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

 
Known also as: Replication protein C

Known abbreviations: PPP2CA, PP2A-alpha, RP-C

 

FUNCTION:
 
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. Dephosphorylates SV40 large T antigen, preferentially on serine residues 120, 123, 677, and perhaps 679. The C subunit was most active, followed by the AC form, which was more active than the ABC form, and activity of all three forms was strongly stimulated by manganese, and to a lesser extent by magnesium. Dephosphorylation by the AC form, but not C or ABC form is inhibited by small T antigen. Activates RAF1 by dephosphorylating it at 'Ser-259'. 
 
CATALYTIC ACTIVITY:
 
A phosphoprotein + H2O = a protein + phosphate.
 
COFACTOR:
 
Binds 1 iron ion per subunit (By similarity.)
Binds 1 manganese ion per subunit (By similarity.)
 
SUBUNIT STRUCTURE:
 
PP2A consists of a common heterodimeric core enzyme, composed of PPP2CA a 36 kDa catalytic subunit (subunit C) and PPP2R1A a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Interacts with NXN; the interaction is direct By similarity. Interacts with TP53, SGOL1 and SGOL2. Interacts with AXIN1; the interaction dephosphorylates AXIN1. Interacts with PIM3; this interaction promotes dephosphorylation, ubiquitination and proteasomal degradation of PIM3. Interacts with RAF1. 
 
CELLULAR LOCALIZATION:
 
Cytoplasm. Nucleus. Chromosome › centromere. Cytoplasm › cytoskeleton › spindle pole. Note: In prometaphase cells, but not in anaphase cells, localizes at centromeres. During mitosis, also found at spindle poles. Centromeric localization requires the presence of SGOL2 (By similarity.)
 
POST-TRANSLATIONAL MODIFICATION:
 
Reversibly methyl esterified on Leu-309. Carboxyl methylation may play a role in holoenzyme assembly, enhancing the affinity of the PP2A core enzyme for some, but not all, regulatory subunits. It varies during the cell cycle.
Phosphorylation of either threonine (by autophosphorylation-activated protein kinase) or tyrosine results in inactivation of the phosphatase. Auto-dephosphorylation has been suggested as a mechanism for reactivation.



Activities in which Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform is involved: Pathways in which Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform is involved:

NCBI GI number(s): 4506017
57222566
Species: Homo sapiens

Links to other databases:

Database ID Link
Uniprot P67775 P67775
BRENDA - -
KEGG hsa:5515 hsa:5515
PFAM: PF00149
PF00149
InterPro: IPR004843
IPR006186
IPR004843
IPR006186
CATH: - -
SCOP: - -
Solved crystal structures: 3P71
3K7W
3K7V
3FGA
3DW8
3C5W
2NYM
2NYL
2NPP
2IE4
2IE3
2IAE
[PDB] [details]
[PDB] [details]
[PDB] [details]
[PDB] [details]
[PDB] [details]
[PDB] [details]
[PDB] [details]
[PDB] [details]
[PDB] [details]
[PDB] [details]
[PDB] [details]
[PDB] [details]


Protein sequence:
MDEKVFTKELDQWIEQLNECKQLSESQVKSLCEKAKEILTKESNVQEVRC
PVTVCGDVHGQFHDLMELFRIGGKSPDTNYLFMGDYVDRGYYSVETVTLL
VALKVRYRERITILRGNHESRQITQVYGFYDECLRKYGNANVWKYFTDLF
DYLPLTALVDGQIFCLHGGLSPSIDTLDHIRALDRLQEVPHEGPMCDLLW
SDPDDRGGWGISPRGAGYTFGQDISETFNHANGLTLVSRAHQLVMEGYNW
CHDRNVVTIFSAPNYCYRCGNQAAIMELDDTLKYSFLQFDPAPRRGEPHV
TRRTPDYFL

Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform (Homo sapiens) is product of expression of PPP2CA gene.

References:

Title Authors Journal Publication date (Issue) PubMed ID
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). 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, K Genome Res 2004-10-01 (14) 15489334
Initial characterization of the human central proteome. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J BMC Syst Biol 2011-01-01 (5) 21269460
Lysine acetylation targets protein complexes and co-regulates major cellular functions. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M Science 2009-08-14 (325) 19608861
The nucleotide sequence of the cDNA encoding the human lung protein phosphatase 2A alpha catalytic subunit. Stone SR, Mayer R, Wernet W, Maurer F, Hofsteenge J, Hemmings BA Nucleic Acids Res 1988-12-09 (16) 2849764
Human liver phosphatase 2A: cDNA and amino acid sequence of two catalytic subunit isotypes. Arino J, Woon CW, Brautigan DL, Miller TB Jr, Johnson GL Proc Natl Acad Sci U S A 1988-06-01 (85) 2837763
Structure and transcriptional regulation of protein phosphatase 2A catalytic subunit genes. Khew-Goodall Y, Mayer RE, Maurer F, Stone SR, Hemmings BA Biochemistry 1991-02-08 (30) 1846293
Dephosphorylation of simian virus 40 large-T antigen and p53 protein by protein phosphatase 2A: inhibition by small-t antigen. Scheidtmann KH, Mumby MC, Rundell K, Walter G Mol Cell Biol 1991-04-01 (11) 1848668
The catalytic subunit of protein phosphatase 2A is carboxyl-methylated in vivo. Favre B, Zolnierowicz S, Turowski P, Hemmings BA J Biol Chem 1994-06-10 (269) 8206937
Methylated C-terminal leucine residue of PP2A catalytic subunit is important for binding of regulatory Balpha subunit. Bryant JC, Westphal RS, Wadzinski BE Biochem J 1999-04-15 (None) 10191253
Protein phosphatase 2A dephosphorylates simian virus 40 large T antigen specifically at residues involved in regulation of DNA-binding activity. Scheidtmann KH, Virshup DM, Kelly TJ J Virol 1991-04-01 (65) 1848320
Activation of SV40 DNA replication in vitro by cellular protein phosphatase 2A. Virshup DM, Kauffman MG, Kelly TJ EMBO J 1989-12-01 (8) 2555176
Identification of a domain of Axin that binds to the serine/threonine protein phosphatase 2A and a self-binding domain. Hsu W, Zeng L, Costantini F J Biol Chem 1999-01-05 (274) 9920888
Raf-1-associated protein phosphatase 2A as a positive regulator of kinase activation. Abraham D, Podar K, Pacher M, Kubicek M, Welzel N, Hemmings BA, Dilworth SM, Mischak H, Kolch W, Baccarini M J Biol Chem 2000-07-21 (275) 10801873
PP2A is required for centromeric localization of Sgo1 and proper chromosome segregation. Tang Z, Shu H, Qi W, Mahmood NA, Mumby MC, Yu H Dev Cell 2006-05-01 (10) 16580887
Shugoshin collaborates with protein phosphatase 2A to protect cohesin. Kitajima TS, Sakuno T, Ishiguro K, Iemura S, Natsume T, Kawashima SA, Watanabe Y Nature 2006-05-04 (441) 16541025
Protein phosphatase 2A regulates the stability of Pim protein kinases. Losman JA, Chen XP, Vuong BQ, Fay S, Rothman PB J Biol Chem 2003-01-14 (278) 12473674
A specific PP2A regulatory subunit, B56gamma, mediates DNA damage-induced dephosphorylation of p53 at Thr55. Li HH, Cai X, Shouse GP, Piluso LG, Liu X EMBO J 2007-02-24 (26) 17245430
Tripin/hSgo2 recruits MCAK to the inner centromere to correct defective kinetochore attachments. Huang H, Feng J, Famulski J, Rattner JB, Liu ST, Kao GD, Muschel R, Chan GK, Yen TJ J Cell Biol 2007-05-07 (177) 17485487
Structural mechanism of demethylation and inactivation of protein phosphatase 2A. Xing Y, Li Z, Chen Y, Stock JB, Jeffrey PD, Shi Y Cell 2008-04-04 (133) 18394995



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Last modification of this entry: Sept. 25, 2012.

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