SGOL1

Shugoshin-like 1 (S. pombe)
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3FGA​, 3Q6S​, 4A0I​
Identifiers
Symbols	SGOL1 ; CAID; NY-BR-85; SGO; Sgo1
External IDs	OMIM: 609168 MGI: 1919665 HomoloGene: 23642 GeneCards: SGOL1 Gene
Gene ontology Molecular function • protein binding • kinase binding Cellular component • chromosome, centromeric region • kinetochore • condensed chromosome kinetochore • condensed chromosome, centromeric region • condensed nuclear chromosome, centromeric region • spindle pole • nucleoplasm • cytoplasm • centrosome • cytosol • mitotic cohesin complex Biological process • mitotic cell cycle • chromosome segregation • mitotic nuclear division • small GTPase mediated signal transduction • attachment of spindle microtubules to kinetochore • centriole-centriole cohesion • meiotic chromosome segregation • cell division Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	151648	72415
Ensembl	ENSG00000129810	ENSMUSG00000023940
UniProt	Q5FBB7	Q9CXH7
RefSeq (mRNA)	NM_001012409	NM_028232
RefSeq (protein)	NP_001012409	NP_082508
Location (UCSC)	Chr 3: 20.16 – 20.19 Mb	Chr 17: 53.67 – 53.69 Mb
PubMed search

Shugoshin-like 1 is a protein that in humans is encoded by the SGOL1 gene.^[1][2]

Model organisms

Sgol1 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Abnormal
Recessive lethal study	Abnormal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Plasma immunoglobulins	Normal
Haematology	Normal
Peripheral blood lymphocytes	Abnormal[3]
Micronucleus test	Normal
Heart weight	Normal
Skin Histopathology	Normal
Brain histopathology	Normal
Eye Histopathology	Normal
Salmonella infection	Normal[4]
Citrobacter infection	Normal[5]
All tests and analysis from[6][7]

Model organisms have been used in the study of SGOL1 function. A conditional knockout mouse line, called Sgol1^{tm1a(EUCOMM)Wtsi[8][9]} has been generated.^[10][11][12]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[6][13] Twenty six tests were carried out on mutant mice and three significant abnormalities were observed. No homozygous mutant embryos were identified during gestation, and thus none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and a decreased regulatory T cell number was observed in male animals.^[6]

Mechanisms

A physical mechanism that guarantees the accurate segregation of sister chromatids during mitosis arises from the ring shaped cohesin complex consisting of 4 subunits (SMC1A/B, SMC3, SCC1, and SA1/2 in humans). This complex encircles the two sister chromatids and resists the pulling force of microtubules.^[14] The characteristic X-shape chromosomes are formed due to the centromeric cohesin protected by Shugoshin-PP2A complex.^[15]

Kinetochore localization of Sgo1-PP2A is dependent upon phosphorylation on histone H2A of nucleosome, which is the important substrate of spindle checkpoint kinase BUB1.^[16] Centromeric cohesin and H2A-pT120 specify two distinct pools of Sgo1-PP2A at inner centromeres and kinetochores respectively,^[17] while the CDK1/cyclin B phosphorylation on Sgo1 is essential for Sgo1-PP2A to protect centromeric cohesin, not only for bringing PP2A to cohesin,^[18] but also physically shield out the negative regulator WAPAL from cohesin.^[19]

References

1. Scanlan MJ, Gout I, Gordon CM, Williamson B, Stockert E, Gure AO, Jäger D, Chen YT, Mackay A, O'Hare MJ, Old LJ (Mar 2001). "Humoral immunity to human breast cancer: antigen definition and quantitative analysis of mRNA expression". Cancer Immunity 1: 4. PMID 12747765.
2. "Entrez Gene: SGOL1 shugoshin-like 1 (S. pombe)".
3. "Peripheral blood lymphocytes data for Sgol1". Wellcome Trust Sanger Institute.
4. "Salmonella infection data for Sgol1". Wellcome Trust Sanger Institute.
5. "Citrobacter infection data for Sgol1". Wellcome Trust Sanger Institute.
6. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
7. Mouse Resources Portal, Wellcome Trust Sanger Institute.
8. "International Knockout Mouse Consortium".
9. "Mouse Genome Informatics".
10. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
11. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
12. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
13. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
14. Nasmyth K, Haering CH. "Cohesin: its roles and mechanisms". Annual Review of Genetics 43: 525–58. doi:10.1146/annurev-genet-102108-134233. PMID 19886810.
15. Kitajima TS, Sakuno T, Ishiguro K, Iemura S, Natsume T, Kawashima SA, Watanabe Y (May 2006). "Shugoshin collaborates with protein phosphatase 2A to protect cohesin". Nature 441 (7089): 46–52. doi:10.1038/nature04663. PMID 16541025.
16. Kawashima SA, Yamagishi Y, Honda T, Ishiguro K, Watanabe Y (Jan 2010). "Phosphorylation of H2A by Bub1 prevents chromosomal instability through localizing shugoshin". Science 327 (5962): 172–7. doi:10.1126/science.1180189. PMID 19965387.
17. Liu H, Jia L, Yu H (Oct 2013). "Phospho-H2A and cohesin specify distinct tension-regulated Sgo1 pools at kinetochores and inner centromeres". Current Biology 23 (19): 1927–33. doi:10.1016/j.cub.2013.07.078. PMID 24055156.
18. Liu H, Rankin S, Yu H (Jan 2013). "Phosphorylation-enabled binding of SGO1-PP2A to cohesin protects sororin and centromeric cohesion during mitosis". Nature Cell Biology 15 (1): 40–9. doi:10.1038/ncb2637. PMID 23242214.
19. Hara K, Zheng G, Qu Q, Liu H, Ouyang Z, Chen Z, Tomchick DR, Yu H (Oct 2014). "Structure of cohesin subcomplex pinpoints direct shugoshin-Wapl antagonism in centromeric cohesion". Nature Structural & Molecular Biology 21 (10): 864–70. doi:10.1038/nsmb.2880. PMID 25173175.

Further reading

• Wang X, Dai W (Oct 2005). "Shugoshin, a guardian for sister chromatid segregation". Experimental Cell Research 310 (1): 1–9. doi:10.1016/j.yexcr.2005.07.018. PMID 16112668.
• Fu G, Ding X, Yuan K, Aikhionbare F, Yao J, Cai X, Jiang K, Yao X (Jul 2007). "Phosphorylation of human Sgo1 by NEK2A is essential for chromosome congression in mitosis". Cell Research 17 (7): 608–18. doi:10.1038/cr.2007.55. PMID 17621308.
• Pouwels J, Kukkonen AM, Lan W, Daum JR, Gorbsky GJ, Stukenberg T, Kallio MJ (Jul 2007). "Shugoshin 1 plays a central role in kinetochore assembly and is required for kinetochore targeting of Plk1". Cell Cycle 6 (13): 1579–85. doi:10.4161/cc.6.13.4442. PMID 17617734.
• Fu G, Hua S, Ward T, Ding X, Yang Y, Guo Z, Yao X (Jun 2007). "D-box is required for the degradation of human Shugoshin and chromosome alignment". Biochemical and Biophysical Research Communications 357 (3): 672–8. doi:10.1016/j.bbrc.2007.03.204. PMID 17448445.
• Yang Y, Wang X, Dai W (Apr 2006). "Human Sgo1 is an excellent target for induction of apoptosis of transformed cells". Cell Cycle 5 (8): 896–901. doi:10.4161/cc.5.8.2691. PMID 16628005.
• Tang Z, Shu H, Qi W, Mahmood NA, Mumby MC, Yu H (May 2006). "PP2A is required for centromeric localization of Sgo1 and proper chromosome segregation". Developmental Cell 10 (5): 575–85. doi:10.1016/j.devcel.2006.03.010. PMID 16580887.
• Kitajima TS, Sakuno T, Ishiguro K, Iemura S, Natsume T, Kawashima SA, Watanabe Y (May 2006). "Shugoshin collaborates with protein phosphatase 2A to protect cohesin". Nature 441 (7089): 46–52. doi:10.1038/nature04663. PMID 16541025.
• McGuinness BE, Hirota T, Kudo NR, Peters JM, Nasmyth K (Mar 2005). "Shugoshin prevents dissociation of cohesin from centromeres during mitosis in vertebrate cells". PLoS Biology 3 (3): e86. doi:10.1371/journal.pbio.0030086. PMC 1054882. PMID 15737064.
• Kitajima TS, Hauf S, Ohsugi M, Yamamoto T, Watanabe Y (Feb 2005). "Human Bub1 defines the persistent cohesion site along the mitotic chromosome by affecting Shugoshin localization". Current Biology 15 (4): 353–9. doi:10.1016/j.cub.2004.12.044. PMID 15723797.
• Tang Z, Sun Y, Harley SE, Zou H, Yu H (Dec 2004). "Human Bub1 protects centromeric sister-chromatid cohesion through Shugoshin during mitosis". Proceedings of the National Academy of Sciences of the United States of America 101 (52): 18012–7. doi:10.1073/pnas.0408600102. PMC 539817. PMID 15604152.