4iyp

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Template:STRUCTURE 4iyp

Contents

structure of the nPP2Ac-alpha4 complex

Template:ABSTRACT PUBMED 23591866

Disease

[IGBP1_HUMAN] Agenesis of the corpus callosum - intellectual deficit - coloboma - micrognathia. Defects in IGBP1 are the cause of mental retardation syndromic X-linked type 28 (MRXS28) [MIM:300472]; also known as agenesis of the corpus callosum with mental retardation, ocular coloboma and micrognathia. A syndrome that is characterized by coloboma of the iris and optic nerve, severe retrognathia, intellectual deficit, and agenesis of the corpus callosum.[1]

Function

[IGBP1_HUMAN] Associated to surface IgM-receptor; may be involved in signal transduction. Involved in regulation of the catalytic activity of PP2A, PP4 and PP6 phosphatases catalytic subunits by protecting them from degradative polyubiquitination until they associate with regulatory subunits.[2] [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'.[3] [4] [5]

About this Structure

4iyp is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

  • Jiang L, Stanevich V, Satyshur KA, Kong M, Watkins GR, Wadzinski BE, Sengupta R, Xing Y. Structural basis of protein phosphatase 2A stable latency. Nat Commun. 2013;4:1699. doi: 10.1038/ncomms2663. PMID:23591866 doi:10.1038/ncomms2663
  1. ↑ Graham JM Jr, Wheeler P, Tackels-Horne D, Lin AE, Hall BD, May M, Short KM, Schwartz CE, Cox TC. A new X-linked syndrome with agenesis of the corpus callosum, mental retardation, coloboma, micrognathia, and a mutation in the Alpha 4 gene at Xq13. Am J Med Genet A. 2003 Nov 15;123A(1):37-44. PMID:14556245 doi:10.1002/ajmg.a.20504
  2. ↑ Kong M, Ditsworth D, Lindsten T, Thompson CB. Alpha4 is an essential regulator of PP2A phosphatase activity. Mol Cell. 2009 Oct 9;36(1):51-60. PMID:19818709 doi:S1097-2765(09)00685-6
  3. ↑ 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
  4. ↑ 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
  5. ↑ 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

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