Difference between revisions of "Pseudophosphatases (obsolete)"

Revision as of 23:19, 11 February 2016

Human pseudophosphatases

PTPs

Second phosphatase domains of 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

PTPRN subfamily

The PTPRN subfamily has two members in human, PTPRN and PTPRN2. They have single phosphatase domain rather than two phosphatase domains as the members of PTPRA, PTPRC, PTPRD, PTPRK subfamilies. Their phosphatase domains mediate the interactions between them to form homo- and hetero-dimers [3]. PTPRN2 also functions as a phosphatidylinositol phosphatase to regulate insulin secretion in mouse [4].

PTPN14 subfamily

The PTPN14 subfamily has two members in human, PTPN14 and PTPN21. Although PTPN14 and PTPN21 are supposed to lack enzymatic activity, PTPN14 has been shown to dephosphorylate p130Cas on Y128, a Src phosphorylation site [5]. It is worthy pointing out that the substitutions are found around WPD loop but not CX₅R motif.

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 [6]. However, another study found SRC, E-cadherin, and beta-catenin are direct substrates of PTPN23 [7]. But, yet another study showed that PTPN23 did not modulate the levels of Src phosphorylation both in vitro and in vivo [8].

DSPs

STYX subfamily

The STYX subfamily has a single member in human, STYX. It binds to phosphorylated tyrosine to module signaling [9]. STYX localizes to the nucleus, competes with DUSP4 for binding to ERK, and acts as a nuclear anchor that regulates ERK nuclear export [10].

STYXL1 subfamily

The STYXL1 subfamily has a single member in human, STYXL1 (MK-STYX). STYXL1 binds to phosphatase PTPMT1 and modulates its activity [11, 12]. However, it is unclear whether the interaction between STYXL1 and PTPMT1 is mediated by the inactive phosphatase domain of STYXL1.

DSP3 subfamily: DUSP27 (1 out 5 members)

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 [13, 14]. The phosphatase domains of both are predicted to be inactive due to arginine in catalytic motif Cx5R is replaced by alanine.

Tensin subfamily: TNS1 and TNS2 (2 out of 3 members)

The tensin subfamily has 3 members containing phosphatase domains, TNS1-3. TNS1 and TNS2 are predicted to be catalytically inactive, given the arginine residue is replaced by asparagine and lysine at CX₅R motif, respectively. However, TNS2 has been reported to dephosphorylate IRS-1 [15]. The phosphatase domain of TNS1 mediates its interaction with PPP1CA in focal adhesions [16]. TNS3 is predicted to be active as it has CX₅R motif.

Myotubularins

MTMR5 subfamily

The MTMR5 subfamily has two genes in human: MTMR5 (SBF1) and MTMR13 (SBF2). MTMR5 interacts with MTMR2 (see MTMR1 subfamily) via its coiled-coil domain and mutations in the coiled-coil domain of either MTMR2 or MTMR5 abrogate this interaction. Through this interaction, MTMR5 increases the enzymatic activity of MTMR2 and dictates its subcellular localization [17]. This is a good example of inactive phosphatase functions as regulator of active phosphatase. The function of MTMR13 is unclear.

MTMR9 subfamily

The MTMR9 subfamily has a single gene in human. MTMR9 binds to phosphatases of MTMR6 subfamily: MTMR6 [18], MTMR7 [19], MTMR8 [20]. The interactions increase the enzymatic activity of these phosphatases. The interaction between MTMR9 and members of MTMR6 subfamily is also observed in C. elegans [21].

MTMR10 subfamily

The MTMR10 subfamily has three genes in human: MTMR10, MTMR11 and MTMR12. The functions of MTMR10 and MTMR11 are unclear. MTMR12 binds to MTM1 [22].

Other families

TIM50 subfamily of HAD family

The TIM50 subfamily has single member in human, TIMM50. It lacks the residues critical to its activity from yeast to human. However, TIMM50 has been show to possess a phosphatase activity toward both phospho-serine/threonine and phospho-tyrosine in vitro assay [23].

PPIP5K subfamily of HP2 family

The PPIP5K subfamily has two members in human, PPIP5K1 and PPIP5K2. Their phosphatase domains bind to polyphosphoinositide[24]).

TAB1 subfamily of PPM family

The TAB1 subfamily has single member in human, TAB1. The phosphatase domain binds to X-linked inhib- itor of apoptosis (XIAP) [25].

References

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7. Error fetching PMID 21724833: [Lin11]
8. Error fetching PMID 18762272: [Mariotti09]
9. Error fetching PMID 9757831: [Wishart98]
10. Error fetching PMID 23847209: [Reiterer13]
11. Error fetching PMID 21262771: [Niemi11]
12. Error fetching PMID 24709986: [Niemi14]
13. Error fetching PMID 16895969: [Lee]
14. Error fetching PMID 23823232: [Kalli]
15. Error fetching PMID 23401856: [Koh13]
16. Error fetching PMID 17435217: [Eto07]
17. Error fetching PMID 12668758: [Kim03]
18. Error fetching PMID 19038970: [zou09]
19. Error fetching PMID 12890864: [Mochizuki03]
20. Error fetching PMID 22647598: [zou12]
21. Error fetching PMID 21076391: [marie10]
22. Error fetching PMID 12847286: [Nandurkar03]
23. Error fetching PMID 15044455: [Guo04]
24. Error fetching PMID 21222653: [Gokhale11]
25. Error fetching PMID 17560374: [Lu07]
26. Error fetching PMID 24064037: [Kharitidi13]