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{{Short description|Protein-coding gene in the species Homo sapiens}}
{{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, Höss 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 = Current Biology | volume = 13 | issue = 7 | pages = 568–74 | date = April 2003 | pmid = 12676087 | doi = 10.1016/S0960-9822(03)00173-8 | s2cid = 14423276 | doi-access = free }}</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 = Current Biology | volume = 13 | issue = 8 | pages = 698–704 | date = April 2003 | pmid = 12699629 | doi = 10.1016/S0960-9822(03)00210-0 | s2cid = 6685276 | doi-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: SMG6 Smg-6 homolog, nonsense mediated mRNA decay factor (C. elegans)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23293}}</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 | vauthors = Takeshita D, Zenno S, Lee WC, Saigo K, Tanokura M | title = Crystallization and preliminary X-ray analysis of the PIN domain of human EST1A | journal = Acta Crystallographica Section F | volume = 62 | issue = Pt 7 | pages = 656–8 | date = July 2006 | pmid = 16820686 | pmc = 2242961 | doi = 10.1107/S1744309106020057 }}</ref> SMG6 functions to bind [[single-stranded DNA]] in [[telomere]] maintenance and [[Single-stranded DNA|single-stranded RNA]] in [[nonsense-mediated mRNA decay]] (NMD).<ref>{{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 = Current Biology | volume = 13 | issue = 8 | pages = 698–704 | date = April 2003 | pmid = 12699629 | doi=10.1016/s0960-9822(03)00210-0| s2cid = 6685276 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Huntzinger E, Kashima I, Fauser M, Saulière J, Izaurralde E | title = SMG6 is the catalytic endonuclease that cleaves mRNAs containing nonsense codons in metazoan | journal = RNA | volume = 14 | issue = 12 | pages = 2609–17 | date = December 2008 | pmid = 18974281 | doi = 10.1261/rna.1386208 | pmc=2590965}}</ref> The ''SMG6'' gene also contains one of 27 [[SNPs]] associated with increased risk of [[coronary artery disease]].<ref name=":0" />
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=== 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 | vauthors = Glavan F, Behm-Ansmant I, Izaurralde E, Conti E | title = Structures of the PIN domains of SMG6 and SMG5 reveal a nuclease within the mRNA surveillance complex | journal = The EMBO Journal | volume = 25 | issue = 21 | pages = 5117–25 | date = November 2006 | pmid = 17053788 | doi = 10.1038/sj.emboj.7601377 | pmc=1630413}}</ref> The PIN domain forms an alpha/beta fold structure that similar to that found in 5' [[Nuclease|nucleases]].<ref>{{cite journal | vauthors = Takeshita D, Zenno S, Lee WC, Saigo K, Tanokura M | title = Crystal structure of the PIN domain of human telomerase-associated protein EST1A | journal = Proteins | volume = 68 | issue = 4 | pages = 980–9 | date = September 2007 | pmid = 17557331 | doi = 10.1002/prot.21351 | s2cid = 43477604 }}</ref> Within the PIN domain is a canonical triad of [[Amino acid|acidic residues]] that functions to cleave single-stranded RNA.<ref>{{cite journal | vauthors = Huntzinger E, Kashima I, Fauser M, Saulière J, Izaurralde E | title = SMG6 is the catalytic endonuclease that cleaves mRNAs containing nonsense codons in metazoan | journal = RNA | volume = 14 | issue = 12 | pages = 2609–17 | date = December 2008 | pmid = 18974281 | doi = 10.1261/rna.1386208 | pmc=2590965}}</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 | vauthors = Chakrabarti S, Bonneau F, Schüssler S, Eppinger E, Conti E | title = Phospho-dependent and phospho-independent interactions of the helicase UPF1 with the NMD factors SMG5-SMG7 and SMG6 | journal = Nucleic Acids Research | volume = 42 | issue = 14 | pages = 9447–60 | date = August 2014 | pmid = 25013172 | doi = 10.1093/nar/gku578 | pmc=4132714}}</ref>
== Function ==
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== Clinical significance ==
In humans, selected genomic regions based on 150 SNPs were identified in a [[genome-wide association study]] (GWAS) on coronary artery disease. Accordingly, the association between recent smoking and the CpG sites within and near these coronary artery disease-related genes were investigated in 724 [[Caucasian race|Caucasian]] subjects from the Rotterdam Study. The identified [[methylation]] sites were found in SMG6 together with other genes, and several of these sites exhibited lower methylation in subjects currently smoking compared to never smoking.<ref>{{cite journal | vauthors = Steenaard RV, Ligthart S, Stolk L, Peters MJ, van Meurs JB, Uitterlinden AG, Hofman A, Franco OH, Dehghan A | title = Tobacco smoking is associated with methylation of genes related to coronary artery disease | journal = Clinical Epigenetics | volume = 7 | pages = 54 | date = 2015-01-01 | issue = 1 | pmid = 26015811 | doi = 10.1186/s13148-015-0088-y | pmc=4443552 | doi-access = free }}</ref>
=== Clinical marker ===
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* {{cite journal | vauthors = Takeshita D, Zenno S, Lee WC, Saigo K, Tanokura M | title = Crystallization and preliminary X-ray analysis of the PIN domain of human EST1A | journal = Acta Crystallographica Section F | volume = 62 | issue = Pt 7 | pages = 656–8 | date = July 2006 | pmid = 16820686 | pmc = 2242961 | doi = 10.1107/S1744309106020057 }}
* {{cite journal | vauthors = Glavan F, Behm-Ansmant I, Izaurralde E, Conti E | title = Structures of the PIN domains of SMG6 and SMG5 reveal a nuclease within the mRNA surveillance complex | journal = The EMBO Journal | volume = 25 | issue = 21 | pages = 5117–25 | date = November 2006 | pmid = 17053788 | pmc = 1630413 | doi = 10.1038/sj.emboj.7601377 }}
* {{cite journal | vauthors = Takeshita D, Zenno S, Lee WC, Saigo K, Tanokura M | title = Crystal structure of the PIN domain of human telomerase-associated protein EST1A | journal = Proteins | volume = 68 | issue = 4 | pages = 980–9 | date = September 2007 | pmid = 17557331 | doi = 10.1002/prot.21351 | s2cid = 43477604 }}
{{refend}}
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