Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform

NameSerine/threonine-protein phosphatase 2A catalytic subunit alpha isoform
Synonyms3.1.3.16 PP2A-alpha Replication protein C RP-C
Gene NamePPP2CA
OrganismHuman
Amino acid sequence
>lcl|BSEQ0004568|Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform
MDEKVFTKELDQWIEQLNECKQLSESQVKSLCEKAKEILTKESNVQEVRCPVTVCGDVHG
QFHDLMELFRIGGKSPDTNYLFMGDYVDRGYYSVETVTLLVALKVRYRERITILRGNHES
RQITQVYGFYDECLRKYGNANVWKYFTDLFDYLPLTALVDGQIFCLHGGLSPSIDTLDHI
RALDRLQEVPHEGPMCDLLWSDPDDRGGWGISPRGAGYTFGQDISETFNHANGLTLVSRA
HQLVMEGYNWCHDRNVVTIFSAPNYCYRCGNQAAIMELDDTLKYSFLQFDPAPRRGEPHV
TRRTPDYFL
Number of residues309
Molecular Weight35593.93
Theoretical pI5.22
GO Classification
Functions
    GABA receptor binding
protein C-terminus binding
phosphoprotein phosphatase activity
metal ion binding
Processes
    regulation of DNA replication
response to organic substance
meiotic cell cycle
regulation of cell adhesion
positive regulation of protein serine/threonine kinase activity
regulation of cell differentiation
mesoderm development
second-messenger-mediated signaling
negative regulation of epithelial to mesenchymal transition
negative regulation of tyrosine phosphorylation of STAT protein
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
RNA splicing
regulation of transcription, DNA-templated
ceramide metabolic process
apoptotic process
inactivation of MAPK activity
regulation of growth
protein dephosphorylation
mitotic nuclear envelope reassembly
negative regulation of cell growth
regulation of Wnt signaling pathway
Components
    spindle pole
mitochondrion
protein phosphatase type 2A complex
membrane
cytosol
chromosome, centromeric region
microtubule cytoskeleton
extracellular exosome
nucleus
plasma membrane
General FunctionPP2A 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 SGO2 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'.
Specific FunctionGaba receptor binding
Transmembrane Regions
GenBank Protein ID36120
UniProtKB IDP67775
UniProtKB Entry NamePP2AA_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0016755|Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform (PPP2CA)
ATGGACGAGAAGGTGTTCACCAAGGAGCTGGACCAGTGGATCGAGCAGCTGAACGAGTGC
AAGCAGCTGTCCGAGTCCCAGGTCAAGAGCCTCTGCGAGAAGGCTAAAGAAATCCTGACA
AAAGAATCCAACGTGCAAGAGGTTCGATGTCCAGTTACTGTCTGTGGAGATGTGCATGGG
CAATTTCATGATCTCATGGAACTGTTTAGAATTGGTGGCAAATCACCAGATACAAATTAC
TTGTTTATGGGAGATTATGTTGACAGAGGATATTATTCAGTTGAAACAGTTACACTGCTT
GTAGCTCTTAAGGTTCGTTACCGTGAACGCATCACCATTCTTCGAGGGAATCATGAGAGC
AGACAGATCACACAAGTTTATGGTTTCTATGATGAATGTTTAAGAAAATATGGAAATGCA
AATGTTTGGAAATATTTTACAGATCTTTTTGACTATCTTCCTCTCACTGCCTTGGTGGAT
GGGCAGATCTTCTGTCTACATGGTGGTCTCTCGCCATCTATAGATACACTGGATCATATC
AGAGCACTTGATCGCCTACAAGAAGTTCCCCATGAGGGTCCAATGTGTGACTTGCTGTGG
TCAGATCCAGATGACCGTGGTGGTTGGGGTATATCTCCTCGAGGAGCTGGTTACACCTTT
GGGCAAGATATTTCTGAGACATTTAATCATGCCAATGGCCTCACGTTGGTGTCTAGAGCT
CACCAGCTAGTGATGGAGGGATATAACTGGTGCCATGACCGGAATGTAGTAACGATTTTC
AGTGCTCCAAACTATTGTTATCGTTGTGGTAACCAAGCTGCAATCATGGAACTTGACGAT
ACTCTAAAATACTCTTTCTTGCAGTTTGACCCAGCACCTCGTAGAGGCGAGCCACATGTT
ACTCGTCGTACCCCAGACTACTTCCTGTAA
GenBank Gene IDX12646
GeneCard IDNone
GenAtlas IDPPP2CA
HGNC IDHGNC:9299
Chromosome Location5
Locus5q31.1
References
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  2. Arino J, Woon CW, Brautigan DL, Miller TB Jr, Johnson GL: Human liver phosphatase 2A: cDNA and amino acid sequence of two catalytic subunit isotypes. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4252-6.[2837763 ]
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  4. Scheidtmann KH, Mumby MC, Rundell K, Walter G: Dephosphorylation of simian virus 40 large-T antigen and p53 protein by protein phosphatase 2A: inhibition by small-t antigen. Mol Cell Biol. 1991 Apr;11(4):1996-2003.[1848668 ]
  5. Favre B, Zolnierowicz S, Turowski P, Hemmings BA: The catalytic subunit of protein phosphatase 2A is carboxyl-methylated in vivo. J Biol Chem. 1994 Jun 10;269(23):16311-7.[8206937 ]
  6. Chen J, Peterson RT, Schreiber SL: Alpha 4 associates with protein phosphatases 2A, 4, and 6. Biochem Biophys Res Commun. 1998 Jun 29;247(3):827-32.[9647778 ]
  7. Bryant JC, Westphal RS, Wadzinski BE: Methylated C-terminal leucine residue of PP2A catalytic subunit is important for binding of regulatory Balpha subunit. Biochem J. 1999 Apr 15;339 ( Pt 2):241-6.[10191253 ]
  8. Virshup DM, Kauffman MG, Kelly TJ: Activation of SV40 DNA replication in vitro by cellular protein phosphatase 2A. EMBO J. 1989 Dec 1;8(12):3891-8.[2555176 ]
  9. 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.[9920888 ]
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  11. 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.[16580887 ]
  12. Kitajima TS, Sakuno T, Ishiguro K, Iemura S, Natsume T, Kawashima SA, Watanabe Y: Shugoshin collaborates with protein phosphatase 2A to protect cohesin. Nature. 2006 May 4;441(7089):46-52. Epub 2006 Mar 15.[16541025 ]
  13. Losman JA, Chen XP, Vuong BQ, Fay S, Rothman PB: Protein phosphatase 2A regulates the stability of Pim protein kinases. J Biol Chem. 2003 Feb 14;278(7):4800-5. Epub 2002 Dec 6.[12473674 ]
  14. 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.[17245430 ]
  15. Huang H, Feng J, Famulski J, Rattner JB, Liu ST, Kao GD, Muschel R, Chan GK, Yen TJ: Tripin/hSgo2 recruits MCAK to the inner centromere to correct defective kinetochore attachments. J Cell Biol. 2007 May 7;177(3):413-24.[17485487 ]
  16. 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. doi: 10.1016/j.molcel.2009.09.025.[19818709 ]
  17. McConnell JL, Watkins GR, Soss SE, Franz HS, McCorvey LR, Spiller BW, Chazin WJ, Wadzinski BE: Alpha4 is a ubiquitin-binding protein that regulates protein serine/threonine phosphatase 2A ubiquitination. Biochemistry. 2010 Mar 2;49(8):1713-8. doi: 10.1021/bi901837h.[20092282 ]
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  19. Migueleti DL, Smetana JH, Nunes HF, Kobarg J, Zanchin NI: Identification and characterization of an alternatively spliced isoform of the human protein phosphatase 2Aalpha catalytic subunit. J Biol Chem. 2012 Feb 10;287(7):4853-62. doi: 10.1074/jbc.M111.283341. Epub 2011 Dec 13.[22167190 ]
  20. Xing Y, Xu Y, Chen Y, Jeffrey PD, Chao Y, Lin Z, Li Z, Strack S, Stock JB, Shi Y: Structure of protein phosphatase 2A core enzyme bound to tumor-inducing toxins. Cell. 2006 Oct 20;127(2):341-53.[17055435 ]
  21. Xing Y, Li Z, Chen Y, Stock JB, Jeffrey PD, Shi Y: Structural mechanism of demethylation and inactivation of protein phosphatase 2A. Cell. 2008 Apr 4;133(1):154-63. doi: 10.1016/j.cell.2008.02.041.[18394995 ]
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