MTMR9 (myotubularin-related protein 9) is a catalytically inactive member of the myotubularin family of phosphoinositide 3-phosphatases. It has an N-terminal PH-GRAM domain, a myotubularin phosphatase-like domain in which the catalytic cysteine and arginine of the CX5R motif are replaced, and a C-terminal coiled coil that mediates dimerization. It acts as a regulatory subunit for the active myotubularins MTMR6, MTMR7 and MTMR8, forming heterodimers that stabilize the active partner, increase its catalytic rate and set its substrate preference: the MTMR6-MTMR9 dimer favours phosphatidylinositol 3,5-bisphosphate, producing PI5P, whereas MTMR8-MTMR9 favours phosphatidylinositol 3-phosphate. MTMR9 is a soluble cytoplasmic protein that associates with intracellular membranes, perinuclear regions, and membrane ruffles during macropinocytosis. Through these partner phosphatases it influences autophagy, resistance to DNA damage-induced apoptosis and macropinocytosis in cultured cells.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:12890864 Characterization of myotubularin-related protein 7 and its b... | REMOVE | Summary: Generic protein binding from the mouse MTMR7/MTMR9 characterisation study; the GOA partner identifier resolves to bovine LONP1. Reason: Bare protein binding is uninformative, and removal does not mean the interaction is false. PMID:12890864 identified MTMR9 as the MTMR7-binding protein, a phosphatase-binding claim already captured by the MTMR7 rows modified to GO:0019902. The partner accession recorded in GOA (UniProtKB:Q59HJ6) currently resolves to bovine LONP1 (Lon protease), which the cached abstract does not mention; this looks like a stale or remapped accession, but the full text was not read, so no stronger claim is made. Supporting Evidence: PMID:12890864 The coiled-coil domain of MTMR9 was sufficient for binding to MTMR7 |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | MODIFY | Summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR8 (UniProtKB:Q96EF0) reported in PMID:16189514. Reason: Bare protein binding is uninformative. The partner MTMR8 is a catalytically active myotubularin phosphoinositide 3-phosphatase, and targeted studies show that MTMR9 heterodimerizes with MTMR8 and raises its catalytic output, so the interaction is better captured as phosphatase binding (GO:0019902). The regulatory consequence is captured separately by phosphatase activator activity (GO:0019211). The proteome-scale screen that GOA cites is an independent detection of the same pair; the replacement term is supported by the focused studies quoted here. Proposed replacements: phosphatase binding Supporting Evidence: PMID:16787938 identified novel heteromeric interactions: MTMR8 with MTMR9 PMID:22647598 MTMR8, all of which dimerize with the catalytically inactive MTMR9 |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | REMOVE | Summary: Generic protein binding with EMILIN1 (UniProtKB:Q9Y6C2) from a high-throughput interaction screen (PMID:16189514). Reason: Bare protein binding is uninformative and removal does not mean the interaction is false. The EMILIN1 interaction comes from a proteome-scale binary or affinity screen; no follow-up study connects it to MTMR9's established role as a noncatalytic regulator of MTMR6/MTMR7/MTMR8 phosphoinositide phosphatases, so there is no informative molecular-function term to substitute. |
| GO:0005515 protein binding | IPI PMID:19447967 Shifted Transversal Design smart-pooling for high coverage i... | REMOVE | Summary: Generic protein binding with EMILIN1 (UniProtKB:Q9Y6C2) from a high-throughput interaction screen (PMID:19447967). Reason: Bare protein binding is uninformative and removal does not mean the interaction is false. The EMILIN1 interaction comes from a proteome-scale binary or affinity screen; no follow-up study connects it to MTMR9's established role as a noncatalytic regulator of MTMR6/MTMR7/MTMR8 phosphoinositide phosphatases, so there is no informative molecular-function term to substitute. |
| GO:0005515 protein binding | IPI PMID:21516116 Next-generation sequencing to generate interactome datasets. | MODIFY | Summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR6 (UniProtKB:Q9Y217) reported in PMID:21516116. Reason: Bare protein binding is uninformative. The partner MTMR6 is a catalytically active myotubularin phosphoinositide 3-phosphatase, and targeted studies show that MTMR9 heterodimerizes with MTMR6 and raises its catalytic output, so the interaction is better captured as phosphatase binding (GO:0019902). The regulatory consequence is captured separately by phosphatase activator activity (GO:0019211). The proteome-scale screen that GOA cites is an independent detection of the same pair; the replacement term is supported by the focused studies quoted here. Proposed replacements: phosphatase binding Supporting Evidence: PMID:19038970 human MTMR6 forms a heteromer with an enzymatically inactive member myotubularin-related protein 9 (MTMR9), both in vitro and in cells PMID:19038970 MTMR9 increased the 3-phosphatase activity of MTMR6 up to 6-fold |
| GO:0005515 protein binding | IPI PMID:21516116 Next-generation sequencing to generate interactome datasets. | REMOVE | Summary: Generic protein binding with EMILIN1 (UniProtKB:Q9Y6C2) from a high-throughput interaction screen (PMID:21516116). Reason: Bare protein binding is uninformative and removal does not mean the interaction is false. The EMILIN1 interaction comes from a proteome-scale binary or affinity screen; no follow-up study connects it to MTMR9's established role as a noncatalytic regulator of MTMR6/MTMR7/MTMR8 phosphoinositide phosphatases, so there is no informative molecular-function term to substitute. |
| GO:0005515 protein binding | IPI PMID:22647598 Myotubularin-related protein (MTMR) 9 determines the enzymat... | MODIFY | Summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR8 (UniProtKB:Q96EF0-1) reported in PMID:22647598. Reason: Bare protein binding is uninformative. The partner MTMR8 is a catalytically active myotubularin phosphoinositide 3-phosphatase, and targeted studies show that MTMR9 heterodimerizes with MTMR8 and raises its catalytic output, so the interaction is better captured as phosphatase binding (GO:0019902). The regulatory consequence is captured separately by phosphatase activator activity (GO:0019211). The proteome-scale screen that GOA cites is an independent detection of the same pair; the replacement term is supported by the focused studies quoted here. Proposed replacements: phosphatase binding Supporting Evidence: PMID:16787938 identified novel heteromeric interactions: MTMR8 with MTMR9 PMID:22647598 MTMR8, all of which dimerize with the catalytically inactive MTMR9 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding with MOS (UniProtKB:P00540) from a high-throughput interaction screen (PMID:25416956). Reason: Bare protein binding is uninformative and removal does not mean the interaction is false. The MOS interaction comes from a proteome-scale binary or affinity screen; no follow-up study connects it to MTMR9's established role as a noncatalytic regulator of MTMR6/MTMR7/MTMR8 phosphoinositide phosphatases, so there is no informative molecular-function term to substitute. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding with VAC14 (UniProtKB:Q08AM6) from a high-throughput interaction screen (PMID:25416956). Reason: Bare protein binding is uninformative and removal does not mean the interaction is false. The VAC14 interaction comes from a proteome-scale binary or affinity screen; no follow-up study connects it to MTMR9's established role as a noncatalytic regulator of MTMR6/MTMR7/MTMR8 phosphoinositide phosphatases, so there is no informative molecular-function term to substitute. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding with NMI (UniProtKB:Q13287) from a high-throughput interaction screen (PMID:25416956). Reason: Bare protein binding is uninformative and removal does not mean the interaction is false. The NMI interaction comes from a proteome-scale binary or affinity screen; no follow-up study connects it to MTMR9's established role as a noncatalytic regulator of MTMR6/MTMR7/MTMR8 phosphoinositide phosphatases, so there is no informative molecular-function term to substitute. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding with LNX1 (UniProtKB:Q8TBB1) from a high-throughput interaction screen (PMID:25416956). Reason: Bare protein binding is uninformative and removal does not mean the interaction is false. The LNX1 interaction comes from a proteome-scale binary or affinity screen; no follow-up study connects it to MTMR9's established role as a noncatalytic regulator of MTMR6/MTMR7/MTMR8 phosphoinositide phosphatases, so there is no informative molecular-function term to substitute. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR7 (UniProtKB:Q9Y216) reported in PMID:25416956. Reason: Bare protein binding is uninformative. The partner MTMR7 is a catalytically active myotubularin phosphoinositide 3-phosphatase, and targeted studies show that MTMR9 heterodimerizes with MTMR7 and raises its catalytic output, so the interaction is better captured as phosphatase binding (GO:0019902). The regulatory consequence is captured separately by phosphatase activator activity (GO:0019211). The proteome-scale screen that GOA cites is an independent detection of the same pair; the replacement term is supported by the focused studies quoted here. Proposed replacements: phosphatase binding Supporting Evidence: PMID:12890864 The coiled-coil domain of MTMR9 was sufficient for binding to MTMR7 PMID:12890864 The binding of MTMR9 increased the Ins(1,3)P2 phosphatase activity of MTMR7 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR6 (UniProtKB:Q9Y217) reported in PMID:25416956. Reason: Bare protein binding is uninformative. The partner MTMR6 is a catalytically active myotubularin phosphoinositide 3-phosphatase, and targeted studies show that MTMR9 heterodimerizes with MTMR6 and raises its catalytic output, so the interaction is better captured as phosphatase binding (GO:0019902). The regulatory consequence is captured separately by phosphatase activator activity (GO:0019211). The proteome-scale screen that GOA cites is an independent detection of the same pair; the replacement term is supported by the focused studies quoted here. Proposed replacements: phosphatase binding Supporting Evidence: PMID:19038970 human MTMR6 forms a heteromer with an enzymatically inactive member myotubularin-related protein 9 (MTMR9), both in vitro and in cells PMID:19038970 MTMR9 increased the 3-phosphatase activity of MTMR6 up to 6-fold |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Generic protein binding with EMILIN1 (UniProtKB:Q9Y6C2) from a high-throughput interaction screen (PMID:25416956). Reason: Bare protein binding is uninformative and removal does not mean the interaction is false. The EMILIN1 interaction comes from a proteome-scale binary or affinity screen; no follow-up study connects it to MTMR9's established role as a noncatalytic regulator of MTMR6/MTMR7/MTMR8 phosphoinositide phosphatases, so there is no informative molecular-function term to substitute. |
| GO:0005515 protein binding | IPI PMID:27880917 Phenotypic and Interaction Profiling of the Human Phosphatas... | MODIFY | Summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR8 (UniProtKB:Q96EF0) reported in PMID:27880917. Reason: Bare protein binding is uninformative. The partner MTMR8 is a catalytically active myotubularin phosphoinositide 3-phosphatase, and targeted studies show that MTMR9 heterodimerizes with MTMR8 and raises its catalytic output, so the interaction is better captured as phosphatase binding (GO:0019902). The regulatory consequence is captured separately by phosphatase activator activity (GO:0019211). The proteome-scale screen that GOA cites is an independent detection of the same pair; the replacement term is supported by the focused studies quoted here. Proposed replacements: phosphatase binding Supporting Evidence: PMID:16787938 identified novel heteromeric interactions: MTMR8 with MTMR9 PMID:22647598 MTMR8, all of which dimerize with the catalytically inactive MTMR9 |
| GO:0005515 protein binding | IPI PMID:27880917 Phenotypic and Interaction Profiling of the Human Phosphatas... | MODIFY | Summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR7 (UniProtKB:Q9Y216) reported in PMID:27880917. Reason: Bare protein binding is uninformative. The partner MTMR7 is a catalytically active myotubularin phosphoinositide 3-phosphatase, and targeted studies show that MTMR9 heterodimerizes with MTMR7 and raises its catalytic output, so the interaction is better captured as phosphatase binding (GO:0019902). The regulatory consequence is captured separately by phosphatase activator activity (GO:0019211). The proteome-scale screen that GOA cites is an independent detection of the same pair; the replacement term is supported by the focused studies quoted here. Proposed replacements: phosphatase binding Supporting Evidence: PMID:12890864 The coiled-coil domain of MTMR9 was sufficient for binding to MTMR7 PMID:12890864 The binding of MTMR9 increased the Ins(1,3)P2 phosphatase activity of MTMR7 |
| GO:0005515 protein binding | IPI PMID:27880917 Phenotypic and Interaction Profiling of the Human Phosphatas... | MODIFY | Summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR6 (UniProtKB:Q9Y217) reported in PMID:27880917. Reason: Bare protein binding is uninformative. The partner MTMR6 is a catalytically active myotubularin phosphoinositide 3-phosphatase, and targeted studies show that MTMR9 heterodimerizes with MTMR6 and raises its catalytic output, so the interaction is better captured as phosphatase binding (GO:0019902). The regulatory consequence is captured separately by phosphatase activator activity (GO:0019211). The proteome-scale screen that GOA cites is an independent detection of the same pair; the replacement term is supported by the focused studies quoted here. Proposed replacements: phosphatase binding Supporting Evidence: PMID:19038970 human MTMR6 forms a heteromer with an enzymatically inactive member myotubularin-related protein 9 (MTMR9), both in vitro and in cells PMID:19038970 MTMR9 increased the 3-phosphatase activity of MTMR6 up to 6-fold |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR8 (UniProtKB:Q96EF0) reported in PMID:28514442. Reason: Bare protein binding is uninformative. The partner MTMR8 is a catalytically active myotubularin phosphoinositide 3-phosphatase, and targeted studies show that MTMR9 heterodimerizes with MTMR8 and raises its catalytic output, so the interaction is better captured as phosphatase binding (GO:0019902). The regulatory consequence is captured separately by phosphatase activator activity (GO:0019211). The proteome-scale screen that GOA cites is an independent detection of the same pair; the replacement term is supported by the focused studies quoted here. Proposed replacements: phosphatase binding Supporting Evidence: PMID:16787938 identified novel heteromeric interactions: MTMR8 with MTMR9 PMID:22647598 MTMR8, all of which dimerize with the catalytically inactive MTMR9 |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR7 (UniProtKB:Q9Y216) reported in PMID:28514442. Reason: Bare protein binding is uninformative. The partner MTMR7 is a catalytically active myotubularin phosphoinositide 3-phosphatase, and targeted studies show that MTMR9 heterodimerizes with MTMR7 and raises its catalytic output, so the interaction is better captured as phosphatase binding (GO:0019902). The regulatory consequence is captured separately by phosphatase activator activity (GO:0019211). The proteome-scale screen that GOA cites is an independent detection of the same pair; the replacement term is supported by the focused studies quoted here. Proposed replacements: phosphatase binding Supporting Evidence: PMID:12890864 The coiled-coil domain of MTMR9 was sufficient for binding to MTMR7 PMID:12890864 The binding of MTMR9 increased the Ins(1,3)P2 phosphatase activity of MTMR7 |
| GO:0005515 protein binding | IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m... | REMOVE | Summary: Generic protein binding with MOS (UniProtKB:P00540) from a high-throughput interaction screen (PMID:29892012). Reason: Bare protein binding is uninformative and removal does not mean the interaction is false. The MOS interaction comes from a proteome-scale binary or affinity screen; no follow-up study connects it to MTMR9's established role as a noncatalytic regulator of MTMR6/MTMR7/MTMR8 phosphoinositide phosphatases, so there is no informative molecular-function term to substitute. |
| GO:0005515 protein binding | IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m... | REMOVE | Summary: Generic protein binding with LNX1 (UniProtKB:Q8TBB1) from a high-throughput interaction screen (PMID:29892012). Reason: Bare protein binding is uninformative and removal does not mean the interaction is false. The LNX1 interaction comes from a proteome-scale binary or affinity screen; no follow-up study connects it to MTMR9's established role as a noncatalytic regulator of MTMR6/MTMR7/MTMR8 phosphoinositide phosphatases, so there is no informative molecular-function term to substitute. |
| GO:0005515 protein binding | IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m... | MODIFY | Summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR8 (UniProtKB:Q96EF0) reported in PMID:29892012. Reason: Bare protein binding is uninformative. The partner MTMR8 is a catalytically active myotubularin phosphoinositide 3-phosphatase, and targeted studies show that MTMR9 heterodimerizes with MTMR8 and raises its catalytic output, so the interaction is better captured as phosphatase binding (GO:0019902). The regulatory consequence is captured separately by phosphatase activator activity (GO:0019211). The proteome-scale screen that GOA cites is an independent detection of the same pair; the replacement term is supported by the focused studies quoted here. Proposed replacements: phosphatase binding Supporting Evidence: PMID:16787938 identified novel heteromeric interactions: MTMR8 with MTMR9 PMID:22647598 MTMR8, all of which dimerize with the catalytically inactive MTMR9 |
| GO:0005515 protein binding | IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m... | MODIFY | Summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR7 (UniProtKB:Q9Y216) reported in PMID:29892012. Reason: Bare protein binding is uninformative. The partner MTMR7 is a catalytically active myotubularin phosphoinositide 3-phosphatase, and targeted studies show that MTMR9 heterodimerizes with MTMR7 and raises its catalytic output, so the interaction is better captured as phosphatase binding (GO:0019902). The regulatory consequence is captured separately by phosphatase activator activity (GO:0019211). The proteome-scale screen that GOA cites is an independent detection of the same pair; the replacement term is supported by the focused studies quoted here. Proposed replacements: phosphatase binding Supporting Evidence: PMID:12890864 The coiled-coil domain of MTMR9 was sufficient for binding to MTMR7 PMID:12890864 The binding of MTMR9 increased the Ins(1,3)P2 phosphatase activity of MTMR7 |
| GO:0005515 protein binding | IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m... | REMOVE | Summary: Generic protein binding with EMILIN1 (UniProtKB:Q9Y6C2) from a high-throughput interaction screen (PMID:29892012). Reason: Bare protein binding is uninformative and removal does not mean the interaction is false. The EMILIN1 interaction comes from a proteome-scale binary or affinity screen; no follow-up study connects it to MTMR9's established role as a noncatalytic regulator of MTMR6/MTMR7/MTMR8 phosphoinositide phosphatases, so there is no informative molecular-function term to substitute. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Generic protein binding with MOS (UniProtKB:P00540) from a high-throughput interaction screen (PMID:31515488). Reason: Bare protein binding is uninformative and removal does not mean the interaction is false. The MOS interaction comes from a proteome-scale binary or affinity screen; no follow-up study connects it to MTMR9's established role as a noncatalytic regulator of MTMR6/MTMR7/MTMR8 phosphoinositide phosphatases, so there is no informative molecular-function term to substitute. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Generic protein binding with LNX1 (UniProtKB:Q8TBB1) from a high-throughput interaction screen (PMID:31515488). Reason: Bare protein binding is uninformative and removal does not mean the interaction is false. The LNX1 interaction comes from a proteome-scale binary or affinity screen; no follow-up study connects it to MTMR9's established role as a noncatalytic regulator of MTMR6/MTMR7/MTMR8 phosphoinositide phosphatases, so there is no informative molecular-function term to substitute. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MODIFY | Summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR8 (UniProtKB:Q96EF0) reported in PMID:31515488. Reason: Bare protein binding is uninformative. The partner MTMR8 is a catalytically active myotubularin phosphoinositide 3-phosphatase, and targeted studies show that MTMR9 heterodimerizes with MTMR8 and raises its catalytic output, so the interaction is better captured as phosphatase binding (GO:0019902). The regulatory consequence is captured separately by phosphatase activator activity (GO:0019211). The proteome-scale screen that GOA cites is an independent detection of the same pair; the replacement term is supported by the focused studies quoted here. Proposed replacements: phosphatase binding Supporting Evidence: PMID:16787938 identified novel heteromeric interactions: MTMR8 with MTMR9 PMID:22647598 MTMR8, all of which dimerize with the catalytically inactive MTMR9 |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MODIFY | Summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR7 (UniProtKB:Q9Y216) reported in PMID:31515488. Reason: Bare protein binding is uninformative. The partner MTMR7 is a catalytically active myotubularin phosphoinositide 3-phosphatase, and targeted studies show that MTMR9 heterodimerizes with MTMR7 and raises its catalytic output, so the interaction is better captured as phosphatase binding (GO:0019902). The regulatory consequence is captured separately by phosphatase activator activity (GO:0019211). The proteome-scale screen that GOA cites is an independent detection of the same pair; the replacement term is supported by the focused studies quoted here. Proposed replacements: phosphatase binding Supporting Evidence: PMID:12890864 The coiled-coil domain of MTMR9 was sufficient for binding to MTMR7 PMID:12890864 The binding of MTMR9 increased the Ins(1,3)P2 phosphatase activity of MTMR7 |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Generic protein binding with EMILIN1 (UniProtKB:Q9Y6C2) from a high-throughput interaction screen (PMID:31515488). Reason: Bare protein binding is uninformative and removal does not mean the interaction is false. The EMILIN1 interaction comes from a proteome-scale binary or affinity screen; no follow-up study connects it to MTMR9's established role as a noncatalytic regulator of MTMR6/MTMR7/MTMR8 phosphoinositide phosphatases, so there is no informative molecular-function term to substitute. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding with MEI4 (UniProtKB:A8MW99) from a high-throughput interaction screen (PMID:32296183). Reason: Bare protein binding is uninformative and removal does not mean the interaction is false. The MEI4 interaction comes from a proteome-scale binary or affinity screen; no follow-up study connects it to MTMR9's established role as a noncatalytic regulator of MTMR6/MTMR7/MTMR8 phosphoinositide phosphatases, so there is no informative molecular-function term to substitute. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding with DEPDC5 (UniProtKB:O75140-2) from a high-throughput interaction screen (PMID:32296183). Reason: Bare protein binding is uninformative and removal does not mean the interaction is false. The DEPDC5 interaction comes from a proteome-scale binary or affinity screen; no follow-up study connects it to MTMR9's established role as a noncatalytic regulator of MTMR6/MTMR7/MTMR8 phosphoinositide phosphatases, so there is no informative molecular-function term to substitute. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding with PTPN3 (UniProtKB:P26045) from a high-throughput interaction screen (PMID:32296183). Reason: Bare protein binding is uninformative and removal does not mean the interaction is false. The PTPN3 interaction comes from a proteome-scale binary or affinity screen; no follow-up study connects it to MTMR9's established role as a noncatalytic regulator of MTMR6/MTMR7/MTMR8 phosphoinositide phosphatases, so there is no informative molecular-function term to substitute. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding with INCA1 (UniProtKB:Q0VD86) from a high-throughput interaction screen (PMID:32296183). Reason: Bare protein binding is uninformative and removal does not mean the interaction is false. The INCA1 interaction comes from a proteome-scale binary or affinity screen; no follow-up study connects it to MTMR9's established role as a noncatalytic regulator of MTMR6/MTMR7/MTMR8 phosphoinositide phosphatases, so there is no informative molecular-function term to substitute. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding with NMI (UniProtKB:Q13287) from a high-throughput interaction screen (PMID:32296183). Reason: Bare protein binding is uninformative and removal does not mean the interaction is false. The NMI interaction comes from a proteome-scale binary or affinity screen; no follow-up study connects it to MTMR9's established role as a noncatalytic regulator of MTMR6/MTMR7/MTMR8 phosphoinositide phosphatases, so there is no informative molecular-function term to substitute. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding with GRAMD4 (UniProtKB:Q6IC98) from a high-throughput interaction screen (PMID:32296183). Reason: Bare protein binding is uninformative and removal does not mean the interaction is false. The GRAMD4 interaction comes from a proteome-scale binary or affinity screen; no follow-up study connects it to MTMR9's established role as a noncatalytic regulator of MTMR6/MTMR7/MTMR8 phosphoinositide phosphatases, so there is no informative molecular-function term to substitute. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding with KRT27 (UniProtKB:Q7Z3Y8) from a high-throughput interaction screen (PMID:32296183). Reason: Bare protein binding is uninformative and removal does not mean the interaction is false. The KRT27 interaction comes from a proteome-scale binary or affinity screen; no follow-up study connects it to MTMR9's established role as a noncatalytic regulator of MTMR6/MTMR7/MTMR8 phosphoinositide phosphatases, so there is no informative molecular-function term to substitute. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding with NECAB2 (UniProtKB:Q7Z6G3-2) from a high-throughput interaction screen (PMID:32296183). Reason: Bare protein binding is uninformative and removal does not mean the interaction is false. The NECAB2 interaction comes from a proteome-scale binary or affinity screen; no follow-up study connects it to MTMR9's established role as a noncatalytic regulator of MTMR6/MTMR7/MTMR8 phosphoinositide phosphatases, so there is no informative molecular-function term to substitute. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding with KIAA1328 (UniProtKB:Q86T90) from a high-throughput interaction screen (PMID:32296183). Reason: Bare protein binding is uninformative and removal does not mean the interaction is false. The KIAA1328 interaction comes from a proteome-scale binary or affinity screen; no follow-up study connects it to MTMR9's established role as a noncatalytic regulator of MTMR6/MTMR7/MTMR8 phosphoinositide phosphatases, so there is no informative molecular-function term to substitute. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding with ZNF655 (UniProtKB:Q8N720) from a high-throughput interaction screen (PMID:32296183). Reason: Bare protein binding is uninformative and removal does not mean the interaction is false. The ZNF655 interaction comes from a proteome-scale binary or affinity screen; no follow-up study connects it to MTMR9's established role as a noncatalytic regulator of MTMR6/MTMR7/MTMR8 phosphoinositide phosphatases, so there is no informative molecular-function term to substitute. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR7 (UniProtKB:Q9Y216) reported in PMID:32296183. Reason: Bare protein binding is uninformative. The partner MTMR7 is a catalytically active myotubularin phosphoinositide 3-phosphatase, and targeted studies show that MTMR9 heterodimerizes with MTMR7 and raises its catalytic output, so the interaction is better captured as phosphatase binding (GO:0019902). The regulatory consequence is captured separately by phosphatase activator activity (GO:0019211). The proteome-scale screen that GOA cites is an independent detection of the same pair; the replacement term is supported by the focused studies quoted here. Proposed replacements: phosphatase binding Supporting Evidence: PMID:12890864 The coiled-coil domain of MTMR9 was sufficient for binding to MTMR7 PMID:12890864 The binding of MTMR9 increased the Ins(1,3)P2 phosphatase activity of MTMR7 |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR6 (UniProtKB:Q9Y217) reported in PMID:32296183. Reason: Bare protein binding is uninformative. The partner MTMR6 is a catalytically active myotubularin phosphoinositide 3-phosphatase, and targeted studies show that MTMR9 heterodimerizes with MTMR6 and raises its catalytic output, so the interaction is better captured as phosphatase binding (GO:0019902). The regulatory consequence is captured separately by phosphatase activator activity (GO:0019211). The proteome-scale screen that GOA cites is an independent detection of the same pair; the replacement term is supported by the focused studies quoted here. Proposed replacements: phosphatase binding Supporting Evidence: PMID:19038970 human MTMR6 forms a heteromer with an enzymatically inactive member myotubularin-related protein 9 (MTMR9), both in vitro and in cells PMID:19038970 MTMR9 increased the 3-phosphatase activity of MTMR6 up to 6-fold |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding with EMILIN1 (UniProtKB:Q9Y6C2-2) from a high-throughput interaction screen (PMID:32296183). Reason: Bare protein binding is uninformative and removal does not mean the interaction is false. The EMILIN1 interaction comes from a proteome-scale binary or affinity screen; no follow-up study connects it to MTMR9's established role as a noncatalytic regulator of MTMR6/MTMR7/MTMR8 phosphoinositide phosphatases, so there is no informative molecular-function term to substitute. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding with FAM169A (UniProtKB:Q9Y6X4) from a high-throughput interaction screen (PMID:32296183). Reason: Bare protein binding is uninformative and removal does not mean the interaction is false. The FAM169A interaction comes from a proteome-scale binary or affinity screen; no follow-up study connects it to MTMR9's established role as a noncatalytic regulator of MTMR6/MTMR7/MTMR8 phosphoinositide phosphatases, so there is no informative molecular-function term to substitute. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR8 (UniProtKB:Q96EF0) reported in PMID:33961781. Reason: Bare protein binding is uninformative. The partner MTMR8 is a catalytically active myotubularin phosphoinositide 3-phosphatase, and targeted studies show that MTMR9 heterodimerizes with MTMR8 and raises its catalytic output, so the interaction is better captured as phosphatase binding (GO:0019902). The regulatory consequence is captured separately by phosphatase activator activity (GO:0019211). The proteome-scale screen that GOA cites is an independent detection of the same pair; the replacement term is supported by the focused studies quoted here. Proposed replacements: phosphatase binding Supporting Evidence: PMID:16787938 identified novel heteromeric interactions: MTMR8 with MTMR9 PMID:22647598 MTMR8, all of which dimerize with the catalytically inactive MTMR9 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR7 (UniProtKB:Q9Y216) reported in PMID:33961781. Reason: Bare protein binding is uninformative. The partner MTMR7 is a catalytically active myotubularin phosphoinositide 3-phosphatase, and targeted studies show that MTMR9 heterodimerizes with MTMR7 and raises its catalytic output, so the interaction is better captured as phosphatase binding (GO:0019902). The regulatory consequence is captured separately by phosphatase activator activity (GO:0019211). The proteome-scale screen that GOA cites is an independent detection of the same pair; the replacement term is supported by the focused studies quoted here. Proposed replacements: phosphatase binding Supporting Evidence: PMID:12890864 The coiled-coil domain of MTMR9 was sufficient for binding to MTMR7 PMID:12890864 The binding of MTMR9 increased the Ins(1,3)P2 phosphatase activity of MTMR7 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR6 (UniProtKB:Q9Y217) reported in PMID:33961781. Reason: Bare protein binding is uninformative. The partner MTMR6 is a catalytically active myotubularin phosphoinositide 3-phosphatase, and targeted studies show that MTMR9 heterodimerizes with MTMR6 and raises its catalytic output, so the interaction is better captured as phosphatase binding (GO:0019902). The regulatory consequence is captured separately by phosphatase activator activity (GO:0019211). The proteome-scale screen that GOA cites is an independent detection of the same pair; the replacement term is supported by the focused studies quoted here. Proposed replacements: phosphatase binding Supporting Evidence: PMID:19038970 human MTMR6 forms a heteromer with an enzymatically inactive member myotubularin-related protein 9 (MTMR9), both in vitro and in cells PMID:19038970 MTMR9 increased the 3-phosphatase activity of MTMR6 up to 6-fold |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR8 (UniProtKB:Q96EF0) reported in PMID:40205054. Reason: Bare protein binding is uninformative. The partner MTMR8 is a catalytically active myotubularin phosphoinositide 3-phosphatase, and targeted studies show that MTMR9 heterodimerizes with MTMR8 and raises its catalytic output, so the interaction is better captured as phosphatase binding (GO:0019902). The regulatory consequence is captured separately by phosphatase activator activity (GO:0019211). The proteome-scale screen that GOA cites is an independent detection of the same pair; the replacement term is supported by the focused studies quoted here. Proposed replacements: phosphatase binding Supporting Evidence: PMID:16787938 identified novel heteromeric interactions: MTMR8 with MTMR9 PMID:22647598 MTMR8, all of which dimerize with the catalytically inactive MTMR9 |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR7 (UniProtKB:Q9Y216) reported in PMID:40205054. Reason: Bare protein binding is uninformative. The partner MTMR7 is a catalytically active myotubularin phosphoinositide 3-phosphatase, and targeted studies show that MTMR9 heterodimerizes with MTMR7 and raises its catalytic output, so the interaction is better captured as phosphatase binding (GO:0019902). The regulatory consequence is captured separately by phosphatase activator activity (GO:0019211). The proteome-scale screen that GOA cites is an independent detection of the same pair; the replacement term is supported by the focused studies quoted here. Proposed replacements: phosphatase binding Supporting Evidence: PMID:12890864 The coiled-coil domain of MTMR9 was sufficient for binding to MTMR7 PMID:12890864 The binding of MTMR9 increased the Ins(1,3)P2 phosphatase activity of MTMR7 |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR6 (UniProtKB:Q9Y217) reported in PMID:40205054. Reason: Bare protein binding is uninformative. The partner MTMR6 is a catalytically active myotubularin phosphoinositide 3-phosphatase, and targeted studies show that MTMR9 heterodimerizes with MTMR6 and raises its catalytic output, so the interaction is better captured as phosphatase binding (GO:0019902). The regulatory consequence is captured separately by phosphatase activator activity (GO:0019211). The proteome-scale screen that GOA cites is an independent detection of the same pair; the replacement term is supported by the focused studies quoted here. Proposed replacements: phosphatase binding Supporting Evidence: PMID:19038970 human MTMR6 forms a heteromer with an enzymatically inactive member myotubularin-related protein 9 (MTMR9), both in vitro and in cells PMID:19038970 MTMR9 increased the 3-phosphatase activity of MTMR6 up to 6-fold |
| GO:0005737 cytoplasm | EXP PMID:19038970 MTMR9 increases MTMR6 enzyme activity, stability, and role i... | ACCEPT | Summary: MTMR9 is a soluble intracellular protein found in the cytoplasm, partly on membranes. Reason: Cytoplasmic localization of human MTMR9 is experimentally recorded (PMID:16787938, PMID:19038970, both cited as ECO:0000269 in UniProt), MTMR9 has no transmembrane segment or signal peptide, and PAINT propagated cytoplasm from a deep node with broad experimental seeding including MTMR9 itself. This is where it engages its active partners. Supporting Evidence: PMID:19038970 human MTMR6 forms a heteromer with an enzymatically inactive member myotubularin-related protein 9 (MTMR9), both in vitro and in cells file:human/MTMR9/MTMR9-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16787938, |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: MTMR9 is a soluble intracellular protein found in the cytoplasm, partly on membranes. Reason: Cytoplasmic localization of human MTMR9 is experimentally recorded (PMID:16787938, PMID:19038970, both cited as ECO:0000269 in UniProt), MTMR9 has no transmembrane segment or signal peptide, and PAINT propagated cytoplasm from a deep node with broad experimental seeding including MTMR9 itself. This is where it engages its active partners. Supporting Evidence: file:human/MTMR9/MTMR9-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16787938, |
| GO:0005737 cytoplasm | IDA PMID:16787938 Systematic analysis of myotubularins: heteromeric interactio... | ACCEPT | Summary: MTMR9 is a soluble intracellular protein found in the cytoplasm, partly on membranes. Reason: Cytoplasmic localization of human MTMR9 is experimentally recorded (PMID:16787938, PMID:19038970, both cited as ECO:0000269 in UniProt), MTMR9 has no transmembrane segment or signal peptide, and PAINT propagated cytoplasm from a deep node with broad experimental seeding including MTMR9 itself. This is where it engages its active partners. Supporting Evidence: file:human/MTMR9/MTMR9-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16787938, |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: MTMR9 is a soluble intracellular protein found in the cytoplasm, partly on membranes. Reason: Cytoplasmic localization of human MTMR9 is experimentally recorded (PMID:16787938, PMID:19038970, both cited as ECO:0000269 in UniProt), MTMR9 has no transmembrane segment or signal peptide, and PAINT propagated cytoplasm from a deep node with broad experimental seeding including MTMR9 itself. This is where it engages its active partners. Supporting Evidence: file:human/MTMR9/MTMR9-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16787938, |
| GO:0005783 endoplasmic reticulum | EXP PMID:19038970 MTMR9 increases MTMR6 enzyme activity, stability, and role i... | KEEP AS NON CORE | Summary: Partial endoplasmic reticulum localization of MTMR9 reported in PMID:19038970. Reason: UniProt records partial ER localization from PMID:19038970 (ECO:0000269); the cached abstract does not state it, so this rests on the curator's reading of the full text. Partial localization to one membrane compartment is not the principal site of the MTMR6/MTMR8 regulatory function. ORGANELLES check (2026-11-05): the full text (PMC2629094) could not be retrieved; UniProt's note says MTMR9 "Partially localizes to the endoplasmic reticulum (PubMed:19038970)", and the cell experiments described in the abstract co-express MTMR6 and MTMR9, so the pool may be that of an overexpressed complex. MTMR9 is a soluble pseudophosphatase with no TM or signal peptide, so any ER pool is on the cytosolic face, a recruited pool like those of A1CF and BRSK2: it stays at the root with no ER membrane row, KEEP_AS_NON_CORE on curator deference (HADHB, IFIT2 precedent). Supporting Evidence: file:human/MTMR9/MTMR9-uniprot.txt Endoplasmic reticulum {ECO:0000269|PubMed:19038970} |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Partial endoplasmic reticulum localization of MTMR9 reported in PMID:19038970. Reason: UniProt records partial ER localization from PMID:19038970 (ECO:0000269); the cached abstract does not state it, so this rests on the curator's reading of the full text. Partial localization to one membrane compartment is not the principal site of the MTMR6/MTMR8 regulatory function. ORGANELLES check (2026-11-05): the full text (PMC2629094) could not be retrieved; UniProt's note says MTMR9 "Partially localizes to the endoplasmic reticulum (PubMed:19038970)", and the cell experiments described in the abstract co-express MTMR6 and MTMR9, so the pool may be that of an overexpressed complex. MTMR9 is a soluble pseudophosphatase with no TM or signal peptide, so any ER pool is on the cytosolic face, a recruited pool like those of A1CF and BRSK2: it stays at the root with no ER membrane row, KEEP_AS_NON_CORE on curator deference (HADHB, IFIT2 precedent). Supporting Evidence: file:human/MTMR9/MTMR9-uniprot.txt Endoplasmic reticulum {ECO:0000269|PubMed:19038970} |
| GO:0005829 cytosol | IEA GO_REF:0000117 | ACCEPT | Summary: MTMR9 acts as a soluble cytosolic protein that engages myotubularin partners at the cytosolic face of membranes. Reason: Cytosol is consistent with the experimental cytoplasmic localization, the absence of transmembrane or secretory signals, and Reactome's placement of the MTMR6/MTMR8-MTMR9 complexes acting on cytosolic-face phosphoinositides. Supporting Evidence: file:human/MTMR9/MTMR9-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16787938, |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6809254 | ACCEPT | Summary: MTMR9 acts as a soluble cytosolic protein that engages myotubularin partners at the cytosolic face of membranes. Reason: Cytosol is consistent with the experimental cytoplasmic localization, the absence of transmembrane or secretory signals, and Reactome's placement of the MTMR6/MTMR8-MTMR9 complexes acting on cytosolic-face phosphoinositides. Supporting Evidence: Reactome:R-HSA-6809254 MTMR8 binds to MTMR9, an enzymatically inactive myotubularin family member, which results in increased stability and increased catalytic activity of MTMR8 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6809309 | ACCEPT | Summary: MTMR9 acts as a soluble cytosolic protein that engages myotubularin partners at the cytosolic face of membranes. Reason: Cytosol is consistent with the experimental cytoplasmic localization, the absence of transmembrane or secretory signals, and Reactome's placement of the MTMR6/MTMR8-MTMR9 complexes acting on cytosolic-face phosphoinositides. Supporting Evidence: Reactome:R-HSA-6809309 MTMR6 binds to MTMR9, an enzymatically inactive myotubularin family member, which leads to increased catalytic activity of MTMR6 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6809320 | ACCEPT | Summary: MTMR9 acts as a soluble cytosolic protein that engages myotubularin partners at the cytosolic face of membranes. Reason: Cytosol is consistent with the experimental cytoplasmic localization, the absence of transmembrane or secretory signals, and Reactome's placement of the MTMR6/MTMR8-MTMR9 complexes acting on cytosolic-face phosphoinositides. Supporting Evidence: Reactome:R-HSA-6809320 Formation of a complex with MTMR9 results in a 30-fold increase of phosphatidylinositol-(3,5)-bisphosphate 3-phosphatase catalytic activity of MTMR6 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6809325 | ACCEPT | Summary: MTMR9 acts as a soluble cytosolic protein that engages myotubularin partners at the cytosolic face of membranes. Reason: Cytosol is consistent with the experimental cytoplasmic localization, the absence of transmembrane or secretory signals, and Reactome's placement of the MTMR6/MTMR8-MTMR9 complexes acting on cytosolic-face phosphoinositides. Supporting Evidence: Reactome:R-HSA-6809325 Formation of a complex with MTMR9 results in a 4-fold increase of the phosphatidylinositol-3-phosphatase catalytic activity of MTMR8 |
| GO:0006661 phosphatidylinositol biosynthetic process | TAS Reactome:R-HSA-1660499 | MODIFY | Summary: Reactome places MTMR9 in 'Synthesis of PIPs at the plasma membrane' through the MTMR9-bound MTMR6/MTMR8 dephosphorylation reactions. Reason: The Reactome pathway groups all phosphoinositide interconversions under 'synthesis of PIPs', which maps to phosphatidylinositol biosynthetic process. The specific reactions in which MTMR9 participates are 3-dephosphorylation of PI3P and PI(3,5)P2 by MTMR9-bound MTMR6 or MTMR8; MTMR9 contributes as the activating, stabilizing subunit of the dimer that performs the step. The precise process is phosphatidylinositol dephosphorylation (GO:0046856), which the gene already carries by IBA; PAINT deliberately retained that process at the MTMR9 node while marking loss of the catalytic activities. Proposed replacements: phosphatidylinositol dephosphorylation Supporting Evidence: Reactome:R-HSA-1660499 Enzymatically inactive myotubularin family members can heterodimerize with catalytically active mytotubularins to regulate their stability, activity and/or substrate specificity Reactome:R-HSA-6809320 Formation of a complex with MTMR9 results in a 30-fold increase of phosphatidylinositol-(3,5)-bisphosphate 3-phosphatase catalytic activity of MTMR6 Reactome:R-HSA-6809325 Formation of a complex with MTMR9 results in a 4-fold increase of the phosphatidylinositol-3-phosphatase catalytic activity of MTMR8 |
| GO:0010507 negative regulation of autophagy | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: MTMR8-MTMR9 complex lowers cellular PI3P and suppresses autophagy in HeLa-cell experiments. Reason: PMID:22647598 shows that co-expressing MTMR8 with MTMR9 lowers PI3P and inhibits autophagic flux, with reciprocal effects after combined knockdown; MTMR9 therefore does part of the work of regulating autophagy by controlling the MTMR8 PI3P phosphatase. The PAINT node (PTN002246859) was seeded only by MTMR9 itself, which is expected and not circular. The term is kept but as non-core: it is a downstream consequence of PI3P-pool control, the evidence is cultured-cell over-expression/RNAi, and MTMR9-only perturbation has not consistently reproduced the phenotype. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002246859 SUPPORTS TRANSFER Node seeded by MTMR9's own experimental annotation (PMID:22647598); transfer within the MTMR9 lineage is sound. Supporting Evidence: PMID:22647598 the MTMR8/R9 complex inhibits autophagy PMID:22647598 the MTMR8/R9 complex reduces cellular PtdIns(3)P levels |
| GO:0010507 negative regulation of autophagy | IPI PMID:22647598 Myotubularin-related protein (MTMR) 9 determines the enzymat... | KEEP AS NON CORE | Summary: MTMR8-MTMR9 complex lowers cellular PI3P and suppresses autophagy in HeLa-cell experiments. Reason: PMID:22647598 shows that co-expressing MTMR8 with MTMR9 lowers PI3P and inhibits autophagic flux, with reciprocal effects after combined knockdown; MTMR9 therefore does part of the work of regulating autophagy by controlling the MTMR8 PI3P phosphatase. The PAINT node (PTN002246859) was seeded only by MTMR9 itself, which is expected and not circular. The term is kept but as non-core: it is a downstream consequence of PI3P-pool control, the evidence is cultured-cell over-expression/RNAi, and MTMR9-only perturbation has not consistently reproduced the phenotype. Supporting Evidence: PMID:22647598 the MTMR8/R9 complex inhibits autophagy PMID:22647598 the MTMR8/R9 complex reduces cellular PtdIns(3)P levels |
| GO:0010922 positive regulation of phosphatase activity | IDA PMID:22647598 Myotubularin-related protein (MTMR) 9 determines the enzymat... | ACCEPT | Summary: MTMR9 increases the catalytic activity of the active myotubularins MTMR6, MTMR7 and MTMR8. Reason: Directly measured in PMID:22647598 and PMID:19038970: MTMR9 raised MTMR6 activity toward PI(3,5)P2 more than 30-fold and MTMR8 activity toward PI3P about 4-fold. This is the process counterpart of its core phosphatase activator activity. Supporting Evidence: PMID:22647598 Complex formation between the active myotubularins and MTMR9 increases their catalytic activity and alters their substrate specificity PMID:19038970 MTMR9 increased the 3-phosphatase activity of MTMR6 up to 6-fold |
| GO:0019211 phosphatase activator activity | EXP PMID:19038970 MTMR9 increases MTMR6 enzyme activity, stability, and role i... | ACCEPT | Summary: MTMR9 binds and activates the lipid phosphatases MTMR6, MTMR7 and MTMR8. Reason: Core molecular function. MTMR9 lacks the catalytic Cys and Arg of the CX5R motif and so has no phosphatase activity of its own; its function is to raise the activity, and shape the substrate preference, of the active partner it dimerizes with. Shown with purified components and in cells (PMID:19038970, PMID:22647598, and for MTMR7 PMID:12890864). Supporting Evidence: PMID:19038970 MTMR9 increased the 3-phosphatase activity of MTMR6 up to 6-fold PMID:22647598 Complex formation between the active myotubularins and MTMR9 increases their catalytic activity and alters their substrate specificity PMID:12890864 The binding of MTMR9 increased the Ins(1,3)P2 phosphatase activity of MTMR7 file:human/MTMR9/MTMR9-uniprot.txt lacks the conserved active site cysteine residue at position file:human/MTMR9/MTMR9-bioinformatics/RESULTS-rereview.md MTMR9 lacks both the catalytic cysteine and the catalytic arginine |
| GO:0019211 phosphatase activator activity | EXP PMID:22647598 Myotubularin-related protein (MTMR) 9 determines the enzymat... | ACCEPT | Summary: MTMR9 binds and activates the lipid phosphatases MTMR6, MTMR7 and MTMR8. Reason: Core molecular function. MTMR9 lacks the catalytic Cys and Arg of the CX5R motif and so has no phosphatase activity of its own; its function is to raise the activity, and shape the substrate preference, of the active partner it dimerizes with. Shown with purified components and in cells (PMID:19038970, PMID:22647598, and for MTMR7 PMID:12890864). Supporting Evidence: PMID:19038970 MTMR9 increased the 3-phosphatase activity of MTMR6 up to 6-fold PMID:22647598 Complex formation between the active myotubularins and MTMR9 increases their catalytic activity and alters their substrate specificity PMID:12890864 The binding of MTMR9 increased the Ins(1,3)P2 phosphatase activity of MTMR7 file:human/MTMR9/MTMR9-uniprot.txt lacks the conserved active site cysteine residue at position file:human/MTMR9/MTMR9-bioinformatics/RESULTS-rereview.md MTMR9 lacks both the catalytic cysteine and the catalytic arginine |
| GO:0019903 protein phosphatase binding | IBA GO_REF:0000033 | MODIFY | Summary: MTMR9 binds the myotubularin lipid phosphatases MTMR6 and MTMR8 (and MTMR7). Reason: The binding is well established (PMID:16787938, PMID:19038970, PMID:22647598) and PAINT propagated this term from MTMR9's own experimental annotation, which is correct and expected. The issue is the term: 'protein phosphatase binding' and its children (PP1, PP2A, PP2B binding, etc.) denote enzymes that dephosphorylate proteins, whereas MTMR6, MTMR7 and MTMR8 are phosphoinositide 3-phosphatases. The parent phosphatase binding (GO:0019902) states the supported claim without implying a protein substrate. The same replacement is applied to every MTMR6/7/8 protein-binding row so the claim is consistent; the question is also raised in suggested_questions. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN002246859 SUPPORTS TRANSFER Eumetazoan MTMR9-lineage node; the IBD is placed correctly and the binding it asserts is real. Only the term's scope (protein vs lipid phosphatase) is at issue. UniProtKB:Q96QG7 SUPPORTS TRANSFER The target's own IPI annotations (PMID:16787938) seed the node; this is expected, not circular. Proposed replacements: phosphatase binding Supporting Evidence: PMID:16787938 identified novel heteromeric interactions: MTMR8 with MTMR9 PMID:19038970 human MTMR6 forms a heteromer with an enzymatically inactive member myotubularin-related protein 9 (MTMR9), both in vitro and in cells PMID:22647598 MTMR8, all of which dimerize with the catalytically inactive MTMR9 |
| GO:0019903 protein phosphatase binding | IPI PMID:16787938 Systematic analysis of myotubularins: heteromeric interactio... | MODIFY | Summary: MTMR9 binds the myotubularin lipid phosphatases MTMR6 and MTMR8 (and MTMR7). Reason: The binding is well established (PMID:16787938, PMID:19038970, PMID:22647598) and PAINT propagated this term from MTMR9's own experimental annotation, which is correct and expected. The issue is the term: 'protein phosphatase binding' and its children (PP1, PP2A, PP2B binding, etc.) denote enzymes that dephosphorylate proteins, whereas MTMR6, MTMR7 and MTMR8 are phosphoinositide 3-phosphatases. The parent phosphatase binding (GO:0019902) states the supported claim without implying a protein substrate. The same replacement is applied to every MTMR6/7/8 protein-binding row so the claim is consistent; the question is also raised in suggested_questions. Proposed replacements: phosphatase binding Supporting Evidence: PMID:16787938 identified novel heteromeric interactions: MTMR8 with MTMR9 PMID:19038970 human MTMR6 forms a heteromer with an enzymatically inactive member myotubularin-related protein 9 (MTMR9), both in vitro and in cells PMID:22647598 MTMR8, all of which dimerize with the catalytically inactive MTMR9 |
| GO:0019903 protein phosphatase binding | IPI PMID:16787938 Systematic analysis of myotubularins: heteromeric interactio... | MODIFY | Summary: MTMR9 binds the myotubularin lipid phosphatases MTMR6 and MTMR8 (and MTMR7). Reason: The binding is well established (PMID:16787938, PMID:19038970, PMID:22647598) and PAINT propagated this term from MTMR9's own experimental annotation, which is correct and expected. The issue is the term: 'protein phosphatase binding' and its children (PP1, PP2A, PP2B binding, etc.) denote enzymes that dephosphorylate proteins, whereas MTMR6, MTMR7 and MTMR8 are phosphoinositide 3-phosphatases. The parent phosphatase binding (GO:0019902) states the supported claim without implying a protein substrate. The same replacement is applied to every MTMR6/7/8 protein-binding row so the claim is consistent; the question is also raised in suggested_questions. Proposed replacements: phosphatase binding Supporting Evidence: PMID:16787938 identified novel heteromeric interactions: MTMR8 with MTMR9 PMID:19038970 human MTMR6 forms a heteromer with an enzymatically inactive member myotubularin-related protein 9 (MTMR9), both in vitro and in cells PMID:22647598 MTMR8, all of which dimerize with the catalytically inactive MTMR9 |
| GO:0030234 enzyme regulator activity | IEA GO_REF:0000120 | MODIFY | Summary: Electronic enzyme regulator activity, correct but general. Reason: True but less specific than the evidence supports. The enzymes MTMR9 regulates are phosphatases and the regulation is activation, so phosphatase activator activity (GO:0019211), which the gene already carries by EXP, is the precise descendant. Proposed replacements: phosphatase activator activity Supporting Evidence: PMID:19038970 MTMR9 increased the 3-phosphatase activity of MTMR6 up to 6-fold PMID:22647598 Complex formation between the active myotubularins and MTMR9 increases their catalytic activity and alters their substrate specificity |
| GO:0032587 ruffle membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Ruffle membrane localization, transferred in UniProt from mouse Mtmr9 during EGF-induced macropinocytosis. Reason: UniProt transfers ruffle localization from the mouse ortholog Q9Z2D0 (same PANTHER subfamily PTHR10807:SF56, ECO:0000250); PMID:24591580 shows that MTMR6 and its partner MTMR9 are needed for late macropinocytosis. This is a context-specific, stimulus-dependent location rather than the principal site of action. Supporting Evidence: file:human/MTMR9/MTMR9-uniprot.txt Localizes to ruffles during EGF-induced macropinocytosis (By similarity) PMID:24591580 its binding partner MTMR9, are required for macropinocytosis |
| GO:0032991 protein-containing complex | IDA PMID:22647598 Myotubularin-related protein (MTMR) 9 determines the enzymat... | ACCEPT | Summary: MTMR9 forms heterodimeric complexes with MTMR6, MTMR7 and MTMR8. Reason: Complex formation is the basis of MTMR9's function: it heterodimerizes with active myotubularins and mutually stabilizes them. GO has no specific complex term for MTMR6-MTMR9 or MTMR8-MTMR9, so the general term is as precise as the ontology allows. Supporting Evidence: PMID:22647598 MTMR8, all of which dimerize with the catalytically inactive MTMR9 PMID:19038970 human MTMR6 forms a heteromer with an enzymatically inactive member myotubularin-related protein 9 (MTMR9), both in vitro and in cells |
| GO:0046856 phosphatidylinositol dephosphorylation | IBA GO_REF:0000033 | ACCEPT | Summary: Phosphatidylinositol dephosphorylation by MTMR9-containing dimers, propagated from the eukaryotic myotubularin node. Reason: MTMR9 itself cannot hydrolyse phosphate, but it is the activating, stabilizing subunit of the MTMR6-MTMR9 and MTMR8-MTMR9 dimers that 3-dephosphorylate PI(3,5)P2 and PI3P, so it contributes structure and activation to the step. The PAINT curator handled this explicitly: at the MTMR9 lineage node PTN000086907 they recorded NOT for GO:0004438 and GO:0106018 (catalytic activities) but did not negate GO:0046856, whereas at the other inactive myotubularin node PTN000850005 they negated the process as well. Retaining the process for MTMR9 is a deliberate, defensible decision. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008506586 SUPPORTS TRANSFER Eukaryotic myotubularin node seeded by experimental data from active MTMR6, MTMR8 and mouse Mtmr7 (MGI:1891693). The curator negated the catalytic MF terms at descendant node PTN000086907 (MTMR9 lineage) but deliberately kept this process, unlike at PTN000850005 where the process was negated too. Supporting Evidence: PMID:22647598 Complex formation between the active myotubularins and MTMR9 increases their catalytic activity and alters their substrate specificity Reactome:R-HSA-6809320 Formation of a complex with MTMR9 results in a 30-fold increase of phosphatidylinositol-(3,5)-bisphosphate 3-phosphatase catalytic activity of MTMR6 Reactome:R-HSA-6809325 Formation of a complex with MTMR9 results in a 4-fold increase of the phosphatidylinositol-3-phosphatase catalytic activity of MTMR8 |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: MTMR9 colocalizes with MTMR6 in the perinuclear region. Reason: Experimentally reported (PMID:16787938, PMID:19038970 via UniProt ECO:0000269); a real but descriptive sub-location of the cytoplasmic pool rather than a defining site of function. Supporting Evidence: file:human/MTMR9/MTMR9-uniprot.txt Colocalizes with MTMR6 to the perinuclear region (PubMed:19038970) |
| GO:0050821 protein stabilization | IDA PMID:22647598 Myotubularin-related protein (MTMR) 9 determines the enzymat... | ACCEPT | Summary: MTMR9 stabilizes its partner phosphatases MTMR6 and MTMR8 at the protein level. Reason: Heterodimer formation raises MTMR6 and MTMR9 protein levels (PMID:19038970) and slows MTMR8 turnover (PMID:22647598, cycloheximide chase per UniProt). Stabilizing the active partner is part of how MTMR9 sets their output, and MTMR9 does this work directly by binding. Supporting Evidence: PMID:19038970 the formation of this heteromer in cells resulted in increased protein levels of both MTMR6 and MTMR9 Reactome:R-HSA-6809254 MTMR8 binds to MTMR9, an enzymatically inactive myotubularin family member, which results in increased stability and increased catalytic activity of MTMR8 |
| GO:0060304 regulation of phosphatidylinositol dephosphorylation | IDA PMID:22647598 Myotubularin-related protein (MTMR) 9 determines the enzymat... | ACCEPT | Summary: MTMR9 regulates phosphatidylinositol dephosphorylation by controlling the activity and substrate preference of MTMR6 and MTMR8. Reason: Core process. MTMR9 shifts MTMR6 toward PI(3,5)P2 and MTMR8 toward PI3P and changes the cellular levels of PI5P and PI3P accordingly (PMID:22647598). Supporting Evidence: PMID:22647598 Complex formation between the active myotubularins and MTMR9 increases their catalytic activity and alters their substrate specificity PMID:22647598 the MTMR8/R9 complex reduces cellular PtdIns(3)P levels |
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Download this section (compressed HTML)Q: Should binding of an inactive myotubularin to an active myotubularin lipid phosphatase be annotated to GO:0019903 protein phosphatase binding, as PAINT does for MTMR9 and MTMR3/MTMR4, or to the parent GO:0019902 phosphatase binding? The children of GO:0019903 all name protein-substrate phosphatases.
Q: Is the reported ER-Golgi intermediate compartment/Golgi localization of MTMR9 and its effect on VSVG and WNT3A secretion (described in secondary sources but not in the cached primary literature) reproducible with endogenous protein, and does it depend on MTMR6/MTMR8?
Q: What is the MTMR9 homodimer for, and does MTMR9 partition between MTMR6, MTMR7 and MTMR8 in cells where all are expressed?
Experiment: Reconstitute MTMR6-MTMR9 and MTMR8-MTMR9 with coiled-coil swap and point mutants and measure PI3P and PI(3,5)P2 3-phosphatase kinetics on liposomes; determine a dimer structure by cryo-EM.
Hypothesis: MTMR9 sets the substrate preference of MTMR6 and MTMR8 through its coiled-coil dimer interface.
Type: biochemical assay
Experiment: MTMR9 knockout and MTMR9/MTMR8 double knockout cells rescued with wild-type or dimerization-defective MTMR9, scoring PI3P (FYVE probe), LC3 flux and p62 turnover.
Hypothesis: Endogenous MTMR9 restrains autophagy by limiting a PI3P pool via MTMR8.
Type: genetic perturbation
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