Overview
| Uniprot ID | Q02928 |
| Protein Name | Cytochrome P450 4A11 |
| Gene Name | CYP4A11 |
| Organism | Homo 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.