The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

CYP4F3  -  cytochrome P450, family 4, subfamily F,...

Homo sapiens

Synonyms: 20-HETE synthase, 20-hydroxyeicosatetraenoic acid synthase, CPF3, CYP4F, CYPIVF3, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

High impact information on CYP4F3

  • To elucidate the role of CYP4F-mediated inactivation of LTB(4) in terminating the responses of PMN to LTB(4) and to identify a target for future genetic studies in mice, we have identified the enzyme that catalyzes the omega-1 and omega-2 oxidation of LTB(4) in mouse myeloid cells as CYP4F18 [1].
  • Initially, we analyzed the distribution of CYP4F3 in human leukocytes and determined a lineage-specific pattern of isoform expression [2].
  • We identified distinct transcriptional features in myeloid, lymphoid, and hepatic cells that indicate the presence of multiple promoters in the CYP4F3 gene [2].
  • Alternative splicing determines the function of CYP4F3 by switching substrate specificity [3].
  • We report that the use of alternate exons, each coding for 48 amino acids, generates isoforms of human CYP4F3 that differ in substrate specificity, tissue distribution, and biological function [3].

Biological context of CYP4F3


Anatomical context of CYP4F3

  • CYP4F3 is the most tissue specific and most efficient LTB4 omega-hydroxylase, judging from its restricted localization in human polymorphonuclear leukocytes (PMN) and its very low Km value for LTB4 [9].
  • Moreover, vicinal diol from both C18-epoxides and EETs were omega-hydroxylated by liver microsomes and by CYP4F2 and CYP4F3 [10].
  • Promoter analysis of the CYP4F3 gene demonstrated that a region (-174/-90) of this gene was important for its promoter activity in the HL60 cells [6].
  • CYP4F3 was expressed in one third of the peripheral monocytes, which omega-hydroxylated leukotriene B(4) (LTB(4)) at a rate 11 times lower than that of PMN [6].
  • The cells that were differentiated into a form similar to monocytes/macrophages in shape by treatment with 12-myristate 13-acetate expressed mRNA for CYP4F3 and CYP4F3B [6].

Associations of CYP4F3 with chemical compounds

  • In a preceding paper (Kikuta et al., 1993), we showed human polymorphonuclear leukocyte (PMN) LTB4 omega-hydroxylase to be a novel form of cytochrome P450, designated CYP4F3, on the basis of its cDNA cloning and expression in yeast cells [4].
  • The HL60 cells, which were differentiated into PMN-like shapes by treatment with all-trans-retinoic acid (RA), also expressed CYP4F3, CYP4F3B and CYP4F12 [6].
  • When expressed in Saccharomyces cerevisiae, the P450 catalyzes leukotriene B(4) omega-hydroxylation and arachidonic acid omega-hydroxylation, typical reactions of CYP4F isoforms [7].
  • However, the inhibitory effects were only partial (about 20%) and thus it was thought that, although human CYP4F was involved in ebastine hydroxylation, another predominant enzyme exists [11].
  • In this study, we have determined the activities of all of the rat and human CYP4A enzymes and two of the rat CYP4F enzymes, with respect to the omega-hydroxylation of phytanic acid [12].

Other interactions of CYP4F3

  • The deduced protein showed 81.2 and 76.7% amino acid identity with the human enzymes CYP4F2 and CYP4F3 [8].
  • This cDNA contains an entire coding region of a 524-amino-acid protein that is 81.7, 78.3, and 78.2% identical to CYP4F2, CYP4F3, and CYP4F8, respectively [7].
  • A cDNA encoding a novel human CYP4F enzyme (designated CYP4F12) was cloned by PCR from a human small intestine cDNA library [7].
  • In addition, treatment of CYP4B1, CYP4F3, and CYP4A5/7 with strong base generated a new, chromatographically distinct, polar heme species with a mass of 632.3 amu rather than 616.2 amu [13].
  • We previously reported the cDNA cloning of a new CYP4F isoform, CYP4F11 [14].

Analytical, diagnostic and therapeutic context of CYP4F3


  1. 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. Christmas, P., Tolentino, K., Primo, V., Berry, K.Z., Murphy, R.C., Chen, M., Lee, D.M., Soberman, R.J. J. Biol. Chem. (2006) [Pubmed]
  2. Myeloid expression of cytochrome P450 4F3 is determined by a lineage-specific alternative promoter. Christmas, P., Carlesso, N., Shang, H., Cheng, S.M., Weber, B.M., Preffer, F.I., Scadden, D.T., Soberman, R.J. J. Biol. Chem. (2003) [Pubmed]
  3. Alternative splicing determines the function of CYP4F3 by switching substrate specificity. Christmas, P., Jones, J.P., Patten, C.J., Rock, D.A., Zheng, Y., Cheng, S.M., Weber, B.M., Carlesso, N., Scadden, D.T., Rettie, A.E., Soberman, R.J. J. Biol. Chem. (2001) [Pubmed]
  4. Human leukotriene B4 omega-hydroxylase (CYP4F3) gene: molecular cloning and chromosomal localization. Kikuta, Y., Kato, M., Yamashita, Y., Miyauchi, Y., Tanaka, K., Kamada, N., Kusunose, M. DNA Cell Biol. (1998) [Pubmed]
  5. Expression and molecular cloning of human liver leukotriene B4 omega-hydroxylase (CYP4F2) gene. Kikuta, Y., Miyauchi, Y., Kusunose, E., Kusunose, M. DNA Cell Biol. (1999) [Pubmed]
  6. Expression and induction of CYP4F subfamily in human leukocytes and HL60 cells. Kikuta, Y., Yamashita, Y., Kashiwagi, S., Tani, K., Okada, K., Nakata, K. Biochim. Biophys. Acta (2004) [Pubmed]
  7. cDNA cloning and expression of a novel cytochrome p450 (cyp4f12) from human small intestine. Hashizume, T., Imaoka, S., Hiroi, T., Terauchi, Y., Fujii, T., Miyazaki, H., Kamataki, T., Funae, Y. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  8. Gene expression of a novel cytochrome P450 of the CYP4F subfamily in human seminal vesicles. Bylund, J., Finnström, N., Oliw, E.H. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  9. Prostaglandin and leukotriene omega-hydroxylases. Kikuta, Y., Kusunose, E., Kusunose, M. Prostaglandins Other Lipid Mediat. (2002) [Pubmed]
  10. Human CYP4F3s are the main catalysts in the oxidation of fatty acid epoxides. Le Quéré, V., Plée-Gautier, E., Potin, P., Madec, S., Salaün, J.P. J. Lipid Res. (2004) [Pubmed]
  11. Involvement of CYP2J2 and CYP4F12 in the metabolism of ebastine in human intestinal microsomes. Hashizume, T., Imaoka, S., Mise, M., Terauchi, Y., Fujii, T., Miyazaki, H., Kamataki, T., Funae, Y. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
  12. CYP4 isoform specificity in the omega-hydroxylation of phytanic acid, a potential route to elimination of the causative agent of Refsum's disease. Xu, F., Ng, V.Y., Kroetz, D.L., de Montellano, P.R. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  13. Covalent linkage of prosthetic heme to CYP4 family P450 enzymes. Henne, K.R., Kunze, K.L., Zheng, Y.M., Christmas, P., Soberman, R.J., Rettie, A.E. Biochemistry (2001) [Pubmed]
  14. Expression and characterization of human cytochrome P450 4F11: Putative role in the metabolism of therapeutic drugs and eicosanoids. Kalsotra, A., Turman, C.M., Kikuta, Y., Strobel, H.W. Toxicol. Appl. Pharmacol. (2004) [Pubmed]
  15. Sexual dimorphism and tissue specificity in the expression of CYP4F forms in Sprague Dawley rats. Kalsotra, A., Anakk, S., Boehme, C.L., Strobel, H.W. Drug Metab. Dispos. (2002) [Pubmed]
WikiGenes - Universities