AGR3 notes

2026-06-03 PN Proteostasis review

• Generated inputs with just fetch-gene human AGR3; this created the UniProt record, GOA table, and a 10-entry review stub from 38 GOA rows. Falcon deep research completed at genes/human/AGR3/AGR3-deep-research-falcon.md.
• PN projection reviewed: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_annotations.tsv:219 proposes GO:0003756 protein disulfide isomerase activity for AGR3 from ER proteostasis|Folding enzyme|Protein disulfide isomerases.
• Conservative decision: do not add GO:0003756 for AGR3. AGR3 is ER-retained and thioredoxin-like, but Falcon synthesis highlights that AGR3 lacks the canonical PDI CXXC/WCXXC motif and "is not a canonical disulfide isomerase" [file:human/AGR3/AGR3-deep-research-falcon.md "Although structurally in the PDI/thioredoxin family, AGR3's DCYQS motif (lacking the second cysteine) supports the view that AGR3 is not a canonical disulfide isomerase"]. This makes the PN projection a family/context projection rather than a safe gene-level GO addition.
• Strongest supported physiological function: ER-localized AGR3 is required for calcium-mediated regulation of airway ciliary beat frequency and mucociliary clearance PMID:25751668.
• ER localization is supported by the KDEL-receptor/retention motif study PMID:18086916 and by the airway paper's ciliated-cell ER-resident framing PMID:25751668.
• Dystroglycan binding is retained as non-core. The underlying evidence is yeast two-hybrid interaction with alpha-dystroglycan/DAG1 and C4.4a/LYPD3 in a cancer context PMID:12592373, with the authors noting that clinical-context confirmation was still needed PMID:12592373.
• Generic protein binding rows from high-throughput interactome maps were marked over-annotated, except the PMID:12592373 row was modified to the more specific existing dystroglycan binding term.