DIAPH3 review notes

17 October 2026

Reviewed all 32 normalized source annotations for human Q9NSV4: 10 ACCEPT, 10 MODIFY, 9 KEEP_AS_NON_CORE and 3 REMOVE. The raw source has 33 records because two nucleus ISS entries normalize to the same assertion. Imported source identities, evidence codes, qualifiers and supporting entities remain intact. The seven official alternative products are preserved with sequence-based descriptions.

The synthesis contains two functional units: actin binding with filament polymerization, and microtubule binding. The latter is supported by biochemical separation from actin assembly in PMID:18458159(https://pmc.ncbi.nlm.nih.gov/articles/PMC2364705/) and human localization in PMID:19457867(https://pmc.ncbi.nlm.nih.gov/articles/PMC2740432/). Historical mDia2 fragments and the 1110-aa human construct in PMID:18755006(https://hdl.handle.net/10033/48543) are kept distinct from current natural products. The curated mouse donor identity does not settle the precise species of every historical fragment template.

Three source mappings were rejected after reading the relevant original experiments. PMID:33036023(https://pmc.ncbi.nlm.nih.gov/articles/PMC7819763/) supports upstream regulation of SRF/Chmp5 and ESCRT-associated remodeling, not membership of ESCRT-I. PMID:23441200(https://pmc.ncbi.nlm.nih.gov/articles/PMC3575478/) measures ribbon and stereociliary phenotypes using other markers, not Diap3 localization at ribbon synapses or tip-link densities. These corrections do not deny auditory or endosomal effects.

Broad cytoplasmic and cytoskeletal terms were refined to supported source-specific locations and filament polymerization. Valid ancestral PAINT placement was retained after reading the actual root IBD and target lineage. The RhoD/mDia3C response in PMID:23034183(https://pmc.ncbi.nlm.nih.gov/articles/PMC3510025/) is not positive mDia2 evidence; independent assembly sources support the inherited function. E-cadherin proximity evidence remains contextual, with no inferred binary-binding interface.

See the source and construct guide for public original locators, exact Reactome chains, PAINT donor distinctions, product boundaries and access limits. Quoted support occurs only in the YAML, avoiding repeated quotation across documents. No NEW annotation is proposed because the existing source assertions already cover the selected core mechanisms.

The ordinary research-provider attempt failed during authentication and its configured fallback reported a quota/authentication error. No provider-named research document was fabricated. The review instead uses the genuine cached publications, separately recovered originals and manual source assessment recorded in the guide.