Pseudophosphatases (obsolete)

Human pseudophosphatases

CC1 fold

PTP family

PTPRN subfamily

Human PTPRN (IA-2) and PTPRN2 have been proposed to be enzymatically inactive due to mutations at catalytic Cx5R motif and WPD motif [1]. However, PTPRN2 has been reported to be phosphatidylinositol phosphatase [2].

PTPN23 (HD-PTP) subfamily

PTPN23 was reported to be catalytically inactive, - no phosphatase activity toward tyrosine or lipid. It was proposed that serine at position 1452 within Cx5R catalytic motif caused the inactivity. Replacing serine with alanine, which is found in catalytically active PTPs, can restore the phosphatase activity [3]. However, another study found SRC, E-cadherin, and beta-catenin are direct substrates of PTPN23 [4]. But, yet another study showed that PTPN23 did not modulate the levels of Src phosphorylation both in vitro and in vivo [5].

Myotubularin family

MTMR5 (SBF) subfamily

MTMR5 (SBF1) and MTMR13 (SBF2)

Miscellaneous

Second phosphatase domain in receptor PTPs

Most receptor PTPs have two tandem phosphatase domains. The 2nd phosphatase domain has no or negligible activity. The 2nd domain can interact with 1st domain in both intra- and intermolecular manners [6].

References

1. Kharitidi D, Manteghi S, and Pause A. Pseudophosphatases: methods of analysis and physiological functions. Methods. 2014 Jan 15;65(2):207-18. DOI:10.1016/j.ymeth.2013.09.009 |
2. Caromile LA, Oganesian A, Coats SA, Seifert RA, and Bowen-Pope DF. The neurosecretory vesicle protein phogrin functions as a phosphatidylinositol phosphatase to regulate insulin secretion. J Biol Chem. 2010 Apr 2;285(14):10487-96. DOI:10.1074/jbc.M109.066563 |
3. Gingras MC, Zhang YL, Kharitidi D, Barr AJ, Knapp S, Tremblay ML, and Pause A. HD-PTP is a catalytically inactive tyrosine phosphatase due to a conserved divergence in its phosphatase domain. PLoS One. 2009;4(4):e5105. DOI:10.1371/journal.pone.0005105 |
4. Lin G, Aranda V, Muthuswamy SK, and Tonks NK. Identification of PTPN23 as a novel regulator of cell invasion in mammary epithelial cells from a loss-of-function screen of the 'PTP-ome'. Genes Dev. 2011 Jul 1;25(13):1412-25. DOI:10.1101/gad.2018911 |
5. Mariotti M, Castiglioni S, Garcia-Manteiga JM, Beguinot L, and Maier JA. HD-PTP inhibits endothelial migration through its interaction with Src. Int J Biochem Cell Biol. 2009 Mar;41(3):687-93. DOI:10.1016/j.biocel.2008.08.005 |
6. Blanchetot C, Tertoolen LG, Overvoorde J, and den Hertog J. Intra- and intermolecular interactions between intracellular domains of receptor protein-tyrosine phosphatases. J Biol Chem. 2002 Dec 6;277(49):47263-9. DOI:10.1074/jbc.M205810200 |