 5..520
FT /note="Cytochrome P450 4F2"
FT /id="PRO_0000051850"
FT BINDING 328
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /note="covalent"
FT /evidence="ECO:0000250|UniProtKB:P24464"
FT BINDING 468
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|UniProtKB:P24464"
FT VAR_SEQ 1..149
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055578"
FT VAR_SEQ 307..339
FT /note="DEDGKKLSDEDIRAEADTFMFEGHDTTASGLSW -> AMTPRPVVSPGSCTT
FT LQSTQNTRSAAGRRCKNF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055579"
FT VAR_SEQ 340..520
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055580"
FT VARIANT 7
FT /note="S -> Y (in dbSNP:rs3093104)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_013116"
FT VARIANT 12
FT /note="W -> G (in dbSNP:rs3093105)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:9799565, ECO:0000269|Ref.5"
FT /id="VAR_013117"
FT VARIANT 185
FT /note="G -> V (in dbSNP:rs3093153)"
FT /evidence="ECO:0000269|PubMed:14702039, ECO:0000269|Ref.5"
FT /id="VAR_013118"
FT VARIANT 269
FT /note="A -> D (in dbSNP:rs1599353639)"
FT /id="VAR_020125"
FT VARIANT 433
FT /note="V -> M (associated with coumarin resistance;
FT increased warfarin maintenance dose in patients on warfarin
FT anti-coagulant therapy due to decreased vitamin K
FT catabolism; decreased phylloquinone omega-hydroxylase
FT activity; decreased production of 20-
FT hydroxyeicosatetraenoic acid (20-HETE); dbSNP:rs2108622)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17341693, ECO:0000269|PubMed:18250228,
FT ECO:0000269|PubMed:18574070, ECO:0000269|PubMed:19207028,
FT ECO:0000269|PubMed:19270263, ECO:0000269|PubMed:19297519,
FT ECO:0000269|PubMed:20555338, ECO:0000269|PubMed:23132553,
FT ECO:0000269|Ref.5"
FT /id="VAR_013119"
FT VARIANT 519
FT /note="L -> M (in dbSNP:rs3093200)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_013120"
FT CONFLICT 12..13
FT /note="WP -> CR (in Ref. 3; AAC50052 and 9; AAF86378)"
FT /evidence="ECO:0000305"
FT CONFLICT 25
FT /note="V -> A (in Ref. 8; AAH67437)"
FT /evidence="ECO:0000305"
FT CONFLICT 169
FT /note="E -> D (in Ref. 8; AAH67440)"
FT /evidence="ECO:0000305"
FT CONFLICT 336
FT /note="G -> V (in Ref. 3; AAC50052)"
FT /evidence="ECO:0000305"
FT CONFLICT 391
FT /note="L -> V (in Ref. 3; AAC50052)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 520 AA; 59853 MW; 1791F9E6EECB59B5 CRC64;
MSQLSLSWLG LWPVAASPWL LLLLVGASWL LAHVLAWTYA FYDNCRRLRC FPQPPRRNWF
WGHQGMVNPT EEGMRVLTQL VATYPQGFKV WMGPISPLLS LCHPDIIRSV INASAAIAPK
DKFFYSFLEP WLGDGLLLSA GDKWSRHRRM LTPAFHFNIL KPYMKIFNES VNIMHAKWQL
LASEGSACLD MFEHISLMTL DSLQKCVFSF DSHCQEKPSE YIAAILELSA LVSKRHHEIL
LHIDFLYYLT PDGQRFRRAC RLVHDFTDAV IQERRRTLPS QGVDDFLQAK AKSKTLDFID
VLLLSKDEDG KKLSDEDIRA EADTFMFEGH DTTASGLSWV LYHLAKHPEY QERCRQEVQE
LLKDREPKEI EWDDLAHLPF LTMCMKESLR LHPPVPVISR HVTQDIVLPD GRVIPKGIIC
LISVFGTHHN PAVWPDPEVY DPFRFDPENI KERSPLAFIP FSAGPRNCIG QTFAMAEMKV
VLALTLLRFR VLPDHTEPRR KPELVLRAEG GLWLRVEPLS
