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
Functions
arachidonic acid monooxygenase activity / aromatase activity / long-chain fatty acid omega-hydroxylase activity / monooxygenase activity
Processes
icosanoid 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
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
ResourceLink
UniProtKB IDQ02928
UniProtKB Entry NameCP4AB_HUMAN
GenBank Protein ID181397
GenBank Gene IDL04751
GeneCard IDCYP4A11
GenAtlas IDCYP4A11
HGNC IDHGNC:2642
KEGG IDhsa:1579
IUPHAR/Guide To Pharmacology ID1341
NCBI Gene ID1579
General References
  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E: The DNA sequence and biological annotation of human chromosome 1. Nature. 2006 May 18;441(7091):315-21. [Article]
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  7. 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]
  8. 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]
  9. 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]
  10. LeBrun LA, Hoch U, Ortiz de Montellano PR: Autocatalytic mechanism and consequences of covalent heme attachment in the cytochrome P4504A family. J Biol Chem. 2002 Apr 12;277(15):12755-61. Epub 2002 Jan 30. [Article]
  11. 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]
  12. 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
DrugDrug groupPharmacological action?TypeActionsDetails
NADHapproved, nutraceuticalunknowntargetDetails
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Clofibrateapproved, investigationalunknownenzymesubstrateinducerDetails
Dexamethasoneapproved, investigational, vet_approvedunknownenzymeinducerDetails
EthanolapprovedunknownenzymeinducerDetails
Pentamidineapproved, investigationalunknownenzymesubstrateDetails
Tretinoinapproved, investigational, nutraceuticalunknownenzymesubstrateDetails
PegvisomantapprovedunknownenzymeinhibitorDetails
CisplatinapprovedunknownenzymeinducerDetails
Polyethylene glycol 400approvedunknownenzymesubstrateDetails
Tildrakizumabapproved, investigationalunknownenzymeinducerDetails
Pyrantelapproved, vet_approvedunknownenzymesubstrateDetails
Lusutrombopagapproved, investigationalunknownenzymesubstrateDetails
Dexamethasone acetateapproved, investigational, vet_approvedunknownenzymeinducerDetails