Difference between revisions of "Pseudophosphatases (obsolete)"

Revision as of 05:27, 2 October 2015

Human pseudophosphatases

PTPs

Second phosphatase domain (D2) 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, therefore regulating receptor PTP stability, specificity, and dimerization [1, 2]. Because the first phosphatase domains are active, these receptor PTPs are active at protein level. These phosphatases include:

• Subfamily PTPRA: PTPRA and PTPRE
• Subfamily PTPRC: PTPRC
• Subfamily PTPRD: PTPRD, PTPRF and PTPRS
• Subfamily PTPRG: PTPRG and PTPRZ1
• Subfamily PTPRK: PTPRK, PTPRM, PTPRT and PTPRU

PTPN23 subfamily

The PTPN23 subfamily has a single member in human, PTPN23 (HD-PTP). Its catalytic activity is plausible. It has been 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].

DSPs

STYX subfamily

The STYX subfamily has a single member in human, STYX. It binds to phosphorylated tyrosine to module signaling [6]. STYX localizes to the nucleus, competes with DUSP4 for binding to ERK, and acts as a nuclear anchor that regulates ERK nuclear export [7].

STYXL1 subfamily

The STYXL1 subfamily has a single member in human, STYXL1 (MK-STYX). STYXL1 binds to phosphatase PTPMT1 and modulates its activity [8, 9]. However, it is unclear whether the interaction between STYXL1 and PTPMT1 is mediated by the inactive phosphatase domain of STYXL1.

One of the five of DSP3 subfamily: DUSP27

The function of DUSP27 is unknown, so is its catalytically inactive phosphatase domain.

PTEN-like phosphatases

Auxilin subfamily

There are two members of auxilin subfamily in human, GAK and DNAJC6. Both GAK and DNAJC6 phosphatase domains have been shown to bind to phospholipids [10, 11]. The phosphatase domains of both are predicted to be inactive due to arginine in catalytic motif Cx5R is replaced by alanine.

Tension subfamily

Myotubularins

MTMR5 subfamily

MTMR10 subfamily

References

1. 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 | PubMed ID:12376545 | HubMed [denHertog02]
2. Barr AJ, Ugochukwu E, Lee WH, King ON, Filippakopoulos P, Alfano I, Savitsky P, Burgess-Brown NA, Müller S, and Knapp S. Large-scale structural analysis of the classical human protein tyrosine phosphatome. Cell. 2009 Jan 23;136(2):352-63. DOI:10.1016/j.cell.2008.11.038 | PubMed ID:19167335 | HubMed [Barr09]
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 | PubMed ID:19340315 | HubMed [Gingras09]
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 | PubMed ID:21724833 | HubMed [Lin11]
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 | PubMed ID:18762272 | HubMed [Mariotti09]
6. Wishart MJ and Dixon JE. Gathering STYX: phosphatase-like form predicts functions for unique protein-interaction domains. Trends Biochem Sci. 1998 Aug;23(8):301-6. DOI:10.1016/s0968-0004(98)01241-9 | PubMed ID:9757831 | HubMed [Wishart98]
7. Reiterer V, Fey D, Kolch W, Kholodenko BN, and Farhan H. Pseudophosphatase STYX modulates cell-fate decisions and cell migration by spatiotemporal regulation of ERK1/2. Proc Natl Acad Sci U S A. 2013 Jul 30;110(31):E2934-43. DOI:10.1073/pnas.1301985110 | PubMed ID:23847209 | HubMed [Reiterer13]
8. Niemi NM, Lanning NJ, Klomp JA, Tait SW, Xu Y, Dykema KJ, Murphy LO, Gaither LA, Xu HE, Furge KA, Green DR, and MacKeigan JP. MK-STYX, a catalytically inactive phosphatase regulating mitochondrially dependent apoptosis. Mol Cell Biol. 2011 Apr;31(7):1357-68. DOI:10.1128/MCB.00788-10 | PubMed ID:21262771 | HubMed [Niemi11]
9. Niemi NM, Sacoman JL, Westrate LM, Gaither LA, Lanning NJ, Martin KR, and MacKeigan JP. The pseudophosphatase MK-STYX physically and genetically interacts with the mitochondrial phosphatase PTPMT1. PLoS One. 2014;9(4):e93896. DOI:10.1371/journal.pone.0093896 | PubMed ID:24709986 | HubMed [Niemi14]
10. Lee DW, Wu X, Eisenberg E, and Greene LE. Recruitment dynamics of GAK and auxilin to clathrin-coated pits during endocytosis. J Cell Sci. 2006 Sep 1;119(Pt 17):3502-12. DOI:10.1242/jcs.03092 | PubMed ID:16895969 | HubMed [Lee]
11. Kalli AC, Morgan G, and Sansom MS. Interactions of the auxilin-1 PTEN-like domain with model membranes result in nanoclustering of phosphatidyl inositol phosphates. Biophys J. 2013 Jul 2;105(1):137-45. DOI:10.1016/j.bpj.2013.05.012 | PubMed ID:23823232 | HubMed [Kalli]
12. 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 | PubMed ID:20097759 | HubMed [Caromile10]
13. 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 | PubMed ID:24064037 | HubMed [Kharitidi13]