CYP4F12

Cytochrome P450 4F12 is a protein that in humans is encoded by the CYP4F12 gene.[5][6]

CYP4F12
Identifiers
Aliases	CYP4F12, CYPIVF12, F22329_1, cytochrome P450 family 4 subfamily F member 12
External IDs	OMIM: 611485 MGI: 1927669 HomoloGene: 81872 GeneCards: CYP4F12
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.12 Start 15,673,018 bp[1] End 15,697,174 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17|17 B1 Start 32,905,070 bp[2] End 32,917,342 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen • alkane 1-monooxygenase activity • aromatase activity • oxidoreductase activity • leukotriene-B4 20-monooxygenase activity • heme binding • metal ion binding • iron ion binding • arachidonic acid epoxygenase activity • monooxygenase activity Cellular component • endoplasmic reticulum • apical plasma membrane • cytoplasm • organelle membrane • integral component of membrane • membrane • endoplasmic reticulum membrane • intracellular membrane-bounded organelle Biological process • arachidonic acid metabolic process • pressure natriuresis • vitamin E metabolic process • epoxygenase P450 pathway • long-chain fatty acid metabolic process • drug metabolic process • leukotriene B4 catabolic process • very long-chain fatty acid metabolic process • sodium ion homeostasis • renal water homeostasis • oxidation-reduction process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	66002	64385
Ensembl	ENSG00000186204	ENSMUSG00000024292
UniProt	Q9HCS2	Q9EP75
RefSeq (mRNA)	NM_023944	NM_001204333 NM_001204334 NM_001204335 NM_001204336 NM_022434 NM_001357788
RefSeq (protein)	NP_076433	NP_001191262 NP_001191263 NP_001191264 NP_001191265 NP_071879 NP_001344717
Location (UCSC)	Chr 19: 15.67 – 15.7 Mb	Chr 17: 32.91 – 32.92 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

This gene encodes a member of the cytochrome P450 superfamily of enzymes and is part of a cluster of cytochrome P450 genes on chromosome 19.[6][7] The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein likely localizes to the endoplasmic reticulum. CYP4F12 is expressed in the liver and throughout the gastrointestinal track, is known to metabolize the anti-histamine drugs, ebastine and terfenadine, and therefore is suggested to be positioned for and possibly involved in the processing of these and perhaps other drugs.[7][8]

When expressed in yeast the enzyme is capable of oxidizing arachidonic acid by adding a hydroxyl residue to carbons 18 or 19 to form 18-hydroxyeicosatetraenoic acid (18-HETE) or 19-HETE; however, its physiological function in doing so has not been determined. CYP4F12 also metabolizes prostaglandin H2 (PGH2) and PGH1 to their corresponding 19-hydroxyl analogs in a reaction that might serve to reduce their activities.[9] In addition to these monooxygenase actions, CYP458 possesses epoxygenase activity: 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.[10] 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-eicosatetraenic acid and 17S,18R-eicosatetraenic acid isomers (termed 17,18-EEQ).[10] 19-HETE is an inhibitor of 20-HETE, a broadly active signaling molecule which acts to onstrict 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.[11][12][13][14] 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.[11][14][15] 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.

The fatty acid metabolizing activity, including the ability to form epoxides, of CYP4F12 is very similar to that of CYP4F8. However, it and CYP4F8 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.[9]