Cytochrome P450 4A11
Details
- Name
- Cytochrome P450 4A11
- Kind
- protein
- Synonyms
- 1.14.14.1
- 20-HETE synthase
- 20-hydroxyeicosatetraenoic acid synthase
- CYP4A2
- CYP4AII
- CYPIVA11
- Cytochrome P-450HK-omega
- Cytochrome P450HL-omega
- Fatty acid omega-hydroxylase
- Lauric acid omega-hydroxylase
- Long-chain fatty acid omega-monooxygenase
- Gene Name
- CYP4A11
- UniProtKB Entry
- Q02928Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0000839|Cytochrome P450 4A11 MSVSVLSPSRLLGDVSGILQAASLLILLLLLIKAVQLYLHRQWLLKALQQFPCPPSHWLF GHIQELQQDQELQRIQKWVETFPSACPHWLWGGKVRVQLYDPDYMKVILGRSDPKSHGSY RFLAPWIGYGLLLLNGQTWFQHRRMLTPAFHYDILKPYVGLMADSVRVMLDKWEELLGQD SPLEVFQHVSLMTLDTIMKCAFSHQGSIQVDRNSQSYIQAISDLNNLVFSRVRNAFHQND TIYSLTSAGRWTHRACQLAHQHTDQVIQLRKAQLQKEGELEKIKRKRHLDFLDILLLAKM ENGSILSDKDLRAEVDTFMFEGHDTTASGISWILYALATHPKHQERCREEIHSLLGDGAS ITWNHLDQMPYTTMCIKEALRLYPPVPGIGRELSTPVTFPDGRSLPKGIMVLLSIYGLHH NPKVWPNPEVFDPFRFAPGSAQHSHAFLPFSGGSRNCIGKQFAMNELKVATALTLLRFEL LPDPTRIPIPIARLVLKSKNGIHLRLRRLPNPCEDKDQL
- Number of residues
- 519
- Molecular Weight
- 59347.31
- Theoretical pI
- 8.99
- GO Classification
- Functionsarachidonic acid monooxygenase activity / aromatase activity / long-chain fatty acid omega-hydroxylase activity / monooxygenase activityProcessesicosanoid biosynthetic process / kidney development / lauric acid metabolic process / linoleic acid metabolic process / oxylipin biosynthetic process
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids and their oxygenated derivatives (oxylipins) (PubMed:10553002, PubMed:10660572, PubMed:15611369, PubMed:1739747, PubMed:7679927, PubMed:8914854). 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:10553002, PubMed:10660572, PubMed:15611369, PubMed:1739747, PubMed:7679927, PubMed:8914854). Catalyzes predominantly the oxidation of the terminal carbon (omega-oxidation) of saturated and unsaturated fatty acids, the catalytic efficiency decreasing in the following order: dodecanoic > tetradecanoic > (9Z)-octadecenoic > (9Z,12Z)-octadecadienoic > hexadecanoic acid (PubMed:10553002, PubMed:10660572). Acts as a major omega-hydroxylase for dodecanoic (lauric) acid in liver (PubMed:15611369, PubMed:1739747, PubMed:7679927, PubMed:8914854). Participates in omega-hydroxylation of (5Z,8Z,11Z,14Z)-eicosatetraenoic acid (arachidonate) to 20-hydroxyeicosatetraenoic acid (20-HETE), a signaling molecule acting both as vasoconstrictive and natriuretic with overall effect on arterial blood pressure (PubMed:10620324, PubMed:10660572, PubMed:15611369). Can also catalyze the oxidation of the penultimate carbon (omega-1 oxidation) of fatty acids with lower efficiency (PubMed:7679927). May contribute to the degradation of saturated very long-chain fatty acids (VLCFAs) such as docosanoic acid, by catalyzing successive omega-oxidations to the corresponding dicarboxylic acid, thereby initiating chain shortening (PubMed:18182499). Omega-hydroxylates (9R,10S)-epoxy-octadecanoate stereoisomer (PubMed:15145985). Plays a minor role in omega-oxidation of long-chain 3-hydroxy fatty acids (PubMed:18065749). Has little activity toward prostaglandins A1 and E1 (PubMed:7679927)
- Specific Function
- alkane 1-monooxygenase activity
- Pfam Domain Function
- p450 (PF00067)
- Signal Regions
- Not Available
- Transmembrane Regions
- Not Available
- Cellular Location
- Endoplasmic reticulum membrane
- Gene sequence
>lcl|BSEQ0020457|Cytochrome P450 4A11 (CYP4A11) ATGAGTGTCTCTGTGCTGAGCCCCAGCAGACTCCTGGGTGATGTCTCTGGAATCCTCCAA GCGGCCTCCCTGCTCATTCTGCTTCTGCTGCTGATCAAGGCAGTTCAGCTCTACCTGCAC AGGCAGTGGCTGCTCAAAGCCCTCCAGCAGTTCCCGTGCCCTCCCTCCCACTGGCTCTTC GGGCACATCCAGGAGCTCCAACAGGACCAGGAGCTACAACGGATTCAGAAATGGGTGGAG ACATTCCCAAGTGCCTGTCCTCATTGGCTATGGGGAGGCAAAGTTCGTGTCCAGCTCTAT GACCCTGACTATATGAAGGTGATTCTGGGGAGATCAGACCCGAAATCCCATGGTTCCTAC AGATTCCTGGCTCCATGGATTGGGTACGGCTTGCTCCTGTTGAATGGGCAGACATGGTTC CAGCATCGACGGATGCTGACCCCAGCCTTCCACTATGACATCCTGAAGCCCTATGTGGGG CTCATGGCAGACTCTGTACGAGTGATGCTGGACAAATGGGAAGAGCTCCTTGGCCAGGAT TCCCCTCTGGAGGTCTTTCAGCACGTCTCCTTGATGACCCTGGACACCATCATGAAGTGT GCCTTCAGCCATCAGGGCAGCATCCAGGTGGACAGGAATTCTCAGTCCTACATACAGGCC ATTAGTGACCTGAACAACCTGGTTTTTTCCCGTGTGAGGAATGCCTTTCACCAGAATGAC ACCATCTACAGCCTGACCTCTGCTGGCCGCTGGACACACCGCGCCTGCCAGCTGGCCCAT CAGCACACAGACCAAGTGATCCAACTGAGGAAGGCTCAACTACAGAAGGAGGGGGAGCTG GAGAAGATCAAGAGGAAGAGGCATTTGGATTTTCTGGATATCCTCCTCTTGGCCAAAATG GAGAATGGGAGCATCTTGTCAGACAAGGACCTCCGTGCTGAGGTGGACACGTTCATGTTT GAGGGCCACGACACCACAGCCAGTGGGATCTCCTGGATCCTCTATGCTCTGGCCACACAC CCCAAGCATCAGGAGAGGTGCCGGGAGGAGATCCACAGCCTCCTGGGTGATGGAGCCTCC ATCACCTGGAACCACCTGGACCAGATGCCCTACACCACCATGTGCATTAAGGAGGCACTG AGGCTCTACCCACCGGTGCCAGGCATTGGCAGAGAGCTCAGCACTCCCGTCACCTTCCCT GATGGGCGCTCCTTGCCCAAAGGTATCATGGTCCTCCTCTCCATTTATGGCCTTCACCAC AACCCAAAAGTGTGGCCCAACCCAGAGGTGTTTGACCCTTTCCGTTTTGCACCGGGTTCT GCTCAACACAGCCACGCTTTCCTGCCCTTCTCAGGAGGATCAAGGAACTGCATCGGGAAA CAATTTGCCATGAACGAGCTGAAGGTGGCCACGGCCCTGACCCTGCTCCGCTTTGAGCTG CTGCCTGATCCCACCAGGATCCCCATCCCCATTGCACGACTTGTGTTGAAATCCAAAAAT GGAATCCACCTGCGTCTCAGGAGGCTCCCTAACCCTTGTGAAGACAAGGACCAGCTTTGA
- Chromosome Location
- 1
- Locus
- 1p33
- External Identifiers
Resource Link UniProtKB ID Q02928 UniProtKB Entry Name CP4AB_HUMAN GenBank Protein ID 181397 GenBank Gene ID L04751 GeneCard ID CYP4A11 GenAtlas ID CYP4A11 HGNC ID HGNC:2642 KEGG ID hsa:1579 IUPHAR/Guide To Pharmacology ID 1341 NCBI Gene ID 1579 - General References
- Palmer CN, Richardson TH, Griffin KJ, Hsu MH, Muerhoff AS, Clark JE, Johnson EF: Characterization of a cDNA encoding a human kidney, cytochrome P-450 4A fatty acid omega-hydroxylase and the cognate enzyme expressed in Escherichia coli. Biochim Biophys Acta. 1993 Feb 20;1172(1-2):161-6. [Article]
- Kawashima H, Kusunose E, Kikuta Y, Kinoshita H, Tanaka S, Yamamoto S, Kishimoto T, Kusunose M: Purification and cDNA cloning of human liver CYP4A fatty acid omega-hydroxylase. J Biochem. 1994 Jul;116(1):74-80. [Article]
- Imaoka S, Ogawa H, Kimura S, Gonzalez FJ: Complete cDNA sequence and cDNA-directed expression of CYP4A11, a fatty acid omega-hydroxylase expressed in human kidney. DNA Cell Biol. 1993 Dec;12(10):893-9. [Article]
- Bellamine A, Wang Y, Waterman MR, Gainer JV 3rd, Dawson EP, Brown NJ, Capdevila JH: Characterization of the CYP4A11 gene, a second CYP4A gene in humans. Arch Biochem Biophys. 2003 Jan 1;409(1):221-7. [Article]
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- Kawashima H, Kusunose E, Kubota I, Maekawa M, Kusunose M: Purification and NH2-terminal amino acid sequences of human and rat kidney fatty acid omega-hydroxylases. Biochim Biophys Acta. 1992 Jan 24;1123(2):156-62. [Article]
- Bell DR, Plant NJ, Rider CG, Na L, Brown S, Ateitalla I, Acharya SK, Davies MH, Elias E, Jenkins NA, et al.: Species-specific induction of cytochrome P-450 4A RNAs: PCR cloning of partial guinea-pig, human and mouse CYP4A cDNAs. Biochem J. 1993 Aug 15;294 ( Pt 1):173-80. [Article]
- Hoch U, Ortiz De Montellano PR: Covalently linked heme in cytochrome p4504a fatty acid hydroxylases. J Biol Chem. 2001 Apr 6;276(14):11339-46. Epub 2001 Jan 3. [Article]
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- 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: Functional variant of CYP4A11 20-hydroxyeicosatetraenoic acid synthase is associated with essential hypertension. Circulation. 2005 Jan 4;111(1):63-9. Epub 2004 Dec 20. [Article]
- Cho BH, Park BL, Kim LH, Chung HS, Shin HD: Highly polymorphic human CYP4A11 gene. J Hum Genet. 2005;50(5):259-63. Epub 2005 May 14. [Article]
Associated Data
- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details NADH approved, nutraceutical unknown target Details Plitidepsin investigational unknown enzyme substrate Details Clofibrate approved, investigational unknown enzyme substrateinducer Details Dexamethasone approved, investigational, vet_approved unknown enzyme inducer Details Ethanol approved unknown enzyme inducer Details Pentamidine approved, investigational unknown enzyme substrate Details Tretinoin approved, investigational, nutraceutical unknown enzyme substrate Details Pegvisomant approved unknown enzyme inhibitor Details Cisplatin approved unknown enzyme inducer Details Polyethylene glycol 400 approved unknown enzyme substrate Details Tildrakizumab approved, investigational unknown enzyme inducer Details Pyrantel approved, vet_approved unknown enzyme substrate Details Lusutrombopag approved, investigational unknown enzyme substrate Details Dexamethasone acetate approved, investigational, vet_approved unknown enzyme inducer Details