CYP4A11

Cytochrome P450, family 4, subfamily A, polypeptide 11
Identifiers
Symbols CYP4A11 ; CP4Y; CYP4A2; CYP4AII
External IDs OMIM: 601310 MGI: 88611 HomoloGene: 128044 ChEMBL: 3978 GeneCards: CYP4A11 Gene
EC number 1.14.15.3
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 1579 13117
Ensembl ENSG00000162365 ENSMUSG00000066072
UniProt Q02928 O88833
RefSeq (mRNA) NM_000778 NM_010011
RefSeq (protein) NP_000769 NP_034141
Location (UCSC) Chr 1:
46.93 – 46.94 Mb		 Chr 4:
115.52 – 115.53 Mb
PubMed search

Cytochrome P450 4A11 is a protein that in humans is encoded by the CYP4A11 gene.[1][2]

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 and other lipids. This protein localizes to the endoplasmic reticulum and hydroxylates medium-chain fatty acids such as laurate and myristate.[2]

CYP4A11 along with CYP4A22, CYP4F2, and CYP4F3 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. [3] Gene polymorphism variants of CYP4A11 are associated with the development of hypertension and cerebral infarction (i.e. ischemic stroke) in humans (see 20-Hydroxyeicosatetraenoic acid).[4][5][6][7][8][9]

Members of the CYP4A and CYP4F sub-families and CYPU21 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.[10][11] 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.[12][13][14]

References

  1. ↑ Palmer CN, Richardson TH, Griffin KJ, Hsu MH, Muerhoff AS, Clark JE, Johnson EF (Feb 1993). "Characterization of a cDNA encoding a human kidney, cytochrome P-450 4A fatty acid omega-hydroxylase and the cognate enzyme expressed in Escherichia coli". Biochimica Et Biophysica Acta 1172 (1-2): 161–6. doi:10.1016/0167-4781(93)90285-L. PMID 7679927.
  2. 1 2 "Entrez Gene: CYP4A11 cytochrome P450, family 4, subfamily A, polypeptide 11".
  3. ↑ 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.
  4. ↑ Circulation. 2005 Jan 4;111(1):63-9
  5. ↑ J Am Soc Nephrol. 2008 Aug;19(8):1606-12. doi:10.1681/ASN.2008010063
  6. ↑ J Hypertens. 2008 Mar;26(3):453-61. doi:10.1097/HJH.0b013e3282f2f10c
  7. ↑ Hypertension. 2005 Oct;46(4):766-71
  8. ↑ Hypertension. 2008 Dec;52(6):1142-8. doi:10.1161/HYPERTENSIONAHA.108.114082
  9. ↑ Pharmacogenet Genomics. 2010 Mar;20(3):187-94. doi:10.1097/FPC.0b013e328336eefe
  10. ↑ Arch Biochem Biophys. 1998 Jul 15;355(2):201
  11. ↑ Biochem Pharmacol. 2008 Jun 15;75(12):2263-75. doi:10.1016/j.bcp.2008.03.004
  12. ↑ Eur J Hum Genet. 2006 Nov;14(11):1215-22
  13. ↑ Drug Metabol Drug Interact. 2012 Apr 19;27(2):63-71. doi:10.1515/dmdi-2011-0037
  14. ↑ Gastroenterology. 2014 Apr;146(4):929-31. doi:10.1053/j.gastro.2013.12.034

Further reading

  • Kawashima H, Kusunose E, Kubota I, Maekawa M, Kusunose M (Jan 1992). "Purification and NH2-terminal amino acid sequences of human and rat kidney fatty acid omega-hydroxylases". Biochimica Et Biophysica Acta 1123 (2): 156–62. doi:10.1016/0005-2760(92)90106-6. PMID 1739747. 
  • Kawashima H, Kusunose E, Kikuta Y, Kinoshita H, Tanaka S, Yamamoto S, Kishimoto T, Kusunose M (Jul 1994). "Purification and cDNA cloning of human liver CYP4A fatty acid omega-hydroxylase". Journal of Biochemistry 116 (1): 74–80. PMID 7798189. 
  • Imaoka S, Ogawa H, Kimura S, Gonzalez FJ (Dec 1993). "Complete cDNA sequence and cDNA-directed expression of CYP4A11, a fatty acid omega-hydroxylase expressed in human kidney". DNA and Cell Biology 12 (10): 893–9. doi:10.1089/dna.1993.12.893. PMID 8274222. 
  • Bell DR, Plant NJ, Rider CG, Na L, Brown S, Ateitalla I, Acharya SK, Davies MH, Elias E, Jenkins NA (Aug 1993). "Species-specific induction of cytochrome P-450 4A RNAs: PCR cloning of partial guinea-pig, human and mouse CYP4A cDNAs". The Biochemical Journal 294 (1): 173–80. doi:10.1042/bj2940173. PMC 1134581. PMID 8363569. 
  • Powell PK, Wolf I, Lasker JM (Nov 1996). "Identification of CYP4A11 as the major lauric acid omega-hydroxylase in human liver microsomes". Archives of Biochemistry and Biophysics 335 (1): 219–26. doi:10.1006/abbi.1996.0501. PMID 8914854. 
  • 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. 
  • Chang YT, Loew GH (Feb 1999). "Homology modeling and substrate binding study of human CYP4A11 enzyme". Proteins 34 (3): 403–15. doi:10.1002/(SICI)1097-0134(19990215)34:3<403::AID-PROT12>3.0.CO;2-D. PMID 10024026. 
  • 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. 
  • Kawashima H, Naganuma T, Kusunose E, Kono T, Yasumoto R, Sugimura K, Kishimoto T (Jun 2000). "Human fatty acid omega-hydroxylase, CYP4A11: determination of complete genomic sequence and characterization of purified recombinant protein". Archives of Biochemistry and Biophysics 378 (2): 333–9. doi:10.1006/abbi.2000.1831. PMID 10860550. 
  • Hoch U, Ortiz De Montellano PR (Apr 2001). "Covalently linked heme in cytochrome p4504a fatty acid hydroxylases". The Journal of Biological Chemistry 276 (14): 11339–46. doi:10.1074/jbc.M009969200. PMID 11139583. 
  • Gonzalez MC, Marteau C, Franchi J, Migliore-Samour D (Nov 2001). "Cytochrome P450 4A11 expression in human keratinocytes: effects of ultraviolet irradiation". The British Journal of Dermatology 145 (5): 749–57. doi:10.1046/j.1365-2133.2001.04490.x. PMID 11736898. 
  • LeBrun LA, Hoch U, Ortiz de Montellano PR (Apr 2002). "Autocatalytic mechanism and consequences of covalent heme attachment in the cytochrome P4504A family". The Journal of Biological Chemistry 277 (15): 12755–61. doi:10.1074/jbc.M112155200. PMID 11821421. 
  • Savas U, Hsu MH, Johnson EF (Jan 2003). "Differential regulation of human CYP4A genes by peroxisome proliferators and dexamethasone". Archives of Biochemistry and Biophysics 409 (1): 212–20. doi:10.1016/S0003-9861(02)00499-X. PMID 12464261. 
  • Bellamine A, Wang Y, Waterman MR, Gainer JV, Dawson EP, Brown NJ, Capdevila JH (Jan 2003). "Characterization of the CYP4A11 gene, a second CYP4A gene in humans". Archives of Biochemistry and Biophysics 409 (1): 221–7. doi:10.1016/S0003-9861(02)00545-3. PMID 12464262. 
  • Jin P, Fu GK, Wilson AD, Yang J, Chien D, Hawkins PR, Au-Young J, Stuve LL (Apr 2004). "PCR isolation and cloning of novel splice variant mRNAs from known drug target genes". Genomics 83 (4): 566–71. doi:10.1016/j.ygeno.2003.09.023. PMID 15028279. 
  • Ramírez J, Innocenti F, Schuetz EG, Flockhart DA, Relling MV, Santucci R, Ratain MJ (Sep 2004). "CYP2B6, CYP3A4, and CYP2C19 are responsible for the in vitro N-demethylation of meperidine in human liver microsomes". Drug Metabolism and Disposition 32 (9): 930–6. PMID 15319333. 
  • Gainer JV, Bellamine A, Dawson EP, Womble KE, Grant SW, Wang Y, Cupples LA, Guo CY, Demissie S, O'Donnell CJ, Brown NJ, Waterman MR, Capdevila JH (Jan 2005). "Functional variant of CYP4A11 20-hydroxyeicosatetraenoic acid synthase is associated with essential hypertension". Circulation 111 (1): 63–9. doi:10.1161/01.CIR.0000151309.82473.59. PMID 15611369. 
  • Mayer B, Lieb W, Götz A, König IR, Aherrahrou Z, Thiemig A, Holmer S, Hengstenberg C, Doering A, Loewel H, Hense HW, Schunkert H, Erdmann J (Oct 2005). "Association of the T8590C polymorphism of CYP4A11 with hypertension in the MONICA Augsburg echocardiographic substudy". Hypertension 46 (4): 766–71. doi:10.1161/01.HYP.0000182658.04299.15. PMID 16144986. 


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