family_id: PANTHER:PTHR10807 family_name: MYOTUBULARIN-RELATED preferred_name: Active and inactive myotubularins summary: Myotubularins include phosphoinositide phosphatases and inactive partners such as MTMR9 and MTMR12. Inactive homologs can stabilize and regulate active partners while lacking the intrinsic catalytic reaction. functional_coherence: HETEROGENEOUS coherence_reason: Experiments on MTMR6-MTMR9 distinguish partner stabilization and increased phosphatase output from MTMR9 catalysis. The mussel target's catalytic-site status and the horse MTMR9 internal deletion require sequence-level scrutiny. Catalytic activity, phosphatase regulation, binding and autophagy phenotypes must not be transferred as one package. subfamilies: - subfamily_id: PANTHER:PTHR10807:SF37 label: MYOTUBULARIN-RELATED PROTEIN 12 description: MTMR12 is a catalytically inactive MTM1 partner that primarily maintains MTM1 protein levels. The rat selected product preserves the complete reference phosphatase-like domain, but its alternative N-terminus and computational signal-peptide call make exact-product cytoplasmic targeting uncertain. representative_members: - id: UniProtKB:A0A8I5ZMD5 gene_symbol: Mtmr12 organism: Rattus norvegicus gene_review: genes/rat/Mtmr12/Mtmr12-ai-review.yaml - subfamily_id: PANTHER:PTHR10807:SF56 label: MYOTUBULARIN-RELATED PROTEIN 9 description: Recorded placement of MTMR9, MTMR9. Experiments on MTMR6-MTMR9 distinguish partner stabilization and increased phosphatase output from MTMR9 catalysis. The mussel target's catalytic-site status and the horse MTMR9 internal deletion require sequence-level scrutiny. Catalytic activity, phosphatase regulation, binding and autophagy phenotypes must not be transferred as one package. representative_members: - id: UniProtKB:A0A9L0T3C1 gene_symbol: MTMR9 organism: Equus caballus gene_review: genes/HORSE/MTMR9/MTMR9-ai-review.yaml - id: UniProtKB:Q96QG7 gene_symbol: MTMR9 organism: Homo sapiens gene_review: genes/human/MTMR9/MTMR9-ai-review.yaml - subfamily_id: PANTHER:PTHR10807:SF73 label: LD06050P description: Recorded placement of A0A8B6GS20. Experiments on MTMR6-MTMR9 distinguish partner stabilization and increased phosphatase output from MTMR9 catalysis. The mussel target's catalytic-site status and the horse MTMR9 internal deletion require sequence-level scrutiny. Catalytic activity, phosphatase regulation, binding and autophagy phenotypes must not be transferred as one package. representative_members: - id: UniProtKB:A0A8B6GS20 gene_symbol: A0A8B6GS20 organism: Mytilus galloprovincialis gene_review: genes/MYTGA/A0A8B6GS20/A0A8B6GS20-ai-review.yaml term_assessments: - assessed_term: id: GO:0004438 label: phosphatidylinositol-3-phosphate phosphatase activity scope: UNRESOLVED scope_reason: 'For phosphatidylinositol-3-phosphate phosphatase activity: Experiments on MTMR6-MTMR9 distinguish partner stabilization and increased phosphatase output from MTMR9 catalysis. The mussel target''s catalytic-site status and the horse MTMR9 internal deletion require sequence-level scrutiny. Catalytic activity, phosphatase regulation, binding and autophagy phenotypes must not be transferred as one package. The evidence does not establish a safe grant to every family member or a complete set of applicable PANTHER subfamilies.' supported_by: - reference_id: PMID:22647598 supporting_text: inactive because they lack the conserved cysteine residue - reference_id: file:genes/MYTGA/A0A8B6GS20/A0A8B6GS20-uniprot.txt supporting_text: DR InterPro; IPR010569; Myotubularin-like_Pase_dom. - reference_id: file:genes/MYTGA/A0A8B6GS20/A0A8B6GS20-uniprot.txt supporting_text: FT DOMAIN 372..544 - reference_id: file:genes/MYTGA/A0A8B6GS20/A0A8B6GS20-uniprot.txt supporting_text: FT /note="Myotubularin phosphatase" - reference_id: PMID:23818870 supporting_text: the catalytically inactive MTMR12 only partially but significantly rescues myotubularin function - assessed_term: id: GO:0010922 label: positive regulation of phosphatase activity scope: UNRESOLVED scope_reason: MTMR9 experiments establish increased catalytic output of active myotubularin partners, and this is a regulatory action rather than intrinsic phosphatase activity. The family contains several other inactive myotubularins and diverse active/inactive partner combinations. The inspected MTMR9 experiments do not establish that positive regulation is absent from every other branch or enumerate all positive regulators. Applicability therefore remains unresolved at the complete family-boundary level, with the horse MTMR9 deletion an additional target-specific qualification. 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: file:genes/HORSE/MTMR9/MTMR9-bioinformatics/RESULTS.md supporting_text: The selected horse sequence lacks human residues 98–139, crossing the GRAM-domain/myotubularin-domain junction; the C-terminal region implicated in partner association is retained. Complex formation and downstream regulation remain inferences with a gene-model caveat. - assessed_term: id: GO:0010507 label: negative regulation of autophagy scope: UNRESOLVED scope_reason: 'For negative regulation of autophagy: Experiments on MTMR6-MTMR9 distinguish partner stabilization and increased phosphatase output from MTMR9 catalysis. The mussel target''s catalytic-site status and the horse MTMR9 internal deletion require sequence-level scrutiny. Catalytic activity, phosphatase regulation, binding and autophagy phenotypes must not be transferred as one package. The evidence does not establish a safe grant to every family member or a complete set of applicable PANTHER subfamilies.' supported_by: - reference_id: PMID:22647598 supporting_text: the MTMR8/R9 complex inhibits autophagy. - reference_id: file:genes/HORSE/MTMR9/MTMR9-bioinformatics/RESULTS.md supporting_text: The selected horse sequence lacks human residues 98–139, crossing the GRAM-domain/myotubularin-domain junction; the C-terminal region implicated in partner association is retained. Complex formation and downstream regulation remain inferences with a gene-model caveat. - assessed_term: id: GO:0050821 label: protein stabilization scope: UNRESOLVED scope_reason: Protein stabilization is directly supported for MTMR6-MTMR9 and for the MTM1-MTMR12 pair. The latter primarily affects MTM1 abundance rather than intrinsic enzyme activity. These positive systems do not establish universal stabilization of every family member or enumerate all relevant branches. The altered N-terminus of the selected rat MTMR12 product adds an exact-product trafficking qualification. 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, probably due to the inhibition of degradation of both proteins.' - 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: file:genes/HORSE/MTMR9/MTMR9-bioinformatics/RESULTS.md supporting_text: The selected horse sequence lacks human residues 98–139, crossing the GRAM-domain/myotubularin-domain junction; the C-terminal region implicated in partner association is retained. Complex formation and downstream regulation remain inferences with a gene-model caveat. - reference_id: PMID:23818870 supporting_text: MTMR12 primarily regulates the function of myotubularin protein by affecting protein levels instead of modulating the enzymatic activity - assessed_term: id: GO:0032991 label: protein-containing complex scope: UNRESOLVED scope_reason: 'For protein-containing complex: Experiments on MTMR6-MTMR9 distinguish partner stabilization and increased phosphatase output from MTMR9 catalysis. The mussel target''s catalytic-site status and the horse MTMR9 internal deletion require sequence-level scrutiny. Catalytic activity, phosphatase regulation, binding and autophagy phenotypes must not be transferred as one package. The evidence does not establish a safe grant to every family member or a complete set of applicable PANTHER subfamilies.' 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: file:genes/HORSE/MTMR9/MTMR9-bioinformatics/RESULTS.md supporting_text: The selected horse sequence lacks human residues 98–139, crossing the GRAM-domain/myotubularin-domain junction; the C-terminal region implicated in partner association is retained. Complex formation and downstream regulation remain inferences with a gene-model caveat. - assessed_term: id: GO:0019903 label: protein phosphatase binding scope: UNRESOLVED scope_reason: 'For protein phosphatase binding: Experiments on MTMR6-MTMR9 distinguish partner stabilization and increased phosphatase output from MTMR9 catalysis. The mussel target''s catalytic-site status and the horse MTMR9 internal deletion require sequence-level scrutiny. Catalytic activity, phosphatase regulation, binding and autophagy phenotypes must not be transferred as one package. The evidence does not establish a safe grant to every family member or a complete set of applicable PANTHER subfamilies.' 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: file:genes/HORSE/MTMR9/MTMR9-bioinformatics/RESULTS.md supporting_text: The selected horse sequence lacks human residues 98–139, crossing the GRAM-domain/myotubularin-domain junction; the C-terminal region implicated in partner association is retained. Complex formation and downstream regulation remain inferences with a gene-model caveat. - assessed_term: id: GO:0030234 label: enzyme regulator activity scope: UNRESOLVED scope_reason: MTMR9 is a positive experimentally supported example of an enzyme regulator in this family. Inactive homologs can regulate active partners without executing their reaction, but activity status alone does not establish each homolog's regulatory effect. Other myotubularin partner combinations have not been comprehensively adjudicated here. The MTMR9 example cannot be used as an exhaustive set of enzyme-regulatory subfamilies. 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: file:genes/HORSE/MTMR9/MTMR9-bioinformatics/RESULTS.md supporting_text: share 97.8% identity among 507 paired residues. Paired coverage is 92.3% of human and 100.0% of horse. - assessed_term: id: GO:0060304 label: regulation of phosphatidylinositol dephosphorylation scope: UNRESOLVED scope_reason: MTMR9-mediated changes in active myotubularin output support regulation of phosphatidylinositol dephosphorylation in that partner system. The relevant mechanism is partner regulation rather than intrinsic catalysis. The family contains other active/inactive pairs, and the inspected evidence does not delimit all branches capable of regulating the process. Family-level applicability remains unresolved without excluding those unenumerated branches. 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: file:genes/HORSE/MTMR9/MTMR9-bioinformatics/RESULTS.md supporting_text: The selected horse sequence lacks human residues 98–139, crossing the GRAM-domain/myotubularin-domain junction; the C-terminal region implicated in partner association is retained. Complex formation and downstream regulation remain inferences with a gene-model caveat. references: - id: PMID:19038970 title: MTMR9 increases MTMR6 enzyme activity, stability, and role in apoptosis. - id: PMID:22647598 title: Myotubularin-related protein (MTMR) 9 determines the enzymatic activity, substrate specificity, and role in autophagy of MTMR8. - id: file:genes/HORSE/MTMR9/MTMR9-bioinformatics/RESULTS.md - id: file:genes/MYTGA/A0A8B6GS20/A0A8B6GS20-uniprot.txt - id: file:interpro/panther/PTHR10807/PTHR10807-entries.csv - id: file:interpro/panther/PTHR10807/PTHR10807-paint.tsv - id: PMID:23818870 title: Loss of catalytically inactive lipid phosphatase myotubularin-related protein 12 impairs myotubularin stability and promotes centronuclear myopathy in zebrafish. - id: file:genes/rat/Mtmr12/Mtmr12-bioinformatics/RESULTS.md review_status: COMPLETE reviewed_by: codex review_date: '2026-09-10' notes: 'MYTGA/A0A8B6GS20: requested accession A0A8B6GS20; current record A0A8B6GS20; sequence length 607; source cohort ARGO50. HORSE/MTMR9: requested accession A0A9L0T3C1; current record A0A9L0T3C1; sequence length 507; source cohort HORSE40. human/MTMR9: requested accession Q96QG7; current record Q96QG7; sequence length 549; source cohort HORSE40_HUMAN_PAIR. rat/Mtmr12: requested accession A0A8I5ZMD5; current record A0A8I5ZMD5; sequence length 732; source cohort MOD_EVOLUTION20. Family boundaries were assessed using the fetched member set and the cited domain, literature and analytical evidence. Gene-review verdicts and ARBA assertions are not independent validation. PANTHER subfamily labels and membership are recorded from the frozen UniProt records and panther.obo; they do not by themselves prove functional uniformity within a subfamily. PAINT rows were inspected as ancestral assertions, but node placement is not adjudicated without the relevant descendant tree/alignment. No residue requirement is encoded without a verified sequence-version anchor. A target-level refutation is not a family-wide NOT_APPLICABLE judgment. Exact protein-name-only predictions are treated as family-identification hypotheses rather than invented GO predictions. The selected MTMR12 name predicts a phosphatase domain, not intrinsic phosphatase activity; it is a correct family-description claim. The exact rat domain maps at 439/439 identical residues to Q5FVM6. A predicted alternative signal peptide is not treated as demonstrated secretion.'