Cytochrome P450 4F3

Details

Name

Cytochrome P450 4F3

Synonyms

• 1.14.14.1
• 20-HETE synthase
• 20-hydroxyeicosatetraenoic acid synthase
• CYPIVF3
• Cytochrome P450-LTB-omega
• Docosahexaenoic acid omega-hydroxylase CYP4F3
• Leukotriene-B(4) 20-monooxygenase 2
• Leukotriene-B(4) omega-hydroxylase 2
• LTB4H

Gene Name

CYP4F3

Organism

Humans

Amino acid sequence

>lcl|BSEQ0052559|Cytochrome P450 4F3
MPQLSLSSLGLWPMAASPWLLLLLVGASWLLARILAWTYTFYDNCCRLRCFPQPPKRNWF
LGHLGLIHSSEEGLLYTQSLACTFGDMCCWWVGPWHAIVRIFHPTYIKPVLFAPAAIVPK
DKVFYSFLKPWLGDGLLLSAGEKWSRHRRMLTPAFHFNILKPYMKIFNESVNIMHAKWQL
LASEGSARLDMFEHISLMTLDSLQKCVFSFDSHCQEKPSEYIAAILELSALVTKRHQQIL
LYIDFLYYLTPDGQRFRRACRLVHDFTDAVIQERRRTLPSQGVDDFLQAKAKSKTLDFID
VLLLSKDEDGKKLSDEDIRAEADTFMFEGHDTTASGLSWVLYHLAKHPEYQERCRQEVQE
LLKDREPKEIEWDDLAQLPFLTMCIKESLRLHPPVPAVSRCCTQDIVLPDGRVIPKGIIC
LISVFGTHHNPAVWPDPEVYDPFRFDPKNIKERSPLAFIPFSAGPRNCIGQAFAMAEMKV
VLGLTLLRFRVLPDHTEPRRKPELVLRAEGGLWLRVEPLS

Number of residues

520

Molecular Weight

59846.085

Theoretical pI

Not Available

GO Classification

Functions

arachidonic acid monooxygenase activity / aromatase activity / heme binding / iron ion binding / leukotriene-B4 20-monooxygenase activity / monooxygenase activity

Processes

arachidonic acid metabolic process / icosanoid metabolic process / leukotriene B4 catabolic process / leukotriene metabolic process / menaquinone catabolic process / phylloquinone catabolic process / vitamin K catabolic process

Components

endoplasmic reticulum membrane / integral component of membrane / intracellular membrane-bounded organelle

General Function

A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and their oxygenated derivatives (oxylipins) (PubMed:8486631, PubMed:9675028, PubMed:11461919, PubMed:15145985, PubMed:16547005, PubMed:16820285, PubMed:18182499, PubMed:18065749, PubMed:18577768). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:9675028). May play a role in inactivation of proinflammatory and anti-inflammatory oxylipins during the resolution of inflammation (PubMed:8486631, PubMed:9675028, PubMed:11461919, PubMed:15145985, PubMed:15364545, PubMed:16547005, PubMed:16820285, PubMed:18182499, PubMed:18065749, PubMed:18577768).

Specific Function

Arachidonic acid monooxygenase activity

Pfam Domain Function

• p450 (PF00067)

Transmembrane Regions

11-31

Cellular Location

Endoplasmic reticulum membrane

Gene sequence

>lcl|BSEQ0052560|Cytochrome P450 4F3 (CYP4F3)
ATGCCACAGCTGAGCCTGTCCTCGCTGGGCCTTTGGCCAATGGCAGCATCCCCGTGGCTG
CTCCTGCTGCTGGTTGGGGCCTCCTGGCTCCTGGCCCGCATCCTGGCCTGGACCTATACC
TTCTATGACAACTGCTGCCGCCTCCGGTGTTTCCCGCAACCCCCGAAACGGAATTGGTTC
TTGGGTCACCTGGGCCTGATTCACAGCTCGGAGGAAGGTCTCCTATACACACAAAGCCTG
GCATGCACCTTCGGTGATATGTGCTGCTGGTGGGTGGGGCCCTGGCACGCAATCGTCCGC
ATCTTCCACCCCACCTACATCAAGCCTGTGCTCTTTGCTCCAGCTGCCATTGTACCAAAG
GACAAGGTCTTCTACAGCTTCCTGAAGCCCTGGCTGGGGGATGGGCTCCTGCTGAGTGCT
GGTGAAAAGTGGAGCCGCCACCGTCGGATGCTGACGCCTGCCTTCCATTTCAACATCCTG
AAGCCCTATATGAAGATTTTCAATGAGAGTGTGAACATCATGCATGCCAAGTGGCAGCTC
CTGGCCTCAGAGGGTAGTGCCCGTCTGGACATGTTTGAGCACATCAGCCTCATGACCTTG
GACAGTCTGCAGAAATGTGTCTTCAGCTTTGACAGCCATTGCCAGGAGAAGCCCAGTGAA
TATATTGCCGCCATCTTGGAGCTCAGTGCCCTTGTGACAAAAAGACACCAGCAGATCCTC
CTGTACATAGACTTCCTGTATTATCTCACCCCTGATGGGCAGCGTTTCCGCAGGGCCTGC
CGCCTGGTGCACGACTTCACAGATGCCGTCATCCAGGAGCGGCGCCGCACCCTCCCTAGC
CAGGGTGTTGATGACTTCCTCCAAGCCAAGGCCAAATCCAAGACTTTGGACTTCATTGAT
GTACTCCTGCTGAGCAAGGATGAAGATGGGAAGAAGTTGTCCGATGAGGACATAAGAGCA
GAAGCTGACACCTTTATGTTTGAGGGCCATGACACCACAGCCAGTGGTCTCTCCTGGGTC
CTGTACCACCTTGCAAAGCACCCGGAATACCAGGAGCGCTGTCGGCAGGAGGTGCAAGAG
CTTCTGAAGGACCGTGAGCCTAAAGAGATTGAATGGGACGACCTGGCCCAGCTGCCCTTC
CTGACCATGTGCATTAAGGAGAGCCTGAGGCTGCATCCCCCAGTCCCTGCCGTCTCTCGC
TGCTGCACCCAAGACATTGTGCTCCCAGACGGCCGGGTCATCCCCAAAGGCATTATCTGC
CTCATCAGTGTTTTTGGAACCCATCACAACCCAGCCGTGTGGCCGGACCCTGAGGTCTAT
GACCCCTTTCGCTTTGACCCAAAGAACATCAAGGAGAGGTCACCTCTGGCTTTTATTCCC
TTCTCAGCAGGGCCCAGGAACTGCATCGGGCAGGCGTTCGCGATGGCGGAGATGAAGGTG
GTCCTGGGGCTCACGCTGCTGCGCTTCCGCGTCCTGCCTGACCACACCGAGCCCCGCAGG
AAGCCGGAGCTGGTCCTGCGCGCAGAGGGCGGACTTTGGCTGCGGGTGGAGCCCCTGAGC
TGA

Chromosome Location

19

Locus

19p13.12

External Identifiers

Resource	Link
UniProtKB ID	Q08477
UniProtKB Entry Name	CP4F3_HUMAN
HGNC ID	HGNC:2646

General References

1. Kikuta Y, Kusunose E, Endo K, Yamamoto S, Sogawa K, Fujii-Kuriyama Y, Kusunose M: A novel form of cytochrome P-450 family 4 in human polymorphonuclear leukocytes. cDNA cloning and expression of leukotriene B4 omega-hydroxylase. J Biol Chem. 1993 May 5;268(13):9376-80. [Article]
2. Kikuta Y, Kato M, Yamashita Y, Miyauchi Y, Tanaka K, Kamada N, Kusunose M: Human leukotriene B4 omega-hydroxylase (CYP4F3) gene: molecular cloning and chromosomal localization. DNA Cell Biol. 1998 Mar;17(3):221-30. doi: 10.1089/dna.1998.17.221. [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]
4. Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, Hellsten U, Goodstein D, Couronne O, Tran-Gyamfi M, Aerts A, Altherr M, Ashworth L, Bajorek E, Black S, Branscomb E, Caenepeel S, Carrano A, Caoile C, Chan YM, Christensen M, Cleland CA, Copeland A, Dalin E, Dehal P, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Garcia C, Georgescu AM, Glavina T, Gomez M, Gonzales E, Groza M, Hammon N, Hawkins T, Haydu L, Ho I, Huang W, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Larionov V, Leem SH, Lopez F, Lou Y, Lowry S, Malfatti S, Martinez D, McCready P, Medina C, Morgan J, Nelson K, Nolan M, Ovcharenko I, Pitluck S, Pollard M, Popkie AP, Predki P, Quan G, Ramirez L, Rash S, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, She X, Smith D, Slezak T, Solovyev V, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wagner M, Wheeler J, Wu K, Xie G, Yang J, Dubchak I, Furey TS, DeJong P, Dickson M, Gordon D, Eichler EE, Pennacchio LA, Richardson P, Stubbs L, Rokhsar DS, Myers RM, Rubin EM, Lucas SM: The DNA sequence and biology of human chromosome 19. Nature. 2004 Apr 1;428(6982):529-35. [Article]
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. Kikuta Y, Kusunose E, Sumimoto H, Mizukami Y, Takeshige K, Sakaki T, Yabusaki Y, Kusunose M: Purification and characterization of recombinant human neutrophil leukotriene B4 omega-hydroxylase (cytochrome P450 4F3). Arch Biochem Biophys. 1998 Jul 15;355(2):201-5. doi: 10.1006/abbi.1998.0724. [Article]
7. Christmas P, Ursino SR, Fox JW, Soberman RJ: Expression of the CYP4F3 gene. tissue-specific splicing and alternative promoters generate high and low K(m) forms of leukotriene B(4) omega-hydroxylase. J Biol Chem. 1999 Jul 23;274(30):21191-9. doi: 10.1074/jbc.274.30.21191. [Article]
8. Christmas P, Jones JP, Patten CJ, Rock DA, Zheng Y, Cheng SM, Weber BM, Carlesso N, Scadden DT, Rettie AE, Soberman RJ: Alternative splicing determines the function of CYP4F3 by switching substrate specificity. J Biol Chem. 2001 Oct 12;276(41):38166-72. doi: 10.1074/jbc.M104818200. Epub 2001 Jul 18. [Article]
9. Le Quere V, Plee-Gautier E, Potin P, Madec S, Salaun JP: Human CYP4F3s are the main catalysts in the oxidation of fatty acid epoxides. J Lipid Res. 2004 Aug;45(8):1446-58. doi: 10.1194/jlr.M300463-JLR200. Epub 2004 May 16. [Article]
10. Kalsotra A, Turman CM, Kikuta Y, Strobel HW: Expression and characterization of human cytochrome P450 4F11: Putative role in the metabolism of therapeutic drugs and eicosanoids. Toxicol Appl Pharmacol. 2004 Sep 15;199(3):295-304. doi: 10.1016/j.taap.2003.12.033. [Article]
11. Sanders RJ, Ofman R, Duran M, Kemp S, Wanders RJA: Omega-oxidation of very long-chain fatty acids in human liver microsomes. Implications for X-linked adrenoleukodystrophy. J Biol Chem. 2006 May 12;281(19):13180-13187. doi: 10.1074/jbc.M513481200. Epub 2006 Mar 17. [Article]
12. Harmon SD, Fang X, Kaduce TL, Hu S, Raj Gopal V, Falck JR, Spector AA: Oxygenation of omega-3 fatty acids by human cytochrome P450 4F3B: effect on 20-hydroxyeicosatetraenoic acid production. Prostaglandins Leukot Essent Fatty Acids. 2006 Sep;75(3):169-77. doi: 10.1016/j.plefa.2006.05.005. Epub 2006 Jul 3. [Article]
13. Sanders RJ, Ofman R, Dacremont G, Wanders RJ, Kemp S: Characterization of the human omega-oxidation pathway for omega-hydroxy-very-long-chain fatty acids. FASEB J. 2008 Jun;22(6):2064-71. doi: 10.1096/fj.07-099150. Epub 2008 Jan 8. [Article]
14. Dhar M, Sepkovic DW, Hirani V, Magnusson RP, Lasker JM: Omega oxidation of 3-hydroxy fatty acids by the human CYP4F gene subfamily enzyme CYP4F11. J Lipid Res. 2008 Mar;49(3):612-24. doi: 10.1194/jlr.M700450-JLR200. Epub 2007 Dec 7. [Article]
15. Fer M, Corcos L, Dreano Y, Plee-Gautier E, Salaun JP, Berthou F, Amet Y: Cytochromes P450 from family 4 are the main omega hydroxylating enzymes in humans: CYP4F3B is the prominent player in PUFA metabolism. J Lipid Res. 2008 Nov;49(11):2379-89. doi: 10.1194/jlr.M800199-JLR200. Epub 2008 Jun 24. [Article]

Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB12016	Ponesimod	approved, investigational	unknown	substrate	Details