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Identification
HMDB Protein ID HMDBP02514
Secondary Accession Numbers
  • 8010
Name Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform
Synonyms
  1. PP2A-alpha
  2. RP-C
  3. Replication protein C
Gene Name PPP2CA
Protein Type Unknown
Biological Properties
General Function Involved in hydrolase activity
Specific 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 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'.
Pathways
  • Chagas disease (American trypanosomiasis)
  • Dopaminergic synapse
  • Hepatitis C
  • Hippo signaling pathway
  • Long-term depression
  • mRNA surveillance pathway
  • Oocyte meiosis
  • PI3K-Akt signaling pathway
  • TGF-beta signaling pathway
  • Tight junction
Reactions
A phosphoprotein + Water → a protein + Phosphate details
GO Classification
Biological Process
regulation of DNA replication
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
ceramide metabolic process
second-messenger-mediated signaling
RNA splicing
regulation of Wnt receptor signaling pathway
induction of apoptosis
positive regulation of protein serine/threonine kinase activity
mesoderm development
negative regulation of cell growth
meiosis
inactivation of MAPK activity
regulation of cell adhesion
negative regulation of epithelial to mesenchymal transition
negative regulation of tyrosine phosphorylation of Stat3 protein
protein heterotrimerization
regulation of protein autophosphorylation
regulation of protein catabolic process
regulation of transcription, DNA-dependent
regulation of receptor activity
fibroblast growth factor receptor signaling pathway
protein dephosphorylation
Cellular Component
cytosol
microtubule cytoskeleton
mitochondrion
plasma membrane
nucleus
chromosome, centromeric region
membrane
protein phosphatase type 2A complex
spindle pole
Function
catalytic activity
hydrolase activity
Molecular Function
phosphoprotein phosphatase activity
metal ion binding
Cellular Location
  1. Nucleus
  2. Cytoplasm
  3. Cytoplasm
  4. cytoskeleton
  5. Chromosome
  6. centromere
  7. spindle pole
Gene Properties
Chromosome Location 5
Locus 5q31.1
SNPs PPP2CA
Gene Sequence
>930 bp
ATGGACGAGAAGGTGTTCACCAAGGAGCTGGACCAGTGGATCGAGCAGCTGAACGAGTGC
AAGCAGCTGTCCGAGTCCCAGGTCAAGAGCCTCTGCGAGAAGGCTAAAGAAATCCTGACA
AAAGAATCCAACGTGCAAGAGGTTCGATGTCCAGTTACTGTCTGTGGAGATGTGCATGGG
CAATTTCATGATCTCATGGAACTGTTTAGAATTGGTGGCAAATCACCAGATACAAATTAC
TTGTTTATGGGAGATTATGTTGACAGAGGATATTATTCAGTTGAAACAGTTACACTGCTT
GTAGCTCTTAAGGTTCGTTACCGTGAACGCATCACCATTCTTCGAGGGAATCATGAGAGC
AGACAGATCACACAAGTTTATGGTTTCTATGATGAATGTTTAAGAAAATATGGAAATGCA
AATGTTTGGAAATATTTTACAGATCTTTTTGACTATCTTCCTCTCACTGCCTTGGTGGAT
GGGCAGATCTTCTGTCTACATGGTGGTCTCTCGCCATCTATAGATACACTGGATCATATC
AGAGCACTTGATCGCCTACAAGAAGTTCCCCATGAGGGTCCAATGTGTGACTTGCTGTGG
TCAGATCCAGATGACCGTGGTGGTTGGGGTATATCTCCTCGAGGAGCTGGTTACACCTTT
GGGCAAGATATTTCTGAGACATTTAATCATGCCAATGGCCTCACGTTGGTGTCTAGAGCT
CACCAGCTAGTGATGGAGGGATATAACTGGTGCCATGACCGGAATGTAGTAACGATTTTC
AGTGCTCCAAACTATTGTTATCGTTGTGGTAACCAAGCTGCAATCATGGAACTTGACGAT
ACTCTAAAATACTCTTTCTTGCAGTTTGACCCAGCACCTCGTAGAGGCGAGCCACATGTT
ACTCGTCGTACCCCAGACTACTTCCTGTAA
Protein Properties
Number of Residues 309
Molecular Weight 35593.93
Theoretical pI 5.537
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform
MDEKVFTKELDQWIEQLNECKQLSESQVKSLCEKAKEILTKESNVQEVRCPVTVCGDVHG
QFHDLMELFRIGGKSPDTNYLFMGDYVDRGYYSVETVTLLVALKVRYRERITILRGNHES
RQITQVYGFYDECLRKYGNANVWKYFTDLFDYLPLTALVDGQIFCLHGGLSPSIDTLDHI
RALDRLQEVPHEGPMCDLLWSDPDDRGGWGISPRGAGYTFGQDISETFNHANGLTLVSRA
HQLVMEGYNWCHDRNVVTIFSAPNYCYRCGNQAAIMELDDTLKYSFLQFDPAPRRGEPHV
TRRTPDYFL
GenBank ID Protein 36120
UniProtKB/Swiss-Prot ID P67775
UniProtKB/Swiss-Prot Entry Name PP2AA_HUMAN
PDB IDs
GenBank Gene ID X12646
GeneCard ID PPP2CA
GenAtlas ID PPP2CA
HGNC ID HGNC:9299
References
General References
  1. 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 ]
  2. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  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. [PubMed:9920888 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. Scheidtmann KH, Virshup DM, Kelly TJ: Protein phosphatase 2A dephosphorylates simian virus 40 large T antigen specifically at residues involved in regulation of DNA-binding activity. J Virol. 1991 Apr;65(4):2098-101. [PubMed:1848320 ]
  11. 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 ]
  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. 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 ]
  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. [PubMed:17485487 ]