id: Q96QG7 gene_symbol: MTMR9 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: '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.' alternative_products: - name: '1' id: Q96QG7-1 - name: '2' id: Q96QG7-2 sequence_note: VSP_056209 existing_annotations: - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:12890864 qualifier: enables supporting_entities: - UniProtKB:Q59HJ6 review: summary: Generic protein binding from the mouse MTMR7/MTMR9 characterisation study; the GOA partner identifier resolves to bovine LONP1. action: REMOVE 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. supported_by: - reference_id: PMID:12890864 supporting_text: The coiled-coil domain of MTMR9 was sufficient for binding to MTMR7 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:16189514 qualifier: enables supporting_entities: - UniProtKB:Q96EF0 review: summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR8 (UniProtKB:Q96EF0) reported in PMID:16189514. action: MODIFY 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_replacement_terms: - id: GO:0019902 label: phosphatase binding supported_by: - reference_id: PMID:16787938 supporting_text: 'identified novel heteromeric interactions: MTMR8 with MTMR9' - reference_id: PMID:22647598 supporting_text: MTMR8, all of which dimerize with the catalytically inactive MTMR9 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:16189514 qualifier: enables supporting_entities: - UniProtKB:Q9Y6C2 review: summary: Generic protein binding with EMILIN1 (UniProtKB:Q9Y6C2) from a high-throughput interaction screen (PMID:16189514). action: REMOVE 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:19447967 qualifier: enables supporting_entities: - UniProtKB:Q9Y6C2 review: summary: Generic protein binding with EMILIN1 (UniProtKB:Q9Y6C2) from a high-throughput interaction screen (PMID:19447967). action: REMOVE 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:21516116 qualifier: enables supporting_entities: - UniProtKB:Q9Y217 review: summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR6 (UniProtKB:Q9Y217) reported in PMID:21516116. action: MODIFY 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_replacement_terms: - id: GO:0019902 label: phosphatase binding supported_by: - reference_id: PMID:19038970 supporting_text: human MTMR6 forms a heteromer with an enzymatically inactive member myotubularin-related protein 9 (MTMR9), both in vitro and in cells - reference_id: PMID:19038970 supporting_text: MTMR9 increased the 3-phosphatase activity of MTMR6 up to 6-fold - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:21516116 qualifier: enables supporting_entities: - UniProtKB:Q9Y6C2 review: summary: Generic protein binding with EMILIN1 (UniProtKB:Q9Y6C2) from a high-throughput interaction screen (PMID:21516116). action: REMOVE 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:22647598 qualifier: enables supporting_entities: - UniProtKB:Q96EF0-1 review: summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR8 (UniProtKB:Q96EF0-1) reported in PMID:22647598. action: MODIFY 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_replacement_terms: - id: GO:0019902 label: phosphatase binding supported_by: - reference_id: PMID:16787938 supporting_text: 'identified novel heteromeric interactions: MTMR8 with MTMR9' - reference_id: PMID:22647598 supporting_text: MTMR8, all of which dimerize with the catalytically inactive MTMR9 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25416956 qualifier: enables supporting_entities: - UniProtKB:P00540 review: summary: Generic protein binding with MOS (UniProtKB:P00540) from a high-throughput interaction screen (PMID:25416956). action: REMOVE 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25416956 qualifier: enables supporting_entities: - UniProtKB:Q08AM6 review: summary: Generic protein binding with VAC14 (UniProtKB:Q08AM6) from a high-throughput interaction screen (PMID:25416956). action: REMOVE 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25416956 qualifier: enables supporting_entities: - UniProtKB:Q13287 review: summary: Generic protein binding with NMI (UniProtKB:Q13287) from a high-throughput interaction screen (PMID:25416956). action: REMOVE 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25416956 qualifier: enables supporting_entities: - UniProtKB:Q8TBB1 review: summary: Generic protein binding with LNX1 (UniProtKB:Q8TBB1) from a high-throughput interaction screen (PMID:25416956). action: REMOVE 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25416956 qualifier: enables supporting_entities: - UniProtKB:Q9Y216 review: summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR7 (UniProtKB:Q9Y216) reported in PMID:25416956. action: MODIFY 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_replacement_terms: - id: GO:0019902 label: phosphatase binding supported_by: - reference_id: PMID:12890864 supporting_text: The coiled-coil domain of MTMR9 was sufficient for binding to MTMR7 - reference_id: PMID:12890864 supporting_text: The binding of MTMR9 increased the Ins(1,3)P2 phosphatase activity of MTMR7 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25416956 qualifier: enables supporting_entities: - UniProtKB:Q9Y217 review: summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR6 (UniProtKB:Q9Y217) reported in PMID:25416956. action: MODIFY 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_replacement_terms: - id: GO:0019902 label: phosphatase binding supported_by: - reference_id: PMID:19038970 supporting_text: human MTMR6 forms a heteromer with an enzymatically inactive member myotubularin-related protein 9 (MTMR9), both in vitro and in cells - reference_id: PMID:19038970 supporting_text: MTMR9 increased the 3-phosphatase activity of MTMR6 up to 6-fold - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25416956 qualifier: enables supporting_entities: - UniProtKB:Q9Y6C2 review: summary: Generic protein binding with EMILIN1 (UniProtKB:Q9Y6C2) from a high-throughput interaction screen (PMID:25416956). action: REMOVE 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:27880917 qualifier: enables supporting_entities: - UniProtKB:Q96EF0 review: summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR8 (UniProtKB:Q96EF0) reported in PMID:27880917. action: MODIFY 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_replacement_terms: - id: GO:0019902 label: phosphatase binding supported_by: - reference_id: PMID:16787938 supporting_text: 'identified novel heteromeric interactions: MTMR8 with MTMR9' - reference_id: PMID:22647598 supporting_text: MTMR8, all of which dimerize with the catalytically inactive MTMR9 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:27880917 qualifier: enables supporting_entities: - UniProtKB:Q9Y216 review: summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR7 (UniProtKB:Q9Y216) reported in PMID:27880917. action: MODIFY 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_replacement_terms: - id: GO:0019902 label: phosphatase binding supported_by: - reference_id: PMID:12890864 supporting_text: The coiled-coil domain of MTMR9 was sufficient for binding to MTMR7 - reference_id: PMID:12890864 supporting_text: The binding of MTMR9 increased the Ins(1,3)P2 phosphatase activity of MTMR7 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:27880917 qualifier: enables supporting_entities: - UniProtKB:Q9Y217 review: summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR6 (UniProtKB:Q9Y217) reported in PMID:27880917. action: MODIFY 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_replacement_terms: - id: GO:0019902 label: phosphatase binding supported_by: - reference_id: PMID:19038970 supporting_text: human MTMR6 forms a heteromer with an enzymatically inactive member myotubularin-related protein 9 (MTMR9), both in vitro and in cells - reference_id: PMID:19038970 supporting_text: MTMR9 increased the 3-phosphatase activity of MTMR6 up to 6-fold - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:28514442 qualifier: enables supporting_entities: - UniProtKB:Q96EF0 review: summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR8 (UniProtKB:Q96EF0) reported in PMID:28514442. action: MODIFY 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_replacement_terms: - id: GO:0019902 label: phosphatase binding supported_by: - reference_id: PMID:16787938 supporting_text: 'identified novel heteromeric interactions: MTMR8 with MTMR9' - reference_id: PMID:22647598 supporting_text: MTMR8, all of which dimerize with the catalytically inactive MTMR9 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:28514442 qualifier: enables supporting_entities: - UniProtKB:Q9Y216 review: summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR7 (UniProtKB:Q9Y216) reported in PMID:28514442. action: MODIFY 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_replacement_terms: - id: GO:0019902 label: phosphatase binding supported_by: - reference_id: PMID:12890864 supporting_text: The coiled-coil domain of MTMR9 was sufficient for binding to MTMR7 - reference_id: PMID:12890864 supporting_text: The binding of MTMR9 increased the Ins(1,3)P2 phosphatase activity of MTMR7 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:29892012 qualifier: enables supporting_entities: - UniProtKB:P00540 review: summary: Generic protein binding with MOS (UniProtKB:P00540) from a high-throughput interaction screen (PMID:29892012). action: REMOVE 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:29892012 qualifier: enables supporting_entities: - UniProtKB:Q8TBB1 review: summary: Generic protein binding with LNX1 (UniProtKB:Q8TBB1) from a high-throughput interaction screen (PMID:29892012). action: REMOVE 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:29892012 qualifier: enables supporting_entities: - UniProtKB:Q96EF0 review: summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR8 (UniProtKB:Q96EF0) reported in PMID:29892012. action: MODIFY 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_replacement_terms: - id: GO:0019902 label: phosphatase binding supported_by: - reference_id: PMID:16787938 supporting_text: 'identified novel heteromeric interactions: MTMR8 with MTMR9' - reference_id: PMID:22647598 supporting_text: MTMR8, all of which dimerize with the catalytically inactive MTMR9 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:29892012 qualifier: enables supporting_entities: - UniProtKB:Q9Y216 review: summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR7 (UniProtKB:Q9Y216) reported in PMID:29892012. action: MODIFY 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_replacement_terms: - id: GO:0019902 label: phosphatase binding supported_by: - reference_id: PMID:12890864 supporting_text: The coiled-coil domain of MTMR9 was sufficient for binding to MTMR7 - reference_id: PMID:12890864 supporting_text: The binding of MTMR9 increased the Ins(1,3)P2 phosphatase activity of MTMR7 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:29892012 qualifier: enables supporting_entities: - UniProtKB:Q9Y6C2 review: summary: Generic protein binding with EMILIN1 (UniProtKB:Q9Y6C2) from a high-throughput interaction screen (PMID:29892012). action: REMOVE 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:31515488 qualifier: enables supporting_entities: - UniProtKB:P00540 review: summary: Generic protein binding with MOS (UniProtKB:P00540) from a high-throughput interaction screen (PMID:31515488). action: REMOVE 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:31515488 qualifier: enables supporting_entities: - UniProtKB:Q8TBB1 review: summary: Generic protein binding with LNX1 (UniProtKB:Q8TBB1) from a high-throughput interaction screen (PMID:31515488). action: REMOVE 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:31515488 qualifier: enables supporting_entities: - UniProtKB:Q96EF0 review: summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR8 (UniProtKB:Q96EF0) reported in PMID:31515488. action: MODIFY 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_replacement_terms: - id: GO:0019902 label: phosphatase binding supported_by: - reference_id: PMID:16787938 supporting_text: 'identified novel heteromeric interactions: MTMR8 with MTMR9' - reference_id: PMID:22647598 supporting_text: MTMR8, all of which dimerize with the catalytically inactive MTMR9 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:31515488 qualifier: enables supporting_entities: - UniProtKB:Q9Y216 review: summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR7 (UniProtKB:Q9Y216) reported in PMID:31515488. action: MODIFY 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_replacement_terms: - id: GO:0019902 label: phosphatase binding supported_by: - reference_id: PMID:12890864 supporting_text: The coiled-coil domain of MTMR9 was sufficient for binding to MTMR7 - reference_id: PMID:12890864 supporting_text: The binding of MTMR9 increased the Ins(1,3)P2 phosphatase activity of MTMR7 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:31515488 qualifier: enables supporting_entities: - UniProtKB:Q9Y6C2 review: summary: Generic protein binding with EMILIN1 (UniProtKB:Q9Y6C2) from a high-throughput interaction screen (PMID:31515488). action: REMOVE 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables supporting_entities: - UniProtKB:A8MW99 review: summary: Generic protein binding with MEI4 (UniProtKB:A8MW99) from a high-throughput interaction screen (PMID:32296183). action: REMOVE 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables supporting_entities: - UniProtKB:O75140-2 review: summary: Generic protein binding with DEPDC5 (UniProtKB:O75140-2) from a high-throughput interaction screen (PMID:32296183). action: REMOVE 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables supporting_entities: - UniProtKB:P26045 review: summary: Generic protein binding with PTPN3 (UniProtKB:P26045) from a high-throughput interaction screen (PMID:32296183). action: REMOVE 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables supporting_entities: - UniProtKB:Q0VD86 review: summary: Generic protein binding with INCA1 (UniProtKB:Q0VD86) from a high-throughput interaction screen (PMID:32296183). action: REMOVE 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables supporting_entities: - UniProtKB:Q13287 review: summary: Generic protein binding with NMI (UniProtKB:Q13287) from a high-throughput interaction screen (PMID:32296183). action: REMOVE 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables supporting_entities: - UniProtKB:Q6IC98 review: summary: Generic protein binding with GRAMD4 (UniProtKB:Q6IC98) from a high-throughput interaction screen (PMID:32296183). action: REMOVE 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables supporting_entities: - UniProtKB:Q7Z3Y8 review: summary: Generic protein binding with KRT27 (UniProtKB:Q7Z3Y8) from a high-throughput interaction screen (PMID:32296183). action: REMOVE 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables supporting_entities: - UniProtKB:Q7Z6G3-2 review: summary: Generic protein binding with NECAB2 (UniProtKB:Q7Z6G3-2) from a high-throughput interaction screen (PMID:32296183). action: REMOVE 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables supporting_entities: - UniProtKB:Q86T90 review: summary: Generic protein binding with KIAA1328 (UniProtKB:Q86T90) from a high-throughput interaction screen (PMID:32296183). action: REMOVE 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables supporting_entities: - UniProtKB:Q8N720 review: summary: Generic protein binding with ZNF655 (UniProtKB:Q8N720) from a high-throughput interaction screen (PMID:32296183). action: REMOVE 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables supporting_entities: - UniProtKB:Q9Y216 review: summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR7 (UniProtKB:Q9Y216) reported in PMID:32296183. action: MODIFY 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_replacement_terms: - id: GO:0019902 label: phosphatase binding supported_by: - reference_id: PMID:12890864 supporting_text: The coiled-coil domain of MTMR9 was sufficient for binding to MTMR7 - reference_id: PMID:12890864 supporting_text: The binding of MTMR9 increased the Ins(1,3)P2 phosphatase activity of MTMR7 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables supporting_entities: - UniProtKB:Q9Y217 review: summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR6 (UniProtKB:Q9Y217) reported in PMID:32296183. action: MODIFY 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_replacement_terms: - id: GO:0019902 label: phosphatase binding supported_by: - reference_id: PMID:19038970 supporting_text: human MTMR6 forms a heteromer with an enzymatically inactive member myotubularin-related protein 9 (MTMR9), both in vitro and in cells - reference_id: PMID:19038970 supporting_text: MTMR9 increased the 3-phosphatase activity of MTMR6 up to 6-fold - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables supporting_entities: - UniProtKB:Q9Y6C2-2 review: summary: Generic protein binding with EMILIN1 (UniProtKB:Q9Y6C2-2) from a high-throughput interaction screen (PMID:32296183). action: REMOVE 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables supporting_entities: - UniProtKB:Q9Y6X4 review: summary: Generic protein binding with FAM169A (UniProtKB:Q9Y6X4) from a high-throughput interaction screen (PMID:32296183). action: REMOVE 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:33961781 qualifier: enables supporting_entities: - UniProtKB:Q96EF0 review: summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR8 (UniProtKB:Q96EF0) reported in PMID:33961781. action: MODIFY 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_replacement_terms: - id: GO:0019902 label: phosphatase binding supported_by: - reference_id: PMID:16787938 supporting_text: 'identified novel heteromeric interactions: MTMR8 with MTMR9' - reference_id: PMID:22647598 supporting_text: MTMR8, all of which dimerize with the catalytically inactive MTMR9 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:33961781 qualifier: enables supporting_entities: - UniProtKB:Q9Y216 review: summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR7 (UniProtKB:Q9Y216) reported in PMID:33961781. action: MODIFY 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_replacement_terms: - id: GO:0019902 label: phosphatase binding supported_by: - reference_id: PMID:12890864 supporting_text: The coiled-coil domain of MTMR9 was sufficient for binding to MTMR7 - reference_id: PMID:12890864 supporting_text: The binding of MTMR9 increased the Ins(1,3)P2 phosphatase activity of MTMR7 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:33961781 qualifier: enables supporting_entities: - UniProtKB:Q9Y217 review: summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR6 (UniProtKB:Q9Y217) reported in PMID:33961781. action: MODIFY 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_replacement_terms: - id: GO:0019902 label: phosphatase binding supported_by: - reference_id: PMID:19038970 supporting_text: human MTMR6 forms a heteromer with an enzymatically inactive member myotubularin-related protein 9 (MTMR9), both in vitro and in cells - reference_id: PMID:19038970 supporting_text: MTMR9 increased the 3-phosphatase activity of MTMR6 up to 6-fold - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:40205054 qualifier: enables supporting_entities: - UniProtKB:Q96EF0 review: summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR8 (UniProtKB:Q96EF0) reported in PMID:40205054. action: MODIFY 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_replacement_terms: - id: GO:0019902 label: phosphatase binding supported_by: - reference_id: PMID:16787938 supporting_text: 'identified novel heteromeric interactions: MTMR8 with MTMR9' - reference_id: PMID:22647598 supporting_text: MTMR8, all of which dimerize with the catalytically inactive MTMR9 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:40205054 qualifier: enables supporting_entities: - UniProtKB:Q9Y216 review: summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR7 (UniProtKB:Q9Y216) reported in PMID:40205054. action: MODIFY 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_replacement_terms: - id: GO:0019902 label: phosphatase binding supported_by: - reference_id: PMID:12890864 supporting_text: The coiled-coil domain of MTMR9 was sufficient for binding to MTMR7 - reference_id: PMID:12890864 supporting_text: The binding of MTMR9 increased the Ins(1,3)P2 phosphatase activity of MTMR7 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:40205054 qualifier: enables supporting_entities: - UniProtKB:Q9Y217 review: summary: Interaction of MTMR9 with the active myotubularin lipid phosphatase MTMR6 (UniProtKB:Q9Y217) reported in PMID:40205054. action: MODIFY 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_replacement_terms: - id: GO:0019902 label: phosphatase binding supported_by: - reference_id: PMID:19038970 supporting_text: human MTMR6 forms a heteromer with an enzymatically inactive member myotubularin-related protein 9 (MTMR9), both in vitro and in cells - reference_id: PMID:19038970 supporting_text: MTMR9 increased the 3-phosphatase activity of MTMR6 up to 6-fold - term: id: GO:0005737 label: cytoplasm evidence_type: EXP original_reference_id: PMID:19038970 qualifier: located_in review: summary: MTMR9 is a soluble intracellular protein found in the cytoplasm, partly on membranes. action: ACCEPT 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. supported_by: - reference_id: PMID:19038970 supporting_text: human MTMR6 forms a heteromer with an enzymatically inactive member myotubularin-related protein 9 (MTMR9), both in vitro and in cells - reference_id: file:human/MTMR9/MTMR9-uniprot.txt record_section: ["CC:SUBCELLULAR LOCATION"] supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16787938,' - term: id: GO:0005737 label: cytoplasm evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in supporting_entities: - AGI_LocusCode:AT3G10550 - AGI_LocusCode:AT5G04540 - FB:FBgn0025742 - FB:FBgn0025802 - MGI:MGI:1099452 - MGI:MGI:1858271 - MGI:MGI:1891693 - MGI:MGI:1921831 - MGI:MGI:1924366 - MGI:MGI:2145637 - MGI:MGI:2442842 - MGI:MGI:2443034 - PANTHER:PTN000743854 - RGD:1305378 - RGD:1311865 - UniProtKB:A4FU01 - UniProtKB:O95248 - UniProtKB:Q13496 - UniProtKB:Q13613 - UniProtKB:Q13614 - UniProtKB:Q13615 - UniProtKB:Q585F9 - UniProtKB:Q86WG5 - UniProtKB:Q96EF0 - UniProtKB:Q96QG7 - UniProtKB:Q9C0I1 - UniProtKB:Q9NXD2 - UniProtKB:Q9NYA4 - UniProtKB:Q9Y216 - UniProtKB:Q9Y217 - WB:WBGene00003475 - WB:WBGene00003476 - WB:WBGene00003478 - WB:WBGene00003479 review: summary: MTMR9 is a soluble intracellular protein found in the cytoplasm, partly on membranes. action: ACCEPT 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. supported_by: - reference_id: file:human/MTMR9/MTMR9-uniprot.txt record_section: ["CC:SUBCELLULAR LOCATION"] supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16787938,' - term: id: GO:0005737 label: cytoplasm evidence_type: IDA original_reference_id: PMID:16787938 qualifier: located_in review: summary: MTMR9 is a soluble intracellular protein found in the cytoplasm, partly on membranes. action: ACCEPT 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. supported_by: - reference_id: file:human/MTMR9/MTMR9-uniprot.txt record_section: ["CC:SUBCELLULAR LOCATION"] supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16787938,' - term: id: GO:0005737 label: cytoplasm evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in supporting_entities: - UniProtKB-SubCell:SL-0086 review: summary: MTMR9 is a soluble intracellular protein found in the cytoplasm, partly on membranes. action: ACCEPT 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. supported_by: - reference_id: file:human/MTMR9/MTMR9-uniprot.txt record_section: ["CC:SUBCELLULAR LOCATION"] supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16787938,' - term: id: GO:0005783 label: endoplasmic reticulum evidence_type: EXP original_reference_id: PMID:19038970 qualifier: located_in review: summary: Partial endoplasmic reticulum localization of MTMR9 reported in PMID:19038970. action: KEEP_AS_NON_CORE 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). supported_by: - reference_id: file:human/MTMR9/MTMR9-uniprot.txt supporting_text: Endoplasmic reticulum {ECO:0000269|PubMed:19038970} - term: id: GO:0005783 label: endoplasmic reticulum evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in supporting_entities: - UniProtKB-SubCell:SL-0095 review: summary: Partial endoplasmic reticulum localization of MTMR9 reported in PMID:19038970. action: KEEP_AS_NON_CORE 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). supported_by: - reference_id: file:human/MTMR9/MTMR9-uniprot.txt supporting_text: Endoplasmic reticulum {ECO:0000269|PubMed:19038970} - term: id: GO:0005829 label: cytosol evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in supporting_entities: - ARBA:ARBA00029243 review: summary: MTMR9 acts as a soluble cytosolic protein that engages myotubularin partners at the cytosolic face of membranes. action: ACCEPT 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. supported_by: - reference_id: file:human/MTMR9/MTMR9-uniprot.txt record_section: ["CC:SUBCELLULAR LOCATION"] supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16787938,' - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-6809254 qualifier: located_in review: summary: MTMR9 acts as a soluble cytosolic protein that engages myotubularin partners at the cytosolic face of membranes. action: ACCEPT 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. supported_by: - reference_id: Reactome:R-HSA-6809254 supporting_text: MTMR8 binds to MTMR9, an enzymatically inactive myotubularin family member, which results in increased stability and increased catalytic activity of MTMR8 - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-6809309 qualifier: located_in review: summary: MTMR9 acts as a soluble cytosolic protein that engages myotubularin partners at the cytosolic face of membranes. action: ACCEPT 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. supported_by: - reference_id: Reactome:R-HSA-6809309 supporting_text: MTMR6 binds to MTMR9, an enzymatically inactive myotubularin family member, which leads to increased catalytic activity of MTMR6 - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-6809320 qualifier: located_in review: summary: MTMR9 acts as a soluble cytosolic protein that engages myotubularin partners at the cytosolic face of membranes. action: ACCEPT 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. supported_by: - reference_id: Reactome:R-HSA-6809320 supporting_text: Formation of a complex with MTMR9 results in a 30-fold increase of phosphatidylinositol-(3,5)-bisphosphate 3-phosphatase catalytic activity of MTMR6 - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-6809325 qualifier: located_in review: summary: MTMR9 acts as a soluble cytosolic protein that engages myotubularin partners at the cytosolic face of membranes. action: ACCEPT 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. supported_by: - reference_id: Reactome:R-HSA-6809325 supporting_text: Formation of a complex with MTMR9 results in a 4-fold increase of the phosphatidylinositol-3-phosphatase catalytic activity of MTMR8 - term: id: GO:0006661 label: phosphatidylinositol biosynthetic process evidence_type: TAS original_reference_id: Reactome:R-HSA-1660499 qualifier: involved_in review: summary: Reactome places MTMR9 in 'Synthesis of PIPs at the plasma membrane' through the MTMR9-bound MTMR6/MTMR8 dephosphorylation reactions. action: MODIFY 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_replacement_terms: - id: GO:0046856 label: phosphatidylinositol dephosphorylation supported_by: - reference_id: Reactome:R-HSA-1660499 supporting_text: Enzymatically inactive myotubularin family members can heterodimerize with catalytically active mytotubularins to regulate their stability, activity and/or substrate specificity - reference_id: Reactome:R-HSA-6809320 supporting_text: Formation of a complex with MTMR9 results in a 30-fold increase of phosphatidylinositol-(3,5)-bisphosphate 3-phosphatase catalytic activity of MTMR6 - reference_id: Reactome:R-HSA-6809325 supporting_text: Formation of a complex with MTMR9 results in a 4-fold increase of the phosphatidylinositol-3-phosphatase catalytic activity of MTMR8 - term: id: GO:0010507 label: negative regulation of autophagy evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in supporting_entities: - PANTHER:PTN002246859 - UniProtKB:Q96QG7 review: summary: MTMR8-MTMR9 complex lowers cellular PI3P and suppresses autophagy in HeLa-cell experiments. action: KEEP_AS_NON_CORE 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.' supported_by: - reference_id: PMID:22647598 supporting_text: the MTMR8/R9 complex inhibits autophagy - reference_id: PMID:22647598 supporting_text: the MTMR8/R9 complex reduces cellular PtdIns(3)P levels propagation_review: root_cause: NO_FAILURE_NON_CORE failure_modes: [] source_entities: - source_id: PANTHER:PTN002246859 comment: Node seeded by MTMR9's own experimental annotation (PMID:22647598); transfer within the MTMR9 lineage is sound. source_status: SUPPORTS_TRANSFER - term: id: GO:0010507 label: negative regulation of autophagy evidence_type: IPI original_reference_id: PMID:22647598 qualifier: involved_in supporting_entities: - UniProtKB:Q96EF0-1 review: summary: MTMR8-MTMR9 complex lowers cellular PI3P and suppresses autophagy in HeLa-cell experiments. action: KEEP_AS_NON_CORE 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.' supported_by: - reference_id: PMID:22647598 supporting_text: the MTMR8/R9 complex inhibits autophagy - reference_id: PMID:22647598 supporting_text: the MTMR8/R9 complex reduces cellular PtdIns(3)P levels - term: id: GO:0010922 label: positive regulation of phosphatase activity evidence_type: IDA original_reference_id: PMID:22647598 qualifier: involved_in review: summary: MTMR9 increases the catalytic activity of the active myotubularins MTMR6, MTMR7 and MTMR8. action: ACCEPT 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.' supported_by: - reference_id: PMID:22647598 supporting_text: Complex formation between the active myotubularins and MTMR9 increases their catalytic activity and alters their substrate specificity - reference_id: PMID:19038970 supporting_text: MTMR9 increased the 3-phosphatase activity of MTMR6 up to 6-fold - term: id: GO:0019211 label: phosphatase activator activity evidence_type: EXP original_reference_id: PMID:19038970 qualifier: enables review: summary: MTMR9 binds and activates the lipid phosphatases MTMR6, MTMR7 and MTMR8. action: ACCEPT 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). supported_by: - reference_id: PMID:19038970 supporting_text: MTMR9 increased the 3-phosphatase activity of MTMR6 up to 6-fold - reference_id: PMID:22647598 supporting_text: Complex formation between the active myotubularins and MTMR9 increases their catalytic activity and alters their substrate specificity - reference_id: PMID:12890864 supporting_text: The binding of MTMR9 increased the Ins(1,3)P2 phosphatase activity of MTMR7 - reference_id: file:human/MTMR9/MTMR9-uniprot.txt record_section: ["CC:CAUTION"] supporting_text: lacks the conserved active site cysteine residue at position - reference_id: file:human/MTMR9/MTMR9-bioinformatics/RESULTS-rereview.md supporting_text: MTMR9 lacks both the catalytic cysteine and the catalytic arginine - term: id: GO:0019211 label: phosphatase activator activity evidence_type: EXP original_reference_id: PMID:22647598 qualifier: enables review: summary: MTMR9 binds and activates the lipid phosphatases MTMR6, MTMR7 and MTMR8. action: ACCEPT 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). supported_by: - reference_id: PMID:19038970 supporting_text: MTMR9 increased the 3-phosphatase activity of MTMR6 up to 6-fold - reference_id: PMID:22647598 supporting_text: Complex formation between the active myotubularins and MTMR9 increases their catalytic activity and alters their substrate specificity - reference_id: PMID:12890864 supporting_text: The binding of MTMR9 increased the Ins(1,3)P2 phosphatase activity of MTMR7 - reference_id: file:human/MTMR9/MTMR9-uniprot.txt record_section: ["CC:CAUTION"] supporting_text: lacks the conserved active site cysteine residue at position - reference_id: file:human/MTMR9/MTMR9-bioinformatics/RESULTS-rereview.md supporting_text: MTMR9 lacks both the catalytic cysteine and the catalytic arginine - term: id: GO:0019903 label: protein phosphatase binding evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables supporting_entities: - PANTHER:PTN002246859 - UniProtKB:Q96QG7 review: summary: MTMR9 binds the myotubularin lipid phosphatases MTMR6 and MTMR8 (and MTMR7). action: MODIFY 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_replacement_terms: - id: GO:0019902 label: phosphatase binding supported_by: - reference_id: PMID:16787938 supporting_text: 'identified novel heteromeric interactions: MTMR8 with MTMR9' - reference_id: PMID:19038970 supporting_text: human MTMR6 forms a heteromer with an enzymatically inactive member myotubularin-related protein 9 (MTMR9), both in vitro and in cells - reference_id: PMID:22647598 supporting_text: MTMR8, all of which dimerize with the catalytically inactive MTMR9 propagation_review: root_cause: TERM_SCOPING_PROBLEM failure_modes: - GRANULARITY_MISMATCH source_entities: - source_id: PANTHER:PTN002246859 comment: 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. source_status: SUPPORTS_TRANSFER - source_id: UniProtKB:Q96QG7 comment: The target's own IPI annotations (PMID:16787938) seed the node; this is expected, not circular. source_status: SUPPORTS_TRANSFER - term: id: GO:0019903 label: protein phosphatase binding evidence_type: IPI original_reference_id: PMID:16787938 qualifier: enables supporting_entities: - UniProtKB:Q96EF0 review: summary: MTMR9 binds the myotubularin lipid phosphatases MTMR6 and MTMR8 (and MTMR7). action: MODIFY 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_replacement_terms: - id: GO:0019902 label: phosphatase binding supported_by: - reference_id: PMID:16787938 supporting_text: 'identified novel heteromeric interactions: MTMR8 with MTMR9' - reference_id: PMID:19038970 supporting_text: human MTMR6 forms a heteromer with an enzymatically inactive member myotubularin-related protein 9 (MTMR9), both in vitro and in cells - reference_id: PMID:22647598 supporting_text: MTMR8, all of which dimerize with the catalytically inactive MTMR9 - term: id: GO:0019903 label: protein phosphatase binding evidence_type: IPI original_reference_id: PMID:16787938 qualifier: enables supporting_entities: - UniProtKB:Q9Y217 review: summary: MTMR9 binds the myotubularin lipid phosphatases MTMR6 and MTMR8 (and MTMR7). action: MODIFY 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_replacement_terms: - id: GO:0019902 label: phosphatase binding supported_by: - reference_id: PMID:16787938 supporting_text: 'identified novel heteromeric interactions: MTMR8 with MTMR9' - reference_id: PMID:19038970 supporting_text: human MTMR6 forms a heteromer with an enzymatically inactive member myotubularin-related protein 9 (MTMR9), both in vitro and in cells - reference_id: PMID:22647598 supporting_text: MTMR8, all of which dimerize with the catalytically inactive MTMR9 - term: id: GO:0030234 label: enzyme regulator activity evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: enables supporting_entities: - ARBA:ARBA00026580 - UniProtKB:Q9Z2D0 - ensembl:ENSMUSP00000059894 review: summary: Electronic enzyme regulator activity, correct but general. action: MODIFY 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_replacement_terms: - id: GO:0019211 label: phosphatase activator activity supported_by: - reference_id: PMID:19038970 supporting_text: MTMR9 increased the 3-phosphatase activity of MTMR6 up to 6-fold - reference_id: PMID:22647598 supporting_text: Complex formation between the active myotubularins and MTMR9 increases their catalytic activity and alters their substrate specificity - term: id: GO:0032587 label: ruffle membrane evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in supporting_entities: - UniProtKB-SubCell:SL-0301 review: summary: Ruffle membrane localization, transferred in UniProt from mouse Mtmr9 during EGF-induced macropinocytosis. action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/MTMR9/MTMR9-uniprot.txt record_section: ["CC:SUBCELLULAR LOCATION"] supporting_text: Localizes to ruffles during EGF-induced macropinocytosis (By similarity) - reference_id: PMID:24591580 supporting_text: its binding partner MTMR9, are required for macropinocytosis - term: id: GO:0032991 label: protein-containing complex evidence_type: IDA original_reference_id: PMID:22647598 qualifier: part_of review: summary: MTMR9 forms heterodimeric complexes with MTMR6, MTMR7 and MTMR8. action: ACCEPT 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.' supported_by: - reference_id: PMID:22647598 supporting_text: MTMR8, all of which dimerize with the catalytically inactive MTMR9 - reference_id: PMID:19038970 supporting_text: human MTMR6 forms a heteromer with an enzymatically inactive member myotubularin-related protein 9 (MTMR9), both in vitro and in cells - term: id: GO:0046856 label: phosphatidylinositol dephosphorylation evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in supporting_entities: - MGI:MGI:1891693 - PANTHER:PTN008506586 - UniProtKB:Q96EF0 - UniProtKB:Q9Y217 review: summary: Phosphatidylinositol dephosphorylation by MTMR9-containing dimers, propagated from the eukaryotic myotubularin node. action: ACCEPT 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.' supported_by: - reference_id: PMID:22647598 supporting_text: Complex formation between the active myotubularins and MTMR9 increases their catalytic activity and alters their substrate specificity - reference_id: Reactome:R-HSA-6809320 supporting_text: Formation of a complex with MTMR9 results in a 30-fold increase of phosphatidylinositol-(3,5)-bisphosphate 3-phosphatase catalytic activity of MTMR6 - reference_id: Reactome:R-HSA-6809325 supporting_text: Formation of a complex with MTMR9 results in a 4-fold increase of the phosphatidylinositol-3-phosphatase catalytic activity of MTMR8 propagation_review: root_cause: NO_FAILURE_CORE failure_modes: [] source_entities: - source_id: PANTHER:PTN008506586 comment: 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. source_status: SUPPORTS_TRANSFER - term: id: GO:0048471 label: perinuclear region of cytoplasm evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in supporting_entities: - UniProtKB-SubCell:SL-0198 review: summary: MTMR9 colocalizes with MTMR6 in the perinuclear region. action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/MTMR9/MTMR9-uniprot.txt record_section: ["CC:SUBCELLULAR LOCATION"] supporting_text: Colocalizes with MTMR6 to the perinuclear region (PubMed:19038970) - term: id: GO:0050821 label: protein stabilization evidence_type: IDA original_reference_id: PMID:22647598 qualifier: involved_in review: summary: MTMR9 stabilizes its partner phosphatases MTMR6 and MTMR8 at the protein level. action: ACCEPT 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. supported_by: - reference_id: PMID:19038970 supporting_text: the formation of this heteromer in cells resulted in increased protein levels of both MTMR6 and MTMR9 - reference_id: Reactome:R-HSA-6809254 supporting_text: MTMR8 binds to MTMR9, an enzymatically inactive myotubularin family member, which results in increased stability and increased catalytic activity of MTMR8 - term: id: GO:0060304 label: regulation of phosphatidylinositol dephosphorylation evidence_type: IDA original_reference_id: PMID:22647598 qualifier: involved_in review: summary: MTMR9 regulates phosphatidylinositol dephosphorylation by controlling the activity and substrate preference of MTMR6 and MTMR8. action: ACCEPT 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). supported_by: - reference_id: PMID:22647598 supporting_text: Complex formation between the active myotubularins and MTMR9 increases their catalytic activity and alters their substrate specificity - reference_id: PMID:22647598 supporting_text: the MTMR8/R9 complex reduces cellular PtdIns(3)P levels references: - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: GO_REF:0000044 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt findings: [] - id: GO_REF:0000117 title: Electronic Gene Ontology annotations created by ARBA machine learning models findings: [] - id: GO_REF:0000120 title: Combined Automated Annotation using Multiple IEA Methods findings: [] - id: PMID:12890864 title: Characterization of myotubularin-related protein 7 and its binding partner, myotubularin-related protein 9. findings: [] full_text_unavailable: true reference_review: relevance: HIGH correctness: VERIFIED review_notes: Mouse MTMR7 study identifying MTMR9 as the MTMR7 partner via the MTMR9 coiled coil and showing MTMR9 increases MTMR7 Ins(1,3)P2 phosphatase activity. Same subfamily (PTHR10807:SF56) ortholog evidence. The GOA protein-binding row citing it lists partner Q59HJ6, which now resolves to bovine LONP1. - id: PMID:16189514 title: Towards a proteome-scale map of the human protein-protein interaction network. findings: [] full_text_unavailable: true reference_review: relevance: LOW correctness: VERIFIED review_notes: Proteome-scale interaction screen; source of generic protein-binding rows only. MTMR6/7/8 hits independently confirm known partners; other hits not followed up. - id: PMID:16787938 title: 'Systematic analysis of myotubularins: heteromeric interactions, subcellular localisation and endosome related functions.' findings: [] full_text_unavailable: true reference_review: relevance: HIGH correctness: VERIFIED review_notes: Systematic myotubularin interaction study; first report of MTMR8-MTMR9 heteromer; abstract-only cache. - id: PMID:19038970 title: MTMR9 increases MTMR6 enzyme activity, stability, and role in apoptosis. findings: [] full_text_unavailable: true reference_review: relevance: HIGH correctness: VERIFIED review_notes: 'Key study: MTMR6-MTMR9 heteromer, activation, mutual stabilization and anti-apoptotic role; abstract-only cache.' - id: PMID:19447967 title: Shifted Transversal Design smart-pooling for high coverage interactome mapping. findings: [] full_text_unavailable: true reference_review: relevance: LOW correctness: VERIFIED review_notes: Proteome-scale interaction screen; source of generic protein-binding rows only. MTMR6/7/8 hits independently confirm known partners; other hits not followed up. - id: PMID:21516116 title: Next-generation sequencing to generate interactome datasets. findings: [] full_text_unavailable: false reference_review: relevance: LOW correctness: VERIFIED review_notes: Proteome-scale interaction screen; source of generic protein-binding rows only. MTMR6/7/8 hits independently confirm known partners; other hits not followed up. - id: PMID:22647598 title: Myotubularin-related protein (MTMR) 9 determines the enzymatic activity, substrate specificity, and role in autophagy of MTMR8. findings: [] full_text_unavailable: true reference_review: relevance: HIGH correctness: VERIFIED review_notes: 'Key study: MTMR9 sets substrate specificity of MTMR6 vs MTMR8; MTMR8/R9 inhibits autophagy; abstract-only cache.' - id: PMID:25416956 title: A proteome-scale map of the human interactome network. findings: [] full_text_unavailable: false reference_review: relevance: LOW correctness: VERIFIED review_notes: Proteome-scale interaction screen; source of generic protein-binding rows only. MTMR6/7/8 hits independently confirm known partners; other hits not followed up. - id: PMID:27880917 title: Phenotypic and Interaction Profiling of the Human Phosphatases Identifies Diverse Mitotic Regulators. findings: [] full_text_unavailable: true reference_review: relevance: LOW correctness: VERIFIED review_notes: Proteome-scale interaction screen; source of generic protein-binding rows only. MTMR6/7/8 hits independently confirm known partners; other hits not followed up. - id: PMID:28514442 title: Architecture of the human interactome defines protein communities and disease networks. findings: [] full_text_unavailable: false reference_review: relevance: LOW correctness: VERIFIED review_notes: Proteome-scale interaction screen; source of generic protein-binding rows only. MTMR6/7/8 hits independently confirm known partners; other hits not followed up. - id: PMID:29892012 title: An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders. findings: [] full_text_unavailable: false reference_review: relevance: LOW correctness: VERIFIED review_notes: Proteome-scale interaction screen; source of generic protein-binding rows only. MTMR6/7/8 hits independently confirm known partners; other hits not followed up. - id: PMID:31515488 title: Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations. findings: [] full_text_unavailable: false reference_review: relevance: LOW correctness: VERIFIED review_notes: Proteome-scale interaction screen; source of generic protein-binding rows only. MTMR6/7/8 hits independently confirm known partners; other hits not followed up. - id: PMID:32296183 title: A reference map of the human binary protein interactome. findings: [] full_text_unavailable: false reference_review: relevance: LOW correctness: VERIFIED review_notes: Proteome-scale interaction screen; source of generic protein-binding rows only. MTMR6/7/8 hits independently confirm known partners; other hits not followed up. - id: PMID:33961781 title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. findings: [] full_text_unavailable: false reference_review: relevance: LOW correctness: VERIFIED review_notes: Proteome-scale interaction screen; source of generic protein-binding rows only. MTMR6/7/8 hits independently confirm known partners; other hits not followed up. - id: PMID:40205054 title: Multimodal cell maps as a foundation for structural and functional genomics. findings: [] full_text_unavailable: false reference_review: relevance: LOW correctness: VERIFIED review_notes: Proteome-scale interaction screen; source of generic protein-binding rows only. MTMR6/7/8 hits independently confirm known partners; other hits not followed up. - id: Reactome:R-HSA-1660499 title: Synthesis of PIPs at the plasma membrane findings: [] - id: Reactome:R-HSA-6809254 title: MTMR8 binds MTMR9 findings: [] - id: Reactome:R-HSA-6809309 title: MTMR6 binds MTMR9 findings: [] - id: Reactome:R-HSA-6809320 title: PI(3,5)P2 is dephosphorylated to PI5P by MTMR9-bound MTMR6 or MTMR8 at the plasma membrane findings: [] - id: Reactome:R-HSA-6809325 title: PI3P is dephosphorylated to PI by MTMR9-bound MTMR8 or MTMR6 at the plasma membrane findings: [] - id: file:human/MTMR9/MTMR9-uniprot.txt title: human/MTMR9/MTMR9-uniprot.txt findings: [] - id: PMID:24591580 title: Sequential breakdown of 3-phosphorylated phosphoinositides is essential for the completion of macropinocytosis. findings: [] full_text_unavailable: true reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: MTMR6 and its partner MTMR9 required for late macropinocytosis; abstract-only cache. Not used for a new annotation (necessity evidence). - id: file:human/MTMR9/MTMR9-bioinformatics/RESULTS-rereview.md title: MTMR9 catalytic-motif check (re-review) findings: [] core_functions: - description: 'Noncatalytic activating subunit of the myotubularin lipid phosphatases MTMR6, MTMR7 and MTMR8: heterodimerizes with them, raises their catalytic rate and sets their substrate preference (PI(3,5)P2 for MTMR6, PI3P for MTMR8), thereby regulating 3-phosphoinositide turnover.' molecular_function: id: GO:0019211 label: phosphatase activator activity directly_involved_in: - id: GO:0060304 label: regulation of phosphatidylinositol dephosphorylation - id: GO:0046856 label: phosphatidylinositol dephosphorylation locations: - id: GO:0005829 label: cytosol supported_by: - reference_id: PMID:19038970 supporting_text: MTMR9 increased the 3-phosphatase activity of MTMR6 up to 6-fold - reference_id: PMID:22647598 supporting_text: Complex formation between the active myotubularins and MTMR9 increases their catalytic activity and alters their substrate specificity - reference_id: PMID:22647598 supporting_text: the MTMR8/R9 complex reduces cellular PtdIns(3)P levels - reference_id: file:human/MTMR9/MTMR9-bioinformatics/RESULTS-rereview.md supporting_text: MTMR9 lacks both the catalytic cysteine and the catalytic arginine - description: Binds and stabilizes its active myotubularin partners (MTMR6, MTMR8), increasing their protein levels by slowing degradation. molecular_function: id: GO:0019902 label: phosphatase binding directly_involved_in: - id: GO:0050821 label: protein stabilization locations: - id: GO:0005737 label: cytoplasm supported_by: - reference_id: PMID:19038970 supporting_text: human MTMR6 forms a heteromer with an enzymatically inactive member myotubularin-related protein 9 (MTMR9), both in vitro and in cells - reference_id: PMID:19038970 supporting_text: the formation of this heteromer in cells resulted in increased protein levels of both MTMR6 and MTMR9 - reference_id: PMID:16787938 supporting_text: 'identified novel heteromeric interactions: MTMR8 with MTMR9' suggested_questions: - question: 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. - question: 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? - question: What is the MTMR9 homodimer for, and does MTMR9 partition between MTMR6, MTMR7 and MTMR8 in cells where all are expressed? suggested_experiments: - hypothesis: MTMR9 sets the substrate preference of MTMR6 and MTMR8 through its coiled-coil dimer interface. description: 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. experiment_type: biochemical assay - hypothesis: Endogenous MTMR9 restrains autophagy by limiting a PI3P pool via MTMR8. description: 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. experiment_type: genetic perturbation