Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform (PPP2R1B)
The protein contains 601 amino acids for an estimated molecular weight of 66214 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. (updated: April 1, 2015)
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.
- 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.
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Biological Process
Apoptotic process involved in morphogenesis
Positive regulation of extrinsic apoptotic signaling pathway in absence of ligand
Protein dephosphorylation
The reference OMIM entry for this protein is 603113
Protein phosphatase 2, structural/regulatory subunit a, beta; ppp2r1b
Pp2aa-beta
DESCRIPTION
Serine/threonine protein phosphatase-2A (PP2A) is an important regulatory enzyme that downregulates the mitogen-activated protein kinase (MAPK) cascade (see 176948), relays signals for cell proliferation, and may be linked to carcinogenesis. The PP2A holoenzyme exists in several trimeric forms consisting of a 36-kD core catalytic subunit (PP2AC; see 176915), a 65-kD structural/regulatory component (PP2AA), and a variable regulatory subunit (PP2AB; see 604941) that confers distinct properties on the holoenzyme. Each subunit exists as multiple isoforms encoded by different genes, resulting in many forms of the PP2A trimer that differ in expression pattern and specificity. PPP2R1B encodes the beta isoform of the structural-regulatory A subunit, or PP2AA-beta. This subunit is necessary for interaction of the catalytic PP2AC and variable PP2AB subunits and is critical for phosphatase activity (Walter and Mumby, 1993; Wang et al., 1998).CLONING
Loss of heterozygosity (LOH) at chromosome 11q22-q24 has been associated with lung, colon, breast, cervical, head and neck, and ovarian cancers, as well as melanoma (Arai et al., 1996). Introduction of a normal chromosome 11, or a derivative t(X;11) chromosome containing 11pter-q23, can reverse the tumorigenic potential of several types of cancer cells and Wilms tumor when introduced into nude mice. These studies suggest that 1 or more tumor suppressor genes are located centromeric to the t(X;11) breakpoint at chromosome 11q23. Because of a high frequency of LOH in lung cancer cells involving D11S1647 and D11S1987, Wang et al. (1998) systematically surveyed the region between these 2 markers for candidate tumor suppressor genes. Over 100 candidate genes and ESTs were identified from a radiation hybrid map of chromosome 11 and from the NCBI transcript map, including an EST corresponding to PPP2R1B.GENE STRUCTURE
Baysal et al. (1998) determined that the PPP2R1B gene contains 15 exons and spans approximately 27 kb.MAPPING
Wang et al. (1998) determined the precise physical location of the PPP2R1B gene by colocalizing it within P1-derived artificial chromosome (PAC) clones containing sequence tagged sites on chromosome 11q22-q23. They confirmed that the PPP2R1B gene is located in a region showing high frequency LOH.GENE FUNCTION
Sablina et al. (2007) found that suppression of PP2A A-beta expression allowed immortalized human cell lines to achieve a tumorigenic state. Cancer-associated A-beta mutants failed to reverse this tumorigenic phenotype, indicating that the mutants functioned as null alleles. Cancer-derived A-beta mutants failed to form a complex with the small GTPase RALA (179550), whereas wildtype A-beta-containing complexes dephosphorylated RALA at ser183 and ser194, inactivating RALA and abolishing its transforming function. Sablina et al. (2007) concluded that PP2A A-beta is a tumor suppressor that transforms immortalized cells by regulating RALA function.MOLECULAR GENETICS
Wang et al. (1998) identified somatic alterations in the PPP2R1B gene in 15% (5 in 32) of primary lung tumors, 6% (4 in 70) of lung tumor-derived cell lines, and 15% (2 in 13) of primary colon tumors. One deletion mutation generated a truncated PP2A-A-beta protein that was unable to bind to the catalytic subunit of the PP2A holoenzyme. The authors suggested that the PPP2R1B gene product may suppress tumor development through its role in cell cy ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 603113 was added.