Phosphatase Subfamily MTMR14

Phosphatase Classification: FoldCC1: Superfamily CC1: Family Myotubularin: Subfamily MTMR14

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Evolution

MTMR14 is found in most metazoan except nematodes. It is also found in choanoflagellates and cellular slime molds, but is absent from almost all the fungi.

Domain Structure

MTMR14 in eumetazoan has a conserved domain combination: a PH/GRAM domain and an active phosphatase domain. It may have a coiled-coil domain, but it is much weaker compared with other myotubularins using coiled-coil detection programs COILS and PAIRCOIL2.

Sponge MTMR14 has an additional protein kinase domain (see database); Choanoflagellate Monosiga has a predicted transmembrane region (see database).

Catalytic activity and functions

MTMR14 may dephosphorylate PtdIns(3,5)P2 and PtdIns (3,4)P2.

It is highly expressed in skeleton muscle and exogenous GFP-MTMR14 localizes to the Golgi apparatus in vitro [1]. Mice deficient in MTMR14 show muscle weakness and fatigue. The mechanism model behind is deficiency in MTMR14 causes accumulation of its substrates, especially PtdIns(3,5)P2 and PtdIns (3,4)P2, which bind, and directly activate, the Ca2+ release channel (ryanodine receptor 1, RyR1) of the internal store - the sarcoplasmic reticulum, and the activation of RyR1 results in the spontaneous Ca2+ leakage from the sarcoplasmic reticulum [2].

MTMR14 has also been shown to be involved in the regulation of autophagy [3, 4].