STAG2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSTAG2, SA-2, SA2, SCC3B, bA517O1.1, stromal antigen 2, NEDXCF, MKMS, HPE13
External IDsOMIM: 300826 MGI: 1098583 HomoloGene: 38206 GeneCards: STAG2
Orthologs
SpeciesHumanMouse
Entrez

10735

20843

Ensembl

ENSG00000101972

ENSMUSG00000025862

UniProt

Q8N3U4

O35638

RefSeq (mRNA)

NM_001077712
NM_001290713
NM_021465
NM_001358225

RefSeq (protein)

NP_001071180
NP_001277642
NP_067440
NP_001345154

Location (UCSC)Chr X: 123.96 – 124.42 MbChr X: 41.24 – 41.37 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Cohesin subunit SA-2 (SA2) is a protein that in humans is encoded by the STAG2 gene.[5][6] SA2 is a subunit of the Cohesin complex which mediates sister chromatid cohesion, homologous recombination and DNA looping. In somatic cells cohesin is formed of SMC3, SMC1, RAD21 and either SA1 or SA2 whereas in meiosis, cohesin is formed of SMC3, SMC1B, REC8 and SA3.

STAG2 is frequently mutated in a range of cancers [7] and several other disorders.

Function

SA2 is part of the cohesin complex, which is a structure that holds the sister chromatids together after DNA replication.[8] STAG2 has been shown to interact with STAG1.[9] Cohesion folds by DNA loop extrusion and this cohesion consists of SMC1, SMC3, RAD21, and either STAG1 or STAG2.[10] SA2 interacts with a ring-like structure composed of SMC1A, SMC3, and RAD21, to form the core of the cohesin complex.[11] The ring-like structure binds chromosomes together until degradation of the cohesin complex is finished during cell division.[12] 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.[13]

Structure

Of the cohesin complex, STAG2 is the subunit where the most variants have been reported in cancer.[14] This is thought to be because this gene is located in the X chromosome, therefore only one mutation is needed to inactivate it.[15] 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.[16] This has all the symptoms of epilepsy with eyelid myoclonia and absences (EMA), and was formally named Jeavons syndrome (JS).[17]

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.[18] 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.[10] 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.[12]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000101972 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000025862 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Carramolino L, Lee BC, Zaballos A, Peled A, Barthelemy I, Shav-Tal Y, et al. (August 1997). "SA-1, a nuclear protein encoded by one member of a novel gene family: molecular cloning and detection in hemopoietic organs". Gene. 195 (2): 151–159. doi:10.1016/S0378-1119(97)00121-2. PMID 9305759.
  6. ↑ "Entrez Gene: STAG2 stromal antigen 2".
  7. ↑ De Koninck M, Losada A (December 2016). "Cohesin Mutations in Cancer". Cold Spring Harbor Perspectives in Medicine. 6 (12): a026476. doi:10.1101/cshperspect.a026476. PMC 5131750. PMID 27742736.
  8. ↑ Mehta GD, Kumar R, Srivastava S, Ghosh SK (August 2013). "Cohesin: functions beyond sister chromatid cohesion". FEBS Letters. 587 (15): 2299–2312. doi:10.1016/j.febslet.2013.06.035. PMID 23831059. S2CID 39397443.
  9. ↑ Sumara I, Vorlaufer E, Gieffers C, Peters BH, Peters JM (November 2000). "Characterization of vertebrate cohesin complexes and their regulation in prophase". The Journal of Cell Biology. 151 (4): 749–762. doi:10.1083/jcb.151.4.749. PMC 2169443. PMID 11076961.
  10. 1 2 Cheng N, Li G, Kanchwala M, Evers BM, Xing C, Yu H (August 2022). "STAG2 promotes the myelination transcriptional program in oligodendrocytes". eLife. 11: e77848. doi:10.7554/eLife.77848. PMC 9439679. PMID 35959892.
  11. ↑ Losada A (June 2014). "Cohesin in cancer: chromosome segregation and beyond". Nature Reviews. Cancer. 14 (6): 389–393. doi:10.1038/nrc3743. PMID 24854081. S2CID 22909640.
  12. 1 2 Arruda NL, Carico ZM, Justice M, Liu YF, Zhou J, Stefan HC, Dowen JM (August 2020). "Distinct and overlapping roles of STAG1 and STAG2 in cohesin localization and gene expression in embryonic stem cells". Epigenetics & Chromatin. 13 (1): 32. doi:10.1186/s13072-020-00353-9. PMC 7418333. PMID 32778134.
  13. ↑ Athans S, Krishnan N, Ramakrishnan S, Cortes Gomez E, Lage-Vickers S, Rak M, et al. (October 2022). "STAG2 expression is associated with adverse survival outcomes and regulates cell phenotype in muscle-invasive bladder cancer". Cancer Research Communications. 2 (10): 1129–1143. doi:10.1158/2767-9764.CRC-22-0155. PMC 9583756. PMID 36275363. S2CID 252025964.
  14. ↑ Cosmic. "STAG2 Gene - COSMIC". cancer.sanger.ac.uk. Retrieved 2018-02-13.
  15. ↑ Kim JS, He X, Orr B, Wutz G, Hill V, Peters JM, et al. (February 2016). "Intact Cohesion, Anaphase, and Chromosome Segregation in Human Cells Harboring Tumor-Derived Mutations in STAG2". PLOS Genetics. 12 (2): e1005865. doi:10.1371/journal.pgen.1005865. PMC 4752446. PMID 26871722.
  16. ↑ Turchi G, Bernardo P, Consales A, Bilo L, Coppola A (April 2020). "Xq25 microduplication syndrome: a further contribution to its definition. A case report and review of the literature". Clinical Dysmorphology. 29 (2): 90–96. doi:10.1097/mcd.0000000000000303. PMID 31609727. S2CID 204703545.
  17. ↑ Gokce-Samar Z, de Bellescize J, Arzimanoglou A, Putoux A, Chatron N, Lesca G, Portes VD (December 2022). "STAG2 microduplication in a patient with eyelid myoclonia and absences and a review of EMA-related reported genes". European Journal of Medical Genetics. 65 (12): 104636. doi:10.1016/j.ejmg.2022.104636. PMID 36216271. S2CID 252792610.
  18. ↑ Gordon NS, Humayun-Zakaria N, Goel A, Abbotts B, Zeegers MP, Cheng KK, et al. (April 2022). "STAG2 Protein Expression in Non-muscle-invasive Bladder Cancer: Associations with Sex, Genomic and Transcriptomic Changes, and Clinical Outcomes". European Urology Open Science. 38: 88–95. doi:10.1016/j.euros.2022.02.004. PMC 9051973. PMID 35495284.
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