Nedd4 (rat) review notes

Session 1 (2026-10-28)

• just fetch-gene rat Nedd4 resolved Q62940 (NEDD4_RAT; RGD:3157; GeneID 25489), 119 GOA
  rows seeded (SynGO rows with several ECO codes collapse to IDA/IMP/IEP rows). UniProt REST
  was rate-limited and needed retries.
• No deep-research API; literature synthesized by hand in Nedd4-deep-research-manual.md.
• Additional PMIDs cached for evidence: 8665844, 11323714, 9351815, 21338354, 20026598,
  18931680, 17996703, 19345204, 22673903.

Key decisions

• MF: HECT E3 ubiquitin protein ligase activity (GO:0061630) is core; the IDA/IEA rows on
  the parent ubiquitin-protein transferase activity are MODIFY to GO:0061630.
  PMID:20159449
• proline-rich region binding accepted as the WW-domain/PY-motif substrate recognition
  mechanism, with rat experimental support PMID:8665844.
• Channel inhibitor terms: Nedd4 lowers ENaC/K channel activity by ubiquitination-dependent
  removal, not by direct gating block; kept as non-core (IBA respected) with that caveat.
  The parent channel inhibitor activity is TOO_GENERAL relative to the sodium term.
• PMID:19125695 (key paper): rat data are an expression change in denervated gastrocnemius
  PMID:19125695;
  the IEP response to denervation involved in regulation of muscle adaptation is kept as
  non-core. The MTMR4 ubiquitination assays used human proteins.
• PMID:11248052 immune response IEP: raft partitioning of Nedd4 in RBL cells is a
  relocalization, not an expression response and not evidence of a role in an immune
  response. Since the mouse T-cell work PMID:18931680 supports adaptive immune response,
  immune response is kept non-core rather than removed.
• Very general ARBA terms (regulation of signaling, regulation of cell communication,
  regulation of transport, regulation of protein catabolic process) are TOO_GENERAL: each is
  entailed by a more specific term kept in this review (checked with runoak ancestors).
• regulation of membrane potential and negative regulation of transcription by RNA polymerase II are indirect consequences: MARK_AS_OVER_ANNOTATED.
• GO:0099576 and GO:0140252 are not is_a related in the ontology version used (runoak).
• No NEW terms proposed.

Open points

• phosphoserine/phosphothreonine residue binding (mouse ISO): source not traced; UNDECIDED.

2026-10-28 review-fix pass

• Removed supported_by self-citations of the gene's own -deep-research-manual.md where a primary citation in the same block already supports the row (the reviewer's own conclusion is not independent evidence). The validator now warns that no annotation cites the deep-research file; that warning is accepted deliberately, which sets the status to DRAFT.