Phylloquinone omega-hydroxylase CYP4F2

Details

Name
Phylloquinone omega-hydroxylase CYP4F2
Synonyms
  • 1.14.13.194
  • 20-HETE synthase
  • 20-hydroxyeicosatetraenoic acid synthase
  • Arachidonic acid omega-hydroxylase
  • CYPIVF2
  • Cytochrome P450 4F2
  • Cytochrome P450-LTB-omega
  • Leukotriene-B(4) 20-monooxygenase 1
  • Leukotriene-B(4) omega-hydroxylase 1
Gene Name
CYP4F2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0008578|Phylloquinone omega-hydroxylase CYP4F2
MSQLSLSWLGLWPVAASPWLLLLLVGASWLLAHVLAWTYAFYDNCRRLRCFPQPPRRNWF
WGHQGMVNPTEEGMRVLTQLVATYPQGFKVWMGPISPLLSLCHPDIIRSVINASAAIAPK
DKFFYSFLEPWLGDGLLLSAGDKWSRHRRMLTPAFHFNILKPYMKIFNESVNIMHAKWQL
LASEGSACLDMFEHISLMTLDSLQKCVFSFDSHCQEKPSEYIAAILELSALVSKRHHEIL
LHIDFLYYLTPDGQRFRRACRLVHDFTDAVIQERRRTLPSQGVDDFLQAKAKSKTLDFID
VLLLSKDEDGKKLSDEDIRAEADTFMFEGHDTTASGLSWVLYHLAKHPEYQERCRQEVQE
LLKDREPKEIEWDDLAHLPFLTMCMKESLRLHPPVPVISRHVTQDIVLPDGRVIPKGIIC
LISVFGTHHNPAVWPDPEVYDPFRFDPENIKERSPLAFIPFSAGPRNCIGQTFAMAEMKV
VLALTLLRFRVLPDHTEPRRKPELVLRAEGGLWLRVEPLS
Number of residues
520
Molecular Weight
59852.825
Theoretical pI
Not Available
GO Classification
Functions
alkane 1-monooxygenase activity / alpha-tocopherol omega-hydroxylase activity / arachidonic acid epoxygenase activity / arachidonic acid omega-hydroxylase activity / heme binding / iron ion binding / leukotriene-B4 20-monooxygenase activity / 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 / tocotrienol omega-hydroxylase activity
Processes
arachidonic acid metabolic process / blood coagulation / drug metabolic process / epoxygenase P450 pathway / icosanoid metabolic process / leukotriene B4 catabolic process / leukotriene metabolic process / long-chain fatty acid metabolic process / menaquinone catabolic process / negative regulation of icosanoid secretion / omega-hydroxylase P450 pathway / oxidation-reduction process / phylloquinone catabolic process / positive regulation of icosanoid secretion / pressure natriuresis / regulation of blood pressure / renal water homeostasis / small molecule metabolic process / sodium ion homeostasis / very long-chain fatty acid metabolic process / vitamin E metabolic process / vitamin K catabolic process / xenobiotic metabolic process
Components
apical plasma membrane / cytoplasm / endoplasmic reticulum membrane / intracellular membrane-bounded organelle
General Function
Not Available
Specific Function
Not Available
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Microsome membrane
Gene sequence
>lcl|BSEQ0013284|Phylloquinone omega-hydroxylase CYP4F2 (CYP4F2)
ATGTCCCAGCTGAGCCTGTCCTGGCTGGGCCTCTGGCCAGTGGCAGCATCCCCTTGGCTG
CTCCTCCTGCTGGTCGGGGCCTCCTGGCTCCTGGCCCATGTCCTGGCCTGGACCTACGCC
TTCTATGACAACTGCCGCCGCCTTCGGTGTTTCCCACAACCCCCAAGACGGAACTGGTTT
TGGGGACACCAGGGCATGGTCAACCCCACAGAGGAGGGCATGAGAGTTCTGACTCAGCTG
GTGGCCACCTACCCCCAGGGCTTTAAGGTCTGGATGGGACCCATCTCCCCCCTCCTCAGT
TTGTGCCACCCCGACATCATCCGGTCTGTCATCAACGCCTCAGCTGCCATTGCACCAAAG
GACAAGTTCTTCTACAGCTTCCTGGAGCCCTGGCTGGGGGATGGGCTCCTGCTGAGTGCT
GGTGACAAGTGGAGCCGCCACCGTCGGATGCTGACGCCTGCCTTCCATTTCAACATCCTG
AAGCCCTATATGAAGATTTTCAATGAGAGTGTGAACATCATGCACGCCAAGTGGCAGCTC
CTGGCCTCAGAGGGTAGTGCCTGTTTGGATATGTTTGAGCACATCAGCCTCATGACCTTG
GACAGTCTACAGAAATGTGTCTTCAGCTTTGACAGCCATTGTCAGGAGAAACCCAGTGAA
TATATTGCCGCCATCTTGGAGCTCAGTGCCCTTGTATCAAAAAGACACCATGAGATCCTC
CTGCATATTGACTTCCTGTATTATCTCACCCCTGATGGGCAGCGTTTCCGCAGGGCCTGC
CGCCTGGTGCACGACTTCACAGATGCCGTCATCCAGGAGCGGCGCCGCACTCTCCCTAGC
CAGGGTGTTGATGACTTCCTCCAAGCCAAGGCCAAATCCAAGACTTTGGACTTCATTGAT
GTACTCCTGCTGAGCAAGGATGAAGACGGGAAGAAGTTATCTGATGAGGACATAAGAGCA
GAAGCTGACACCTTTATGTTTGAGGGCCATGACACCACGGCCAGTGGTCTCTCCTGGGTC
CTGTACCACCTTGCAAAGCACCCAGAATACCAGGAGCGCTGCCGGCAGGAGGTGCAAGAA
CTTCTGAAGGACCGTGAGCCTAAAGAGATTGAATGGGACGACCTGGCCCATTTGCCCTTC
CTGACCATGTGCATGAAGGAGAGCCTGCGGCTGCATCCCCCAGTCCCGGTCATCTCCCGC
CATGTCACCCAGGACATTGTGCTCCCAGACGGCCGGGTCATCCCCAAAGGCATTATCTGC
CTCATCAGTGTTTTCGGAACCCATCACAACCCAGCTGTGTGGCCGGACCCTGAGGTCTAC
GACCCCTTTCGCTTTGACCCAGAGAACATCAAGGAGAGGTCACCTCTGGCTTTTATTCCC
TTCTCGGCAGGGCCCAGGAACTGCATCGGGCAGACGTTCGCGATGGCGGAGATGAAGGTG
GTCCTGGCGCTCACGCTGCTGCGCTTCCGCGTCCTGCCTGACCACACCGAGCCCCGCAGG
AAGCCGGAGCTGGTCCTGCGCGCAGAGGGCGGACTTTGGCTGCGGGTGGAGCCCCTGAGC
TGA
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP78329
UniProtKB Entry NameCP4F2_HUMAN
HGNC IDHGNC:2645
General References
  1. Kikuta Y, Kusunose E, Kondo T, Yamamoto S, Kinoshita H, Kusunose M: Cloning and expression of a novel form of leukotriene B4 omega-hydroxylase from human liver. FEBS Lett. 1994 Jul 4;348(1):70-4. [Article]
  2. Kikuta Y, Miyauchi Y, Kusunose E, Kusunose M: Expression and molecular cloning of human liver leukotriene B4 omega-hydroxylase (CYP4F2) gene. DNA Cell Biol. 1999 Sep;18(9):723-30. [Article]
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
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  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  6. Zhang X, Chen L, Hardwick JP: Promoter activity and regulation of the CYP4F2 leukotriene B(4) omega-hydroxylase gene by peroxisomal proliferators and retinoic acid in HepG2 cells. Arch Biochem Biophys. 2000 Jun 15;378(2):364-76. [Article]
  7. Jin R, Koop DR, Raucy JL, Lasker JM: Role of human CYP4F2 in hepatic catabolism of the proinflammatory agent leukotriene B4. Arch Biochem Biophys. 1998 Nov 1;359(1):89-98. [Article]
  8. Lasker JM, Chen WB, Wolf I, Bloswick BP, Wilson PD, Powell PK: Formation of 20-hydroxyeicosatetraenoic acid, a vasoactive and natriuretic eicosanoid, in human kidney. Role of Cyp4F2 and Cyp4A11. J Biol Chem. 2000 Feb 11;275(6):4118-26. [Article]
  9. Stec DE, Roman RJ, Flasch A, Rieder MJ: Functional polymorphism in human CYP4F2 decreases 20-HETE production. Physiol Genomics. 2007 Jun 19;30(1):74-81. Epub 2007 Mar 6. [Article]
  10. Fava C, Montagnana M, Almgren P, Rosberg L, Lippi G, Hedblad B, Engstrom G, Berglund G, Minuz P, Melander O: The V433M variant of the CYP4F2 is associated with ischemic stroke in male Swedes beyond its effect on blood pressure. Hypertension. 2008 Aug;52(2):373-80. doi: 10.1161/HYPERTENSIONAHA.108.114199. Epub 2008 Jun 23. [Article]
  11. Caldwell MD, Awad T, Johnson JA, Gage BF, Falkowski M, Gardina P, Hubbard J, Turpaz Y, Langaee TY, Eby C, King CR, Brower A, Schmelzer JR, Glurich I, Vidaillet HJ, Yale SH, Qi Zhang K, Berg RL, Burmester JK: CYP4F2 genetic variant alters required warfarin dose. Blood. 2008 Apr 15;111(8):4106-12. doi: 10.1182/blood-2007-11-122010. Epub 2008 Feb 4. [Article]
  12. Perez-Andreu V, Roldan V, Anton AI, Garcia-Barbera N, Corral J, Vicente V, Gonzalez-Conejero R: Pharmacogenetic relevance of CYP4F2 V433M polymorphism on acenocoumarol therapy. Blood. 2009 May 14;113(20):4977-9. doi: 10.1182/blood-2008-09-176222. Epub 2009 Mar 6. [Article]
  13. McDonald MG, Rieder MJ, Nakano M, Hsia CK, Rettie AE: CYP4F2 is a vitamin K1 oxidase: An explanation for altered warfarin dose in carriers of the V433M variant. Mol Pharmacol. 2009 Jun;75(6):1337-46. doi: 10.1124/mol.109.054833. Epub 2009 Mar 18. [Article]
  14. Borgiani P, Ciccacci C, Forte V, Sirianni E, Novelli L, Bramanti P, Novelli G: CYP4F2 genetic variant (rs2108622) significantly contributes to warfarin dosing variability in the Italian population. Pharmacogenomics. 2009 Feb;10(2):261-6. doi: 10.2217/14622416.10.2.261. [Article]
  15. Ross KA, Bigham AW, Edwards M, Gozdzik A, Suarez-Kurtz G, Parra EJ: Worldwide allele frequency distribution of four polymorphisms associated with warfarin dose requirements. J Hum Genet. 2010 Sep;55(9):582-9. doi: 10.1038/jhg.2010.73. Epub 2010 Jun 17. [Article]
  16. Bardowell SA, Stec DE, Parker RS: Common variants of cytochrome P450 4F2 exhibit altered vitamin E-{omega}-hydroxylase specific activity. J Nutr. 2010 Nov;140(11):1901-6. doi: 10.3945/jn.110.128579. Epub 2010 Sep 22. [Article]
  17. Danese E, Montagnana M, Johnson JA, Rettie AE, Zambon CF, Lubitz SA, Suarez-Kurtz G, Cavallari LH, Zhao L, Huang M, Nakamura Y, Mushiroda T, Kringen MK, Borgiani P, Ciccacci C, Au NT, Langaee T, Siguret V, Loriot MA, Sagreiya H, Altman RB, Shahin MH, Scott SA, Khalifa SI, Chowbay B, Suriapranata IM, Teichert M, Stricker BH, Taljaard M, Botton MR, Zhang JE, Pirmohamed M, Zhang X, Carlquist JF, Horne BD, Lee MT, Pengo V, Guidi GC, Minuz P, Fava C: Impact of the CYP4F2 p.V433M polymorphism on coumarin dose requirement: systematic review and meta-analysis. Clin Pharmacol Ther. 2012 Dec;92(6):746-56. doi: 10.1038/clpt.2012.184. Epub 2012 Nov 7. [Article]
  18. Edson KZ, Prasad B, Unadkat JD, Suhara Y, Okano T, Guengerich FP, Rettie AE: Cytochrome P450-dependent catabolism of vitamin K: omega-hydroxylation catalyzed by human CYP4F2 and CYP4F11. Biochemistry. 2013 Nov 19;52(46):8276-85. doi: 10.1021/bi401208m. Epub 2013 Nov 7. [Article]
  19. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB08868Fingolimodapproved, investigationalunknownsubstrateinducerDetails
DB09148Florbetaben (18F)approvednosubstrateDetails
DB11251Tocopherolapproved, investigationalnosubstrateDetails
DB14003alpha-Tocopherol acetateapprovednosubstrateDetails
DB11635TocofersolanapprovedunknownsubstrateDetails
DB09568Omega-3-carboxylic acidsapproved, investigationalnosubstrateDetails
DB01026Ketoconazoleapproved, investigationalunknowninhibitorDetails
DB01022Phylloquinoneapproved, investigationalunknownsubstrateDetails
DB12151Brincidofovirapproved, investigationalnosubstrateinhibitorDetails