tub (Tube, P22812) review notes

Identity

• Drosophila melanogaster Tube, FBgn0003882; N-terminal death domain (Pfam Death_2 / IPR029397 Tube_Death), C-terminal Tube repeats (UniProt P22812). No kinase domain.
• Interacts with Pelle (Q05652), Myd88 (Q7K105) and Dorsal (P15330) per UniProt INTERACTION.

Core biology (with provenance)

• Adaptor bridging MyD88 and Pelle: PMID:12351681; PMID:12351681.
• Tube-Pelle death domain heterodimer structure: PMID:10589682; interface required in vivo.
• Tube-Pelle DD binding in two-hybrid and with purified proteins, Kd about 0.5 uM PMID:10512628.
• Membrane recruitment model: PMID:7635064; Tube associates with plasma membrane in interphase embryos PMID:7635064.
• dMyD88 recruits Tube from cytosol to the plasma membrane in S2 cells [PMID:22464168 "Expressing Tube in S2 cells revealed that Tube is found to be evenly distributed throughout the cytosol"; "Rather, Tube co-localized with full length dMyD88 at the plasma membrane"].
• Tube binds Dorsal via Tube repeats PMID:12351681; PMID:9367441.
• Genetics: dorsal-group maternal gene; strong alleles give embryos lacking ventral and lateral pattern elements; acts downstream of Toll PMID:8244004. Kra/dMyD88 acts between Toll and Tube PMID:12559494.
• Immunity: required for drosomycin induction and survival after fungal infection [PMID:8808632; PMID:11743586]. In S2 cells required for Drosomycin but not Attacin reporter (LPS/Imd readout) PMID:12351681.
• Muscle: spz, tube, pelle required for embryonic muscle patterning via epidermal Toll PMID:9676200.

Curation decisions (summary)

• ACCEPT all GO:0008063 Toll signaling pathway rows (correct fly-specific term; no vertebrate GO:0002224 rows present).
• REMOVE GO:0031663 lipopolysaccharide-mediated signaling pathway (IBA): ligand-specific mammalian TLR4-lineage term; Tube is not needed for the LPS/Attacin readout. This bears on the project question on ligand-specific pathway terms reaching orthologues.
• REMOVE nucleus IBA (kinase-family node; no evidence Tube is nuclear).
• REMOVE apoptotic process NAS (inferred from death-domain naming).
• MODIFY GO:1990782 protein tyrosine kinase binding: Pelle is a Ser/Thr IRAK-family kinase -> death domain binding / protein kinase binding.
• protein binding rows -> death domain binding (DD papers), protein kinase binding (Pelle), NF-kappaB binding (Dorsal); DPIM2 AP-MS row REMOVE.
• NEW GO:0035591 signaling adaptor activity (comparator: human MYD88 and TIRAP and fly Myd88 carry it in GOA).
• hemocyte proliferation TAS from a review whose cached abstract does not mention Tube -> UNDECIDED.

Deep research

The review was drafted from UniProt and cached publications before Falcon deep research (tub-deep-research-falcon.md) was finished. The report was read afterwards and agrees with the curation decisions:
- Tube is a non-enzymatic death-domain adaptor that bridges MyD88 and Pelle, which do not bind each other directly. This supports the NEW signaling adaptor activity annotation.
- Tube acts at the cytoplasmic face of the plasma membrane, and forced membrane targeting activates signalling.
- Tube belongs to the Toll (not Imd) pathway, and it is a maternal dorsal-group gene.
- The report explicitly warns against annotating Tube as an IRAK-like enzyme on the basis of distant homology. This is consistent with removing the kinase-family-derived nucleus IBA and the LPS-pathway IBA.
Nothing in the report changes any action.