id: A0A9L0T3C1 gene_symbol: MTMR9 taxon: id: NCBITaxon:9796 label: Equus caballus status: COMPLETE description: MTMR9 regulatory, complex, and negative-autophagy predictions are supported; specific stabilization and protein-phosphatase-binding transfers remain uncertain for the shortened horse sequence. source_documents: - projects/PROTNLM_EVALUATION/mammal-benchmark/horse40-predictions.csv - projects/PROTNLM_EVALUATION/mammal-benchmark/predictions.jsonl.gz - projects/PROTNLM_EVALUATION/mammal-benchmark/paired-sequences/MTMR9.json - genes/HORSE/MTMR9/MTMR9-hypotheses/horse40-negative-autophagy-regulation/openscientist.md references: - id: PMID:22647598 title: Myotubularin-related protein (MTMR) 9 determines the enzymatic activity, substrate specificity, and role in autophagy of MTMR8. full_text_unavailable: true findings: [] - id: file:HORSE/MTMR9/MTMR9-bioinformatics/RESULTS.md title: HORSE/MTMR9/MTMR9-bioinformatics/RESULTS.md findings: [] - id: PMID:19038970 title: MTMR9 increases MTMR6 enzyme activity, stability, and role in apoptosis. full_text_unavailable: true findings: [] - id: file:HORSE/MTMR9/MTMR9-hypotheses/horse40-negative-autophagy-regulation/openscientist.md title: 'OpenScientist hypothesis run: MTMR9 negative regulation of autophagy' publication_type: DEEP_RESEARCH findings: - statement: OpenScientist confirmed that the shortened horse MTMR9 sequence retains the inactive PTP-like domain and C-terminal coiled-coil dimerization region needed for partner-mediated activity. supporting_text: The **PTP-like pseudophosphatase domain** (P-loop `LIHGTEGTDSTLQVT`) and the **C-terminal coiled-coil dimerization region** are fully conserved - statement: OpenScientist reported that the autophagy-suppressive role of MTMR9 is context- and partner-dependent rather than uniform across cell types, supporting a non-primary interpretation of GO:0010507. supporting_text: knockdown of MTMR5 or MTMR2, but not the unrelated phosphatase MTMR9, significantly enhances neuronal degradation of TDP-43 predictions: - source_method: ProtNLM2 source_version: UniProt API snapshot 2026-09-08 predicted_term: id: GO:0010922 label: positive regulation of phosphatase activity predicted_term_type: GO_BP review: assessment: COR confidence_score: 2 summary: Human MTMR9 directly complexes with and regulates MTMR6/MTMR8; catalytic inactivity of MTMR9 is compatible with this regulatory or complex-associated claim. The horse protein is 97.8% identical over 507 aligned residues, retaining the C-terminal association region. The 42-residue deletion at the GRAM/phosphatase-domain junction is a gene-model caveat, but does not remove the entire partner-binding region. This is an inferred conserved regulatory role, new relative to the frozen horse GOA, rather than evidence for intrinsic phosphatase catalysis. supported_by: - &id001 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: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. - source_method: ProtNLM2 source_version: UniProt API snapshot 2026-09-08 predicted_term: id: GO:0010507 label: negative regulation of autophagy predicted_term_type: GO_BP review: assessment: COR confidence_score: 2 summary: Human MTMR9 can contribute to negative regulation of autophagy as a catalytically inactive activating subunit of the MTMR8-MTMR9 phosphoinositide-phosphatase complex. The OpenScientist audit confirmed that the horse sequence is a 1:1 MTMR9 ortholog with an identical inactive P-loop and a conserved C-terminal coiled-coil dimerization region, resolving the 42-residue deletion as a gene-model caveat rather than loss of the partner-dependent mechanism. This role should be framed as a contributes_to, MTMR8-MTMR9-complex-mediated, context-dependent, non-primary autophagy effect; MTMR9 knockdown does not uniformly enhance autophagic clearance in neurons. The GO:0010507 prediction is supported by mammalian transfer, not direct horse evidence or an intrinsic lipid-phosphatase activity. supported_by: - reference_id: PMID:22647598 supporting_text: the MTMR8/R9 complex inhibits autophagy. - reference_id: file: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: file:HORSE/MTMR9/MTMR9-hypotheses/horse40-negative-autophagy-regulation/openscientist.md supporting_text: The **PTP-like pseudophosphatase domain** (P-loop `LIHGTEGTDSTLQVT`) and the **C-terminal coiled-coil dimerization region** are fully conserved - source_method: ProtNLM2 source_version: UniProt API snapshot 2026-09-08 predicted_term: id: GO:0050821 label: protein stabilization predicted_term_type: GO_BP review: assessment: UNC confidence_score: 1 summary: Human MTMR9 association stabilizes its partners, but protein stabilization is a specific downstream consequence of productive association. It is not established merely by sequence similarity, annotation overlap, or the domain conservation that supports complex-mediated autophagy transfer. Direct evidence that this shortened horse model retains partner stabilization is needed. 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.' - *id001 - reference_id: file: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. - source_method: ProtNLM2 source_version: UniProt API snapshot 2026-09-08 predicted_term: id: GO:0032991 label: protein-containing complex predicted_term_type: GO_CC review: assessment: COR confidence_score: 2 summary: Human MTMR9 directly complexes with and regulates MTMR6/MTMR8; catalytic inactivity of MTMR9 is compatible with this regulatory or complex-associated claim. The horse protein is 97.8% identical over 507 aligned residues, retaining the C-terminal association region. The 42-residue deletion at the GRAM/phosphatase-domain junction is a gene-model caveat, but does not remove the entire partner-binding region. This is an inferred conserved regulatory role, new relative to the frozen horse GOA, rather than evidence for intrinsic phosphatase catalysis. supported_by: - *id001 - reference_id: file: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. - source_method: ProtNLM2 source_version: UniProt API snapshot 2026-09-08 predicted_term: id: GO:0019903 label: protein phosphatase binding predicted_term_type: GO_MF review: assessment: UNC confidence_score: 1 summary: Human MTMR9 directly binds the lipid phosphatases MTMR6/7/8, but this prediction names protein phosphatase binding. The interaction evidence should not be conflated with a phosphoprotein-substrate partner class. A verified protein-phosphatase interaction or clarified ontology scope is needed before accepting this exact MF; the shortened horse domain junction adds a transfer caveat. supported_by: - *id001 - reference_id: file: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. - source_method: ProtNLM2 source_version: UniProt API snapshot 2026-09-08 predicted_term: id: GO:0030234 label: enzyme regulator activity predicted_term_type: GO_MF review: assessment: CNN confidence_score: 2 summary: Enzyme regulation is supported by human MTMR9 stimulation of MTMR6 and MTMR8 in biochemical experiments and the highly conserved horse sequence with retained C-terminal association region. The exact broad term already occurs in the frozen horse GOA. The internal 42-residue deletion leaves a caveat about the magnitude and substrate specificity of regulation in this selected gene model; it does not turn this regulator prediction into a catalytic claim. supported_by: - *id001 - reference_id: file: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. - source_method: ProtNLM2 source_version: UniProt API snapshot 2026-09-08 predicted_term: id: GO:0060304 label: regulation of phosphatidylinositol dephosphorylation predicted_term_type: GO_BP review: assessment: COR confidence_score: 2 summary: Human MTMR9 directly complexes with and regulates MTMR6/MTMR8; catalytic inactivity of MTMR9 is compatible with this regulatory or complex-associated claim. The horse protein is 97.8% identical over 507 aligned residues, retaining the C-terminal association region. The 42-residue deletion at the GRAM/phosphatase-domain junction is a gene-model caveat, but does not remove the entire partner-binding region. This is an inferred conserved regulatory role, new relative to the frozen horse GOA, rather than evidence for intrinsic phosphatase catalysis. supported_by: - *id001 - reference_id: file: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.