PTPA ( protein phosphatase 2 phosphatase activator)

	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.
Pseudogene	None has been described.

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	Stimulates the phosphotyrosyl phosphatase activity of the PP2A core heterodimer in the presence of ATP/Mg2+ (in vitro). Reactivates the phosphoserine/threonine phosphatase activity of an inactive PP2A form in the presence of ATP/Mg2+. This inactive PP2A is associated with the PP2A methylesterase (PME-1). ATP/Mg2+-dependent peptidyl prolyl cis/trans isomerase acting on Pro190 in the PP2A catalytic subunit. Binds to the PP2A heterodimeric core enzyme (A and C subunit). Required for the biogenesis of active PP2A. Reported to be pro- as well as anti-apoptotic. In Saccharomyces cerevisiae: two orthologues found. Involved in protection against oxidative damage, G1 progression, G2/M transition, Target of Rapamycin (TOR) pathway.
	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.

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