View source for Pseudophosphatases (obsolete)


== 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 <cite>denHertog02, Barr09</cite>. Because the first phosphatase domains are active, these receptor PTPs are active at protein level. These phosphatases include: 
* [[Phosphatase_Subfamily_PTPRA|Subfamily PTPRA]]: PTPRA and PTPRE
* [[Phosphatase_Subfamily_PTPRC|Subfamily PTPRC]]: PTPRC
* [[Phosphatase_Subfamily_PTPRG|Subfamily PTPRD]]: PTPRD, PTPRF and PTPRS
* [[Phosphatase_Subfamily_PTPRG|Subfamily PTPRG]]: PTPRG and PTPRZ1
* [[Phosphatase_Subfamily_PTPRG|Subfamily PTPRK]]: PTPRK, PTPRM, PTPRT and PTPRU

==== PTPRN subfamily ====


==== PTPN14 subfamily ====
The [[Phosphatase_Subfamily_PTPN14|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 <cite>Zhang13</cite>. It is worthy pointing out that the substitutions are found around WPD loop but not CX<sub>5</sub>R motif.

==== PTPN23 subfamily ====
The [[Phosphatase_Subfamily_PTPN23|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 <cite>Gingras09</cite>. However, another study found SRC, E-cadherin, and beta-catenin are direct substrates of PTPN23 <cite>Lin11</cite>. But, yet another study showed that PTPN23 did not modulate the levels of Src phosphorylation both in vitro and in vivo <cite>Mariotti09</cite>.

=== DSPs ===
==== STYX subfamily ====
The [[Phosphatase_Subfamily_STYX|STYX subfamily]] has a single member in human, STYX. It binds to phosphorylated tyrosine to module signaling <cite>Wishart98</cite>. STYX localizes to the nucleus, competes with DUSP4 for binding to ERK, and acts as a nuclear anchor that regulates ERK nuclear export <cite>Reiterer13</cite>.

==== STYXL1 subfamily ====
The [[Phosphatase_Subfamily_STYXL1|STYXL1 subfamily]] has a single member in human, STYXL1 (MK-STYX). STYXL1 binds to phosphatase PTPMT1 and modulates its activity <cite> Niemi11, Niemi14</cite>. 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 [[Phosphatase_Subfamily_DSP3#DUSP27|DUSP27]] is unknown, so is its catalytically inactive phosphatase domain.

=== PTEN-like phosphatases ===
==== Auxilin subfamily ====
There are two members of [[Phosphatase_Subfamily_Auxilin|auxilin subfamily]] in human, GAK and DNAJC6. Both GAK and DNAJC6 phosphatase domains have been shown to bind to phospholipids <cite>Lee, Kalli</cite>. 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 [[Phosphatase_Subfamily_Tensin|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 CX<sub>5</sub>R motif, respectively. However, TNS2 has been reported to dephosphorylate IRS-1 <cite> Koh13 </cite>. The phosphatase domain of TNS1 mediates its interaction with PPP1CA in focal adhesions <cite>Eto07</cite>. TNS3 is predicted to be active as it has CX<sub>5</sub>R motif.

=== Myotubularins ===
==== MTMR5 subfamily ====
The [[Phosphatase_Subfamily_MTMR5|MTMR5 subfamily]] has two genes in human: MTMR5 (SBF1) and MTMR13 (SBF2). MTMR5 interacts with MTMR2 (see [[Phosphatase_Subfamily_MTMR1|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 <cite>Kim03</cite>. This is a good example of inactive phosphatase functions as regulator of active phosphatase. The function of MTMR13 is unclear.

==== MTMR9 subfamily ====
The [[Phosphatase_Subfamily_MTMR9|MTMR9 subfamily]] has a single gene in human. MTMR9 binds to phosphatases of MTMR6 subfamily: MTMR6 <cite>zou09</cite>, MTMR7 <cite>Mochizuki03</cite>, MTMR8 <cite>zou12</cite>. The interactions increase the enzymatic activity of these phosphatases. The interaction between MTMR9 and members of MTMR6 subfamily is also observed in ''C. elegans'' <cite>marie10</cite>.

==== MTMR10 subfamily ====
The [[Phosphatase_Subfamily_MTMR10|MTMR10 subfamily]] has three genes in human: MTMR10, MTMR11 and MTMR12. The functions of MTMR10 and MTMR11 are unclear. MTMR12 binds to MTM1 <cite> Nandurkar03</cite>.

=== Other families ===
==== TIM50 subfamily of HAD family ====

==== PPIP5K subfamily of HP2 family ====

==== TAB1 subfamily of PPM family ====

== References ==
<biblio>
#Barr09 pmid=19167335
#Caromile10 pmid=20097759
#denHertog02 pmid=12376545
#Eto07 pmid=17435217
#Gingras09 pmid=19340315
#Kalli pmid=23823232
#Kharitidi13 pmid=24064037
#Kim03 pmid=12668758
#Koh13 pmid=23401856
#Lee pmid=16895969
#Lin11 pmid=21724833
#marie10 pmid=21076391
#Mariotti09 pmid=18762272
#Mochizuki03 pmid=12890864
#Nandurkar03 pmid=12847286
#Niemi11 pmid=21262771
#Niemi14 pmid=24709986
#Reiterer13 pmid=23847209
#Wishart98 pmid=9757831
#Zhang13 pmid=22710723
#zou09 pmid=19038970
#zou12 pmid=22647598
</biblio>