View source for Phosphatase Subfamily MTMR6

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[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_CC1|FoldCC1]]: [[Phosphatase_Superfamily_CC1|Superfamily CC1]]:  [[Phosphatase_Family_Myotubularin|Family Myotubularin]]: [[Phosphatase_Subfamily_MTMR6|Subfamily MTMR6]]

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===Evolution===
MTMR6 subfamily is found throughout holozoan. Human and most if not all vertebrates has three members per genome: MTMR6, MTMR7 and MTMR8. Other metazoan such as fruit fly and ''C elegans'' has a single member.

===Domain Structure===
MTMR6 subfamily has three domains: [http://pfam.xfam.org/family/PF02893.15 PH/GRAM], phosphatase domain and coiled-coil domain. The GRAM domain is similar to PH domain in structure and is found in membrane-associated proteins. As shown in [[Phosphatase_Subfamily_MTMR3|MTMR3 subfamily]], PH/GRAM domain can bind to phosphoinositide lipids. Coiled-coil domain has been shown to mediate the interaction with [[Phosphatase_Subfamily_MTMR9|MTMR9]] in human <cite>Mochizuki03, zou09, zou12</cite>.

===Catalytic activity and functions===
The enzymatic activity of all three human MTMR6s are up-regulated by pseudophosphatase MTMR9 through protein interactions <cite>zou09, Mochizuki03, zou12</cite>. The interaction between MTMR9 and MTMR6 subfamily is also observed in C elegans <cite>marie10</cite>.

Though all of MTMR6, MTMR7 and MTMR8 are 3-phosphatase, they have different preferences of substrates. MTMR6/R9 complex that regulates PtdIns (3, 5)P2 levels and thereby affects apoptosis; MTMR8/R9 complex down-regulates the levels of PthIns(3)P and blocks the autophagic process <cite>zou09, zou12</cite>; MTMR7/MTMR9 dephosphorylates phosphatidylinositol 3-phosphate and Ins(1,3)P2 in neuronal cells <cite>Mochizuki03</cite>.

MTMR7 has also been reported to regulate T-cell differentiation and Protein kinase B AKT signaling, possibly through regulation of phosphatidylinositol [3,4,5]-trisphosphate activity <cite>guo13</cite>.

===References===
<biblio>
#Mochizuki03 pmid=12890864
#zou09 pmid=19038970
#zou12 pmid=22647598
#marie10 pmid=21076391
</biblio>