CYP4F8

Cytochrome P450 4F8 is a protein that in humans is encoded by the CYP4F8 gene.^[5][6]

CYP4F8
Identifiers
Aliases	CYP4F8, CPF8, CYPIVF8, cytochrome P450 family 4 subfamily F member 8
External IDs	OMIM: 611545; MGI: 2146921; HomoloGene: 80199; GeneCards: CYP4F8; OMA:CYP4F8 - orthologs
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.12 Start 15,615,218 bp[1] End 15,630,639 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17|17 B1 Start 32,904,601 bp[2] End 32,922,326 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in seminal vesicula skin of thigh vulva skin of abdomen skin of arm prostate sperm right uterine tube nipple urinary bladder Top expressed in transitional epithelium of urinary bladder left lobe of liver superior frontal gyrus primary visual cortex embryo respiratory epithelium nasal epithelium olfactory epithelium embryo dentate gyrus of hippocampal formation granule cell More reference expression data BioGPS More reference expression data
Gene ontology Molecular function iron ion binding oxidoreductase activity aromatase activity alkane 1-monooxygenase activity heme binding oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen metal ion binding monooxygenase activity Cellular component integral component of membrane organelle membrane endoplasmic reticulum membrane endoplasmic reticulum membrane intracellular membrane-bounded organelle Biological process prostaglandin metabolic process icosanoid metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 11283 106648 Ensembl ENSG00000186526 ENSMUSG00000073424 UniProt P98187 n/a RefSeq (mRNA) NM_007253 NM_134127 NM_001346538 RefSeq (protein) NP_009184 n/a Location (UCSC) Chr 19: 15.62 – 15.63 Mb Chr 17: 32.9 – 32.92 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Gene

This gene, CYP4F8, encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that catalyze many reactions involved in drug metabolism and the synthesis of cholesterol, steroids, and other lipids. This gene is part of a cluster of cytochrome P450 genes on chromosome 19. Another member of this family, CYP4F3, is located approximately 18 kb away.^[6]

Tissue distribution

In addition to seminal vesicles, CYP4F8 is expressed in the kidney, prostate, epidermis, and corneal epithelium, and its mRNA has been detected in the retina. CYP4F8 is also greatly up-regulated in psoriatic skin.^[7]

Function

The CYP4F8 protein localizes to the endoplasmic reticulum and functions as a 19-hydroxylase of the arachidonic acid metabolite prostaglandin H2 (PGH2), and the Dihomo-γ-linolenic acid metabolite PGH1. These activities are particularly relevant in the seminal vesicles, where these metabolic pathways may influence local prostaglandin signaling.

In addition to its ability to metabolize and presumably thereby to inactivate or reduce the activity of PGH2 and PGH1, CYP4F8 adds hydroxyl residues to carbons 18 and 19 of arachidonic acid and Dihomo-γ-linolenic acid,^[8] CYP458 possesses epoxygenase activity in that it metabolizes the omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid, (EPA) to their corresponding epoxides, the epoxydocosapentaenoic acids (EDPs) and epoxyeicosatetraenoic acids (EEQs), respectively.^[9] The enzyme metabolizes DHA primarily to 19R,20S-epoxyeicosapentaenoic acid and 19S,20R-epoxyeicosapentaenoic acid isomers (termed 19,20-EDP) and EPA primarily to 17R,18S-eicosatetraenoic acid and 17S,18R-eicosatetraenoic acid isomers (termed 17,18-EEQ).^[9] 19-HETE is an inhibitor of 20-HETE, a broadly active signaling molecule which acts to constrict arterioles, elevate blood pressure, promote inflammation responses, and stimulates the growth of various types of tumor cells; however the in vivo ability and significance of 19-HETE in inhibiting 20-HETE has not been demonstrated (see 20-Hydroxyeicosatetraenoic acid). The EDPs (see Epoxydocosapentaenoic acid) and EEQs (see epoxyeicosatetraenoic acid) have a broad range of activities. In various animal models and in vitro studies on animal and human tissues, they decrease hypertension and pain perception; suppress inflammation; inhibit angiogenesis, endothelial cell migration and endothelial cell proliferation; and inhibit the growth and metastasis of human breast and prostate cancer cell lines.^{[10][11][12][13]} It is suggested that the EDP and EEQ metabolites function in humans as they do in animal models and that, as products of the omega-3 fatty acids, DHA acid and EPA, the EDP and EEQ metabolites contribute to many of the beneficial effects attributed to dietary omega-3 fatty acids.^[10][13][14] EDP and EEQ metabolites are short-lived, being inactivated within seconds or minutes of formation by epoxide hydrolases, particularly soluble epoxide hydrolase, and therefore act locally.

CYP4F8 has little activity in omega-hydroxylating leukotriene B4, prostaglandin D2, prostaglandin E2, prostaglandin E1, or prostaglandin F2.^[15]

The fatty acid metabolizing activity, including the ability to form epoxides, of CYP4F8 is very similar to that of CYP4F12. However, it and CYP4F12 are not regarded as being major contributors in forming the cited epoxides in humans although they might do so in tissues where they are highly expressed.^[8]