CYP4F2

Cytochrome P450, family 4, subfamily F, polypeptide 2
Identifiers
Symbols CYP4F2 ; CPF2
External IDs OMIM: 604426 MGI: 2158641 HomoloGene: 128623 IUPHAR: 1344 ChEMBL: 3379 GeneCards: CYP4F2 Gene
EC number 1.14.13.194, 1.14.13.30
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 8529 72054
Ensembl ENSG00000186115 ENSMUSG00000003484
UniProt P78329 Q99N16
RefSeq (mRNA) NM_001082 NM_024444
RefSeq (protein) NP_001073 NP_077764
Location (UCSC) Chr 19:
15.88 – 15.9 Mb		 Chr 8:
71.99 – 72.01 Mb
PubMed search

Leukotriene-B(4) omega-hydroxylase 1 is an enzyme that in humans is encoded by the CYP4F2 gene.[1][2][3]

Function

This gene 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, CYP4F11, is approximately 16 kb away.[3]

CYP4F2 along with CYP4A22, CYP4A11, and CYP4F3 and CYP2U1 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] Gene polymorphism variants of CYP4F2 are associated with the development of hypertension, cerebral infarction (i.e. ischemic stroke), and myocardial infarction in humans (see 20-Hydroxyeicosatetraenoic acid for details).,[5][6][7][7][8][6][7][9][9][10][11][12][13]

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.[14][15] This hydroxylation-induced inactivation may underlie the proposed roles of the cytochromes in dampening inflammatory responses and the reported associations of certain CYP4F2 single nucleotide variants (RSPs) with human Krohn's disease (RSPs termed Rs2108622[16] and Coeliac disease (rs3093156 and rs3093156).[17][18][19][20][21]

References

  1. ↑ Chen L, Hardwick JP (Jan 1993). "Identification of a new P450 subfamily, CYP4F1, expressed in rat hepatic tumors". Archives of Biochemistry and Biophysics 300 (1): 18–23. doi:10.1006/abbi.1993.1003. PMID 8424651.
  2. ↑ 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.
  3. 1 2 "Entrez Gene: CYP4F2 cytochrome P450, family 4, subfamily F, polypeptide 2".
  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. ↑ Hypertension. 2008 May;51(5):1393-8. doi:10.1161/HYPERTENSIONAHA.107.104463
  6. 1 2 Hypertension. 2008 Aug;52(2):373-80. doi:10.1161/HYPERTENSIONAHA.108.114199
  7. 1 2 3 Mol Biol Rep. 2012 Feb;39(2):1677-82. doi:10.1007/s11033-011-0907-y
  8. ↑ Hypertens Res. 2008 Sep;31(9):1719-26. doi:10.1291/hypres.31.1719
  9. 1 2 Am J Hypertens. 2008 Nov;21(11):1216-23. doi:10.1038/ajh.2008.276
  10. ↑ J Hypertens. 2014 Jul;32(7):1495-502; discussion 1502. doi:10.1097/HJH.0000000000000208
  11. ↑ Pharmacogenet Genomics. 2010 Mar;20(3):187-94. doi:10.1097/FPC.0b013e328336eefe
  12. ↑ Mol Genet Metab. 2009 Mar;96(3):145-7. doi:10.1016/j.ymgme.2008.11.161
  13. ↑ Physiol Genomics. 2007 Jun 19;30(1):74-81
  14. ↑ Arch Biochem Biophys. 1998 Jul 15;355(2):201
  15. ↑ Biochem Pharmacol. 2008 Jun 15;75(12):2263-75. doi:10.1016/j.bcp.2008.03.004
  16. ↑ http://www.snpedia.com/index.php/Rs2108622
  17. ↑ Eur J Hum Genet. 2006 Nov;14(11):1215-22
  18. ↑ Drug Metabol Drug Interact. 2012 Apr 19;27(2):63-71. doi:10.1515/dmdi-2011-0037
  19. ↑ Gastroenterology. 2014 Apr;146(4):929-31. doi:10.1053/j.gastro.2013.12.034
  20. ↑ PLoS One. 2010 Dec 20;5(12):e15672. doi: 10.1371/journal.pone.0015672
  21. ↑ Biochem Pharmacol. 2008 Jun 15;75(12):2263-75. doi: 10.1016/j.bcp.2008.03.004. Epub 2008 Mar 15.PMID 18433732

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. 
  • Powell PK, Wolf I, Jin R, Lasker JM (Jun 1998). "Metabolism of arachidonic acid to 20-hydroxy-5,8,11, 14-eicosatetraenoic acid by P450 enzymes in human liver: involvement of CYP4F2 and CYP4A11". The Journal of Pharmacology and Experimental Therapeutics 285 (3): 1327–36. PMID 9618440. 
  • Kikuta Y, Miyauchi Y, Kusunose E, Kusunose M (Sep 1999). "Expression and molecular cloning of human liver leukotriene B4 omega-hydroxylase (CYP4F2) gene". DNA and Cell Biology 18 (9): 723–30. doi:10.1089/104454999315006. PMID 10492403. 
  • Lasker JM, Chen WB, Wolf I, Bloswick BP, Wilson PD, Powell PK (Feb 2000). "Formation of 20-hydroxyeicosatetraenoic acid, a vasoactive and natriuretic eicosanoid, in human kidney. Role of Cyp4F2 and Cyp4A11". The Journal of Biological Chemistry 275 (6): 4118–26. doi:10.1074/jbc.275.6.4118. PMID 10660572. 
  • Zhang X, Chen L, Hardwick JP (Jun 2000). "Promoter activity and regulation of the CYP4F2 leukotriene B(4) omega-hydroxylase gene by peroxisomal proliferators and retinoic acid in HepG2 cells". Archives of Biochemistry and Biophysics 378 (2): 364–76. doi:10.1006/abbi.2000.1836. PMID 10860554. 
  • Zhang X, Hardwick JP (Dec 2000). "Regulation of CYP4F2 leukotriene B4 omega-hydroxylase by retinoic acids in HepG2 cells". Biochemical and Biophysical Research Communications 279 (3): 864–71. doi:10.1006/bbrc.2000.4020. PMID 11162441. 
  • Peng X, Pan X, Kenga M (Nov 1999). "[Isolation and sequencing of a novel form of cytochrome p-450 4F family from human liver]". Zhonghua Yi Xue Za Zhi 79 (11): 860–2. PMID 11715494. 
  • Nagata T, Takahashi Y, Ishii Y, Asai S, Sugahara M, Nishida Y, Murata A, Chin M, Schichino H, Koshinaga T, Fukuzawa M, Mugishima H (Jun 2003). "Profiling of genes differentially expressed between fetal liver and postnatal liver using high-density oligonucleotide DNA array". International Journal of Molecular Medicine 11 (6): 713–21. doi:10.3892/ijmm.11.6.713. PMID 12736711. 
  • Hsu MH, Savas U, Griffin KJ, Johnson EF (Feb 2007). "Regulation of human cytochrome P450 4F2 expression by sterol regulatory element-binding protein and lovastatin". The Journal of Biological Chemistry 282 (8): 5225–36. doi:10.1074/jbc.M608176200. PMID 17142457. 
  • Sontag TJ, Parker RS (May 2007). "Influence of major structural features of tocopherols and tocotrienols on their omega-oxidation by tocopherol-omega-hydroxylase". Journal of Lipid Research 48 (5): 1090–8. doi:10.1194/jlr.M600514-JLR200. PMID 17284776. 
  • Stec DE, Roman RJ, Flasch A, Rieder MJ (Jun 2007). "Functional polymorphism in human CYP4F2 decreases 20-HETE production". Physiological Genomics 30 (1): 74–81. doi:10.1152/physiolgenomics.00003.2007. PMID 17341693. 
This article is issued from Wikipedia - version of the Friday, April 29, 2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.