N (Notch) — curation notes (DROME, P07207)

Session 2026-09-30 (Notch signaling module)

Deep research: just deep-research-falcon DROME N --fallback perplexity-lite — the wrapper reported
a 600 s falcon timeout, but the falcon client completed and wrote N-deep-research-falcon.md
later in the session; it was used for corroboration (NRR autoinhibition, glycan tuning). The review
is primarily based on UniProt P07207, cached publications, and the GOA set (298 rows, 163 distinct
terms; no IBA rows for N).

Key findings (with provenance)

• Receptor: EGF repeats 11-12 are necessary and sufficient for Delta binding, and also bind
  Serrate PMID:1657403.
• Signal-competent adhesion with Delta needs both ectodomain and ICD PMID:15611340.
• ICD has intrinsic activity PMID:8343960.
• Su(H) binds the RAM region directly PMID:8749394 and is retained in the
  cytoplasm by Notch until ligand binding PMID:7954795.
• Ternary complex with Su(H) and Mam PMID:11390662; Mam lengthens CSL dwell time at targets PMID:29478922.
• NICD ChIP at the chn promoter and E(spl)m-delta (PMID:16763555, full text) — basis of the
  chromatin binding IDA (kept non-core: indirect via Su(H)).

Decisions

• Core MF: GO:0004888 transmembrane signaling receptor activity (plasma membrane / apical PM);
  GO:0003713 transcription coactivator activity (nucleus, in GO:1990433).
• NEW: GO:0007221 positive regulation of transcription of Notch receptor target (IDA,
  PMID:11390662).
• REMOVE: all 27 GO:0005515 protein binding rows (uninformative; specific functions captured
  elsewhere), GO:0019899 enzyme binding and GO:0019904 protein domain specific binding (ARBA IEA).
• MODIFY: GO:0038023 -> GO:0004888; GO:0032991 -> GO:1990433.
• ~140 developmental BP terms kept as non-core (pleiotropic Notch contexts); lateral inhibition and
  Notch signaling pathway accepted as core.
• Trafficking/biosynthetic compartments (endosomes, MVB, lysosome, ER/Golgi lumen) kept non-core.

Variant-relevant biology

• Single Notch receptor in Drosophila (vs 4 in mammals), 36 EGF repeats; Fringe (fng)
  GlcNAc-extension of O-fucose alters Notch-Delta binding PMID:10935637 and inhibits responsiveness
  to Serrate while potentiating responsiveness to Delta PMID:9202123.
• Ligand-independent activation from endosomes/lysosomes when ESCRT sorting is disrupted
  (UniProt summary; PMID:23178945 etc.).
• PANTHER assignment in the UniProt record: PTHR24049 / PTHR24049:SF22 (labels "CRUMBS FAMILY
  MEMBER" / "DROSOPHILA CRUMBS HOMOLOG" — PANTHER naming quirk; the same family also contains Dl).