id: A0A8B6GS20 gene_symbol: A0A8B6GS20 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:29158 label: Mytilus galloprovincialis description: >- A0A8B6GS20 (ORF MGAL_10B089004) is a partial gene model from the Mediterranean mussel genome. Its C-terminal 246 residues belong to a myotubularin-related protein 9 (MTMR9)-type pseudophosphatase, placed in PANTHER subfamily PTHR10807:SF73 with Caenorhabditis elegans MTM-9. Its first ~360 residues are three D8C_UMOD-like cysteine-rich repeats of a kind found in extracellular proteins and unrelated to myotubularins. The retained myotubularin region covers only the C-terminal half of the phosphatase-like domain and the C-terminal region. It carries the MTMR9-type inactive site, with glycine at the catalytic cysteine position of the CX5R motif and threonine at the arginine position. The PH-GRAM domain and the N-terminal half of the phosphatase-like fold are absent. A full-length MTMR9-type model (ORF MGAL_10B079678) exists in the same genome and is 97% identical over the shared region. MTMR9-family proteins are catalytically inactive partners of active myotubularin 3-phosphatases (MTMR6/7/8 in mammals, MTM-6 in nematodes). They bind the active partner, stabilise it and raise its phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate 3-phosphatase output in the cytoplasm. Through that complex they act in endosomal trafficking. No experiments have been reported for the mussel protein, and the product encoded by this particular model is unlikely to fold as a complete MTMR9 protein. existing_annotations: - term: id: GO:0005737 label: cytoplasm evidence_type: IEA original_reference_id: GO_REF:0000118 qualifier: located_in review: summary: >- TreeGrafter transfer from the MTMR9 clade node PANTHER:PTN000086907. MTMR9-family proteins are cytoplasmic, membrane-associated partners of active myotubularins. In the mammalian studies they relocalise with active partners, and in C. elegans MTM-9 acts with MTM-6 in endocytic traffic. The A0A8B6GS20 model carries extracellular-type D8C_UMOD repeats at its N-terminus, which probably come from a gene-model fusion and do not argue against cytoplasmic localisation of the mussel MTMR9 gene product. Cytoplasm is as precise as the phylogenetic evidence allows for this species. action: ACCEPT reason: >- Cytoplasmic localisation is conserved across the MTMR9 clade. That clade includes the worm protein in this PANTHER subfamily (SF73), and the endocytic-pathway work places MTM-9 in the cytoplasm. The target's MTMR9-homologous region is the clade member. Gene-model caveat: the N-terminal D8C_UMOD region of this model is not part of an MTMR9 protein. supported_by: - reference_id: PMID:14565969 supporting_text: >- We demonstrate that MTM-6 and MTM-9 function as part of a complex to regulate an endocytic pathway that involves the Arf6 GTPase - reference_id: file:MYTGA/A0A8B6GS20/A0A8B6GS20-bioinformatics/RESULTS-rereview.md supporting_text: >- A0A8B6GS20 (ORF MGAL_10B089004) is a partial MTMR9 gene model. - term: id: GO:0010507 label: negative regulation of autophagy evidence_type: IEA original_reference_id: GO_REF:0000118 qualifier: involved_in review: summary: >- The underlying IBA rests on one donor, human MTMR9. In human cells the MTMR8-MTMR9 complex lowered PtdIns(3)P and inhibited autophagy. The node placement is a legitimate PAINT judgement and is not challenged on donor count. The biology behind it is narrower than the clade, though. The autophagy effect was shown for the pairing with MTMR8, a member of the vertebrate MTMR6/7/8 expansion. Invertebrates have a single MTM-6-type partner, and the C. elegans MTM-6/MTM-9 work describes endocytic traffic and Wnt-carrier recycling, not autophagy. It is a regulatory outcome of the partner phosphatase's PtdIns(3)P turnover, so it sits downstream of the core activity. action: KEEP_AS_NON_CORE reason: >- The term is supported for vertebrate MTMR9 with MTMR8. For a mollusc it is a plausible but untested regulatory consequence of partner-phosphatase activation. It is peripheral to the core function, which is partner binding and activation of a 3-phosphatase. The fragmentary gene model adds uncertainty for this accession. supported_by: - reference_id: PMID:22647598 supporting_text: >- the MTMR8/R9 complex reduces cellular PtdIns(3)P levels. Consequentially, the MTMR6/R9 complex serves to inhibit stress-induced apoptosis and the MTMR8/R9 complex inhibits autophagy. - reference_id: PMID:21076391 supporting_text: >- We conclude that regulation of endosomal trafficking by the MTM-6/MTM-9 myotubularin complex is required for the retromer-dependent recycling of MIG-14/Wls and Wnt secretion. - term: id: GO:0019903 label: protein phosphatase binding evidence_type: IEA original_reference_id: GO_REF:0000118 qualifier: enables review: summary: >- Partner binding is the central activity of MTMR9-family proteins. They heterodimerise with active myotubularins (MTMR6, MTMR7 and MTMR8 in human; MTM-6 in C. elegans). Those partners are lipid 3-phosphatases acting on PtdIns(3)P and PtdIns(3,5)P2, not phosphoprotein phosphatases. GO:0019903 is defined as binding to a protein phosphatase, so the bound partner does not strictly fit it. The parent term phosphatase binding (GO:0019902) describes the interaction accurately. The human MTMR9 review left the same partner-class question UNDECIDED. The target keeps the C-terminal region of MTMR9 (human residues 313-542), so the region needed for partner association is plausibly present even in this partial model. action: MODIFY reason: >- The interaction is real and core, but the partner is a lipid phosphatase, so the right level is the parent GO:0019902 phosphatase binding. Phosphatase activator activity (GO:0019211, human EXP) was not propagated by PAINT to the clade node and is not proposed here. proposed_replacement_terms: - id: GO:0019902 label: phosphatase binding supported_by: - reference_id: PMID:16787938 supporting_text: >- The myotubularins are a large family of lipid phosphatases with specificity towards PtdIns3P and PtdIns(3,5)P(2). - reference_id: PMID:22647598 supporting_text: >- including myotubularin-related protein 6 (MTMR6), MTMR7, and MTMR8, all of which dimerize with the catalytically inactive MTMR9. - reference_id: PMID:14565969 supporting_text: >- We demonstrate that MTM-6 and MTM-9 function as part of a complex - term: id: GO:0046856 label: phosphatidylinositol dephosphorylation evidence_type: IEA original_reference_id: GO_REF:0000118 qualifier: involved_in review: summary: >- PAINT placed this process at the active ancestral node PTN008506586. At the MTMR9 clade node PTN000086907 the curators negated only the catalytic activities, recording loss of phosphatidylinositol-3-phosphate phosphatase activity (GO:0004438) and phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity (GO:0106018) as IRD rows. They did not negate the process, so the retained process is a deliberate decision. Biologically, MTMR9 is the noncatalytic subunit of the heteromeric phosphatase: it raises partner activity up to 30-fold toward PtdIns(3,5)P2 and fixes substrate preference. That is the scaffold/regulatory-subunit kind of participation that justifies a process annotation for a noncatalytic complex member. The worm MTM-6/MTM-9 complex is described as acting to dephosphorylate PtdIns(3)P. The target has the same MTMR9-type inactive site (Gly at the Cys position, Thr at the Arg position), so it has no intrinsic catalysis. action: ACCEPT reason: >- MTMR9-family proteins do part of the work of this process as obligate regulatory subunits of the active 3-phosphatase complex. PAINT deliberately retained the process while negating the activities at this node. This review accepts it; the earlier review proposed replacing it with regulation of phosphatidylinositol dephosphorylation. Gene-model caveat: this accession lacks the N-terminal half of the MTMR9 fold. 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:21076391 supporting_text: >- MTM-6 and MTM-9 are myotubularin lipid phosphatases that function as a complex to dephosphorylate phosphatidylinositol-3-phosphate - reference_id: file:MYTGA/A0A8B6GS20/A0A8B6GS20-bioinformatics/RESULTS-rereview.md supporting_text: >- So the retained region has the MTMR9-type inactive site. references: - id: GO_REF:0000118 title: TreeGrafter-generated GO annotations findings: [] - id: file:MYTGA/A0A8B6GS20/A0A8B6GS20-deep-research-falcon.md title: Deep research report on MTMR9 in Mytilus galloprovincialis findings: - statement: >- MTMR9 is a catalytically inactive pseudophosphatase that lacks the catalytic cysteine in the CX5R motif - statement: >- MTMR9 forms heterodimeric complexes with MTMR6, MTMR7, and MTMR8, modulating their localization and substrate specificity - statement: >- MTMR9 recruits MTMR6 and MTMR8 to the intermediate compartment and Golgi apparatus, sustaining Golgi integrity and ER-to-Golgi transport - statement: >- No direct experimental data exist for A0A8B6GS20 in Mytilus galloprovincialis; all functional annotations are inferred from orthologous proteins in model organisms reference_review: relevance: LOW correctness: UNVERIFIED review_notes: >- Family-level literature summary that does not analyse the domain architecture of this gene model (D8C_UMOD fusion, missing GRAM and N-terminal phosphatase half). It is kept for provenance but is no longer cited as support; primary papers and the re-review sequence analysis are cited instead. - id: file:MYTGA/A0A8B6GS20/A0A8B6GS20-bioinformatics/RESULTS-rereview.md title: A0A8B6GS20 architecture and identity check (2026-10-21 re-review) findings: - statement: >- Only residues 362-588 align to human MTMR9 (residues 313-542). Residues 1-361 are D8C_UMOD-type repeats; the model is a partial/fused MTMR9 gene model. - statement: >- The retained phosphatase-like region carries the MTMR9-type inactive motif VHGSEGFDTT, with Gly and Thr at the positions of the MTMR6 catalytic Cys and Arg. - statement: >- The full-length M. galloprovincialis MTMR9-type models from ORF MGAL_10B079678 are 97.2% identical over the shared C-terminal 246 residues. - id: PMID:22647598 title: Myotubularin-related protein (MTMR) 9 determines the enzymatic activity, substrate specificity, and role in autophagy of MTMR8. findings: - statement: >- MTMR9 dimerises with MTMR6, MTMR7 and MTMR8, increases their 3-phosphatase activity and sets substrate preference; the MTMR8/R9 complex inhibits autophagy. reference_review: relevance: HIGH correctness: VERIFIED review_notes: Abstract-only cache; quotes verified against the cached abstract. Human proteins. - id: PMID:19038970 title: MTMR9 increases MTMR6 enzyme activity, stability, and role in apoptosis. findings: - statement: >- MTMR9 heteromerises with MTMR6, increases its 3-phosphatase activity and stabilises both proteins. supporting_text: >- MTMR9 increased the 3-phosphatase activity of MTMR6 up to 6-fold. reference_review: relevance: HIGH correctness: VERIFIED review_notes: Abstract-only cache. Human proteins. - id: PMID:16787938 title: 'Systematic analysis of myotubularins: heteromeric interactions, subcellular localisation and endosome related functions.' findings: - statement: >- Myotubularins are lipid phosphatases; inactive members pair with active ones (MTMR8 with MTMR9). reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Abstract-only cache. Human proteins. - id: PMID:14565969 title: Disease-related myotubularins function in endocytic traffic in Caenorhabditis elegans. findings: - statement: >- C. elegans MTM-6 and MTM-9 act as a complex in coelomocyte endocytosis and their loss disorganises PI3P localisation. reference_review: relevance: HIGH correctness: VERIFIED review_notes: >- Characterises MTM-9 (Q965W9), the experimentally studied member of the same PANTHER subfamily (SF73) as the target. - id: PMID:21076391 title: Wnt signalling requires MTM-6 and MTM-9 myotubularin lipid-phosphatase function in Wnt-producing cells. findings: - statement: >- The MTM-6/MTM-9 complex dephosphorylates PI3P and regulates MIG-14/Wls recycling in Wnt-producing cells. reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Abstract-only cache. C. elegans proteins in the target's PANTHER subfamily. core_functions: - description: >- Noncatalytic MTMR9-type subunit of a myotubularin phosphatase complex. It binds an active myotubularin 3-phosphatase, stabilises it and raises its activity toward phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate in the cytoplasm. This is inferred for the mussel MTMR9 gene from PANTHER subfamily SF73 (with C. elegans MTM-9) and from the conserved MTMR9-type inactive site. This partial gene model keeps only the C-terminal ~45% of the protein. molecular_function: id: GO:0019902 label: phosphatase binding directly_involved_in: - id: GO:0046856 label: phosphatidylinositol dephosphorylation locations: - id: GO:0005737 label: cytoplasm 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:21076391 supporting_text: >- MTM-6 and MTM-9 are myotubularin lipid phosphatases that function as a complex to dephosphorylate phosphatidylinositol-3-phosphate suggested_questions: - question: >- Is MGAL_10B089004 a haplotig-derived partial copy of the MTMR9 gene MGAL_10B079678, or a real partial duplicate fused to D8C_UMOD exons? If it is an assembly or annotation artefact, should UniProt merge or flag the entry? - question: >- PANTHER places C. elegans MTM-9 and this mussel protein in SF73 and vertebrate MTMR9 in SF56. Is the split only taxonomic, or does it mark a functional difference in partner choice (single MTM-6-type partner vs the vertebrate MTMR6/7/8 set)? suggested_experiments: - description: >- Use RT-PCR or long-read transcript evidence across the junction between the D8C_UMOD repeats and the MTMR9 region of MGAL_10B089004 to find out whether a fused transcript exists in mussel tissues.