Wikipedia

SMG6: Difference between revisions

Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
→‎Clinical Significance: consistent citation formatting
Added Structure section and edited Introduction
Line 1:
{{Infobox_gene}}
'''Telomerase-binding protein EST1A''' is an [[enzyme]] that in humans is encoded by the ''SMG6'' [[gene]] on [[Chromosome 17 (human)|chromosome 17]].<ref name="pmid12676087">{{cite journal | vauthors = Reichenbach P, Hoss M, Azzalin CM, Nabholz M, Bucher P, Lingner J | title = A human homolog of yeast Est1 associates with telomerase and uncaps chromosome ends when overexpressed | journal = Curr Biol | volume = 13 | issue = 7 | pages = 568–74 |date=Apr 2003 | pmid = 12676087 | pmc = | doi =10.1016/S0960-9822(03)00173-8 }}</ref><ref name="pmid12699629">{{cite journal | vauthors = Snow BE, Erdmann N, Cruickshank J, Goldman H, Gill RM, Robinson MO, Harrington L | title = Functional conservation of the telomerase protein Est1p in humans | journal = Curr Biol | volume = 13 | issue = 8 | pages = 698–704 |date=Apr 2003 | pmid = 12699629 | pmc = | doi =10.1016/S0960-9822(03)00210-0 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: SMG6 Smg-6 homolog, nonsense mediated mRNA decay factor (C. elegans)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23293| accessdate = }}</ref> It is ubiquitously expressed in many tissues and cell types.<ref>{{Cite web|url=http://biogps.org/#goto=genereport&id=23293|title=BioGPS - your Gene Portal System|website=biogps.org|access-date=2016-10-12}}</ref> The C-terminus of the EST1A protein contains a [[PIN domain|PilT N-terminus (PIN) domain]]. This structure for this domain has been determined by [[X-ray crystallography]].<ref>{{cite journal |vauthorsyear=Takeshita D, Zenno S, Lee WC, etal 2006|title=Crystallization and preliminary X-ray analysis of the PIN domain of human EST1A. |journal=Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. |volume=62 |issue= Pt 7 |pages= 656–8 |yeardoi=10.1107/S1744309106020057|pmc=2242961|pmid=16820686|vauthors=Takeshita 2006D, Zenno S, Lee WC, etal}}</ref> SMG6 functions to bind [[single-stranded DNA]] in [[telomere]] maintenance and [[Single-stranded DNA|pmidsingle-stranded RNA]] in [[nonsense-mediated mRNA decay]] (NMD).<ref>{{Cite journal|last=Snow|first=Bryan 16820686E.|last2=Erdmann|first2=Natalie|last3=Cruickshank|first3=Jennifer|last4=Goldman|first4=Hartt|last5=Gill|first5=R. Montgomery|doilast6=Robinson|first6=Murray 10O.1107|last7=Harrington|first7=Lea|date=2003-04-15|title=Functional conservation of the telomerase protein Est1p in humans|url=https:/S1744309106020057/www.ncbi.nlm.nih.gov/pubmed/12699629|journal=Current biology: CB|volume=13|issue=8|pages=698–704|issn=0960-9822|pmid=12699629}}</ref><ref>{{Cite pmcjournal|last=2242961Huntzinger|first=Eric|last2=Kashima|first2=Isao|last3=Fauser|first3=Maria|last4=Saulière|first4=Jérôme|last5=Izaurralde|first5=Elisa|date=2008-12-01|title=SMG6 is the catalytic endonuclease that cleaves mRNAs containing nonsense codons in metazoan|url=https://www.ncbi.nlm.nih.gov/pubmed/18974281|journal=RNA (New York, N.Y.)|volume=14|issue=12|pages=2609–2617|doi=10.1261/rna.1386208|issn=1469-9001|pmid=18974281}}</ref> The ''SMG6'' gene also contains one of 27 [[SNPs]] associated with increased risk of [[coronary artery disease]].<ref name=":0" />
 
== Structure ==
<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
 
{{PBB_Summary
=== Gene ===
| section_title =
The ''SMG6'' gene resides on chromosome 17 at the band 17p13.3 and contains 30 [[Exon|exons]].<ref>{{Cite web|url=http://www.ncbi.nlm.nih.gov/gene/23293|title=SMG6 SMG6, nonsense mediated mRNA decay factor [Homo sapiens (human)] - Gene - NCBI|website=www.ncbi.nlm.nih.gov|access-date=2016-10-12}}</ref> This gene produces 3 [[isoforms]] through [[alternative splicing]].<ref>{{Cite web|url=http://www.uniprot.org/uniprot/Q86US8|title=SMG6 - Telomerase-binding protein EST1A - Homo sapiens (Human) - SMG6 gene & protein|website=www.uniprot.org|access-date=2016-10-12}}</ref>
| summary_text =
 
}}
=== Protein ===
SMG6 is one of three human [[homologs]] for Est1p found in [[Saccharomyces cerevisiae]]. It contains a PIN domain, which is characteristic of proteins with [[ribonuclease]] activity.<ref>{{Cite journal|last=Glavan|first=Filip|last2=Behm-Ansmant|first2=Isabelle|last3=Izaurralde|first3=Elisa|last4=Conti|first4=Elena|date=2006-11-01|title=Structures of the PIN domains of SMG6 and SMG5 reveal a nuclease within the mRNA surveillance complex|url=https://www.ncbi.nlm.nih.gov/pubmed/17053788|journal=The EMBO journal|volume=25|issue=21|pages=5117–5125|doi=10.1038/sj.emboj.7601377|issn=0261-4189|pmid=17053788}}</ref> The PIN domain forms an alpha/beta fold structure that similar to that found in 5' [[Nuclease|nucleases]].<ref>{{Cite journal|last=Takeshita|first=Daijiro|last2=Zenno|first2=Shuhei|last3=Lee|first3=Woo Cheol|last4=Saigo|first4=Kaoru|last5=Tanokura|first5=Masaru|date=2007-09-01|title=Crystal structure of the PIN domain of human telomerase-associated protein EST1A|url=https://www.ncbi.nlm.nih.gov/pubmed/17557331|journal=Proteins|volume=68|issue=4|pages=980–989|doi=10.1002/prot.21351|issn=1097-0134|pmid=17557331}}</ref> Within the PIN domain is a canonical triad of [[Amino acid|acidic residues]] that functions to cleave single-stranded RNA.<ref>{{Cite journal|last=Huntzinger|first=Eric|last2=Kashima|first2=Isao|last3=Fauser|first3=Maria|last4=Saulière|first4=Jérôme|last5=Izaurralde|first5=Elisa|date=2008-12-01|title=SMG6 is the catalytic endonuclease that cleaves mRNAs containing nonsense codons in metazoan|url=https://www.ncbi.nlm.nih.gov/pubmed/18974281|journal=RNA (New York, N.Y.)|volume=14|issue=12|pages=2609–2617|doi=10.1261/rna.1386208|issn=1469-9001|pmid=18974281}}</ref> SMG6 also shares a [[phosphoserine]]-binding domain resembling the one in [[14-3-3 protein|14–3–3 proteins]] with its other two homologs, [[SMG5]] and [[SMG7]]. This 14–3–3-like domain and a C-terminal helical hairpins domain with seven α-helices stacked perpendicular to the 14–3–3-like domain together form a monomeric tetratricopeptide region (TPR). Differences in the orientation and specific residues in the TPR between SMG6 and its homologs may account for why SMG6 does not form a [[Protein complexes|complex]] with SMG5 and SMG7 when recruited by [[UPF1]].<ref>{{Cite journal|last=Chakrabarti|first=Sutapa|last2=Bonneau|first2=Fabien|last3=Schüssler|first3=Steffen|last4=Eppinger|first4=Elfriede|last5=Conti|first5=Elena|date=2014-08-01|title=Phospho-dependent and phospho-independent interactions of the helicase UPF1 with the NMD factors SMG5-SMG7 and SMG6|url=https://www.ncbi.nlm.nih.gov/pubmed/25013172|journal=Nucleic Acids Research|volume=42|issue=14|pages=9447–9460|doi=10.1093/nar/gku578|issn=1362-4962|pmid=25013172}}</ref>
 
== Clinical significance ==
Line 12 ⟶ 14:
 
=== Clinical marker ===
A multi-locus genetic risk score study based on a combination of 27 loci, including the SMG6 gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22).<ref name=":0">{{cite journal | vauthors = Mega JL, Stitziel NO, Smith JG, Chasman DI, Caulfield MJ, Devlin JJ, Nordio F, Hyde CL, Cannon CP, Sacks FM, Poulter NR, Sever PS, Ridker PM, Braunwald E, Melander O, Kathiresan S, Sabatine MS | title = Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials | journal = Lancet | volume = 385 | issue = 9984 | pages = 2264–71 | date = June 2015 | pmid = 25748612 | doi = 10.1016/S0140-6736(14)61730-X }}</ref>
 
==References==
Retrieved from "https://en.wikipedia.org/wiki/SMG6"