CYP4F3

CYP4F3
Identifiers
Aliases	CYP4F3, CPF3, CYP4F, LTB4H, cytochrome P450 family 4 subfamily F member 3, CYPIVF3
External IDs	OMIM: 601270 MGI: 2158641 HomoloGene: 73902 GeneCards: CYP4F3
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.12 Start 15,640,897 bp[1] End 15,662,825 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17|17 B1 Start 33,143,662 bp[2] End 33,166,376 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver trabecular bone blood bone marrow kidney tubule bone marrow cells metanephric glomerulus jejunal mucosa kidney gallbladder Top expressed in yolk sac duodenum jejunum left lobe of liver lip proximal tubule superior frontal gyrus urethra ileum lens More reference expression data BioGPS n/a
Gene ontology Molecular function iron ion binding alpha-tocopherol omega-hydroxylase activity tocopherol omega-hydroxylase activity metal ion binding monooxygenase activity heme binding oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen oxidoreductase activity 20-hydroxy-leukotriene B4 omega oxidase activity leukotriene-B4 20-monooxygenase activity 20-aldehyde-leukotriene B4 20-monooxygenase activity Cellular component integral component of membrane organelle membrane endoplasmic reticulum membrane membrane intracellular membrane-bounded organelle endoplasmic reticulum Biological process leukotriene metabolic process lipid metabolism icosanoid metabolic process leukotriene B4 catabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4051 170716 Ensembl ENSG00000186529 ENSMUSG00000024055 UniProt Q08477 n/a RefSeq (mRNA) NM_000896 NM_001199208 NM_001199209 NM_001369696 NM_130882 RefSeq (protein) NP_000887 NP_001186137 NP_001186138 NP_001356625 n/a Location (UCSC) Chr 19: 15.64 – 15.66 Mb Chr 17: 33.14 – 33.17 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Cytochrome P450 4F3, also leukotriene-B(4) omega-hydroxylase 2, is an enzyme that in humans is encoded by the CYP4F3 gene.^[5][6][7] CYP4F3 encodes two distinct enzymes, CYP4F3A and CYP4F3B, which originate from the alternative splicing of a single pre-mRNA precursor molecule; selection of either isoform is tissue-specific with CYP3F3A being expressed mostly in leukocytes and CYP4F3B mostly in the liver.^[8]

Function

The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids, fatty acids and other lipids. CYP4F3 actually encodes two splice-variants, CYP4F3A and CYP4F3B, of the cytochrome P450 superfamily of enzymes. The gene is part of a cluster of cytochrome P450 genes on chromosome 19. Another member of this family, CYP4F8, is approximately 18 kb away.^[7] Both variants localize on the endoplasmic reticulum and metabolize leukotriene B4 and very likely 5-hydroxyeicosatetraenoic acid, 5-oxo-eicosatetraenoic acid, and 12-hydroxyeicosatetraenoic acid by an omega oxidation reaction, i.e. by adding a hydroxyl residue to their terminal (i.e. C-20) carbon.^[9] This addition starts the process of inactivating and degrading all of these well-known mediators of inflammation^[10] CYP3FA is the major enzyme accomplishing these omega oxidations in leukocytes.^[10]

CYP4F3A and/or CYP43FB also omega oxidize arachidonic acid to 20-Hydroxyeicosatetraenoic acid (20-HETE) as well as epoxyeicosatrienoic acids (EETs) to 20-hydroxy-EETs.^[10] 20-HETE regulates blood flow, vascularization, blood pressure, and kidney tubule absorption of ions in rodents and possibly humans;^[8] it has also been proposed to be involved in regulating the growth of various types of human cancers (see 20-Hydroxyeicosatetraenoic acid#Cancer). EETS have a similar set of regulatory functions but often act in a manner opposite to 20-HETE (see epoxyeicosatrienoic acid#Cancer); since, however, the activities of the 20-HEETs have not been well-defined, the function of EET omega oxidation is unclear.^[8]

Genetic variants

The hydroxylation-induced inactivation of the mediators of inflammation, perhaps particularly of leukotriene B4, may underlie the proposed roles of these cytochromes in dampening inflammatory responses as well as the reported associations of certain CYP4F3 single nucleotide variants (SNPs) with human Crohn's disease (SNPs are designated rs1290617^[11] and rs1290620^[12] and Celiac disease (rs1290622 and rs1290625).^{[8][13][14][15][16]}

There is also a study that have found an association within Guangzhou population between the single nucleotide variation rs3794987 and susceptibility to the SARS-CoV-1 virus, discovered in 2003. The GG/AG genotype was associated with an increased susceptibility to SARS-CoV-1, comparing to the AA genotype. However, the results of this association were not replicated in another study, on the Beijing population. The combined analysis of the two studies does not show any association of the CYP4F3 SNPs analyzed with SARS-CoV-1 susceptibility.^[17]

References

Further reading

This article on a gene on human chromosome 19 is a stub. You can help Wikipedia by expanding it.

• v
• t
• e