“SEP15”的意思、由来-开放百科全书

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

The protein this gene encodes for is often called Sep15 however in the case of mice, it is named SelM. This protein is a 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. ^¹²{{cite web | title = Entrez Gene: SEP15 15 kDa selenoprotein| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9403| accessdate = }}
2. ^¹²{{cite journal | vauthors = Ferguson AD, Labunskyy VM, Fomenko DE, Araç D, Chelliah Y, Amezcua CA, Rizo J, Gladyshev VN, Deisenhofer J | title = NMR structures of the selenoproteins Sep15 and SelM reveal redox activity of a new thioredoxin-like family | journal = The Journal of Biological Chemistry | volume = 281 | issue = 6 | pages = 3536–43 | date = February 2006 | pmid = 16319061 | doi = 10.1074/jbc.M511386200 }}
3. ^{{cite journal | vauthors = Tsuji PA, Naranjo-Suarez S, Carlson BA, Tobe R, Yoo MH, Davis CD | title = Deficiency in the 15 kDa selenoprotein inhibits human colon cancer cell growth | journal = Nutrients | volume = 3 | issue = 9 | pages = 805–17 | date = September 2011 | pmid = 22254125 | pmc = 3257736 | doi = 10.3390/nu3090805 }}

Further reading

{{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}

{{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | date = October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}

{{cite journal | vauthors = Gladyshev VN, Jeang KT, Wootton JC, Hatfield DL | title = A new human selenium-containing protein. Purification, characterization, and cDNA sequence | journal = The Journal of Biological Chemistry | volume = 273 | issue = 15 | pages = 8910–5 | date = April 1998 | pmid = 9535873 | doi = 10.1074/jbc.273.15.8910 }}

{{cite journal | vauthors = 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 | title = Structure-expression relationships of the 15-kDa selenoprotein gene. Possible role of the protein in cancer etiology | journal = The Journal of Biological Chemistry | volume = 275 | issue = 45 | pages = 35540–7 | date = November 2000 | pmid = 10945981 | doi = 10.1074/jbc.M004014200 }}

{{cite journal | vauthors = Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A | title = Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs | journal = Genome Research | volume = 11 | issue = 3 | pages = 422–35 | date = March 2001 | pmid = 11230166 | pmc = 311072 | doi = 10.1101/gr.GR1547R }}

{{cite journal | vauthors = Korotkov KV, Kumaraswamy E, Zhou Y, Hatfield DL, Gladyshev VN | title = Association between the 15-kDa selenoprotein and UDP-glucose:glycoprotein glucosyltransferase in the endoplasmic reticulum of mammalian cells | journal = The Journal of Biological Chemistry | volume = 276 | issue = 18 | pages = 15330–6 | date = May 2001 | pmid = 11278576 | doi = 10.1074/jbc.M009861200 }}

{{cite book | vauthors = Kumaraswamy E, Korotkov KV, Diamond AM, Gladyshev VN, Hatfield DL | title = Genetic and functional analysis of mammalian Sep15 selenoprotein | volume = 347 | issue = | pages = 187–97 | year = 2002 | pmid = 11898406 | doi = 10.1016/S0076-6879(02)47017-6 | isbn = 978-0-12-182248-4 | series = Methods in Enzymology }}

{{cite journal | vauthors = Wu HJ, Lin C, Zha YY, Yang JG, Zhang MC, Zhang XY, Liang X, Fu M, Wu M | title = [Redox reactions of Sep15 and its relationship with tumor development] | journal = AI Zheng = Aizheng = Chinese Journal of Cancer | volume = 22 | issue = 2 | pages = 119–22 | date = February 2003 | pmid = 12600282 | doi = }}

{{cite journal | vauthors = Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J | title = Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides | journal = Nature Biotechnology | volume = 21 | issue = 5 | pages = 566–9 | date = May 2003 | pmid = 12665801 | doi = 10.1038/nbt810 }}

{{cite journal | vauthors = Apostolou S, Klein JO, Mitsuuchi Y, Shetler JN, Poulikakos PI, Jhanwar SC, Kruger WD, Testa JR | title = Growth inhibition and induction of apoptosis in mesothelioma cells by selenium and dependence on selenoprotein SEP15 genotype | journal = Oncogene | volume = 23 | issue = 29 | pages = 5032–40 | date = June 2004 | pmid = 15107826 | doi = 10.1038/sj.onc.1207683 }}

{{cite journal | vauthors = Wellenreuther R, Schupp I, Poustka A, Wiemann S | title = SMART amplification combined with cDNA size fractionation in order to obtain large full-length clones | journal = BMC Genomics | volume = 5 | issue = 1 | pages = 36 | date = June 2004 | pmid = 15198809 | pmc = 436056 | doi = 10.1186/1471-2164-5-36 }}

1 : Selenoproteins