Phosphatase Subfamily MTMR3

Phosphatase Classification: Fold CC1: Superfamily CC1: Family Myotubularin: Subfamily MTMR3

MTMR3 is an inositol lipid 3-phosphatase. It is probably a protein phosphatase of receptor-regulated SMAD.

Evolution

MTMR3 is a metazoan phosphatase, with two human members (MTMR3 and MTMR4) and single copies in Drosophila and C. elegans.

Domain Structure

MTMR3 subfamily has a conserved domain combination: a divergent PH/GRAM domain, an active phosphatase domain and an atypical FYVE domain. It has been shown that the FYVE domain of MTMR3 is atypical in that it neither confers endosomal localisation nor binds to the lipid PtdIns3P. Furthermore it is not required for in vitro enzyme activity of MTMR3. In contrast, the PH/GRAM domain is able to bind to phosphoinositide lipids [1].

Catalytic activity and functions

Mammal MTMR3

Human MTMR3 is an inositol lipid 3-phosphatase, with a so-far-unique substrate specificity. It is able to hydrolyze PtdIns3P and PtdIns(3,5)P2, both in vitro and when heterologously expressed in S. cerevisiae. Thus, MTMR3 plays critical role in the cellular production of PtdIns5P [2].

MTMR3 risk polymorphism (rs713875), associated with Inflammatory bowel disease (IBD), increases MTMR3 expression, enhances innate receptor-induced signaling and cytokines by decreasing autophagy and increasing caspase-1 activation [3].

Mammal MTMR4

Human MTMR4 is also an inositol lipid 3-phosphatase, with amino acid sequence identity about ~47% [4]. More recently, human MTMR4 has been reported to dephosphorylate receptor-regulated SMAD proteins [5, 6]. Ectopic expression of human MTMR4 or Drosophila CG3632, the single member of MTMR3 subfamily in fruit fly, genetically interacted with Bone morphogenetic proteins (BMP) signaling axis in regulation of the vein development of Drosophila wings [6].

Related Kinases

See PI3K.

References

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