Protein: Phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR6 (EC 3.1.3.95) (Myotubularin-related protein 6) (Phosphatidylinositol-3-phosphate phosphatase) (Q9Y217)
Organism: Homo sapiens (Human)
Function: Phosphatase that acts on lipids with a phosphoinositol headgroup. Dephosphorylates phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol 3,5-bisphosphate (Probable). Binds with high affinity to phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) but also to phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 4-phosphate (PtdIns(4)P), and phosphatidylinositol 5-phosphate (PtdIns(5)P), phosphatidic acid and phosphatidylserine. Negatively regulates ER-Golgi protein transport (By similarity). Probably in association with MTMR9, plays a role in the late stages of macropinocytosis by dephosphorylating phosphatidylinositol 3-phosphate in membrane ruffles. Acts as a negative regulator of KCNN4/KCa3.1 channel activity in CD4(+) T-cells possibly by decreasing intracellular levels of phosphatidylinositol 3-phosphate. Negatively regulates proliferation of reactivated CD4(+) T-cells. In complex with MTMR9, negatively regulates DNA damage-induced apoptosis. The formation of the MTMR6-MTMR9 complex stabilizes both MTMR6 and MTMR9 protein levels.
Subcellular location: Cytoplasm {ECO:0000269|PubMed:19038970}. Endoplasmic reticulum-Golgi intermediate compartment {ECO:0000269|PubMed:16787938, ECO:0000269|PubMed:19038970}. Endoplasmic reticulum {ECO:0000269|PubMed:19038970}. Cell projection, ruffle membrane {ECO:0000250|UniProtKB:Q8VE11}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:19038970}. Note=Localizes to ruffles during EGF-induced macropinocytosis (By similarity). Colocalizes with MTMR9 to the perinuclear region (PubMed:19038970). Partially localizes to the endoplasmic reticulum (PubMed:19038970). Co-localizes with RAB1B to the endoplasmic reticulum-Golgi intermediate compartment and to the peri-Golgi region (By similarity). {ECO:0000250|UniProtKB:A0A0G2JXT6, ECO:0000250|UniProtKB:Q8VE11, ECO:0000269|PubMed:19038970}.
Interaction partners:
- Myotubularin-related protein 9
- 1-phosphatidylinositol 3-phosphate 5-kinase
- Polyphosphoinositide phosphatase
- Inositol polyphosphate-4-phosphatase type I A
- Inositol polyphosphate 4-phosphatase type II
- Phosphatidylinositide phosphatase SAC2
- CDP-diacylglycerol--inositol 3-phosphatidyltransferase
- Type 2 phosphatidylinositol 4,5-bisphosphate 4-phosphatase
- Type 1 phosphatidylinositol 4,5-bisphosphate 4-phosphatase
- Phosphatidylinositol 3-kinase catalytic subunit type 3
Sequence:
MEHIRTTKVEQVKLLDRFSTSNKSLTGTLYLTATHLLFIDSHQKETWILHHHIASVEKLALTTSGCPLVIQCKNFRTVHFIVPRERDCHDIYNSLLQLSKQAKYEDLYAFSYNPKQNDSERLQGWQLIDLAEEYKRMGVPNSHWQLSDANRDYKICETYPRELYVPRIASKPIIVGSSKFRSKGRFPVLSYYHQDKEAAICRCSQPLSGFSARCLEDEHLLQAISKANPVNRYMYVMDTRPKLNAMANRAAGKGYENEDNYSNIRFQFVGIENIHVMRSSLQKLLEVNGTKGLSVNDFYSGLESSGWLRHIKAVMDAAIFLAKAITVENASVLVHCSDGWDRTSQVCSLGSLLLDSYYRTIKGFMVLIEKDWISFGHKFSERCGQLDGDPKEVSPVFTQFLECVWHLTEQFPQAFEFSEAFLLQIHEHIHSCQFGNFLGNCQKEREELKLKEKTYSLWPFLLEDQKKYLNPLYSSESHRFTVLEPNTVSFNFKFWRNMYHQFDRTLHPRQSVFNIIMNMNEQNKQLEKDIKDLESKIKQRKNKQTDGILTKELLHSVHPESPNLKTSLCFKEQTLLPVNDALRTIEGSSPADNRYSEYAEEFSKSEPAVVSLEYGVARMTC