15 kDa selenoprotein is a protein that in humans is encoded by the SEP15gene.[5] Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.
Function
This gene encodes a selenoprotein, which contains a selenocysteine (Sec) residue at its active site. The selenocysteine is encoded by the UGAcodon that normally signals translation termination. The 3' UTR of selenoprotein genes have a common stem-loop structure, the sec insertion sequence (SECIS), that is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. Studies in mouse suggest that this selenoprotein may have redox function and may be involved in the quality control of protein folding.[5]
Clinical significance
This gene is localized on chromosome 1p31, a genetic locus commonly mutated or deleted in human cancers.[5]
Recent studies have shown in mice, where the SEP15 gene has been silenced the mice subsequently became deficient in SEP15 and were able to inhibit the development of colorectal cancer.[7]
Structure
The particular structure has an alpha/beta central domain which is actually made up of three alpha helices and a mixed parallel/anti-parallel four-stranded beta-sheet.[6]
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Kumaraswamy E, Malykh A, Korotkov KV, Kozyavkin S, Hu Y, Kwon SY, Moustafa ME, Carlson BA, Berry MJ, Lee BJ, Hatfield DL, Diamond AM, Gladyshev VN (November 2000). "Structure-expression relationships of the 15-kDa selenoprotein gene. Possible role of the protein in cancer etiology". The Journal of Biological Chemistry. 275 (45): 35540–7. doi:10.1074/jbc.M004014200. PMID10945981.{{cite journal}}: CS1 maint: unflagged free DOI (link)
Korotkov KV, Kumaraswamy E, Zhou Y, Hatfield DL, Gladyshev VN (May 2001). "Association between the 15-kDa selenoprotein and UDP-glucose:glycoprotein glucosyltransferase in the endoplasmic reticulum of mammalian cells". The Journal of Biological Chemistry. 276 (18): 15330–6. doi:10.1074/jbc.M009861200. PMID11278576.{{cite journal}}: CS1 maint: unflagged free DOI (link)
Kumaraswamy E, Korotkov KV, Diamond AM, Gladyshev VN, Hatfield DL (2002). "Genetic and functional analysis of mammalian Sep15 selenoprotein". Methods in Enzymology. Methods in Enzymology. 347: 187–97. doi:10.1016/S0076-6879(02)47017-6. ISBN978-0-12-182248-4. PMID11898406.
Wu HJ, Lin C, Zha YY, Yang JG, Zhang MC, Zhang XY, Liang X, Fu M, Wu M (February 2003). "[Redox reactions of Sep15 and its relationship with tumor development]". Ai Zheng = Aizheng = Chinese Journal of Cancer. 22 (2): 119–22. PMID12600282.
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Apostolou S, Klein JO, Mitsuuchi Y, Shetler JN, Poulikakos PI, Jhanwar SC, Kruger WD, Testa JR (June 2004). "Growth inhibition and induction of apoptosis in mesothelioma cells by selenium and dependence on selenoprotein SEP15 genotype". Oncogene. 23 (29): 5032–40. doi:10.1038/sj.onc.1207683. PMID15107826.
