Search Results

Overview

Uniprot IDQ02928
Protein NameCytochrome P450 4A11
Gene NameCYP4A11
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
276 LRKAQLQKEGELEKI
460 GSRNCIGKQFAMNEL
499 ARLVLKSKNGIHLRL
516 LPNPCEDKDQL****

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)

Protein Sequence

10 MSVSVLSPSR 20 LLGDVSGILQ 30 AASLLILLLL 40 LIKAVQLYLH 50 RQWLLKALQQ 60 FPCPPSHWLF 70 GHIQELQQDQ 80 ELQRIQKWVE 90 TFPSACPHWL 100 WGGKVRVQLY 110 DPDYMKVILG 120 RSDPKSHGSY 130 RFLAPWIGYG 140 LLLLNGQTWF 150 QHRRMLTPAF 160 HYDILKPYVG 170 LMADSVRVML 180 DKWEELLGQD 190 SPLEVFQHVS 200 LMTLDTIMKC 210 AFSHQGSIQV 220 DRNSQSYIQA 230 ISDLNNLVFS 240 RVRNAFHQND 250 TIYSLTSAGR 260 WTHRACQLAH 270 QHTDQVIQLR 280 KAQLQKEGEL 290 EKIKRKRHLD 300 FLDILLLAKM 310 ENGSILSDKD 320 LRAEVDTFMF 330 EGHDTTASGI 340 SWILYALATH 350 PKHQERCREE 360 IHSLLGDGAS 370 ITWNHLDQMP 380 YTTMCIKEAL 390 RLYPPVPGIG 400 RELSTPVTFP 410 DGRSLPKGIM 420 VLLSIYGLHH 430 NPKVWPNPEV 440 FDPFRFAPGS 450 AQHSHAFLPF 460 SGGSRNCIGK 470 QFAMNELKVA 480 TALTLLRFEL 490 LPDPTRIPIP 500 IARLVLKSKN 510 GIHLRLRRLP NPCEDKDQL

Gene Ontology

Classification GO ID Description
Cellular Component GO:0016324 apical plasma membrane
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005789 endoplasmic reticulum membrane
Cellular Component GO:0043231 intracellular membrane-bounded organelle
Molecular Function GO:0018685 alkane 1-monooxygenase activity
Molecular Function GO:0008392 arachidonate epoxygenase activity
Molecular Function GO:0008391 arachidonate monooxygenase activity
Molecular Function GO:0052869 arachidonate omega-hydroxylase activity
Molecular Function GO:0020037 heme binding
Molecular Function GO:0005506 iron ion binding
Molecular Function GO:0050051 leukotriene-B4 20-monooxygenase activity
Molecular Function GO:0102033 long-chain fatty acid omega-hydroxylase activity
Molecular Function GO:0004497 monooxygenase activity
Biological Process GO:0019369 arachidonate metabolic process
Biological Process GO:0019373 epoxygenase P450 pathway
Biological Process GO:0006631 fatty acid metabolic process
Biological Process GO:0046456 icosanoid biosynthetic process
Biological Process GO:0001822 kidney development
Biological Process GO:0048252 lauric acid metabolic process
Biological Process GO:0006691 leukotriene metabolic process
Biological Process GO:0043651 linoleic acid metabolic process
Biological Process GO:0001676 long-chain fatty acid metabolic process
Biological Process GO:0097267 omega-hydroxylase P450 pathway
Biological Process GO:0031408 oxylipin biosynthetic process
Biological Process GO:0032305 positive regulation of icosanoid secretion
Biological Process GO:0003095 pressure natriuresis
Biological Process GO:0003091 renal water homeostasis
Biological Process GO:0055078 sodium ion homeostasis

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.