CP4AB_HUMAN
ID CP4AB_HUMAN Reviewed; 519 AA.
AC Q02928; Q06766; Q16865; Q16866; Q5VSP8; Q86SU6; Q8IWY5;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=Cytochrome P450 4A11 {ECO:0000303|PubMed:10553002};
DE EC=1.14.14.1 {ECO:0000269|PubMed:10553002, ECO:0000269|PubMed:10660572, ECO:0000269|PubMed:15611369, ECO:0000269|PubMed:1739747, ECO:0000269|PubMed:7679927, ECO:0000269|PubMed:8914854};
DE AltName: Full=20-hydroxyeicosatetraenoic acid synthase {ECO:0000305|PubMed:10660572, ECO:0000305|PubMed:15611369};
DE Short=20-HETE synthase;
DE AltName: Full=CYP4AII;
DE AltName: Full=CYPIVA11;
DE AltName: Full=Cytochrome P-450HK-omega;
DE AltName: Full=Cytochrome P450HL-omega;
DE AltName: Full=Fatty acid omega-hydroxylase;
DE AltName: Full=Lauric acid omega-hydroxylase {ECO:0000303|PubMed:8914854};
DE AltName: Full=Long-chain fatty acid omega-monooxygenase;
DE EC=1.14.14.80 {ECO:0000269|PubMed:1739747, ECO:0000269|PubMed:7679927};
DE Flags: Precursor;
GN Name=CYP4A11 {ECO:0000303|PubMed:8274222, ECO:0000312|HGNC:HGNC:2642};
GN Synonyms=CYP4A2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP ACTIVITY REGULATION, AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=7679927; DOI=10.1016/0167-4781(93)90285-l;
RA Palmer C.N.A., Richardson T.H., Griffin K.J., Hsu M.-H., Muerhoff A.S.,
RA Clark J.E., Johnson E.F.;
RT "Characterization of a cDNA encoding a human kidney, cytochrome P-450 4A
RT fatty acid omega-hydroxylase and the cognate enzyme expressed in
RT Escherichia coli.";
RL Biochim. Biophys. Acta 1172:161-166(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 5-24, AND
RP CHARACTERIZATION.
RC TISSUE=Liver;
RX PubMed=7798189; DOI=10.1093/oxfordjournals.jbchem.a124506;
RA Kawashima H., Kusunose E., Kikuta Y., Kinoshita H., Tanaka S., Yamamoto S.,
RA Kishimoto T., Kusunose M.;
RT "Purification and cDNA cloning of human liver CYP4A fatty acid omega-
RT hydroxylase.";
RL J. Biochem. 116:74-80(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT SER-434, AND
RP CHARACTERIZATION.
RC TISSUE=Kidney;
RX PubMed=8274222; DOI=10.1089/dna.1993.12.893;
RA Imaoka S., Ogawa H., Kimura S., Gonzalez F.J.;
RT "Complete cDNA sequence and cDNA-directed expression of CYP4A11, a fatty
RT acid omega-hydroxylase expressed in human kidney.";
RL DNA Cell Biol. 12:893-899(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=12464262; DOI=10.1016/s0003-9861(02)00545-3;
RA Bellamine A., Wang Y., Waterman M.R., Gainer J.V. III, Dawson E.P.,
RA Brown N.J., Capdevila J.H.;
RT "Characterization of the CYP4A11 gene, a second CYP4A gene in humans.";
RL Arch. Biochem. Biophys. 409:221-227(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANT SER-434.
RG SeattleSNPs variation discovery resource;
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 5-39, FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Kidney;
RX PubMed=1739747; DOI=10.1016/0005-2760(92)90106-6;
RA Kawashima H., Kusunose E., Kubota I., Maekawa M., Kusunose M.;
RT "Purification and NH2-terminal amino acid sequences of human and rat kidney
RT fatty acid omega-hydroxylases.";
RL Biochim. Biophys. Acta 1123:156-162(1992).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 317-457, AND VARIANTS GLY-353 AND SER-434.
RC TISSUE=Liver;
RX PubMed=8363569; DOI=10.1042/bj2940173;
RA Bell D.R., Plant N.J., Rider C.G., Na L., Brown S., Ateitalla I.,
RA Acharya S.K., Davies M.H., Elias E.E., Jenkins N.A., Gilbert D.J.,
RA Copeland N.G., Elcombe C.R.;
RT "Species-specific induction of cytochrome P-450 4A RNAs: PCR cloning of
RT partial guinea-pig, human and mouse CYP4A cDNAs.";
RL Biochem. J. 294:173-180(1993).
RN [10]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=8914854; DOI=10.1006/abbi.1996.0501;
RA Powell P.K., Wolf I., Lasker J.M.;
RT "Identification of CYP4A11 as the major lauric acid omega-hydroxylase in
RT human liver microsomes.";
RL Arch. Biochem. Biophys. 335:219-226(1996).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=10553002;
RA Adas F., Salauen J.P., Berthou F., Picart D., Simon B., Amet Y.;
RT "Requirement for omega and (omega;-1)-hydroxylations of fatty acids by
RT human cytochromes P450 2E1 and 4A11.";
RL J. Lipid Res. 40:1990-1997(1999).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RX PubMed=10620324; DOI=10.1006/abbi.1999.1504;
RA Hoch U., Zhang Z., Kroetz D.L., Ortiz de Montellano P.R.;
RT "Structural determination of the substrate specificities and
RT regioselectivities of the rat and human fatty acid omega-hydroxylases.";
RL Arch. Biochem. Biophys. 373:63-71(2000).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND PATHWAY.
RX PubMed=10660572; DOI=10.1074/jbc.275.6.4118;
RA Lasker J.M., Chen W.B., Wolf I., Bloswick B.P., Wilson P.D., Powell P.K.;
RT "Formation of 20-hydroxyeicosatetraenoic acid, a vasoactive and natriuretic
RT eicosanoid, in human kidney. Role of CYP4F2 and CYP4A11.";
RL J. Biol. Chem. 275:4118-4126(2000).
RN [14]
RP COVALENT HEME ATTACHMENT.
RX PubMed=11139583; DOI=10.1074/jbc.m009969200;
RA Hoch U., Ortiz de Montellano P.R.;
RT "Covalently linked heme in cytochrome P4504A fatty acid hydroxylases.";
RL J. Biol. Chem. 276:11339-11346(2001).
RN [15]
RP COVALENT HEME ATTACHMENT, AND MUTAGENESIS OF GLU-321.
RX PubMed=11821421; DOI=10.1074/jbc.m112155200;
RA LeBrun L.A., Hoch U., Ortiz de Montellano P.R.;
RT "Autocatalytic mechanism and consequences of covalent heme attachment in
RT the cytochrome P4504A family.";
RL J. Biol. Chem. 277:12755-12761(2002).
RN [16]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15145985; DOI=10.1194/jlr.m300463-jlr200;
RA Le Quere V., Plee-Gautier E., Potin P., Madec S., Salauen J.P.;
RT "Human CYP4F3s are the main catalysts in the oxidation of fatty acid
RT epoxides.";
RL J. Lipid Res. 45:1446-1458(2004).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF GLY-130, VARIANT SER-434,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RX PubMed=15611369; DOI=10.1161/01.cir.0000151309.82473.59;
RA Gainer J.V., Bellamine A., Dawson E.P., Womble K.E., Grant S.W., Wang Y.,
RA Cupples L.A., Guo C.-Y., Demissie S., O'Donnell C.J., Brown N.J.,
RA Waterman M.R., Capdevila J.H.;
RT "Functional variant of CYP4A11 20-hydroxyeicosatetraenoic acid synthase is
RT associated with essential hypertension.";
RL Circulation 111:63-69(2005).
RN [18]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=18182499; DOI=10.1096/fj.07-099150;
RA Sanders R.J., Ofman R., Dacremont G., Wanders R.J., Kemp S.;
RT "Characterization of the human omega-oxidation pathway for omega-hydroxy-
RT very-long-chain fatty acids.";
RL FASEB J. 22:2064-2071(2008).
RN [19]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=18065749; DOI=10.1194/jlr.m700450-jlr200;
RA Dhar M., Sepkovic D.W., Hirani V., Magnusson R.P., Lasker J.M.;
RT "Omega oxidation of 3-hydroxy fatty acids by the human CYP4F gene subfamily
RT enzyme CYP4F11.";
RL J. Lipid Res. 49:612-624(2008).
RN [20]
RP VARIANTS GLY-353 AND SER-434.
RX PubMed=15895287; DOI=10.1007/s10038-005-0245-9;
RA Cho B.H., Park B.L., Kim L.H., Chung H.S., Shin H.D.;
RT "Highly polymorphic human CYP4A11 gene.";
RL J. Hum. Genet. 50:259-263(2005).
CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of
CC fatty acids and their oxygenated derivatives (oxylipins)
CC (PubMed:7679927, PubMed:1739747, PubMed:8914854, PubMed:10553002,
CC PubMed:10660572, PubMed:15611369). Mechanistically, uses molecular
CC oxygen inserting one oxygen atom into a substrate, and reducing the
CC second into a water molecule, with two electrons provided by NADPH via
CC cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase)
CC (PubMed:7679927, PubMed:1739747, PubMed:8914854, PubMed:10553002,
CC PubMed:10660572, PubMed:15611369). Catalyzes predominantly the
CC oxidation of the terminal carbon (omega-oxidation) of saturated and
CC unsaturated fatty acids, the catalytic efficiency decreasing in the
CC following order: dodecanoic > tetradecanoic > (9Z)-octadecenoic >
CC (9Z,12Z)-octadecadienoic > hexadecanoic acid (PubMed:10553002,
CC PubMed:10660572). Acts as a major omega-hydroxylase for dodecanoic
CC (lauric) acid in liver (PubMed:7679927, PubMed:1739747, PubMed:8914854,
CC PubMed:15611369). Participates in omega-hydroxylation of
CC (5Z,8Z,11Z,14Z)-eicosatetraenoic acid (arachidonate) to 20-
CC hydroxyeicosatetraenoic acid (20-HETE), a signaling molecule acting
CC both as vasoconstrictive and natriuretic with overall effect on
CC arterial blood pressure (PubMed:10620324, PubMed:10660572,
CC PubMed:15611369). Can also catalyze the oxidation of the penultimate
CC carbon (omega-1 oxidation) of fatty acids with lower efficiency
CC (PubMed:7679927). May contribute to the degradation of saturated very
CC long-chain fatty acids (VLCFAs) such as docosanoic acid, by catalyzing
CC successive omega-oxidations to the corresponding dicarboxylic acid,
CC thereby initiating chain shortening (PubMed:18182499). Omega-
CC hydroxylates (9R,10S)-epoxy-octadecanoate stereoisomer
CC (PubMed:15145985). Plays a minor role in omega-oxidation of long-chain
CC 3-hydroxy fatty acids (PubMed:18065749). Has little activity toward
CC prostaglandins A1 and E1 (PubMed:7679927).
CC {ECO:0000269|PubMed:10553002, ECO:0000269|PubMed:10620324,
CC ECO:0000269|PubMed:10660572, ECO:0000269|PubMed:15145985,
CC ECO:0000269|PubMed:15611369, ECO:0000269|PubMed:1739747,
CC ECO:0000269|PubMed:18065749, ECO:0000269|PubMed:18182499,
CC ECO:0000269|PubMed:7679927, ECO:0000269|PubMed:8914854}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an organic molecule + O2 + reduced [NADPH--hemoprotein
CC reductase] = an alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:17149, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:30879, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:142491; EC=1.14.14.1;
CC Evidence={ECO:0000269|PubMed:10553002, ECO:0000269|PubMed:10660572,
CC ECO:0000269|PubMed:15611369, ECO:0000269|PubMed:1739747,
CC ECO:0000269|PubMed:7679927, ECO:0000269|PubMed:8914854};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17150;
CC Evidence={ECO:0000305|PubMed:15611369};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an omega-methyl-long-chain fatty acid + O2 + reduced [NADPH--
CC hemoprotein reductase] = an omega-hydroxy-long-chain fatty acid +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:56748, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:140991,
CC ChEBI:CHEBI:140992; EC=1.14.14.80;
CC Evidence={ECO:0000269|PubMed:10553002, ECO:0000269|PubMed:1739747,
CC ECO:0000269|PubMed:7679927};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:56749;
CC Evidence={ECO:0000305|PubMed:10553002, ECO:0000305|PubMed:10620324};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dodecanoate + O2 + reduced [NADPH--hemoprotein reductase] =
CC 12-hydroxydodecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:38947, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:18262, ChEBI:CHEBI:36204, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:10553002,
CC ECO:0000269|PubMed:10620324, ECO:0000269|PubMed:15611369,
CC ECO:0000269|PubMed:1739747, ECO:0000269|PubMed:18065749,
CC ECO:0000269|PubMed:8914854};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38948;
CC Evidence={ECO:0000305|PubMed:10620324};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + reduced [NADPH--hemoprotein reductase] + tetradecanoate =
CC 14-hydroxytetradecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:40203, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:30807, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:77033; Evidence={ECO:0000269|PubMed:10553002,
CC ECO:0000269|PubMed:10620324, ECO:0000269|PubMed:1739747};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40204;
CC Evidence={ECO:0000305|PubMed:10620324};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecanoate + O2 + reduced [NADPH--hemoprotein reductase] =
CC 16-hydroxyhexadecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:40199, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:55329, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.80;
CC Evidence={ECO:0000269|PubMed:10553002, ECO:0000269|PubMed:10620324,
CC ECO:0000269|PubMed:1739747};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40200;
CC Evidence={ECO:0000305|PubMed:10553002, ECO:0000305|PubMed:10620324};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoate + O2 + reduced [NADPH--hemoprotein
CC reductase] = 18-hydroxy-(9Z)-octadecenoate + H(+) + H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:41728, Rhea:RHEA-
CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:78424;
CC EC=1.14.14.80; Evidence={ECO:0000269|PubMed:10553002};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41729;
CC Evidence={ECO:0000305|PubMed:10553002};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = 20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:39755, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:76624; Evidence={ECO:0000269|PubMed:10620324,
CC ECO:0000269|PubMed:10660572, ECO:0000269|PubMed:15611369};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39756;
CC Evidence={ECO:0000305|PubMed:10620324, ECO:0000305|PubMed:10660572};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=22-hydroxydocosanoate + O2 + reduced [NADPH--hemoprotein
CC reductase] = 22-oxodocosanoate + H(+) + 2 H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:39055, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:76298, ChEBI:CHEBI:76304;
CC Evidence={ECO:0000269|PubMed:18182499};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39056;
CC Evidence={ECO:0000305|PubMed:18182499};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=22-oxodocosanoate + O2 + reduced [NADPH--hemoprotein
CC reductase] = docosanedioate + 2 H(+) + H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:39043, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:76298, ChEBI:CHEBI:76299;
CC Evidence={ECO:0000269|PubMed:18182499};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39044;
CC Evidence={ECO:0000305|PubMed:18182499};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9R,10S)-epoxy-octadecanoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = 18-hydroxy-(9R,10S)-epoxy-octadecanoate +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:53556, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:137459,
CC ChEBI:CHEBI:137460; Evidence={ECO:0000269|PubMed:15145985};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53557;
CC Evidence={ECO:0000305|PubMed:15145985};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-hydroxyhexadecanoate + O2 + reduced [NADPH--hemoprotein
CC reductase] = 3,16-dihydroxyhexadecanoate + H(+) + H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:39731, Rhea:RHEA-
CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:63904, ChEBI:CHEBI:76613;
CC Evidence={ECO:0000269|PubMed:18065749};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39732;
CC Evidence={ECO:0000305|PubMed:18065749};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000269|PubMed:11139583};
CC -!- ACTIVITY REGULATION: Activated by cytochrome b5.
CC {ECO:0000269|PubMed:10553002, ECO:0000269|PubMed:7679927}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=11 uM for dodecanoic acid {ECO:0000269|PubMed:15611369};
CC KM=37 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoic acid
CC {ECO:0000269|PubMed:15611369};
CC Note=kcat is 42 min(-1) with dodecanoic acid as substrate. kcat is 50
CC min(-1) with tetradecanoic acid as substrate. kcat is 10 min(-1) with
CC hexadecanoic acid as substrate. kcat is 0.4 min(-1) with (9Z)-
CC octadecenoic acid as substrate. kcat is 0.4 min(-1) with
CC (5Z,8Z,11Z,14Z)-eicosatetraenoic acid as substrate.
CC {ECO:0000269|PubMed:10620324};
CC -!- PATHWAY: Lipid metabolism; arachidonate metabolism.
CC {ECO:0000269|PubMed:15611369}.
CC -!- PATHWAY: Lipid metabolism; oxylipin biosynthesis.
CC {ECO:0000269|PubMed:10620324, ECO:0000269|PubMed:10660572,
CC ECO:0000269|PubMed:15611369}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000305|PubMed:1739747}; Peripheral membrane protein
CC {ECO:0000305}. Microsome membrane {ECO:0000305|PubMed:1739747};
CC Peripheral membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q02928-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q02928-2; Sequence=VSP_034595;
CC -!- TISSUE SPECIFICITY: Expressed in liver (PubMed:7679927). Expressed in
CC S2 and S3 segments of proximal tubules in cortex and outer medulla of
CC kidney (PubMed:7679927, PubMed:10660572). {ECO:0000269|PubMed:10660572,
CC ECO:0000269|PubMed:7679927}.
CC -!- POLYMORPHISM: CYP4A11v seems to be a rare allelic variant of CYP4A11,
CC it seems to be unstable and not to metabolize lauric acid.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=PharmVar Pharmacogen Variation Consortium;
CC Note=CYP4A11 alleles;
CC URL="https://www.pharmvar.org/gene/CYP4A11";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/cyp4a11/";
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DR EMBL; L04751; AAA58436.1; -; mRNA.
DR EMBL; D26481; BAA05491.1; -; mRNA.
DR EMBL; S67580; AAB29502.1; -; mRNA.
DR EMBL; S67581; AAB29503.1; -; mRNA.
DR EMBL; AF525488; AAO16078.1; -; Genomic_DNA.
DR EMBL; AY369778; AAQ56847.1; -; Genomic_DNA.
DR EMBL; AL731892; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC041158; AAH41158.1; -; mRNA.
DR EMBL; X71480; CAA50586.1; -; mRNA.
DR CCDS; CCDS543.1; -. [Q02928-1]
DR PIR; A56859; A56859.
DR PIR; I53015; I53015.
DR PIR; I65981; I65981.
DR PIR; JX0331; JX0331.
DR RefSeq; NP_000769.2; NM_000778.3. [Q02928-1]
DR RefSeq; NP_001306084.1; NM_001319155.1.
DR AlphaFoldDB; Q02928; -.
DR SMR; Q02928; -.
DR BioGRID; 107951; 4.
DR IntAct; Q02928; 3.
DR STRING; 9606.ENSP00000311095; -.
DR BindingDB; Q02928; -.
DR ChEMBL; CHEMBL3978; -.
DR DrugBank; DB00515; Cisplatin.
DR DrugBank; DB00636; Clofibrate.
DR DrugBank; DB01234; Dexamethasone.
DR DrugBank; DB14649; Dexamethasone acetate.
DR DrugBank; DB00898; Ethanol.
DR DrugBank; DB13125; Lusutrombopag.
DR DrugBank; DB00157; NADH.
DR DrugBank; DB00082; Pegvisomant.
DR DrugBank; DB00738; Pentamidine.
DR DrugBank; DB04977; Plitidepsin.
DR DrugBank; DB11077; Polyethylene glycol 400.
DR DrugBank; DB11156; Pyrantel.
DR DrugBank; DB14004; Tildrakizumab.
DR DrugBank; DB00755; Tretinoin.
DR GuidetoPHARMACOLOGY; 1341; -.
DR SwissLipids; SLP:000000398; -.
DR iPTMnet; Q02928; -.
DR PhosphoSitePlus; Q02928; -.
DR BioMuta; CYP4A11; -.
DR DMDM; 2493371; -.
DR MassIVE; Q02928; -.
DR PaxDb; Q02928; -.
DR PeptideAtlas; Q02928; -.
DR PRIDE; Q02928; -.
DR ProteomicsDB; 58135; -. [Q02928-1]
DR ProteomicsDB; 58136; -. [Q02928-2]
DR Antibodypedia; 32832; 244 antibodies from 31 providers.
DR DNASU; 1579; -.
DR Ensembl; ENST00000310638.9; ENSP00000311095.4; ENSG00000187048.14. [Q02928-1]
DR GeneID; 1579; -.
DR KEGG; hsa:1579; -.
DR MANE-Select; ENST00000310638.9; ENSP00000311095.4; NM_000778.4; NP_000769.2.
DR UCSC; uc001cqp.5; human. [Q02928-1]
DR CTD; 1579; -.
DR DisGeNET; 1579; -.
DR GeneCards; CYP4A11; -.
DR HGNC; HGNC:2642; CYP4A11.
DR HPA; ENSG00000187048; Group enriched (kidney, liver).
DR MIM; 601310; gene.
DR neXtProt; NX_Q02928; -.
DR OpenTargets; ENSG00000187048; -.
DR PharmGKB; PA27118; -.
DR VEuPathDB; HostDB:ENSG00000187048; -.
DR eggNOG; KOG0157; Eukaryota.
DR GeneTree; ENSGT00940000163504; -.
DR InParanoid; Q02928; -.
DR OMA; IAWNISG; -.
DR OrthoDB; 1247045at2759; -.
DR PhylomeDB; Q02928; -.
DR TreeFam; TF105088; -.
DR BRENDA; 1.14.14.80; 2681.
DR PathwayCommons; Q02928; -.
DR Reactome; R-HSA-1989781; PPARA activates gene expression.
DR Reactome; R-HSA-211935; Fatty acids.
DR Reactome; R-HSA-211958; Miscellaneous substrates.
DR Reactome; R-HSA-211979; Eicosanoids.
DR Reactome; R-HSA-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX).
DR Reactome; R-HSA-2142816; Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).
DR SABIO-RK; Q02928; -.
DR SignaLink; Q02928; -.
DR UniPathway; UPA00382; -.
DR UniPathway; UPA00383; -.
DR BioGRID-ORCS; 1579; 10 hits in 1063 CRISPR screens.
DR ChiTaRS; CYP4A11; human.
DR GeneWiki; CYP4A11; -.
DR GenomeRNAi; 1579; -.
DR Pharos; Q02928; Tbio.
DR PRO; PR:Q02928; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q02928; protein.
DR Bgee; ENSG00000187048; Expressed in right lobe of liver and 91 other tissues.
DR ExpressionAtlas; Q02928; baseline and differential.
DR Genevisible; Q02928; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:UniProtKB.
DR GO; GO:0018685; F:alkane 1-monooxygenase activity; IDA:BHF-UCL.
DR GO; GO:0008392; F:arachidonic acid epoxygenase activity; IDA:UniProtKB.
DR GO; GO:0008391; F:arachidonic acid monooxygenase activity; IBA:GO_Central.
DR GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0050051; F:leukotriene-B4 20-monooxygenase activity; IDA:UniProtKB.
DR GO; GO:0102033; F:long-chain fatty acid omega-hydroxylase activity; IDA:UniProtKB.
DR GO; GO:0004497; F:monooxygenase activity; TAS:Reactome.
DR GO; GO:0019369; P:arachidonic acid metabolic process; IDA:UniProtKB.
DR GO; GO:0019373; P:epoxygenase P450 pathway; IDA:UniProtKB.
DR GO; GO:0006631; P:fatty acid metabolic process; TAS:Reactome.
DR GO; GO:0046456; P:icosanoid biosynthetic process; IBA:GO_Central.
DR GO; GO:0001822; P:kidney development; IBA:GO_Central.
DR GO; GO:0048252; P:lauric acid metabolic process; IBA:GO_Central.
DR GO; GO:0006691; P:leukotriene metabolic process; IDA:UniProtKB.
DR GO; GO:0043651; P:linoleic acid metabolic process; IBA:GO_Central.
DR GO; GO:0001676; P:long-chain fatty acid metabolic process; IDA:BHF-UCL.
DR GO; GO:0097267; P:omega-hydroxylase P450 pathway; TAS:Reactome.
DR GO; GO:0031408; P:oxylipin biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0032305; P:positive regulation of icosanoid secretion; IMP:UniProtKB.
DR GO; GO:0003095; P:pressure natriuresis; IEP:UniProtKB.
DR GO; GO:0003091; P:renal water homeostasis; IEP:UniProtKB.
DR GO; GO:0055078; P:sodium ion homeostasis; IEP:UniProtKB.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Direct protein sequencing; Endoplasmic reticulum;
KW Fatty acid metabolism; Heme; Iron; Lipid metabolism; Membrane;
KW Metal-binding; Microsome; Monooxygenase; NADP; Oxidoreductase;
KW Phosphoprotein; Reference proteome.
FT PROPEP 1..4
FT /evidence="ECO:0000269|PubMed:1739747,
FT ECO:0000269|PubMed:7798189"
FT /id="PRO_0000003579"
FT CHAIN 5..519
FT /note="Cytochrome P450 4A11"
FT /id="PRO_0000003580"
FT BINDING 321
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /note="covalent"
FT /evidence="ECO:0000269|PubMed:11139583"
FT BINDING 457
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000269|PubMed:11139583"
FT MOD_RES 440
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P20816"
FT VAR_SEQ 356..519
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_034595"
FT VARIANT 226
FT /note="N -> S (in dbSNP:rs12759923)"
FT /id="VAR_048452"
FT VARIANT 353
FT /note="S -> G (in dbSNP:rs3899049)"
FT /evidence="ECO:0000269|PubMed:15895287,
FT ECO:0000269|PubMed:8363569"
FT /id="VAR_044377"
FT VARIANT 434
FT /note="F -> S (associated with hypertension; significantly
FT reduced arachidonic acid and lauric acid metabolizing
FT activity; dbSNP:rs1126742)"
FT /evidence="ECO:0000269|PubMed:15611369,
FT ECO:0000269|PubMed:15895287, ECO:0000269|PubMed:8274222,
FT ECO:0000269|PubMed:8363569, ECO:0000269|Ref.5"
FT /id="VAR_019160"
FT VARIANT 500..519
FT /note="NGIHLRLRRLPNPCEDKDQL -> MESTCVSGGSLTLVKTRTSFEGLHLPSC
FT LPDPRFCPLPVCPYPVFCLPTFPSSHLPAVPQSACPSLSHLSPGLPTCLSTCLLPTCIS
FT CWEKS (in CYP4A11V)"
FT /id="VAR_001257"
FT MUTAGEN 130
FT /note="G->S: Loss of activity."
FT /evidence="ECO:0000269|PubMed:15611369"
FT MUTAGEN 321
FT /note="E->A: Loss of covalent heme binding."
FT /evidence="ECO:0000269|PubMed:11821421"
FT CONFLICT 5
FT /note="V -> A (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 383
FT /note="Y -> F (in Ref. 4; AAO16078)"
FT /evidence="ECO:0000305"
FT CONFLICT 390
FT /note="G -> S (in Ref. 9; CAA50586)"
FT /evidence="ECO:0000305"
FT CONFLICT 410..412
FT /note="MVL -> TVM (in Ref. 9; CAA50586)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 519 AA; 59348 MW; A8D3073EEFF48AE9 CRC64;
MSVSVLSPSR LLGDVSGILQ AASLLILLLL LIKAVQLYLH RQWLLKALQQ FPCPPSHWLF
GHIQELQQDQ ELQRIQKWVE TFPSACPHWL WGGKVRVQLY DPDYMKVILG RSDPKSHGSY
RFLAPWIGYG LLLLNGQTWF QHRRMLTPAF HYDILKPYVG LMADSVRVML DKWEELLGQD
SPLEVFQHVS LMTLDTIMKC AFSHQGSIQV DRNSQSYIQA ISDLNNLVFS RVRNAFHQND
TIYSLTSAGR WTHRACQLAH QHTDQVIQLR KAQLQKEGEL EKIKRKRHLD FLDILLLAKM
ENGSILSDKD LRAEVDTFMF EGHDTTASGI SWILYALATH PKHQERCREE IHSLLGDGAS
ITWNHLDQMP YTTMCIKEAL RLYPPVPGIG RELSTPVTFP DGRSLPKGIM VLLSIYGLHH
NPKVWPNPEV FDPFRFAPGS AQHSHAFLPF SGGSRNCIGK QFAMNELKVA TALTLLRFEL
LPDPTRIPIP IARLVLKSKN GIHLRLRRLP NPCEDKDQL
