View source for STAG2

{{Short description|Protein-coding gene in humans}}
{{Infobox_gene}}
'''Cohesin subunit SA-2''' ('''SA2''') is a [[protein]] that in humans is encoded by the ''STAG2'' [[gene]].<ref name="pmid9305759">{{cite journal | vauthors = Carramolino L, Lee BC, Zaballos A, Peled A, Barthelemy I, Shav-Tal Y, Prieto I, Carmi P, Gothelf Y, González de Buitrago G, Aracil M, Márquez G, Barbero JL, Zipori D | display-authors = 6 | title = SA-1, a nuclear protein encoded by one member of a novel gene family: molecular cloning and detection in hemopoietic organs | journal = Gene | volume = 195 | issue = 2 | pages = 151–159 | date = August 1997 | pmid = 9305759 | doi = 10.1016/S0378-1119(97)00121-2 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: STAG2 stromal antigen 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10735}}</ref> SA2 is a subunit of the [[Cohesin]] complex which mediates [[Establishment of sister chromatid cohesion|sister chromatid cohesion]], [[homologous recombination]] and [[Topologically associating domain|DNA looping]]. In somatic cells cohesin is formed of [[SMC3]], [[SMC1A|SMC1]], [[RAD21]] and either [[STAG1|SA1]] or SA2 whereas in [[meiosis]], cohesin is formed of SMC3, [[SMC1B]], [[REC8]] and [[STAG3|SA3]].
''STAG2'' is frequently mutated in a range of cancers <ref>{{cite journal | vauthors = De Koninck M, Losada A | title = Cohesin Mutations in Cancer | journal = Cold Spring Harbor Perspectives in Medicine | volume = 6 | issue = 12 | pages = a026476 | date = December 2016 | pmid = 27742736 | pmc = 5131750 | doi = 10.1101/cshperspect.a026476 | doi-access = free }}</ref> and several other disorders.
== Function ==
SA2 is part of the [[Cohesin|cohesin complex]], which is a structure that holds the sister [[chromatid]]s together after [[DNA replication]].<ref>{{cite journal | vauthors = Mehta GD, Kumar R, Srivastava S, Ghosh SK | title = Cohesin: functions beyond sister chromatid cohesion | journal = FEBS Letters | volume = 587 | issue = 15 | pages = 2299–2312 | date = August 2013 | pmid = 23831059 | doi = 10.1016/j.febslet.2013.06.035 | s2cid = 39397443 | doi-access =  }}</ref>  STAG2 has been shown to [[Protein-protein interaction|interact]] with [[STAG1]].<ref name=pmid11076961>{{cite journal | vauthors = Sumara I, Vorlaufer E, Gieffers C, Peters BH, Peters JM | title = Characterization of vertebrate cohesin complexes and their regulation in prophase | journal = The Journal of Cell Biology | volume = 151 | issue = 4 | pages = 749–762 | date = November 2000 | pmid = 11076961 | pmc = 2169443 | doi = 10.1083/jcb.151.4.749 }}</ref> Cohesion folds by DNA loop extrusion and this cohesion consists of SMC1, SMC3, RAD21, and either STAG1 or STAG2.<ref name=":0">{{cite journal | vauthors = Cheng N, Li G, Kanchwala M, Evers BM, Xing C, Yu H | title = STAG2 promotes the myelination transcriptional program in oligodendrocytes | journal = eLife | volume = 11 | pages = e77848 | date = August 2022 | pmid = 35959892 | pmc = 9439679 | doi = 10.7554/eLife.77848 | doi-access = free }}</ref> SA2 interacts with a ring-like structure composed of SMC1A, SMC3, and RAD21, to form the core of the cohesin complex.<ref>{{cite journal | vauthors = Losada A | title = Cohesin in cancer: chromosome segregation and beyond | journal = Nature Reviews. Cancer | volume = 14 | issue = 6 | pages = 389–393 | date = June 2014 | pmid = 24854081 | doi = 10.1038/nrc3743 | s2cid = 22909640 }}</ref> The ring-like structure binds chromosomes together until degradation of the cohesin complex is finished during cell division.<ref name=":1">{{cite journal | vauthors = Arruda NL, Carico ZM, Justice M, Liu YF, Zhou J, Stefan HC, Dowen JM | title = Distinct and overlapping roles of STAG1 and STAG2 in cohesin localization and gene expression in embryonic stem cells | journal = Epigenetics & Chromatin | volume = 13 | issue = 1 | pages = 32 | date = August 2020 | pmid = 32778134 | pmc = 7418333 | doi = 10.1186/s13072-020-00353-9 | doi-access = free }}</ref> This allows for the replicated chromosomes to separate into two new cells. Another role of ''STAG2'' is to encode the stromal antigen 2 protein, which is involved in chromatin organization'','' transcription, DNA repair and control of downstream gene expression.<ref>{{cite journal | vauthors = Athans S, Krishnan N, Ramakrishnan S, Cortes Gomez E, Lage-Vickers S, Rak M, Kazmierczak Z, Ohm J, Attwood K, Wang J, Woloszynska A | display-authors = 6 | title = STAG2 expression is associated with adverse survival outcomes and regulates cell phenotype in muscle-invasive bladder cancer | journal = Cancer Research Communications| volume = 2 | issue = 10 | pages = 1129–1143 | date = October 2022 | pmid = 36275363 | doi = 10.1158/2767-9764.CRC-22-0155 | s2cid = 252025964 | pmc = 9583756 }}</ref>
== Structure ==
Of the cohesin complex, ''STAG2'' is the subunit where the most variants have been reported in cancer.<ref>{{Cite web|url=http://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=STAG2|title=STAG2 Gene - COSMIC|last=Cosmic|website=cancer.sanger.ac.uk|access-date=2018-02-13}}</ref> This is thought to be because this gene is located in the [[X chromosome]], therefore only one mutation is needed to inactivate it.<ref>{{cite journal | vauthors = Kim JS, He X, Orr B, Wutz G, Hill V, Peters JM, Compton DA, Waldman T | display-authors = 6 | title = Intact Cohesion, Anaphase, and Chromosome Segregation in Human Cells Harboring Tumor-Derived Mutations in STAG2 | journal = PLOS Genetics | volume = 12 | issue = 2 | pages = e1005865 | date = February 2016 | pmid = 26871722 | pmc = 4752446 | doi = 10.1371/journal.pgen.1005865 | doi-access = free }}</ref> [https://www.ncbi.nlm.nih.gov/gtr/conditions/C4311049/ Xq25 duplication syndrome], is an X-linked neurodevelopmental disorder that results in delayed development and intellectual disability associated with abnormal behavior and dysmorphic facial features, and the whole STAG2 gene can develop ''STAG2'' [[encephalopathy]].<ref>{{cite journal | vauthors = Turchi G, Bernardo P, Consales A, Bilo L, Coppola A | title = Xq25 microduplication syndrome: a further contribution to its definition. A case report and review of the literature | journal = Clinical Dysmorphology | volume = 29 | issue = 2 | pages = 90–96 | date = April 2020 | pmid = 31609727 | doi = 10.1097/mcd.0000000000000303 | s2cid = 204703545 }}</ref> This has all the symptoms of epilepsy with [https://www.medlink.com/articles/eyelid-myoclonia-with-and-without-absences eyelid myoclonia and absences] (EMA), and was formally named Jeavons syndrome (JS).<ref>{{cite journal | vauthors = Gokce-Samar Z, de Bellescize J, Arzimanoglou A, Putoux A, Chatron N, Lesca G, Portes VD | title = STAG2 microduplication in a patient with eyelid myoclonia and absences and a review of EMA-related reported genes | journal = European Journal of Medical Genetics | volume = 65 | issue = 12 | pages = 104636 | date = December 2022 | pmid = 36216271 | doi = 10.1016/j.ejmg.2022.104636 | s2cid = 252792610 }}</ref>
== Mutations ==
One result of mutations in ''STAG2'' can result in one third of non-muscle-invasive bladder cancer to have complete loss of SA2 protein.<ref>{{cite journal | vauthors = Gordon NS, Humayun-Zakaria N, Goel A, Abbotts B, Zeegers MP, Cheng KK, James ND, Arnold R, Bryan RT, Ward DG | display-authors = 6 | title = STAG2 Protein Expression in Non-muscle-invasive Bladder Cancer: Associations with Sex, Genomic and Transcriptomic Changes, and Clinical Outcomes | journal = European Urology Open Science | volume = 38 | pages = 88–95 | date = April 2022 | pmid = 35495284 | pmc = 9051973 | doi = 10.1016/j.euros.2022.02.004 }}</ref> The loss of this protein has been shown to indicate the prognosis of disease and survival. it has been shown there was a delay in maturation of oligodendrocytes and transcription of myelination-related genes was reduced. Cohesion is needed in proper gene expression in specific cells and an implication the myelination is affected in a negative way.<ref name=":0" /> Mutations of STAG2 occur frequently in many cancers, which indicates this protein has a role in cancer. Mutations of the ''STAG2'' gene are frequently seen in multiple adult and pediatric cancers. ''STAG'' has been found to be the only gene of 12 that is mutated significantly in at least four types of cancers.<ref name=":1" />
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== References ==
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