3fga is a 5 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
[SGOL1_HUMAN] Plays a central role in chromosome cohesion during mitosis by preventing premature dissociation of cohesin complex from centromeres after prophase, when most of cohesin complex dissociates from chromosomes arms. May act by preventing phosphorylation of the STAG2 subunit of cohesin complex at the centromere, ensuring cohesin persistence at centromere until cohesin cleavage by ESPL1/separase at anaphase. Essential for proper chromosome segregation during mitosis and this function requires interaction with PPP2R1A. Its phosphorylated form is necessary for chromosome congression and for the proper attachment of spindle microtubule to the kinetochore. Necessary for kinetochore localization of PLK1 and CENPF. May play a role in the tension sensing mechanism of the spindle-assembly checkpoint by regulating PLK1 kinetochore affinity. Isoform 3 plays a role in maintaining centriole cohesion involved in controlling spindle pole integrity.[1][2][3][4][5][6][7] [2AAA_MOUSE] The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. Required for proper chromosome segregation and for centromeric localization of SGOL1 in mitosis (By similarity). [PP2AA_HUMAN] PP2A is the major phosphatase for microtubule-associated proteins (MAPs). PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase. Cooperates with SGOL2 to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I (By similarity). Can dephosphorylate SV40 large T antigen and p53/TP53. Activates RAF1 by dephosphorylating it at 'Ser-259'.[8][9][10] [2A5G_HUMAN] The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment. The PP2A-PPP2R5C holoenzyme may specifically dephosphorylate and activate TP53 and play a role in DNA damage-induced inhibition of cell proliferation. PP2A-PPP2R5C may also regulate the ERK signaling pathway through ERK dephosphorylation.[11][12]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Accurate chromosome segregation during mitosis and meiosis depends on shugoshin proteins that prevent precocious dissociation of cohesin from centromeres. Shugoshins associate with PP2A, which is thought to dephosphorylate cohesin and thereby prevent cleavage by separase during meiosis I. A crystal structure of a complex between a fragment of human Sgo1 and an AB'C PP2A holoenzyme reveals that Sgo1 forms a homodimeric parallel coiled coil that docks simultaneously onto PP2A's C and B' subunits. Sgo1 homodimerization is a prerequisite for PP2A binding. While hSgo1 interacts only with the AB'C holoenzymes, its relative, Sgo2, interacts with all PP2A forms and may thus lead to dephosphorylation of distinct substrates. Mutant shugoshin proteins defective in the binding of PP2A cannot protect centromeric cohesin from separase during meiosis I or support the spindle assembly checkpoint in yeast. Finally, we provide evidence that PP2A's recruitment to chromosomes may be sufficient to protect cohesin from separase in mammalian oocytes.
Structure and function of the PP2A-shugoshin interaction.,Xu Z, Cetin B, Anger M, Cho US, Helmhart W, Nasmyth K, Xu W Mol Cell. 2009 Aug 28;35(4):426-41. PMID:19716788[13]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
↑McGuinness BE, Hirota T, Kudo NR, Peters JM, Nasmyth K. Shugoshin prevents dissociation of cohesin from centromeres during mitosis in vertebrate cells. PLoS Biol. 2005 Mar;3(3):e86. Epub 2005 Mar 1. PMID:15737064 doi:https://dx.doi.org/04-PLBI-RA-0678R1
↑Kitajima TS, Hauf S, Ohsugi M, Yamamoto T, Watanabe Y. Human Bub1 defines the persistent cohesion site along the mitotic chromosome by affecting Shugoshin localization. Curr Biol. 2005 Feb 22;15(4):353-9. PMID:15723797 doi:https://dx.doi.org/S0960982204010267
↑Tang Z, Sun Y, Harley SE, Zou H, Yu H. Human Bub1 protects centromeric sister-chromatid cohesion through Shugoshin during mitosis. Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18012-7. Epub 2004 Dec 16. PMID:15604152 doi:https://dx.doi.org/0408600102
↑Tang Z, Shu H, Qi W, Mahmood NA, Mumby MC, Yu H. PP2A is required for centromeric localization of Sgo1 and proper chromosome segregation. Dev Cell. 2006 May;10(5):575-85. Epub 2006 Mar 30. PMID:16580887 doi:10.1016/j.devcel.2006.03.010
↑Pouwels J, Kukkonen AM, Lan W, Daum JR, Gorbsky GJ, Stukenberg T, Kallio MJ. Shugoshin 1 plays a central role in kinetochore assembly and is required for kinetochore targeting of Plk1. Cell Cycle. 2007 Jul 1;6(13):1579-85. Epub 2007 May 16. PMID:17617734
↑Fu G, Ding X, Yuan K, Aikhionbare F, Yao J, Cai X, Jiang K, Yao X. Phosphorylation of human Sgo1 by NEK2A is essential for chromosome congression in mitosis. Cell Res. 2007 Jul;17(7):608-18. PMID:17621308 doi:10.1038/cr.2007.55
↑Wang X, Yang Y, Duan Q, Jiang N, Huang Y, Darzynkiewicz Z, Dai W. sSgo1, a major splice variant of Sgo1, functions in centriole cohesion where it is regulated by Plk1. Dev Cell. 2008 Mar;14(3):331-41. doi: 10.1016/j.devcel.2007.12.007. PMID:18331714 doi:10.1016/j.devcel.2007.12.007
↑Hsu W, Zeng L, Costantini F. Identification of a domain of Axin that binds to the serine/threonine protein phosphatase 2A and a self-binding domain. J Biol Chem. 1999 Feb 5;274(6):3439-45. PMID:9920888
↑Abraham D, Podar K, Pacher M, Kubicek M, Welzel N, Hemmings BA, Dilworth SM, Mischak H, Kolch W, Baccarini M. Raf-1-associated protein phosphatase 2A as a positive regulator of kinase activation. J Biol Chem. 2000 Jul 21;275(29):22300-4. PMID:10801873 doi:10.1074/jbc.M003259200
↑Watkins GR, Wang N, Mazalouskas MD, Gomez RJ, Guthrie CR, Kraemer BC, Schweiger S, Spiller BW, Wadzinski BE. Monoubiquitination promotes calpain cleavage of the protein phosphatase 2A (PP2A) regulatory subunit alpha4, altering PP2A stability and microtubule-associated protein phosphorylation. J Biol Chem. 2012 Jul 13;287(29):24207-15. doi: 10.1074/jbc.M112.368613. Epub, 2012 May 21. PMID:22613722 doi:10.1074/jbc.M112.368613
↑Letourneux C, Rocher G, Porteu F. B56-containing PP2A dephosphorylate ERK and their activity is controlled by the early gene IEX-1 and ERK. EMBO J. 2006 Feb 22;25(4):727-38. Epub 2006 Feb 2. PMID:16456541 doi:https://dx.doi.org/10.1038/sj.emboj.7600980
↑Li HH, Cai X, Shouse GP, Piluso LG, Liu X. A specific PP2A regulatory subunit, B56gamma, mediates DNA damage-induced dephosphorylation of p53 at Thr55. EMBO J. 2007 Jan 24;26(2):402-11. PMID:17245430 doi:https://dx.doi.org/10.1038/sj.emboj.7601519
↑Xu Z, Cetin B, Anger M, Cho US, Helmhart W, Nasmyth K, Xu W. Structure and function of the PP2A-shugoshin interaction. Mol Cell. 2009 Aug 28;35(4):426-41. PMID:19716788 doi:10.1016/j.molcel.2009.06.031
