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

Details

Name
Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform
Synonyms
  • 3.1.3.16
  • PP2A-alpha
  • Replication protein C
  • RP-C
Gene Name
PPP2CA
Organism
Humans
Amino acid sequence
>lcl|BSEQ0004568|Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform
MDEKVFTKELDQWIEQLNECKQLSESQVKSLCEKAKEILTKESNVQEVRCPVTVCGDVHG
QFHDLMELFRIGGKSPDTNYLFMGDYVDRGYYSVETVTLLVALKVRYRERITILRGNHES
RQITQVYGFYDECLRKYGNANVWKYFTDLFDYLPLTALVDGQIFCLHGGLSPSIDTLDHI
RALDRLQEVPHEGPMCDLLWSDPDDRGGWGISPRGAGYTFGQDISETFNHANGLTLVSRA
HQLVMEGYNWCHDRNVVTIFSAPNYCYRCGNQAAIMELDDTLKYSFLQFDPAPRRGEPHV
TRRTPDYFL
Number of residues
309
Molecular Weight
35593.93
Theoretical pI
5.22
GO Classification
Functions
GABA receptor binding / metal ion binding / phosphoprotein phosphatase activity / protein C-terminus binding
Processes
apoptotic process / ceramide metabolic process / inactivation of MAPK activity / meiotic cell cycle / mesoderm development / mitotic nuclear envelope reassembly / negative regulation of cell growth / negative regulation of epithelial to mesenchymal transition / negative regulation of tyrosine phosphorylation of STAT protein / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / positive regulation of protein serine/threonine kinase activity / protein dephosphorylation / regulation of cell adhesion / regulation of cell differentiation / regulation of DNA replication / regulation of growth / regulation of transcription, DNA-templated / regulation of Wnt signaling pathway / response to organic substance / RNA splicing / second-messenger-mediated signaling
Components
chromosome, centromeric region / cytosol / extracellular exosome / membrane / microtubule cytoskeleton / mitochondrion / nucleus / plasma membrane / protein phosphatase type 2A complex / spindle pole
General Function
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 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 Function
Gaba receptor binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
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
Chromosome Location
5
Locus
5q31.1
External Identifiers
ResourceLink
UniProtKB IDP67775
UniProtKB Entry NamePP2AA_HUMAN
GenBank Protein ID36120
GenBank Gene IDX12646
GenAtlas IDPPP2CA
HGNC IDHGNC:9299
General References
  1. Stone SR, Mayer R, Wernet W, Maurer F, Hofsteenge J, Hemmings BA: The nucleotide sequence of the cDNA encoding the human lung protein phosphatase 2A alpha catalytic subunit. Nucleic Acids Res. 1988 Dec 9;16(23):11365. [PubMed:2849764]
  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. [PubMed: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. [PubMed:1846293]
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:10801873]
  12. 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. [PubMed:16580887]
  13. 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. [PubMed:16541025]
  14. 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. [PubMed:12473674]
  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. [PubMed: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. [PubMed:17485487]
  17. 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. [PubMed:19818709]
  18. 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. [PubMed:20092282]
  19. Xie D, Gore C, Liu J, Pong RC, Mason R, Hao G, Long M, Kabbani W, Yu L, Zhang H, Chen H, Sun X, Boothman DA, Min W, Hsieh JT: Role of DAB2IP in modulating epithelial-to-mesenchymal transition and prostate cancer metastasis. Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2485-90. doi: 10.1073/pnas.0908133107. Epub 2010 Jan 13. [PubMed:20080667]
  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. [PubMed: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. [PubMed:22613722]
  22. 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. [PubMed:17055435]
  23. 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. [PubMed:18394995]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00163Vitamin Eapproved, nutraceutical, vet_approvedunknownDetails
DB06905(2S,3S,4E,6E,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acidexperimentalunknownDetails
DB025062,6,8-Trimethyl-3-Amino-9-Benzyl-9-Methoxynonanoic AcidexperimentalunknownDetails