dl (dorsal, P15330) review notes

Reviewed together with Dif (P98149) for the INNATE_IMMUNITY project (batch 1, Toll/TLR axis). Actions were kept consistent between the two paralogues.

Biology (with provenance)

• Rel homology domain TF; DNA binding through the rel domain PMID:1988156
• Morphogen: nuclear gradient specifies D/V fates PMID:2598266
• Activator of twist PMID:1648449
• Repressor at zen VRR via Groucho PMID:9774673
• Cactus retains Dorsal in cytoplasm PMID:9025065
• Toll/Tube/Pelle relay releases Dorsal PMID:9367441
• Larval immunity, redundant with Dif PMID:10369678
• Obligate dimers; all homo/heterodimer combinations with Dif and Relish form PMID:20679214
• Hemocytes PMID:17060622
• Dorsal B at NMJ, no nuclear translocation PMID:26167685
• The fly IKKbeta (ird5) is not needed for Cactus degradation in D/V patterning PMID:11156609

Key curation decisions

1. Toll signaling pathway (GO:0008063): all rows accepted. This is the correct Drosophila-specific pathway term. Neither dl nor Dif carries GO:0002224 (TLR signaling), and none should be added: Toll is activated by the cytokine Spaetzle, not by microbial patterns.
2. Canonical NF-kappaB signal transduction (GO:0007249): kept as non-core. The definition requires IKK, but Cactus degradation downstream of Toll is ird5-independent (PMID:11156609). The cassette (IkB degradation followed by NF-kB release) is conserved; the IKK clause is not met. This is raised as a suggested question and not removed.
3. Non-canonical NF-kappaB (GO:0038061) IBA: removed. It is defined by NIK/IKKalpha-dependent p100 processing; Dorsal is a class II Rel protein released from Cactus. propagation_review points at PTN000652441.
4. Protein binding: the Dif/Rel rows become MODIFY to protein heterodimerization activity, and identical protein binding becomes protein homodimerization activity. The Cactus, Tube and Tamo rows are REMOVEd as uninformative (inhibitor/cargo interactions).
5. GO:0140297 DNA-binding TF binding: the partners are Groucho (FBgn0001139, a corepressor with no DNA-binding activity) and DSP1 (HMGB, a putative corepressor). Both become MODIFY to GO:0001222 transcription corepressor binding.
6. NEW: GO:0001227 DNA-binding transcription repressor activity, RNA pol II-specific and GO:0000122 negative regulation of transcription by RNA pol II. Dorsal's repression of zen/dpp via the VRR is textbook biology, it is Dorsal's own DNA-binding activity, and it is absent from GOA. The other NEW candidates did not pass the participation test and were not added.
7. Rows citing papers whose cached abstract does not mention Dorsal (PMID:9806924 Apterous/FMRFa, PMID:12748300 CtBP, PMID:12556495 dTRAP80/Dif): these are abstract-only, and the functions (DNA binding, nucleus) are well established, so they were ACCEPTed in deference to the curator, per CLAUDE.md.
8. NMJ, subsynaptic reticulum, hemocyte, PNS, melanization and immune-response rows are kept as non-core.
9. GO:0002225 (positive regulation of antimicrobial peptide production) is KEEP_AS_NON_CORE for dl, but ACCEPT for Dif. Dif alone is required in adults; Dorsal's role is larval and redundant PMID:10843389.

Deep research

Falcon deep research (dl__P15330-deep-research-falcon.md) finished after the first draft. It was read and is consistent with the review (no conflicting claims), and it is cited as supporting evidence in core_functions. The review rests mainly on the UniProt record and the cached publications.