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 27-MAR-2024, entry version 204. 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 CC [NADPH--hemoprotein reductase] = 20-hydroxy-(5Z,8Z,11Z,14Z)- CC eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:39755, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, 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 CC [NADPH--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 CC [NADPH--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 CC [NADPH--hemoprotein reductase] = 18-hydroxy-(9S,10R)-epoxy- CC octadecanoate + 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 CC [NADPH--hemoprotein reductase] = 18-hydroxy-(9R,10S)-epoxy- CC octadecanoate + 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 CC [NADPH--hemoprotein reductase] = 18-hydroxy-12,13-epoxy-(9Z)- CC octadecenoate + 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 CC [NADPH--hemoprotein reductase] = 18-hydroxy-9,10-epoxy-(12Z)- CC octadecenoate + 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 CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:39055, 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: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 CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:39043, 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: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 CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:39059, 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: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 CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:39047, 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: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 CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:41520, 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:78277, ChEBI:CHEBI:78278; CC EC=1.14.14.78; 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 CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:41516, Rhea:RHEA- CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:18067, CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:78276; CC EC=1.14.14.78; 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 CC dual-enzyme Michaelis-Menten kinetics, suggesting simultaneous CC binding of two substrate molecules. The high affinity CC Michaelis-Menten constants are shown (PubMed:16547005). CC {ECO:0000269|PubMed:16547005, 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/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 45. 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; 9606-ENSP00000221700; -. DR PeptideAtlas; P78329; -. DR ProteomicsDB; 5249; -. DR ProteomicsDB; 57568; -. [P78329-1] DR Pumba; P78329; -. DR Antibodypedia; 2706; 180 antibodies from 27 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 AGR; HGNC:2645; -. 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 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; KPWQSRR; -. DR OrthoDB; 1611592at2759; -. DR PhylomeDB; P78329; -. DR TreeFam; TF105088; -. DR BioCyc; MetaCyc:HS02675-MONOMER; -. 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; 36 hits in 1140 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 112 other cell types or tissues. DR ExpressionAtlas; P78329; baseline and differential. 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:0052869; F:arachidonic acid omega-hydroxylase activity; IDA:UniProtKB. DR GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC. 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 CDD; cd20679; CYP4F; 1. DR Gene3D; 1.10.630.10; Cytochrome P450; 1. DR InterPro; IPR001128; Cyt_P450. DR InterPro; IPR017972; Cyt_P450_CS. DR InterPro; IPR002401; Cyt_P450_E_grp-I. DR InterPro; IPR036396; Cyt_P450_sf. DR PANTHER; PTHR24291:SF112; CYTOCHROME P450 4F2; 1. DR PANTHER; PTHR24291; CYTOCHROME P450 FAMILY 4; 1. DR Pfam; PF00067; p450; 1. DR PRINTS; PR00463; EP450I. DR PRINTS; PR00385; P450. DR SUPFAM; SSF48264; Cytochrome P450; 1. DR PROSITE; PS00086; CYTOCHROME_P450; 1. DR Genevisible; P78329; HS. 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 (risk factor for 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 FT 20-hydroxyeicosatetraenoic acid (20-HETE); FT 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 //