IKKbeta (ird5, DLAK; CG4201; UniProt Q9VEZ5) notes

Identity

• Drosophila ortholog of mammalian IKKbeta/IKKalpha; Ser/Thr protein kinase, I-kappa-B kinase subfamily (UniProt).
• Forms the Drosophila IKK complex with the regulatory subunit Kenny (key, IKKgamma/NEMO ortholog)
  PMID:11018014.

Imd pathway / Relish activation

• ird5 mutants fail to induce antibacterial peptides, but antifungal Drosomycin induction is unaffected
  PMID:11156609.
• IKK complex is required for Relish cleavage and can phosphorylate Relish in vitro
  PMID:11018014.
• IKK is not needed for Toll-pathway activation of Dif/Dorsal
  PMID:11018014.
• Two roles: direct phosphorylation of Relish S528/S529 required for RNA Pol II recruitment; noncatalytic support of Dredd-mediated cleavage
  PMID:19497884.
• TAK1 is the IKK-activating kinase PMID:14519762.
• Early work (DLAK) showed in vitro Cactus binding/phosphorylation in cell lines PMID:10636911;
  in vivo genetics (PMID:11018014, PMID:11156609) indicate the IKK complex is dispensable for Toll/Cactus signalling, so Relish is the physiological substrate.

Antiviral / STING

• dIKKbeta and Relish required against picorna-like viruses; dSTING acts upstream of dIKKbeta
  PMID:30119996.
• Imd pathway antiviral roles: Sindbis PMID:19763182, CrPV PMID:19829691.

Other contexts

• Hypoxia activates IKK-NF-kB, required for survival PMID:24993778.

Deep research

• Falcon deep research: the first run was killed (exit 137, memory pressure on the shared host); a retry produced IKKbeta-deep-research-falcon.md. It agrees with the review: Relish S528/S529 is the principal immune-inducible substrate, and [file:DROME/IKKbeta/IKKbeta-deep-research-falcon.md "DREDD is the caspase that cleaves Relish"], so IKKbeta is not the protease.

Review decisions

• Core MF: protein Ser/Thr kinase phosphorylating Relish within the IKK complex (with Kenny).
• generic protein binding rows removed (uninformative); protein catabolic process and TNF-mediated signaling marked over-annotated.