CYP4F3

Cytochrome P450, family 4, subfamily F, polypeptide 3
Identifiers
Symbols CYP4F3 ; CPF3; CYP4F; LTB4H
External IDs OMIM: 601270 MGI: 1919304 HomoloGene: 73902 GeneCards: CYP4F3 Gene
EC number 1.14.13.199, 1.14.13.30
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 4051 170716
Ensembl ENSG00000186529 ENSMUSG00000024055
UniProt Q08477 n/a
RefSeq (mRNA) NM_000896 NM_130882
RefSeq (protein) NP_000887 NP_570952
Location (UCSC) Chr 19:
15.62 – 15.66 Mb		 Chr 17:
32.92 – 32.95 Mb
PubMed search

Leukotriene-B(4) omega-hydroxylase 2 is an enzyme that in humans is encoded by the CYP4F3 gene.[1][2][3]

Function

This gene, CYP4F3, encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids, fatty acids and other lipids. This protein localizes to the endoplasmic reticulum. The enzyme starts the process of inactivating and degrading leukotriene B4, a potent mediator of inflammation. This gene is part of a cluster of cytochrome P450 genes on chromosome 19. Another member of this family, CYP4F8, is approximately 18 kb away.[3]

CYP4A3 along with CYP4A22, CYP4F2, and CYP4A11 also metabolize arachidonic acid to 20-Hydroxyeicosatetraenoic acid (20-HETE) by an Omega oxidation reaction with the predominant 20-HETE-synthesizing enzymes in humans being CYP4F2 followed by CYP4A11; 20-HETE regulates blood flow, vascularization, blood pressure, and kidney tubule absorption of ions in rodents and possibly humans.[4]

Members of the CYP4A and CYP4F sub-families may also ω-hydroxylate and thereby reduce the activity of various fatty acid metabolites of arachidonic acid including LTB4, 5-HETE, 5-oxo-eicosatetraenoic acid, 12-HETE, and several prostaglandins that are involved in regulating various inflammatory, vascular, and other responses in animals and humans.[5][6] This hydroxylation-induced inactivation may underlie the proposed roles of the cytochromes in dampening inflammatory responses and the reported associations of certain CYP4F2 and CYP4F3 single nucleotide variants with human Krohn's disease and Coeliac disease, respectively.[7][8][9]

References

  1. ↑ Kikuta Y, Kusunose E, Endo K, Yamamoto S, Sogawa K, Fujii-Kuriyama Y, Kusunose M (May 1993). "A novel form of cytochrome P-450 family 4 in human polymorphonuclear leukocytes. cDNA cloning and expression of leukotriene B4 omega-hydroxylase". The Journal of Biological Chemistry 268 (13): 9376–80. PMID 8486631.
  2. ↑ Kikuta Y, Kato M, Yamashita Y, Miyauchi Y, Tanaka K, Kamada N, Kusunose M (Mar 1998). "Human leukotriene B4 omega-hydroxylase (CYP4F3) gene: molecular cloning and chromosomal localization". DNA and Cell Biology 17 (3): 221–30. doi:10.1089/dna.1998.17.221. PMID 9539102.
  3. 1 2 "Entrez Gene: CYP4F3 cytochrome P450, family 4, subfamily F, polypeptide 3".
  4. ↑ Hoopes SL, Garcia V, Edin ML, Schwartzman ML, Zeldin DC (Jul 2015). "Vascular actions of 20-HETE". Prostaglandins & Other Lipid Mediators 120: 9–16. doi:10.1016/j.prostaglandins.2015.03.002. PMID 25813407.
  5. ↑ Arch Biochem Biophys. 1998 Jul 15;355(2):201
  6. ↑ Biochem Pharmacol. 2008 Jun 15;75(12):2263-75. doi:10.1016/j.bcp.2008.03.004
  7. ↑ Eur J Hum Genet. 2006 Nov;14(11):1215-22
  8. ↑ Drug Metabol Drug Interact. 2012 Apr 19;27(2):63-71. doi:10.1515/dmdi-2011-0037
  9. ↑ Gastroenterology. 2014 Apr;146(4):929-31. doi:10.1053/j.gastro.2013.12.034

Further reading

  • Simpson AE (Mar 1997). "The cytochrome P450 4 (CYP4) family". General Pharmacology 28 (3): 351–9. doi:10.1016/S0306-3623(96)00246-7. PMID 9068972. 
  • Kikuta Y, Kusunose E, Kondo T, Yamamoto S, Kinoshita H, Kusunose M (Jul 1994). "Cloning and expression of a novel form of leukotriene B4 omega-hydroxylase from human liver". FEBS Letters 348 (1): 70–4. doi:10.1016/0014-5793(94)00587-7. PMID 8026587. 
  • Christmas P, Ursino SR, Fox JW, Soberman RJ (Jul 1999). "Expression of the CYP4F3 gene. tissue-specific splicing and alternative promoters generate high and low K(m) forms of leukotriene B(4) omega-hydroxylase". The Journal of Biological Chemistry 274 (30): 21191–9. doi:10.1074/jbc.274.30.21191. PMID 10409674. 
  • Christmas P, Jones JP, Patten CJ, Rock DA, Zheng Y, Cheng SM, Weber BM, Carlesso N, Scadden DT, Rettie AE, Soberman RJ (Oct 2001). "Alternative splicing determines the function of CYP4F3 by switching substrate specificity". The Journal of Biological Chemistry 276 (41): 38166–72. doi:10.1074/jbc.M104818200. PMID 11461919. 
  • Christmas P, Carlesso N, Shang H, Cheng SM, Weber BM, Preffer FI, Scadden DT, Soberman RJ (Jul 2003). "Myeloid expression of cytochrome P450 4F3 is determined by a lineage-specific alternative promoter". The Journal of Biological Chemistry 278 (27): 25133–42. doi:10.1074/jbc.M302106200. PMID 12709424. 
  • Mizukami Y, Sumimoto H, Takeshige K (Jan 2004). "Induction of cytochrome CYP4F3A in all-trans-retinoic acid-treated HL60 cells". Biochemical and Biophysical Research Communications 314 (1): 104–9. doi:10.1016/j.bbrc.2003.12.062. PMID 14715252. 
  • Christmas P, Tolentino K, Primo V, Berry KZ, Murphy RC, Chen M, Lee DM, Soberman RJ (Mar 2006). "Cytochrome P-450 4F18 is the leukotriene B4 omega-1/omega-2 hydroxylase in mouse polymorphonuclear leukocytes: identification as the functional orthologue of human polymorphonuclear leukocyte CYP4F3A in the down-regulation of responses to LTB4". The Journal of Biological Chemistry 281 (11): 7189–96. doi:10.1074/jbc.M513101200. PMID 16380383. 


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