Overview
| Uniprot ID | P78329 |
|---|
| Protein Name | Cytochrome P450 4F2 |
|---|
| Gene Name | CYP4F2 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 120 |
ASAAIAPKDKFFYSF |
| 290 |
VDDFLQAKAKSKTLD |
| 294 |
LQAKAKSKTLDFIDV |
Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, eicosanoids and vitamins (PubMed:10660572, PubMed:10833273, PubMed:11997390, PubMed:17341693, PubMed:18574070, PubMed:18577768). 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). Catalyzes predominantly the oxidation of the terminal carbon (omega-oxidation) of long- and very long-chain fatty acids. Displays high omega-hydroxylase activity toward polyunsaturated fatty acids (PUFAs) (PubMed:18577768). Participates in the conversion of arachidonic acid to omega-hydroxyeicosatetraenoic acid (20-HETE), a signaling molecule acting both as vasoconstrictive and natriuretic with overall effect on arterial blood pressure (PubMed:10660572, PubMed:17341693, PubMed:18574070). Plays a role in the oxidative inactivation of eicosanoids, including both pro-inflammatory and anti-inflammatory mediators such as leukotriene B4 (LTB4), lipoxin A4 (LXA4), and several HETEs (PubMed:10660572, PubMed:10833273, PubMed:17341693, PubMed:18574070, PubMed:18577768, PubMed:8026587, PubMed:9799565). Catalyzes omega-hydroxylation of 3-hydroxy fatty acids (PubMed:18065749). Converts monoepoxides of linoleic acid leukotoxin and isoleukotoxin to omega-hydroxylated metabolites (PubMed:15145985). Contributes to the degradation of very long-chain fatty acids (VLCFAs) by catalyzing successive omega-oxidations and chain shortening (PubMed:16547005, PubMed:18182499). Plays an important role in vitamin metabolism by chain shortening. Catalyzes omega-hydroxylation of the phytyl chain of tocopherols (forms of vitamin E), with preference for gamma-tocopherols over alpha-tocopherols, thus promoting retention of alpha-tocopherols in tissues (PubMed:11997390). Omega-hydroxylates and inactivates phylloquinone (vitamin K1), and menaquinone-4 (MK-4, a form of vitamin K2), both acting as cofactors in blood coagulation (PubMed:19297519, PubMed:24138531)
Protein Sequence
10
MSQLSLSWLG
20
LWPVAASPWL
30
LLLLVGASWL
40
LAHVLAWTYA
50
FYDNCRRLRC
60
FPQPPRRNWF
70
WGHQGMVNPT
80
EEGMRVLTQL
90
VATYPQGFKV
100
WMGPISPLLS
110
LCHPDIIRSV
120
INASAAIAPK
130
DKFFYSFLEP
140
WLGDGLLLSA
150
GDKWSRHRRM
160
LTPAFHFNIL
170
KPYMKIFNES
180
VNIMHAKWQL
190
LASEGSACLD
200
MFEHISLMTL
210
DSLQKCVFSF
220
DSHCQEKPSE
230
YIAAILELSA
240
LVSKRHHEIL
250
LHIDFLYYLT
260
PDGQRFRRAC
270
RLVHDFTDAV
280
IQERRRTLPS
290
QGVDDFLQAK
300
AKSKTLDFID
310
VLLLSKDEDG
320
KKLSDEDIRA
330
EADTFMFEGH
340
DTTASGLSWV
350
LYHLAKHPEY
360
QERCRQEVQE
370
LLKDREPKEI
380
EWDDLAHLPF
390
LTMCMKESLR
400
LHPPVPVISR
410
HVTQDIVLPD
420
GRVIPKGIIC
430
LISVFGTHHN
440
PAVWPDPEVY
450
DPFRFDPENI
460
KERSPLAFIP
470
FSAGPRNCIG
480
QTFAMAEMKV
490
VLALTLLRFR
500
VLPDHTEPRR
510
KPELVLRAEG
520
GLWLRVEPLS
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0016324 |
apical plasma membrane |
| Molecular Function |
GO:0052871 |
alpha-tocopherol omega-hydroxylase activity |
| Molecular Function |
GO:0008392 |
arachidonate epoxygenase 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 |
| Molecular Function |
GO:0016709 |
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen |
| Biological Process |
GO:0019369 |
arachidonate metabolic process |
| Biological Process |
GO:0007596 |
blood coagulation |
| Biological Process |
GO:0019373 |
epoxygenase P450 pathway |
| Biological Process |
GO:0010430 |
fatty acid omega-oxidation |
| Biological Process |
GO:0006690 |
icosanoid metabolic process |
| Biological Process |
GO:0036101 |
leukotriene B4 catabolic process |
| Biological Process |
GO:0006691 |
leukotriene metabolic process |
| Biological Process |
GO:0001676 |
long-chain fatty acid metabolic process |
| Biological Process |
GO:0042361 |
menaquinone catabolic process |
| Biological Process |
GO:0032304 |
negative regulation of icosanoid secretion |
| Biological Process |
GO:0097267 |
omega-hydroxylase P450 pathway |
| Biological Process |
GO:0042376 |
phylloquinone catabolic process |
| Biological Process |
GO:0032305 |
positive regulation of icosanoid secretion |
| Biological Process |
GO:0003095 |
pressure natriuresis |
| Biological Process |
GO:0008217 |
regulation of blood pressure |
| Biological Process |
GO:0003091 |
renal water homeostasis |
| Biological Process |
GO:0055078 |
sodium ion homeostasis |
| Biological Process |
GO:0000038 |
very long-chain fatty acid metabolic process |
| Biological Process |
GO:0042360 |
vitamin E metabolic process |
| Biological Process |
GO:0042377 |
vitamin K catabolic process |
| Biological Process |
GO:0006805 |
xenobiotic metabolic process |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0005789 |
endoplasmic reticulum membrane |
| Cellular Component |
GO:0043231 |
intracellular membrane-bounded organelle |
| Molecular Function |
GO:0097259 |
20-aldehyde-leukotriene B4 20-monooxygenase activity |
| Molecular Function |
GO:0097258 |
20-hydroxy-leukotriene B4 omega oxidase activity |
| Molecular Function |
GO:0018685 |
alkane 1-monooxygenase activity |
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.