SEP15
| 15 kDa selenoprotein | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||||||
| Symbol | SEP15 | ||||||||||||
| External IDs | OMIM: 606254 MGI: 1927947 HomoloGene: 3145 GeneCards: SEP15 Gene | ||||||||||||
| |||||||||||||
| Orthologs | |||||||||||||
| Species | Human | Mouse | |||||||||||
| Entrez | 9403 | 93684 | |||||||||||
| Ensembl | ENSG00000183291 | ENSMUSG00000037072 | |||||||||||
| UniProt | O60613 | Q9ERR7 | |||||||||||
| RefSeq (mRNA) | NM_004261 | NM_053102 | |||||||||||
| RefSeq (protein) | NP_004252 | NP_444332 | |||||||||||
| Location (UCSC) |
Chr 1: 86.86 – 86.91 Mb |
Chr 3: 144.57 – 144.6 Mb | |||||||||||
| PubMed search | |||||||||||||
15 kDa selenoprotein is a protein that in humans is encoded by the SEP15 gene.[1] 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 UGA codon 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.[1]
Clinical significance
This gene is localized on chromosome 1p31, a genetic locus commonly mutated or deleted in human cancers.[1]
Protein domain
| Sep15 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 Solution structure of SelM from Mus musculus | |||||||||
| Identifiers | |||||||||
| Symbol | Sep15_SelM | ||||||||
| Pfam | PF08806 | ||||||||
| InterPro | IPR014912 | ||||||||
| |||||||||
The protein this gene encodes for is often called Sep15 however in the case of mice, it is named SelM. This protein is an selenoprotein only found in eukaryotes. This domain has a thioredoxin-like domain and a surface accessible active site redox motif.[2] This suggests that they function as thiol-disulfide isomerases involved in disulfide bond formation in the endoplasmic reticulum.[2]
Function
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.[3]
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.[2]
References
- 1 2 3 "Entrez Gene: SEP15 15 kDa selenoprotein".
- 1 2 3 Ferguson AD, Labunskyy VM, Fomenko DE, Araç D, Chelliah Y, Amezcua CA, Rizo J, Gladyshev VN, Deisenhofer J (February 2006). "NMR structures of the selenoproteins Sep15 and SelM reveal redox activity of a new thioredoxin-like family". J. Biol. Chem. 281 (6): 3536–43. doi:10.1074/jbc.M511386200. PMID 16319061.
- ↑ Tsuji PA, Naranjo-Suarez S, Carlson BA, Tobe R, Yoo MH, Davis CD (2011). "Deficiency in the 15 kDa selenoprotein inhibits human colon cancer cell growth.". Nutrients 3 (9): 805–17. doi:10.3390/nu3090805. PMC 3257736. PMID 22254125.
Further reading
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–174. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–156. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Gladyshev VN, Jeang KT, Wootton JC, Hatfield DL (1998). "A new human selenium-containing protein. Purification, characterization, and cDNA sequence". J. Biol. Chem. 273 (15): 8910–8915. doi:10.1074/jbc.273.15.8910. PMID 9535873.
- Kumaraswamy E, Malykh A, Korotkov KV, et al. (2001). "Structure-expression relationships of the 15-kDa selenoprotein gene. Possible role of the protein in cancer etiology". J. Biol. Chem. 275 (45): 35540–35547. doi:10.1074/jbc.M004014200. PMID 10945981.
- Wiemann S, Weil B, Wellenreuther R, et al. (2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Res. 11 (3): 422–435. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
- Korotkov KV, Kumaraswamy E, Zhou Y, et al. (2001). "Association between the 15-kDa selenoprotein and UDP-glucose:glycoprotein glucosyltransferase in the endoplasmic reticulum of mammalian cells". J. Biol. Chem. 276 (18): 15330–15336. doi:10.1074/jbc.M009861200. PMID 11278576.
- Kumaraswamy E, Korotkov KV, Diamond AM, et al. (2002). "Genetic and functional analysis of mammalian Sep15 selenoprotein". Meth. Enzymol. Methods in Enzymology 347: 187–197. doi:10.1016/S0076-6879(02)47017-6. ISBN 978-0-12-182248-4. PMID 11898406.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–16903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Wu HJ, Lin C, Zha YY, et al. (2003). "[Redox reactions of Sep15 and its relationship with tumor development]". Ai Zheng 22 (2): 119–22. PMID 12600282.
- Gevaert K, Goethals M, Martens L, et al. (2004). "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides". Nat. Biotechnol. 21 (5): 566–569. doi:10.1038/nbt810. PMID 12665801.
- Apostolou S, Klein JO, Mitsuuchi Y, et al. (2004). "Growth inhibition and induction of apoptosis in mesothelioma cells by selenium and dependence on selenoprotein SEP15 genotype". Oncogene 23 (29): 5032–5040. doi:10.1038/sj.onc.1207683. PMID 15107826.
- Wellenreuther R, Schupp I, Poustka A, et al. (2004). "SMART amplification combined with cDNA size fractionation in order to obtain large full-length clones". BMC Genomics 5 (1): 36. doi:10.1186/1471-2164-5-36. PMC 436056. PMID 15198809.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–2127. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Gregory SG, Barlow KF, McLay KE, et al. (2006). "The DNA sequence and biological annotation of human chromosome 1". Nature 441 (7091): 315–321. doi:10.1038/nature04727. PMID 16710414.