Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform (PPP2CA)
The protein contains 309 amino acids for an estimated molecular weight of 35594 Da.
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' (PubMed:10801873). Mediates dephosphorylation of WEE1, preventing its ubiquitin-mediated proteolysis, increasing WEE1 protein levels, and promoting the G2/M checkpoint (PubMed:33108758). (updated: Feb. 10, 2021)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
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Biological Process
Apoptotic process
Ceramide metabolic process
Fibroblast growth factor receptor signaling pathway
Gene expression
Inactivation of MAPK activity
Meiotic cell cycle
Mesoderm development
Mitotic cell cycle
Mitotic nuclear membrane reassembly
Negative regulation of cell growth
Negative regulation of epithelial to mesenchymal transition
Negative regulation of tyrosine phosphorylation of STAT protein
Negative regulation of tyrosine phosphorylation of Stat3 protein
Nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
Peptidyl-serine dephosphorylation
Peptidyl-threonine dephosphorylation
Positive regulation of microtubule binding
Positive regulation of protein serine/threonine kinase activity
Protein dephosphorylation
Protein heterotrimerization
Regulation of cell adhesion
Regulation of cell differentiation
Regulation of DNA replication
Regulation of growth
Regulation of microtubule binding
Regulation of protein autophosphorylation
Regulation of protein catabolic process
Regulation of protein phosphorylation
Regulation of signaling receptor activity
Regulation of transcription, DNA-templated
Regulation of Wnt signaling pathway
Response to lead ion
Response to organic substance
RNA splicing
Second-messenger-mediated signaling
The reference OMIM entry for this protein is 176915
Protein phosphatase 2, catalytic subunit, alpha isoform; ppp2ca
Protein phosphatase 2a, catalytic subunit, alpha isoform; pp2ca
DESCRIPTION
Protein phosphorylation, a crucial posttranslational modification step controlling many diverse cellular functions, is dependent on the opposing actions of protein kinases and protein phosphatases. The enzyme protein phosphatase 2A is 1 of 4 major protein phosphatases identified in the cytosol of eukaryotic cells which are responsible for the dephosphorylation of serine and threonine residues in proteins. Although all 4 protein phosphatases, PP1, PP2A, PP2B, and PP2C, have overlapping substrate specificities in vitro, they can be distinguished by the use of inhibitor proteins and by their dependence on metal ions. PP1 is inhibited by nanomolar concentrations of 2 thermostable proteins, inhibitor 1 and inhibitor 2, whereas the type 2 phosphatases are unaffected by these inhibitors. The type 2 phosphatases can be distinguished by how their activity is regulated: PP2A activity is independent of metal ions, PP2B is activated by Ca(2+)/calmodulin, and PP2C is activated by Mg(2+) (Cohen and Cohen, 1989). Protein phosphatase 2A appears to play a role in the regulation of most major metabolic pathways, as well as translation, transcription, and control of transition from G2 to the M phase of the cell cycle. PP2A may function as either a tumor promoter or tumor suppressor, depending on the cell type or the transforming agent. The mammalian enzyme can be isolated as a catalytic subunit of 36 kD complexed to 1 regulatory subunit of 65 kD and to another regulatory subunit of varying molecular mass, depending on the tissue and the separation technique used. Two isoforms of the catalytic subunit of PP2A, alpha and beta (176916), are demonstrable in many mammalian species. The structures of these catalytic subunits show the highest evolutionary conservation of all known enzymes, supporting the idea that they may serve crucial functions.CLONING
Stone et al. (1988) isolated the human cDNA for the PPP2CA subunit from lung and lung fibroblast libraries. The cDNA encodes a 309-amino acid polypeptide.MAPPING
Jones et al. (1993) mapped the PPP2CA gene to human chromosome 5 by somatic cell hybridization and refined the mapping to 5q23-q31 by in situ hybridization.BIOCHEMICAL FEATURES
- Crystal Structure Herzog et al. (2012) gained distance restraints on a modular interaction network of protein complexes affinity-purified from human cells by applying an adapted crosslinking and mass spectrometry (XL-MS) protocol. Systematic analysis of human protein phosphatase 2A (PP2A) complexes identified 176 interprotein and 570 intraprotein crosslinks that link specific trimeric PP2A complexes to a multitude of adaptor proteins that control their cellular functions. Spatial restraints guided molecular modeling of the binding interface between immunoglobulin binding protein-1 (IGBP1; 300139) and PP2A and revealed the topology of TCP1 (186980) ring complex (TRiC) chaperonin (see 605139) interacting with the PP2A regulatory subunit 2ABG. Herzog et al. (2012) concluded that this study established XL-MS as an integral part of hybrid structural biology approaches for the analysis of endogenous protein complexes.GENE FUNCTION
Using yeast 2-hybrid and protein pull-down assays, Kono et al. (2002) found that mouse G5pr (PPP2R3C; 615902) interacted with Ganp DNA primase (MCM3AP; 603294) and with 2 types of catalytic protein phosphatases, Pp2ca and Pp5 (PPP5C; 600658). G5pr did not interact with Pp2ca and Pp5 simu ... More on the omim web site
Feb. 16, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for PPP2CA
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 176915 was added.