CYP2S1

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External IDs	GeneCards: [1]
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Species	Human	Mouse
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Cytochrome P450 2S1 is a protein that in humans is encoded by the CYP2S1 gene. The gene is located in chromosome 19q13.2 within a cluster including other CYP2 family members such as CYP2A6, CYP2A13, CYP2B6, and CYP2F1.

Expression

CYP2S1 is highly expressed in epithelial tissues of the respiratory, gastrointestinal, urinary tracts, and skin and in leukocytes of the monocyte/macrophage and lymphocyte series; it is also expressed throughout Embryogenesis and, as discussed below, certain types of cancers.

Function

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum. In rodents, the homologous protein has been shown to metabolize certain carcinogens although its specific function(s) in humans has not been clearly determined. In in vitro studies, the human enzyme has been found to metabolize all-trans-retinoic acid to 4-hydroxy-retinoic acid and 5, 6-epoxy-retinoic acid and therefore may play a role in processing retinoic acid in tissues where it is highly expressed such as the skin. CYP2S1 is significantly overexpressed and, perhaps directly related to this, its gene is significantly hypometylated (see gene methylation in the skin of Han Chinese patients with psoriasis suggesting that it plays a role in the development of this disease.

CYP2S1 has been suggested to be involved in the growth and/or spread of certain tumors of epithelial cell origin: its higher expression in breast or colorectal cancer tissues appears associated respectively with shorter survival times or poor prognoses, and it is more highly expressed in metastasis compared to primary tumor tissues of ovarian cancer.

CYP2S1 has recently been assigned epoxygenase activity. It metabolizes 1) arachidonic acid to its various epoxides, i.e., the epoxyeicosatrienoic acids (also termed EETs); 2) docosahexaenoic acid to its various epoxides, i.e. the epoxydocosapentaenoic acids (also termed EDPs); and 3) linoleic acid to its various epoxides, i.e. vernolic acid (also termed leukotoxin) and coronaric acid (also termed isoleukotoxin). It seems likely, although not yet tested, that CYP231 will also prove able to metabolize other polyunsaturated fatty acids to their epoxides; for example, the enzyme may metabolize eicosapentaenoic acid to epoxyeicosatetraenoic acids (also termed EEQs). Animal model studies implicate the EET, EDP, and EEQ epoxides in regulating blood pressure, tissue blood flow, new blood vessel formation (i.e. angiogenesis, pain perception, and the growth of various cancers; limited studies suggest but have not proven that these epoxides may function similarly in humans (see epoxyeicosatrienoic acid, epoxydocosapentaenoic acid, eicosatetraenoic acid, and epoxygenase pages). The CYP2S1-dependent production of EETs, which stimulate the growth of various types of cancer cells, including those of he colon (see epoxyeicosatrienoic acid#cancer), could contribute to the unfavorable effects of this CYP in the sited cancers.

Vernolic and coronaric acids are potentially toxic, causing multiple organ failure and acute respiratory distress when injected into animals and suggested to be involved in causing these syndromes in humans.

CYP2S1 has also been found to metabolize Prostaglandin G2 and Prostaglandin H2 to the biologically active product, 12-Hydroxyheptadecatrienoic acid (i.e. 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid, also termed 12-HHT).

External links

• Human CYP2S1 genome location and CYP2S1 gene details page in the UCSC Genome Browser.

Further reading

• Adams MD, Kerlavage AR, Fleischmann RD, Fuldner RA, Bult CJ, Lee NH, Kirkness EF, Weinstock KG, Gocayne JD, White O (September 1995). "Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence" (PDF). Nature. 377 (6547 Suppl): 3–174. PMID 7566098.
• Smith G, Wolf CR, Deeni YY, Dawe RS, Evans AT, Comrie MM, Ferguson J, Ibbotson SH (April 2003). "Cutaneous expression of cytochrome P450 CYP2S1: individuality in regulation by therapeutic agents for psoriasis and other skin diseases". Lancet. 361 (9366): 1336–43. doi:10.1016/S0140-6736(03)13081-4. PMID 12711469.
• Saito S, Iida A, Sekine A, Kawauchi S, Higuchi S, Ogawa C, Nakamura Y (2003). "Catalog of 680 variations among eight cytochrome p450 ( CYP) genes, nine esterase genes, and two other genes in the Japanese population". Journal of Human Genetics. 48 (5): 249–70. doi:10.1007/s10038-003-0021-7. PMID 12721789.
• Rivera SP, Wang F, Saarikoski ST, Taylor RT, Chapman B, Zhang R, Hankinson O (April 2007). "A novel promoter element containing multiple overlapping xenobiotic and hypoxia response elements mediates induction of cytochrome P4502S1 by both dioxin and hypoxia". The Journal of Biological Chemistry. 282 (15): 10881–93. doi:10.1074/jbc.M609617200. PMID 17277313.
• Marek CJ, Tucker SJ, Koruth M, Wallace K, Wright MC (February 2007). "Expression of CYP2S1 in human hepatic stellate cells". FEBS Letters. 581 (4): 781–6. doi:10.1016/j.febslet.2007.01.056. PMID 17280660.
• Hanzawa Y, Sasaki T, Hiratsuka M, Ishikawa M, Mizugaki M (April 2007). "Three novel single nucleotide polymorphisms (SNPs) of CYP2S1 gene in Japanese individuals". Drug Metabolism and Pharmacokinetics. 22 (2): 136–40. doi:10.2133/dmpk.22.136. PMID 17495422.
• Jang YJ, Cha EY, Kim WY, Park SW, Shon JH, Lee SS, Shin JG (June 2007). "CYP2S1 gene polymorphisms in a Korean population". Therapeutic Drug Monitoring. 29 (3): 292–8. doi:10.1097/FTD.0b013e318058a4e0. PMID 17529885.