ProtNLM2 External predictions
View prediction review YAML · MTMR9-protnlm-predictions-review.yaml · Review status: COMPLETE
ProtNLM2 (UniProt API snapshot 2026-09-08) emitted seven GO terms for the exon-skipped horse MTMR9 product A0A9L0T3C1. Five are correct novel predictions transferred from experimentally characterized human and mouse MTMR9 orthologs in the same PANTHER subfamily (PTHR10807:SF56): positive regulation of phosphatase activity, regulation of phosphatidylinositol dephosphorylation, protein-containing complex, protein stabilization and negative regulation of autophagy (the last a non-core, partner-dependent effect). Enzyme regulator activity is correct but already in horse GOA. Protein phosphatase binding is uncertain because MTMR9's partners are phosphoinositide phosphatases, not protein phosphatases. All transfers carry the caveat that this product lacks human residues 98-139.
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 · genes/HORSE/MTMR9/MTMR9-ai-review.yaml · genes/human/MTMR9/MTMR9-ai-review.yaml · genes/mouse/Mtmr9/Mtmr9-ai-review.yaml · interpro/panther/PTHR10807/PTHR10807-review.yaml
Review score: 2 = concordant with evidence; 1 = uncertain; 0 = discordant with evidence. This is an assessment score, not a model probability.
COR — Correct novel prediction Review score: 2/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: Human MTMR9 raises the catalytic activity of its active partners MTMR6 and MTMR8 (direct assays, PMID:22647598), and mouse MTMR9 binds MTMR7 through its coiled coil and increases MTMR7 activity (PMID:12890864). The human and mouse gene reviews accept this term, and the horse protein is a 1:1 ortholog in the same PANTHER subfamily (PTHR10807:SF56), 97.8% identical over 507 aligned residues and retaining the C-terminal partner-binding region. Horse GOA lacks this process term (it carries only enzyme regulator activity), so this is a correct novel prediction by justified orthology transfer. It describes regulation of partner catalysis, not intrinsic phosphatase activity; the 42-residue deletion at the GRAM/phosphatase-like domain junction leaves the activity of this exact product untested.
Supporting Evidence:
- PMID:22647598: "Complex formation between the active myotubularins and MTMR9 increases their catalytic activity and alters their substrate specificity"
- PMID:12890864: "The coiled-coil domain of MTMR9 was sufficient for binding to MTMR7. The binding of MTMR9 increased the Ins(1,3)P2 phosphatase activity of MTMR7."
- file:HORSE/MTMR9/MTMR9-bioinformatics/RESULTS.md: "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."
COR — Correct novel prediction Review score: 2/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: Human MTMR9 contributes to negative regulation of autophagy as the catalytically inactive activating subunit of the MTMR8-MTMR9 PtdIns(3)P phosphatase complex (PMID:22647598); the human and mouse reviews keep this term as non-core, and PAINT places it on node PTN002246859 within the MTMR9 lineage, which the horse gene descends from. The OpenScientist audit found that the horse sequence retains the inactive PTP-like domain and the C-terminal coiled-coil dimerization region, supporting transfer of the partner-dependent mechanism despite the 42-residue deletion. Horse GOA lacks this term, so it is a correct novel prediction. It is a context-dependent, non-primary effect: MTMR9 knockdown does not enhance autophagic clearance of TDP-43 in neurons.
Supporting Evidence:
- PMID:22647598: "the MTMR8/R9 complex inhibits autophagy."
- file:HORSE/MTMR9/MTMR9-bioinformatics/RESULTS.md: "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."
- file:HORSE/MTMR9/MTMR9-hypotheses/horse40-negative-autophagy-regulation/openscientist.md: "The **PTP-like pseudophosphatase domain** (P-loop `LIHGTEGTDSTLQVT`) and the **C-terminal coiled-coil dimerization region** are fully conserved"
- file:HORSE/MTMR9/MTMR9-hypotheses/horse40-negative-autophagy-regulation/openscientist.md: "knockdown of MTMR5 or MTMR2, but not the unrelated phosphatase MTMR9, significantly enhances neuronal degradation of TDP-43"
COR — Correct novel prediction Review score: 2/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: Formation of the MTMR6-MTMR9 heteromer increases protein levels of both partners, attributed to inhibition of their degradation (PMID:19038970), and MTMR9 binding raises MTMR8 stability. The human and mouse MTMR9 reviews accept protein stabilization as part of a core partner-binding function. The horse product is a 1:1 SF56 ortholog that retains the C-terminal coiled coil through which MTMR9 binds its partners, so the transfer is justified on the same grounds as the regulatory terms; it is an inference rather than an observation on the horse protein. Horse GOA carries no stabilization term, so the prediction is correct and novel, with the caveat that the 42-residue internal deletion has not been tested for effects on folding or partner stabilization.
Supporting Evidence:
- PMID:19038970: "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."
- PMID:22647598: "Complex formation between the active myotubularins and MTMR9 increases their catalytic activity and alters their substrate specificity"
- file:HORSE/MTMR9/MTMR9-bioinformatics/RESULTS.md: "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."
COR — Correct novel prediction Review score: 2/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: Human MTMR9 forms heterodimers with the active myotubularins MTMR6, MTMR7 and MTMR8 (PMID:22647598, PMID:19038970), and mouse MTMR9 forms a complex with MTMR7 through its coiled coil (PMID:12890864). The human review accepts this IDA term as the most precise complex term GO offers. The horse product retains the coiled coil and is a same-subfamily ortholog, so membership in a protein-containing complex transfers. Horse GOA has no complex annotation, making this a correct novel prediction, although the term is broad.
Supporting Evidence:
- PMID:22647598: "Complex formation between the active myotubularins and MTMR9 increases their catalytic activity and alters their substrate specificity"
- PMID:12890864: "The coiled-coil domain of MTMR9 was sufficient for binding to MTMR7. The binding of MTMR9 increased the Ins(1,3)P2 phosphatase activity of MTMR7."
- file:HORSE/MTMR9/MTMR9-bioinformatics/RESULTS.md: "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."
UNC — Uncertain Review score: 1/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: MTMR9 binds the myotubularin lipid phosphatases MTMR6, MTMR7 and MTMR8, and that binding transfers to the horse ortholog. The predicted term, however, names protein phosphatase binding. The human and mouse MTMR9 reviews replace this term with phosphatase binding (GO:0019902) because the partners dephosphorylate phosphoinositides rather than proteins. No evidence identifies a protein-dephosphorylating partner of MTMR9, and the binding data do not refute the term outright given the ontology-scope question, so the exact claim remains uncertain.
Supporting Evidence:
- PMID:22647598: "Complex formation between the active myotubularins and MTMR9 increases their catalytic activity and alters their substrate specificity"
- PMID:12890864: "The coiled-coil domain of MTMR9 was sufficient for binding to MTMR7. The binding of MTMR9 increased the Ins(1,3)P2 phosphatase activity of MTMR7."
- file:HORSE/MTMR9/MTMR9-bioinformatics/RESULTS.md: "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."
CNN — Correct but not novel Review score: 2/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: Enzyme regulator activity is supported by human MTMR9 stimulation of MTMR6 and MTMR8 (PMID:22647598) and mouse MTMR9 stimulation of MTMR7 (PMID:12890864), transferred to the 1:1 horse ortholog that is 97.8% identical over its length. The exact term is already in horse GOA for this product, so the prediction is correct but not novel. The horse gene review refines it to phosphatase activator activity, which this broad prediction entails.
Supporting Evidence:
- PMID:22647598: "Complex formation between the active myotubularins and MTMR9 increases their catalytic activity and alters their substrate specificity"
- PMID:12890864: "The coiled-coil domain of MTMR9 was sufficient for binding to MTMR7. The binding of MTMR9 increased the Ins(1,3)P2 phosphatase activity of MTMR7."
- file:HORSE/MTMR9/MTMR9-bioinformatics/RESULTS.md: "share 97.8% identity among 507 paired residues. Paired coverage is 92.3% of human and 100.0% of horse."
COR — Correct novel prediction Review score: 2/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: Complex formation with MTMR9 increases the activity of MTMR6 and MTMR8 and shifts their phosphoinositide substrate preference (PMID:22647598); the human and mouse MTMR9 reviews accept this term as core. MTMR9 does this work directly as the activating subunit of the heterodimer, without catalysing the dephosphorylation itself. The horse product is a same-subfamily ortholog retaining the partner-binding coiled coil, and horse GOA has no corresponding process term, so this is a correct novel prediction by orthology transfer, with the internal-deletion caveat.
Supporting Evidence:
- PMID:22647598: "Complex formation between the active myotubularins and MTMR9 increases their catalytic activity and alters their substrate specificity"
- PMID:12890864: "The coiled-coil domain of MTMR9 was sufficient for binding to MTMR7. The binding of MTMR9 increased the Ins(1,3)P2 phosphatase activity of MTMR7."
- file:HORSE/MTMR9/MTMR9-bioinformatics/RESULTS.md: "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."