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NameSerine/threonine-protein phosphatase 2A catalytic subunit alpha isoform
Synonyms
  • 3.1.3.16
  • 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
  • phosphoprotein phosphatase activity
  • metal ion binding
  • protein C-terminus binding
  • GABA receptor binding
Processes
  • second-messenger-mediated signaling
  • regulation of growth
  • nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
  • regulation of DNA replication
  • RNA splicing
  • regulation of cell adhesion
  • ceramide metabolic process
  • regulation of cell differentiation
  • inactivation of MAPK activity
  • mitotic nuclear envelope reassembly
  • regulation of Wnt signaling pathway
  • meiotic cell cycle
  • regulation of transcription, DNA-templated
  • apoptotic process
  • mesoderm development
  • protein dephosphorylation
  • negative regulation of epithelial to mesenchymal transition
  • negative regulation of cell growth
  • negative regulation of tyrosine phosphorylation of STAT protein
  • response to organic substance
  • positive regulation of protein serine/threonine kinase activity
Components
  • spindle pole
  • chromosome, centromeric region
  • protein phosphatase type 2A complex
  • cytosol
  • extracellular exosome
  • mitochondrion
  • membrane
  • microtubule cytoskeleton
  • 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
Pfam Domain Function
Transmembrane RegionsNot Available
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 IDNot Available
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
  3. Khew-Goodall Y, Mayer RE, Maurer F, Stone SR, Hemmings BA: Structure and transcriptional regulation of protein phosphatase 2A catalytic subunit genes. Biochemistry. 1991 Jan 8;30(1):89-97. 1846293
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  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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. 10801873
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  15. 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
  16. 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
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  20. 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
  21. 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. 22613722
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