General Information of Target

Target ID LDTP05563
Target Name Cytochrome P450 4F3 (CYP4F3)
Gene Name CYP4F3
Gene ID 4051
Synonyms
LTB4H; Cytochrome P450 4F3; EC 1.14.14.1; 20-hydroxyeicosatetraenoic acid synthase; 20-HETE synthase; CYPIVF3; Cytochrome P450-LTB-omega; Docosahexaenoic acid omega-hydroxylase CYP4F3; EC 1.14.14.79; Leukotriene-B(4) 20-monooxygenase 2; Leukotriene-B(4) omega-hydroxylase 2; EC 1.14.14.94
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Sequence
MPQLSLSSLGLWPMAASPWLLLLLVGASWLLARILAWTYTFYDNCCRLRCFPQPPKRNWF
LGHLGLIHSSEEGLLYTQSLACTFGDMCCWWVGPWHAIVRIFHPTYIKPVLFAPAAIVPK
DKVFYSFLKPWLGDGLLLSAGEKWSRHRRMLTPAFHFNILKPYMKIFNESVNIMHAKWQL
LASEGSARLDMFEHISLMTLDSLQKCVFSFDSHCQEKPSEYIAAILELSALVTKRHQQIL
LYIDFLYYLTPDGQRFRRACRLVHDFTDAVIQERRRTLPSQGVDDFLQAKAKSKTLDFID
VLLLSKDEDGKKLSDEDIRAEADTFMFEGHDTTASGLSWVLYHLAKHPEYQERCRQEVQE
LLKDREPKEIEWDDLAQLPFLTMCIKESLRLHPPVPAVSRCCTQDIVLPDGRVIPKGIIC
LISVFGTHHNPAVWPDPEVYDPFRFDPKNIKERSPLAFIPFSAGPRNCIGQAFAMAEMKV
VLGLTLLRFRVLPDHTEPRRKPELVLRAEGGLWLRVEPLS
Target Bioclass
Enzyme
Family
Cytochrome P450 family
Subcellular location
Endoplasmic reticulum membrane
Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and their oxygenated derivatives (oxylipins). 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). May play a role in inactivation of pro-inflammatory and anti-inflammatory oxylipins during the resolution of inflammation .; [Isoform CYP4F3A]: Catalyzes predominantly the oxidation of the terminal carbon (omega-oxidation) of oxylipins in myeloid cells, displaying higher affinity for arachidonate metabolite leukotriene B4 (LTB4). Inactivates LTB4 via three successive oxidative transformations to 20-hydroxy-LTB4, then to 20-oxo-LTB4 and to 20-carboxy-LTB4. Has omega-hydroxylase activity toward long-chain fatty acid epoxides with preference for 8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoate (EET) and 9,10-epoxyoctadecanoate. Omega-hydroxylates monohydroxy polyunsaturated fatty acids (PUFAs), including hydroxyeicosatetraenoates (HETEs) and hydroxyeicosapentaenoates (HEPEs), to dihydroxy compounds. Contributes 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. Has low hydroxylase activity toward PUFAs.; [Isoform CYP4F3B]: Catalyzes predominantly the oxidation of the terminal carbon (omega-oxidation) of polyunsaturated fatty acids (PUFAs). Participates in the conversion of arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), a signaling molecule acting both as vasoconstrictive and natriuretic with overall effect on arterial blood pressure. Has high omega-hydroxylase activity toward other PUFAs, including eicosatrienoic acid (ETA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Can also catalyze the oxidation of the penultimate carbon (omega-1 oxidation) of PUFAs with lower efficiency. Contributes to the degradation of saturated very long-chain fatty acids (VLCFAs) such as docosanoic acid and hexacosanoic acid, by catalyzing successive omega-oxidations to the corresponding dicarboxylic acids, thereby initiating chain shortening. Omega-hydroxylates long-chain 3-hydroxy fatty acids, likely initiating the oxidative conversion to the corresponding 3-hydroxydicarboxylic fatty acids. Has omega-hydroxylase activity toward long-chain fatty acid epoxides with preference for 8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoate (EET) and 9,10-epoxyoctadecanoate.
Uniprot ID
Q08477
Ensemble ID
ENST00000221307.13
HGNC ID
HGNC:2646
ChEMBL ID
CHEMBL3508692

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
CCK81 SNV: p.C206R .
COLO792 SNV: p.P114L .
HCC1187 SNV: p.Q377E .
HCT15 SNV: p.F245L .
OPM2 SNV: p.G417C .
OVK18 SNV: p.V92A .
RKO SNV: p.T332A .
SAOS2 SNV: p.M198T .
SHP77 SNV: p.R488S .
TE1 SNV: p.C468S .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 3 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
YN-4
 Probe Info 
100.00  LDD0445  [1]
N1
 Probe Info 
N.A.  LDD0245  [2]
IA-alkyne
 Probe Info 
C354(0.00); C384(0.00); C420(0.00); C468(0.00)  LDD0162  [3]

The Interaction Atlas With This Target

The Drug(s) Related To This Target

Approved
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Ponesimod Small molecular drug DB12016

References

1 Ynamide Electrophile for the Profiling of Ligandable Carboxyl Residues in Live Cells and the Development of New Covalent Inhibitors. J Med Chem. 2022 Aug 11;65(15):10408-10418. doi: 10.1021/acs.jmedchem.2c00272. Epub 2022 Jul 26.
2 Cyclopropenone, Cyclopropeniminium Ion, and Cyclopropenethione as Novel Electrophilic Warheads for Potential Target Discovery of Triple-Negative Breast Cancer. J Med Chem. 2023 Feb 23;66(4):2851-2864. doi: 10.1021/acs.jmedchem.2c01889. Epub 2023 Feb 10.
3 SP3-FAIMS Chemoproteomics for High-Coverage Profiling of the Human Cysteinome*. Chembiochem. 2021 May 14;22(10):1841-1851. doi: 10.1002/cbic.202000870. Epub 2021 Feb 18.
Mass spectrometry data entry: PXD023056 , PXD023059 , PXD023058 , PXD023057 , PXD023060