Alternative titles; symbols
HGNC Approved Gene Symbol: SGO2
Cytogenetic location: 2q33.1 Genomic coordinates (GRCh38): 2:200,526,142-200,584,096 (from NCBI)
Kitajima et al. (2004) cloned yeast Sgo1 and Sgo2, and by database analysis, they identified 2 similar human proteins, SGOL1 (609168) and SGOL2, which they referred to as Q9BVA8 and tripin, respectively. All Sgo-like protein contain an N-terminal coiled-coil domain and a C-terminal basic region.
In mitotic cells, phosphorylation of cohesin (see RAD21; 606462) promotes its dissociation from chromosomes, but centromeric cohesin is protected from phosphorylation until kinetochores are properly captured by the spindle microtubules. Kitajima et al. (2006) found that a shugoshin complex made up of SGO1, SGO2, and a specific subtype of serine/threonine phosphatase-2A (PP2A; see 176915) containing the regulatory B56 subunit (see 601643) was required for protection of centromeric cohesin in HeLa cells. The shugoshin-PP2A complex protected cohesin by reversing phosphorylation of the cohesin subunit SA2 (STAG2; 300826). Both SGO1 and SGO2 bound PP2A directly, although SGO1 appeared to bind the regulatory subunit PP2A-B56, while SGO2 appeared to bind the core subunit PP2A-A (see 605983). Knockdown studies showed that SGO2 tethered PP2A to the centromere, whereas SGO1 had the more important role in centromere protection and appeared to facilitate PP2A function at centromeres.
Huang et al. (2007) confirmed that SGO2 was a component of the inner centromere in HeLa cells, and they showed that SGO2 exhibited a dynamic localization pattern during the cell cycle. SGO2 concentrated between sister kinetochores during prometaphase and extended toward kinetochores by metaphase. SGO2 was released from the inner centromere shortly after the onset of anaphase and did not reappear until late G2/prophase. The dynamic localization of SGO2 near kinetochores depended on the kinases BUB1 (602452) and Aurora B (AURKB; 604970). Depletion of SGO2 via small interfering RNA resulted in kinetochore attachment defects, delayed entry into anaphase, and lagging chromosomes. The kinetochore attachment defects were due to mislocalization of the microtubule depolymerase MCAK (KIF2C; 604538) in SGO2-depleted cells. Huang et al. (2007) confirmed that SGO2 associated with PP2A, and they proposed that SGO2 contributes to the spatial regulation of MCAK activity within the inner centromere and kinetochore.
Hellmuth et al. (2020) showed that human SGO2, an essential protector of meiotic cohesin, is turned into a separase (ESPL1; 604143) inhibitor upon association with spindle assembly checkpoint (SAC)-activated MAD2 (601467). SGO2-MAD2 can functionally replace securin (604147) and sequesters most separase in securin-knockout cells. Acute loss of securin and SGO2, but not of either protein individually, resulted in separase deregulation associated with premature cohesin cleavage and cytotoxicity. Similar to securin, SGO2 is a competitive inhibitor that uses a pseudosubstrate sequence to block the active site of separase. APC/C-dependent ubiquitylation and action of the AAA-ATPase TRIP13 (604507) in conjunction with the MAD2-specific adaptor p31(comet) (MAD2L1BP; 618136) liberate separase from SGO2-MAD2 in vitro. The latter mechanism facilitates a considerable degree of sister chromatid separation in securin-knockout cells that lack APC/C activity. Thus, Hellmuth et al. (2020) concluded that their results identified an unexpected function of SGO2 in mitotically dividing cells and a mechanism of separase regulation that is independent of securin but still supervised by the SAC.
Hartz (2008) mapped the SGOL2 gene to chromosome 2q33.1 based on an alignment of the SGOL2 sequence (GenBank AK057940) with the genomic sequence (build 36.1).
Llano et al. (2008) found that Sgol2 -/- mice developed normally and survived to adulthood with no apparent abnormalities. Cultured Sgol2 -/- embryonic fibroblasts and adult Sgol2 -/- somatic cells showed no disruption of sister chromatid cohesion. However, both male and female Sgol2 -/- mice were infertile. Llano et al. (2008) demonstrated that Sgol2 was necessary to protect centromeric cohesion during meiosis I. In vivo, loss of Sgol2 promoted premature release of meiosis-specific Rec8 (REC8L1; 608193) cohesin complexes from anaphase I centromeres. This defect appeared cytologically as complete loss of centromere cohesion at metaphase II, leading to single chromatids, and physiologically as formation of aneuploid gametes that gave rise to infertility.
Hartz, P. A. Personal Communication. Baltimore, Md. 11/20/2008.
Hellmuth, S., Gomez-H, L., Pendas, A. M., Stemmann, O. Securin-independent regulation of separase by checkpoint-induced shugoshin-MAD2. Nature 580: 536-541, 2020. [PubMed: 32322060] [Full Text: https://doi.org/10.1038/s41586-020-2182-3]
Huang, H., Feng, J., Famulski, J., Rattner, J. B., Liu, S. T., Kao, G. D., Muschel, R., Chan, G. K. T., Yen, T. J. Tripin/hSgo2 recruits MCAK to the inner centromere to correct defective kinetochore attachments. J. Cell Biol. 177: 413-424, 2007. [PubMed: 17485487] [Full Text: https://doi.org/10.1083/jcb.200701122]
Kitajima, T. S., Kawashima, S. A., Watanabe, Y. The conserved kinetochore protein shugoshin protects centromeric cohesion during meiosis. Nature 427: 510-517, 2004. [PubMed: 14730319] [Full Text: https://doi.org/10.1038/nature02312]
Kitajima, T. S., Sakuno, T., Ishiguro, K., Iemura, S., Natsume, T., Kawashima, S. A., Watanabe, Y. Shugoshin collaborates with protein phosphatase 2A to protect cohesin. Nature 441: 46-52, 2006. [PubMed: 16541025] [Full Text: https://doi.org/10.1038/nature04663]
Llano, E., Gomez, R., Gutierrez-Caballero, C., Herran, Y., Sanchez-Martin, M., Vazquez-Quinones, L., Hernandez, T., de Alava, E., Cuadrado, A., Barbero, J. L., Suja, J. A., Pendas, A. M. Shugoshin-2 is essential for the completion of meiosis but not for mitotic cell division in mice. Genes Dev. 22: 2400-2413, 2008. [PubMed: 18765791] [Full Text: https://doi.org/10.1101/gad.475308]