Written | 2009-02 | Veerle Janssens |
Protein 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 |
Alias (NCBI) | PPP2R4 (protein phosphatase 2A activator, regulatory subunit 4) | MGC2184 | OTTHUMP00000022333 | PP2A | PR53 | PTPA |
HGNC (Hugo) | PTPA |
HGNC Alias symb | PR53 |
HGNC Alias name | phosphotyrosyl phosphatase activator | PP2A phosphatase activator |
HGNC Previous name | PPP2R4 |
HGNC Previous name | "protein phosphatase 2A, regulatory subunit B' (PR 53) | protein phosphatase 2A activator, regulatory subunit 4 | protein phosphatase 2 regulatory subunit 4" |
LocusID (NCBI) | 5524 |
Atlas_Id | 41817 |
Location | 9q34.11 [Link to chromosome band 9q34] |
Location_base_pair | Starts at 129111415 and ends at 129148946 bp from pter ( according to GRCh38/hg38-Dec_2013) [Mapping PTPA.png] |
Local_order | From centromere to telomere: DOLPP1 (dolichyl pyrophosphate phosphatase 1), CRAT (carnitine acetyltransferase), PPP2R4, IER5L (immediate early response 5-like), C9orf106. |
Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
DPH7 (9q34.3) / PTPA (9q34) | DPH7 (9q34.3) / PTPA (9q34.11) | PTPA (9q34) / MIGA2 (9Q34.13) | |
PTPA (9q34) / NEK6 (9q33.3) | PTPA (9q34) / NUP188 (9q34.11) | PTPA (9q34.11) / NEK6 (9q33.3) | |
PTPA (9q34.11) / NUP188 (9q34.11) | TMEM104 (17q25.1) / PTPA (9q34) |
Note | In fact the gene name would be better: 'protein phosphatase 2A, regulatory subunit 4' or 'protein phosphatase 2A activator', and not a mixture of the two. |
DNA/RNA |
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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, 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. |
Protein |
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 | |
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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. |
To be noted |
Although there is a huge and accumulating literature implicating PP2A in cancer etiology, PP2A enzymes represent a large and diverse family of holoenzymes, and the functional implications of specific complexes are only beginning to emerge. As such, it is clear that some PP2A holoenzymes may act as tumor suppressors, whereas others may on the contrary rather promote tumorigenesis. As for PPP2R4, one of the many cellular regulators/subunits of PP2A, there is as yet no direct evidence that this gene product is directly involved in these pathological processes. |
Bibliography |
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, Donella-Deana A, Van Hoof C, Cesaro L, Brunati AM, Ruzzene M, Merlevede W, Pinna LA, Goris J. |
Eur J Biochem. 1996 Mar 1;236(2):548-57. |
PMID 8612628 |
Overexpression of the cis/trans isomerase PTPA triggers caspase 3-dependent apoptosis. |
Azam S, Drobetsky E, Ramotar D. |
Apoptosis. 2007 Jul;12(7):1243-55. |
PMID 17333320 |
Isolation and characterization of a tyrosyl phosphatase activator from rabbit skeletal muscle and Xenopus laevis oocytes. |
Cayla X, Goris J, Hermann J, Hendrix P, Ozon R, Merlevede W. |
Biochemistry. 1990 Jan 23;29(3):658-67. |
PMID 2159785 |
Molecular cloning, expression, and characterization of PTPA, a protein that activates the tyrosyl phosphatase activity of protein phosphatase 2A. |
Cayla X, Van Hoof C, Bosch M, Waelkens E, Vandekerckhove J, Peeters B, Merlevede W, Goris J. |
J Biol Chem. 1994 Jun 3;269(22):15668-75. |
PMID 8195217 |
Structure and mechanism of the phosphotyrosyl phosphatase activator. |
Chao Y, Xing Y, Chen Y, Xu Y, Lin Z, Li Z, Jeffrey PD, Stock JB, Shi Y. |
Mol Cell. 2006 Aug;23(4):535-46. |
PMID 16916641 |
A novel and essential mechanism determining specificity and activity of protein phosphatase 2A (PP2A) in vivo. |
Fellner T, Lackner DH, Hombauer H, Piribauer P, Mudrak I, Zaragoza K, Juno C, Ogris E. |
Genes Dev. 2003 Sep 1;17(17):2138-50. |
PMID 12952889 |
Generation of active protein phosphatase 2A is coupled to holoenzyme assembly. |
Hombauer H, Weismann D, Mudrak I, Stanzel C, Fellner T, Lackner DH, Ogris E. |
PLoS Biol. 2007 Jun;5(6):e155. |
PMID 17550305 |
Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling. |
Janssens V, Goris J. |
Biochem J. 2001 Feb 1;353(Pt 3):417-39. (Review) |
PMID 11171037 |
The protein phosphatase 2A phosphatase activator is a novel peptidyl-prolyl cis/trans-isomerase. |
Jordens J, Janssens V, Longin S, Stevens I, Martens E, Bultynck G, Engelborghs Y, Lescrinier E, Waelkens E, Goris J, Van Hoof C. |
J Biol Chem. 2006 Mar 10;281(10):6349-57. Epub 2005 Dec 27. |
PMID 16380387 |
Crystal structure of the PP2A phosphatase activator: implications for its PP2A-specific PPIase activity. |
Leulliot N, Vicentini G, Jordens J, Quevillon-Cheruel S, Schiltz M, Barford D, van Tilbeurgh H, Goris J. |
Mol Cell. 2006 Aug 4;23(3):413-24. |
PMID 16885030 |
An inactive protein phosphatase 2A population is associated with methylesterase and can be re-activated by the phosphotyrosyl phosphatase activator. |
Longin S, Jordens J, Martens E, Stevens I, Janssens V, Rondelez E, De Baere I, Derua R, Waelkens E, Goris J, Van Hoof C. |
Biochem J. 2004 May 15;380(Pt 1):111-9. |
PMID 14748741 |
Sensitized RNAi screen of human kinases and phosphatases identifies new regulators of apoptosis and chemoresistance. |
MacKeigan JP, Murphy LO, Blenis J. |
Nat Cell Biol. 2005 Jun;7(6):591-600. Epub 2005 May 1. |
PMID 15864305 |
The crystal structure of a human PP2A phosphatase activator reveals a novel fold and highly conserved cleft implicated in protein-protein interactions. |
Magnusdottir A, Stenmark P, Flodin S, Nyman T, Hammarstrom M, Ehn M, Bakali H MA, Berglund H, Nordlund P. |
J Biol Chem. 2006 Aug 11;281(32):22434-8. Epub 2006 Jun 16. |
PMID 16782712 |
The phosphotyrosyl phosphatase activator, Ncs1p (Rrd1p), functions with Cla4p to regulate the G(2)/M transition in Saccharomyces cerevisiae. |
Mitchell DA, Sprague GF Jr. |
Mol Cell Biol. 2001 Jan;21(2):488-500. |
PMID 11134337 |
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, Belanger E, Brodeur I, Masson JY, Drobetsky EA. |
J Biol Chem. 1998 Aug 21;273(34):21489-96. |
PMID 9705277 |
Anaerobic growth of Saccharomyces cerevisiae alleviates the lethal effect of phosphotyrosyl phosphatase activators depletion. |
Rempola B, Kaniak A, di Rago JP, Rytka J. |
Acta Biochim Pol. 2001;48(4):1043-9. |
PMID 11995966 |
Specific interactions of PP2A and PP2A-like phosphatases with the yeast PTPA homologues, Ypa1 and Ypa2. |
Van Hoof C, Martens E, Longin S, Jordens J, Stevens I, Janssens V, Goris J. |
Biochem J. 2005 Feb 15;386(Pt 1):93-102. |
PMID 15447631 |
The yeast phosphotyrosyl phosphatase activator is part of the Tap42-phosphatase complexes. |
Zheng Y, Jiang Y. |
Mol Biol Cell. 2005 Apr;16(4):2119-27. Epub 2005 Feb 2. |
PMID 15689491 |
Citation |
This paper should be referenced as such : |
Janssens, V |
PPP2R4 (protein phosphatase 2A activator, regulatory subunit 4) |
Atlas Genet Cytogenet Oncol Haematol. 2010;14(1):48-51. |
Free journal version : [ pdf ] [ DOI ] |
Other Leukemias implicated (Data extracted from papers in the Atlas) [ 2 ] |
Chronic myelogenous leukaemia (CML)
t(11;18)(p15;q12) NUP98/SETBP1 |
External links |
REVIEW articles | automatic search in PubMed |
Last year publications | automatic search in PubMed |
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