PTPA ( protein phosphatase 2 phosphatase activator)
2009-02-01 Veerle Janssens AffiliationProtein Phosphorylation, Proteomics Group, Department of Molecular Cell Biology, Faculty of Medicine, University of Leuven, Campus GHB O&N1, Herestraat 49, box 901, B-3000 Leuven, Belgium
Identity
HGNC
LOCATION
9q34.11
LOCUSID
ALIAS
PP2A,PPP2R4,PR53
FUSION GENES
DNA/RNA
Figure 1. Schematic representation of PPP2R4 splice variants.
The top line represents the PPP2R4 gene. Exons are boxed (5 and 3 UTR are speckled). Introns and the 3 UTR are not drawn to scale. PTPA alpha and beta are the major transcripts/proteins; PTPA gamma, zeta and eta do not encode functional proteins and probably result from splicing errors.
Gene promoter has been analyzed and resides in a non-methylated CpG island. No TATA or CAAT box. Two functional yin-yang-1 (YY1) binding sites direct basal promoter expression. Tumor suppressor p53 represses transcription through a mechanism involving YY1 inhibition.
Figure 2. Schematic structure of the PPP2R4 promoter.
Two YY1 sites are required for basal PPP2R4 promoter activity and reside within the minimal promoter (nt -67/+38 relative to the start of transcription which is at +1). Upstream of this minimal promoter a GC-rich Sp1-cluster is present (nt -670/-470) of which the functionality has not yet been proven. The PPP2R4 promoter resides within an unmethylated CpG island.
Description
The gene encompasses around 40 kb; 11 exons.
Transcription
Several transcripts have been identified, resulting from alternative splicing; two transcripts in Northern blot of human placental RNA with probe encompassing exons 1-10: 4.1 kb and 2.8 kb (likely resulting from the use of different polyadenylation signals).
Alpha isoform: encompasses exons 1,2,3,5-11.
Beta isoform: encompasses exons 1-11.
Gamma isoform: encompasses exons 1,3-11.
Delta isoform: encompasses exons 1,2,5-11.
Epsilon isoform: encompasses exons 1,2,3,6-11.
Zeta isoform: encompasses exons 1,3,5-11.
Eta isoform: encompasses exons 1,5-11.
Alpha, beta, delta, epsilon isoforms can be translated into functional proteins in vitro; gamma, zeta, eta, are probably the result of splicing errors.
Alpha, beta, delta, epsilon isoforms can be translated into functional proteins in vitro; gamma, zeta, eta, are probably the result of splicing errors.
Pseudogene
None has been described.
Proteins
Description
Two isoforms detectable in Western blot of human placenta and several human cell lines: PTPA alpha, 323 amino acids, 36.8 kDa; PTPA beta, 358 amino acids, 40.7 kDa. pI around 5.8; trypsin-resistant.
Expression
Both isoforms are widely expressed. In a given cell line, PTPA alpha is about 10x more abundant than PTPA beta. Very high expression in p53-negative cell lines (for instance the osteosarcoma cell line Saos-2).
Localisation
Predominantly cytoplasmic.
Function
Figure 3. PTPA protein structure.
PTPA is an all alpha-helical polypeptide, organized into two domains separated by a groove. Here the ribbon structure of human PTPA is displayed (derived from PDB code: 2IXM, Leulliot et al., 2006).
Homology
No other human homologues known. Defines a new family of peptidyl prolyl cis/trans isomerases (PPIases) with all alpha-helical structure, organized into two domains separated by a groove.
Implicated in
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 8612628 | 1996 | A comparative study of the phosphotyrosyl phosphatase specificity of protein phosphatase type 2A and phosphotyrosyl phosphatase type 1B using phosphopeptides and the phosphoproteins p50/HS1, c-Fgr and Lyn. | Agostinis P et al |
| 17333320 | 2007 | Overexpression of the cis/trans isomerase PTPA triggers caspase 3-dependent apoptosis. | Azam S et al |
| 2159785 | 1990 | Isolation and characterization of a tyrosyl phosphatase activator from rabbit skeletal muscle and Xenopus laevis oocytes. | Cayla X et al |
| 8195217 | 1994 | Molecular cloning, expression, and characterization of PTPA, a protein that activates the tyrosyl phosphatase activity of protein phosphatase 2A. | Cayla X et al |
| 16916641 | 2006 | Structure and mechanism of the phosphotyrosyl phosphatase activator. | Chao Y et al |
| 12952889 | 2003 | A novel and essential mechanism determining specificity and activity of protein phosphatase 2A (PP2A) in vivo. | Fellner T et al |
| 17550305 | 2007 | Generation of active protein phosphatase 2A is coupled to holoenzyme assembly. | Hombauer H et al |
| 11171037 | 2001 | Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling. | Janssens V et al |
| 16380387 | 2006 | The protein phosphatase 2A phosphatase activator is a novel peptidyl-prolyl cis/trans-isomerase. | Jordens J et al |
| 16885030 | 2006 | Crystal structure of the PP2A phosphatase activator: implications for its PP2A-specific PPIase activity. | Leulliot N et al |
| 14748741 | 2004 | An inactive protein phosphatase 2A population is associated with methylesterase and can be re-activated by the phosphotyrosyl phosphatase activator. | Longin S et al |
| 15864305 | 2005 | Sensitized RNAi screen of human kinases and phosphatases identifies new regulators of apoptosis and chemoresistance. | MacKeigan JP et al |
| 16782712 | 2006 | The crystal structure of a human PP2A phosphatase activator reveals a novel fold and highly conserved cleft implicated in protein-protein interactions. | Magnusdottir A et al |
| 11134337 | 2001 | The phosphotyrosyl phosphatase activator, Ncs1p (Rrd1p), functions with Cla4p to regulate the G(2)/M transition in Saccharomyces cerevisiae. | Mitchell DA et al |
| 9705277 | 1998 | A yeast homologue of the human phosphotyrosyl phosphatase activator PTPA is implicated in protection against oxidative DNA damage induced by the model carcinogen 4-nitroquinoline 1-oxide. | Ramotar D et al |
| 11995966 | 2001 | Anaerobic growth of Saccharomyces cerevisiae alleviates the lethal effect of phosphotyrosyl phosphatase activators depletion. | Rempola B et al |
| 15447631 | 2005 | Specific interactions of PP2A and PP2A-like phosphatases with the yeast PTPA homologues, Ypa1 and Ypa2. | Van Hoof C et al |
| 15689491 | 2005 | The yeast phosphotyrosyl phosphatase activator is part of the Tap42-phosphatase complexes. | Zheng Y et al |
Other Information
Locus ID:
NCBI: 5524
MIM: 600756
HGNC: 9308
Ensembl: ENSG00000119383
Variants:
dbSNP: 5524
ClinVar: 5524
TCGA: ENSG00000119383
COSMIC: PTPA
RNA/Proteins
Expression (GTEx)
Pathways
| Pathway | Source | External ID |
|---|---|---|
| Insulin resistance | KEGG | hsa04931 |
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37934606 | 2024 | PP2A inhibition causes synthetic lethality in BRCA2-mutated prostate cancer models via spindle assembly checkpoint reactivation. | 0 |
| 38141761 | 2024 | PP2A inhibitor SET promotes mTORC1 and Bmi1 signaling through Akt activation and maintains the colony-formation ability of cancer cells. | 0 |
| 38441530 | 2024 | PR55α-controlled protein phosphatase 2A inhibits p16 expression and blocks cellular senescence induction by γ-irradiation. | 0 |
| 38582449 | 2024 | Structural characterization of methylation-independent PP2A assembly guides alphafold2Multimer prediction of family-wide PP2A complexes. | 0 |
| 38588804 | 2024 | The luciferase-based in vivo protein-protein interaction assay revealed that CHK1 promotes PP2A and PME-1 interaction. | 0 |
| 37934606 | 2024 | PP2A inhibition causes synthetic lethality in BRCA2-mutated prostate cancer models via spindle assembly checkpoint reactivation. | 0 |
| 38141761 | 2024 | PP2A inhibitor SET promotes mTORC1 and Bmi1 signaling through Akt activation and maintains the colony-formation ability of cancer cells. | 0 |
| 38441530 | 2024 | PR55α-controlled protein phosphatase 2A inhibits p16 expression and blocks cellular senescence induction by γ-irradiation. | 0 |
| 38582449 | 2024 | Structural characterization of methylation-independent PP2A assembly guides alphafold2Multimer prediction of family-wide PP2A complexes. | 0 |
| 38588804 | 2024 | The luciferase-based in vivo protein-protein interaction assay revealed that CHK1 promotes PP2A and PME-1 interaction. | 0 |
| 36047562 | 2023 | PP2A-B55 and its adapter proteins IER2 and IER5 regulate the activity of RB family proteins and the expression of cell cycle-related genes. | 4 |
| 36073231 | 2023 | PTPA variants and impaired PP2A activity in early-onset parkinsonism with intellectual disability. | 5 |
| 36216457 | 2023 | Clinical, neuroimaging and molecular characteristics of PPP2R5D-related neurodevelopmental disorders: an expanded series with functional characterisation and genotype-phenotype analysis. | 8 |
| 36324030 | 2023 | Protein Phosphatase 2a Inhibits Gastric Cancer Cell Glycolysis by Reducing MYC Signaling. | 0 |
| 36756741 | 2023 | Hsa-miR-409-3p regulates endothelial progenitor senescence via PP2A-P38 and is a potential ageing marker in humans. | 5 |
Citation
Veerle Janssens
PTPA ( protein phosphatase 2 phosphatase activator)
Atlas Genet Cytogenet Oncol Haematol. 2009-02-01
Online version: http://atlasgeneticsoncology.org/gene/41817/ptpa
