RIMBP2

Summary: The historical neuromuscular-transmission IBA is biologically plausible through conserved RIM-BP presynaptic function, but its specific vertebrate context remains unresolved. The current human QuickGO record instead carries broader presynaptic annotations.

Reason: GO:0007274 describes transmission from neuron to muscle; it does not require exclusive function at neuromuscular junctions. Mammalian central/ribbon-synapse function therefore does not refute this IBA. The OpenScientist investigation documents fly neuromuscular evidence, mammalian coupling mechanisms, and no identified experiment refuting a mammalian neuromuscular role. Its conclusion that missing mammalian experiments alone precludes phylogenetic transfer is not sufficient: inheritance depends on the ancestral assertion and evidence of conservation or divergence. The historical PTN002306629 node is absent from the refreshed PTHR14234 PAINT slice, and a direct QuickGO query confirms that human O15034 no longer carries GO:0007274. This establishes a snapshot difference, not proof of biological loss. Retain UNDECIDED for the historical assertion pending resolution of its context-specific phylogenetic placement. Skeletal-muscle expression is not a useful exclusion test for a presynaptic protein made in motor neurons.

Summary: RIMBP2 associates with the synaptic plasma membrane as part of the presynaptic active-zone scaffold.

Reason: The broad cellular-component annotation is supported by the curated UniProt subcellular location and mammalian active-zone localization. It does not imply uniform localization across the entire plasma membrane. The more specific active-zone annotation can coexist with this correct parent-level location.

Summary: RIMBP2 localizes to presynaptic active zones at synapses.

Reason: Synaptic localization is supported by mammalian imaging and the conserved active-zone scaffold function. The broad synapse term remains correct alongside a more specific presynaptic annotation.

Summary: Mammalian RIM-BP2 is part of the presynaptic active-zone scaffold.

Reason: Super-resolution microscopy and complex analysis in mouse hippocampal synapses establish active-zone localization. Transfer to the conserved human RIMBP2 ortholog is appropriate; the evidence is on the mouse protein rather than a direct human localization experiment.

Summary: RIMBP2 contributes structural scaffolding to the presynaptic active zone.

Reason: RIMBP2 forms an active-zone complex with RIM and Munc13-1 and organizes calcium channels relative to vesicle release sites. The spatial and functional evidence supports structural-constituent activity by orthology from mammalian RIM-BP2, beyond a generic interaction annotation.

Summary: RIMBP2 promotes synaptic vesicle priming through stabilization of Munc13-1 at mossy-fiber active zones.

Reason: The mouse study links RIMBP2 to Munc13-1 positioning and stabilization and to vesicle docking/priming. This is a mechanistic scaffold contribution to priming, not merely a downstream transmission phenotype. Transfer to human RIMBP2 is an ortholog inference, and the magnitude of this role depends on synapse type.