Serine/threonine-protein phosphatase 2A activator (PPP2R4)
The protein contains 358 amino acids for an estimated molecular weight of 40668 Da.
PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Acts as a regulatory subunit for serine/threonine-protein phosphatase 2A (PP2A) modulating its activity or substrate specificity, probably by inducing a conformational change in the catalytic subunit, a proposed direct target of the PPIase. Can reactivate inactive phosphatase PP2A-phosphatase methylesterase complexes (PP2A(i)) in presence of ATP and Mg(2+) (By similarity). Reversibly stimulates the variable phosphotyrosyl phosphatase activity of PP2A core heterodimer PP2A(D) in presence of ATP and Mg(2+) (in vitro). The phosphotyrosyl phosphatase activity is dependent of an ATPase activity of the PP2A(D):PPP2R4 complex. Is involved in apoptosis; the function appears to be independent from PP2A. (updated: March 4, 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.
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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| Variant | Description |
|---|---|
| dbSNP:rs17481693 | |
| dbSNP:rs4836639 | |
| dbSNP:rs2480452 |
Biological Process
Metabolic process
Mitotic spindle organization
Mitotic spindle organization in nucleus
Negative regulation of phosphoprotein phosphatase activity
Negative regulation of protein dephosphorylation
Positive regulation of apoptotic process
Positive regulation of phosphoprotein phosphatase activity
Positive regulation of protein dephosphorylation
Protein peptidyl-prolyl isomerization
Regulation of phosphoprotein phosphatase activity
Cellular Component
Calcium channel complex
Cytoplasm
Extracellular exosome
Nucleoplasm
Nucleus
Protein phosphatase type 2A complex
Molecular Function
ATP binding
Peptidyl-prolyl cis-trans isomerase activity
Phosphatase activator activity
Protein heterodimerization activity
Protein homodimerization activity
Protein phosphatase 2A binding
Protein phosphatase regulator activity
Protein phosphatase type 2A regulator activity
Protein tyrosine phosphatase activator activity
Signaling receptor binding
The reference OMIM entry for this protein is 600756
Protein phosphatase 2, regulatory subunit b-prime; ppp2r4
Protein phosphatase 2a, regulatory subunit b-prime
Phosphotyrosyl phosphatase activator; ptpa
Pr53
DESCRIPTION
PPP2R4, or PTPA, encodes a specific phosphotyrosyl phosphatase activator of the dimeric form of protein phosphatase-2A (PP2A; see 176915) (Van Hoof et al., 1995).GENE FUNCTION
The core component of PP2A consists of a catalytic (C) subunit (e.g., PPP2CA; 176915) and a scaffold protein (A) subunit (e.g., PPP2R1A; 605983). Using purified recombinant proteins, Chao et al. (2006) found that PTPA and PP2A A-C dimers constituted a composite ATPase, and the interaction was independent of ATP or magnesium ion. The inclusion of PTPA altered the substrate specificity of PP2A, with enhanced phosphotyrosine phosphatase activity and decreased phosphoserine phosphatase activity.BIOCHEMICAL FEATURES
Chao et al. (2006) reported the 1.9-angstrom crystal structure of human PTPA, which revealed a fold consisting of a core, a lid, and an extended linker joining the core and lid. Structural analysis uncovered a highly conserved surface patch bordering these 3 subdomains, as well as an associated deep pocket between the core and linker subdomains. Further analysis showed that the surface patch binds the PP2A A-C dimer, and the deep pocket binds ATP.GENE STRUCTURE
Van Hoof et al. (1995) demonstrated that human PTPA is encoded by a single-copy gene composed of 10 exons and 9 introns with a total length of about 60 kb. The 5-prime flanking sequence of the transcription start site was analyzed for its potential as a promoter. This region lacks a TATA sequence in the appropriate position relative to the transcription start. However, this region is very GC-rich and contains 4 Sp1 sites (SP1; 189906) upstream of the transcription start site, a feature common to many TATA-less promoters. Based on homology with DNA-binding consensus sequences of transcription factors, Van Hoof et al. (1995) identified several additional putative transcription factor binding sites in the promoter region. Transfection experiments with a construct containing the PTPA promoter region inserted 5-prime of a luciferase reporter gene demonstrated that the 5-prime flanking sequence of the PTPA gene indeed has promoter activity that seems to be cell-line dependent.MAPPING
By fluorescence in situ hybridization, Van Hoof et al. (1995) mapped the PTPA gene to 9q34. Fluorescence in situ analysis of metaphase chromosomes of patients bearing the Philadelphia chromosome indicated that PTPA is positioned centromeric of ABL1 (189980) and probably is not involved in chronic myeloid leukemia. ... 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 25, 2017: Additional information
No protein expression data in P. Mayeux work for PPP2R4
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 600756 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed