Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform (PPP2R1A)
The protein contains 589 amino acids for an estimated molecular weight of 65309 Da.
The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. Upon interaction with GNA12 promotes dephosphorylation of microtubule associated protein TAU/MAPT (PubMed:15525651). Required for proper chromosome segregation and for centromeric localization of SGO1 in mitosis (PubMed:16580887). (updated: Dec. 20, 2017)
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.
- 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 UniProt.
Biological Process
Apoptotic process
Ceramide metabolic process
Chromosome segregation
Ciliary basal body-plasma membrane docking
Female meiotic nuclear division
Fibroblast growth factor receptor signaling pathway
G2/M transition of mitotic cell cycle
Gene expression
Inactivation of MAPK activity
Meiotic sister chromatid cohesion, centromeric
Meiotic spindle elongation
Mitotic cell cycle
Mitotic nuclear membrane reassembly
Mitotic sister chromatid separation
Negative regulation of cell growth
Negative regulation of tyrosine phosphorylation of STAT protein
Negative regulation of tyrosine phosphorylation of Stat3 protein
Nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
Organelle organization
Peptidyl-serine dephosphorylation
Positive regulation of extrinsic apoptotic signaling pathway in absence of ligand
Protein complex assembly
Protein dephosphorylation
Protein-containing complex assembly
Regulation of cell adhesion
Regulation of cell differentiation
Regulation of DNA replication
Regulation of G2/M transition of mitotic cell cycle
Regulation of growth
Regulation of meiotic cell cycle process involved in oocyte maturation
Regulation of transcription, DNA-templated
Regulation of Wnt signaling pathway
Response to organic substance
RNA splicing
Second-messenger-mediated signaling
The reference OMIM entry for this protein is 605983
Protein phosphatase 2, structural/regulatory subunit a, alpha; ppp2r1a
Protein phosphatase 2, 65-kd regulatory subunit a, alpha
Pr65-alpha
DESCRIPTION
The PR65/A regulatory subunit of protein phosphatase-2A (PP2A) serves as a scaffolding molecule that coordinates the assembly of the catalytic subunit, PPP2CA (176915), and a variable regulatory B subunit to generate functionally diverse heterotrimers. The PR65/A subunit exists as 2 isoforms, PPP2R1A and PPP2R1B (603113) (Groves et al., 1999).CLONING
Hemmings et al. (1990) cloned the cDNA corresponding to the PPP2R1A gene, encoding the alpha isoform of the 65-kD structural/regulatory subunit A of the PP2A holoenzyme. The PPP2R1A gene has 86% identity with the PPP2R1B gene, as demonstrated by Hendrix et al. (1993). Everett et al. (1999) showed that expression of all 3 subunits of PP2A, including Ppp2r1a, is regulated in a cell-specific and developmentally stage-specific manner in rat kidney, with the highest levels of enzyme activity present in the nephrogenic cortex of fetal kidney.GENE FUNCTION
To explore the genetic origin of ovarian clear cell carcinoma (167000), Jones et al. (2010) determined the exomic sequences of 8 tumors after immunoaffinity purification of cancer cells. Through comparative analyses of normal cells from the same patients, Jones et al. (2010) identified 4 genes that were mutated in at least 2 tumors. Two of these genes, PPP2R1A and ARID1A (603024), which encodes a protein that participates in chromatin remodeling, were not known to be involved in ovarian clear cell carcinoma. The other 2 genes, PIK3CA (171834) and KRAS (190070), had previously been implicated in ovarian clear cell carcinoma. The nature and pattern of the mutations suggested that PPP2R1A functions as an oncogene and ARID1A as a tumor-suppressor gene. In a total of 42 ovarian clear cell carcinomas, 7% had mutations in PPP2R1A and 57% had mutations in ARID1A. Jones et al. (2010) concluded that their results suggested that aberrant chromatin remodeling contributes to the pathogenesis of ovarian clear cell carcinoma.BIOCHEMICAL FEATURES
Groves et al. (1999) reported that the crystal structure of the PPP2R1A subunit at 2.3-angstrom resolution revealed the conformation of its 15 tandemly repeated 'heat' sequences, degenerate motifs of 39 amino acids present in a variety of proteins, including huntingtin (HTT; 613004) and importin-beta (see 602738). Individual motifs are composed of a pair of antiparallel alpha-helices that assemble in a mainly linear, repetitive fashion to form an elongated molecule characterized by a double layer of alpha-helices. The protein interaction interface is formed from the intrarepeat turns that are aligned to form a continuous ridge.GENE STRUCTURE
Ruteshouser et al. (2001) found that the PPP2R1A gene consists of 15 exons, spanning a region 36 kb in length.MAPPING
The PPP2R1A gene is located on chromosome 19q13.4 (Ruteshouser et al., 2001).MOLECULAR GENETICS
The Deciphering Developmental Disorders Study (2015) identified 3 patients with autosomal dominant mental retardation-36 (MRD36; 616362) who had missense mutations in the PPP2R1A gene (R182W, 605983.0001; P179L, 605983.0002). No functional studies were performed. ... More on the omim web site
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 16, 2016: Protein entry updated
Automatic update: OMIM entry 605983 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed