Tube is a cytoplasmic adaptor protein of the Drosophila Toll pathway. It has an N-terminal death domain and C-terminal Tube repeats and no catalytic activity. On Toll activation by cleaved Spaetzle, the membrane-bound adaptor MyD88 recruits Tube to the cytoplasmic face of the plasma membrane. Tube uses two distinct surfaces of its death domain to bind the MyD88 and Pelle death domains, forming a MyD88-Tube-Pelle heterotrimeric complex that recruits and activates the IRAK-family kinase Pelle. Pelle then phosphorylates the IkappaB protein Cactus, leading to its degradation and to nuclear entry of the Rel proteins Dorsal and Dif. Tube also binds Dorsal through its C-terminal repeats. Maternally, tube is a dorsal-group gene required for ventral and lateral cell fates along the embryonic dorsoventral axis. In larvae and adults it is required for Toll-dependent induction of the antifungal peptide drosomycin and for resistance to fungal and Gram-positive bacterial infection. Zygotic Toll signalling through Tube also contributes to embryonic somatic muscle patterning. Zygotic tube mutations, like those in Toll and pelle, also alter pupal morphology, matching a second peak of tube expression late in larval development.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002804 positive regulation of antifungal peptide production | IDA PMID:11743586 Drosophila MyD88 is required for the response to fungal and ... | ACCEPT | Summary: DmMyD88-induced drosomycin expression requires Tube and Pelle. Reason: Tube is a required signal-relay adaptor for Toll-dependent induction of the antifungal peptide drosomycin; the regulatory term is appropriate for a positive pathway component. Supporting Evidence: PMID:11743586 DmMyD88 interacted with Toll through its TIR domain and required the death domain proteins Tube and Pelle to activate expression of Drs |
| GO:0002804 positive regulation of antifungal peptide production | IMP PMID:8808632 The dorsoventral regulatory gene cassette spΓ€tzle/Toll/cactu... | ACCEPT | Summary: tube mutants fail to induce drosomycin in adults (spz/Toll/cactus cassette). Reason: Classic genetic evidence that the intracellular dorsoventral pathway components, including tube, are required for drosomycin induction. Supporting Evidence: PMID:8808632 the intracellular components of the dorsoventral signaling pathway (except for dorsal) and the extracellular Toll ligand |
| GO:0005515 protein binding | IPI PMID:10330490 Oligomerisation of Tube and Pelle leads to nuclear localisat... | MODIFY | Summary: Deletion analysis mapped the domains mediating the Tube-Pelle physical interaction. Reason: The partner is the protein kinase Pelle; protein kinase binding is more informative than protein binding and is supported. (Other papers establish that the interface is death domain to death domain.) Proposed replacements: protein kinase binding Supporting Evidence: PMID:10330490 By deletion analysis we determined the domains of Tube and Pelle mediating the physical interaction and the signalling to downstream components. |
| GO:0005515 protein binding | IPI PMID:10512628 Formation and biochemical characterization of tube/pelle dea... | MODIFY | Summary: The Tube and Pelle death domains bind each other directly, forming a heterodimer. Reason: Binding is mediated by the death domains of both proteins (two-hybrid, purified proteins, crystal structure). Death domain binding is the informative MF; protein binding is uninformative. Proposed replacements: death domain binding Supporting Evidence: PMID:10512628 we show using the yeast two-hybrid system that the wild-type tube and pelle death domains bind together PMID:10512628 Mutant tube proteins which do not support signaling in the embryo are also unable to bind pelle in the 2-hybrid assay. |
| GO:0005515 protein binding | IPI PMID:10589682 Three-dimensional structure of a complex between the death d... | MODIFY | Summary: The Tube and Pelle death domains bind each other directly, forming a heterodimer. Reason: Binding is mediated by the death domains of both proteins (two-hybrid, purified proteins, crystal structure). Death domain binding is the informative MF; protein binding is uninformative. Proposed replacements: death domain binding Supporting Evidence: PMID:10589682 Crystal structure of the Pelle and Tube death domain heterodimer reveals that the two death domains adopt a six-helix bundle fold PMID:10589682 In vivo assays of Pelle and Tube mutants confirmed that the integrity of the major heterodimer interface is critical to the activity of these molecules. |
| GO:0005515 protein binding | IPI PMID:12351681 A heterotrimeric death domain complex in Toll signaling. | MODIFY | Summary: Tube death domain binds the death domains of both MyD88 and Pelle in a heterotrimer. Reason: Tube uses two distinct surfaces on its death domain to recruit MyD88 and Pelle; replace protein binding with death domain binding. Proposed replacements: death domain binding Supporting Evidence: PMID:12351681 Tube recruits MyD88 and Pelle into the heterotrimer by two distinct binding surfaces on the Tube death domain PMID:12351681 we find a heterotrimeric association of the death domains of MyD88, Tube, and the protein kinase Pelle |
| GO:0005515 protein binding | IPI PMID:12351681 A heterotrimeric death domain complex in Toll signaling. | MODIFY | Summary: Tube death domain binds the death domains of both MyD88 and Pelle in a heterotrimer. Reason: Tube uses two distinct surfaces on its death domain to recruit MyD88 and Pelle; replace protein binding with death domain binding. Proposed replacements: death domain binding Supporting Evidence: PMID:12351681 Tube recruits MyD88 and Pelle into the heterotrimer by two distinct binding surfaces on the Tube death domain PMID:12351681 we find a heterotrimeric association of the death domains of MyD88, Tube, and the protein kinase Pelle |
| GO:0005515 protein binding | IPI PMID:38944040 Next-generation Drosophila protein interactome map and its f... | REMOVE | Summary: Tube-MyD88 co-purification in the DPIM2 AP-MS interactome. Reason: Generic protein binding from high-throughput AP-MS is uninformative. The specific Tube-MyD88 death-domain interaction is captured by the death domain binding replacement proposed on the PMID:12351681 row. Removal does not dispute the interaction. Supporting Evidence: PMID:38944040 established from affinity purification-mass spectrometry of 5,805 baits |
| GO:0005515 protein binding | IPI PMID:9367441 An activity-dependent network of interactions links the Rel ... | MODIFY | Summary: Tube binds the Rel protein Dorsal via its C-terminal Tube repeats. Reason: The partner is Dorsal, a Rel/NF-kappaB family transcription factor, and the interaction is reported as specific and regulated by Pelle kinase activity. NF-kappaB binding is more informative than protein binding. Proposed replacements: NF-kappaB binding Supporting Evidence: PMID:9367441 We show that Dorsal binds specifically to Tube, Pelle and Cactus, and that the protein kinase activity of Pelle differentially regulates its interactions with Dorsal and Tube. PMID:12351681 Tube is a scaffolding protein containing an N-terminal interaction motif belonging to the death domain family, as well as C-terminal Tube repeats that mediate binding to Dorsal |
| GO:0005515 protein binding | IPI PMID:9367441 An activity-dependent network of interactions links the Rel ... | MODIFY | Summary: Tube binds Pelle kinase; Pelle kinase activity regulates the interaction. Reason: Partner is the Pelle protein kinase; replace uninformative protein binding with protein kinase binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:9367441 We show that Dorsal binds specifically to Tube, Pelle and Cactus, and that the protein kinase activity of Pelle differentially regulates its interactions with Dorsal and Tube. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | REMOVE | Summary: IBA for nucleus from an ancestral node dominated by IRAK/Pelle-family kinases. Reason: No experimental report places Tube in the nucleus. It is membrane-associated in the syncytial embryo and cytoplasmic later, and it acts upstream of Cactus degradation, which releases Dorsal into nuclei. The nucleus assertion derives from experimental data on kinase-family members of the node. Tube has no kinase domain and is a death-domain adaptor, so the nuclear role is not inherited by the target. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000784925 SUPPORTS SOURCE BUT NOT TARGET Ancestral node whose nuclear assertion is grounded in kinase-family members; Tube is a kinase-less death-domain adaptor with experimental localization only at the plasma membrane and cytoplasm/cytosol. Supporting Evidence: PMID:7635064 We show by immunolocalization that tube protein associates with the plasma membrane during interphase. PMID:22464168 Expressing Tube in S2 cells revealed that Tube is found to be evenly distributed throughout the cytosol |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: cytoplasmic activity inherited from the IRAK/Pelle/Tube family node. Reason: Consistent with experimental data; Tube acts on the cytoplasmic face of the membrane and is cytoplasmic outside signalling. Supporting Evidence: PMID:22464168 Expressing Tube in S2 cells revealed that Tube is found to be evenly distributed throughout the cytosol |
| GO:0005737 cytoplasm | IDA PMID:7635064 Interaction of the pelle kinase with the membrane-associated... | ACCEPT | Summary: Immunolocalization of Tube in embryos: membrane-associated during interphase, otherwise cytoplasmic. Reason: Direct evidence; Tube is a cytoplasmic adaptor. Supporting Evidence: PMID:7635064 We show by immunolocalization that tube protein associates with the plasma membrane during interphase. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping to cytoplasm. Reason: Correct and consistent with experimental data. Supporting Evidence: PMID:22464168 Expressing Tube in S2 cells revealed that Tube is found to be evenly distributed throughout the cytosol |
| GO:0005829 cytosol | IDA PMID:22464168 Phosphoinositide binding by the Toll adaptor dMyD88 controls... | ACCEPT | Summary: Tube expressed alone in S2 cells is evenly distributed in the cytosol and is recruited to the plasma membrane by dMyD88. Reason: Direct imaging evidence of the cytosolic pool of Tube. Supporting Evidence: PMID:22464168 Expressing Tube in S2 cells revealed that Tube is found to be evenly distributed throughout the cytosol |
| GO:0005829 cytosol | TAS Reactome:R-DME-209057 | ACCEPT | Summary: Reactome places Tube in the cytosol in Toll pathway reactions. Reason: Consistent with experimental evidence; the Toll signalling complex assembles on the cytosolic face of the plasma membrane. Supporting Evidence: PMID:22464168 Expressing Tube in S2 cells revealed that Tube is found to be evenly distributed throughout the cytosol |
| GO:0005829 cytosol | TAS Reactome:R-DME-209072 | ACCEPT | Summary: Reactome places Tube in the cytosol in Toll pathway reactions. Reason: Consistent with experimental evidence; the Toll signalling complex assembles on the cytosolic face of the plasma membrane. Supporting Evidence: PMID:22464168 Expressing Tube in S2 cells revealed that Tube is found to be evenly distributed throughout the cytosol |
| GO:0005829 cytosol | TAS Reactome:R-DME-209100 | ACCEPT | Summary: Reactome places Tube in the cytosol in Toll pathway reactions. Reason: Consistent with experimental evidence; the Toll signalling complex assembles on the cytosolic face of the plasma membrane. Supporting Evidence: PMID:22464168 Expressing Tube in S2 cells revealed that Tube is found to be evenly distributed throughout the cytosol |
| GO:0005829 cytosol | TAS Reactome:R-DME-209156 | ACCEPT | Summary: Reactome places Tube in the cytosol in Toll pathway reactions. Reason: Consistent with experimental evidence; the Toll signalling complex assembles on the cytosolic face of the plasma membrane. Supporting Evidence: PMID:22464168 Expressing Tube in S2 cells revealed that Tube is found to be evenly distributed throughout the cytosol |
| GO:0005829 cytosol | TAS Reactome:R-DME-214845 | ACCEPT | Summary: Reactome places Tube in the cytosol in Toll pathway reactions. Reason: Consistent with experimental evidence; the Toll signalling complex assembles on the cytosolic face of the plasma membrane. Supporting Evidence: PMID:22464168 Expressing Tube in S2 cells revealed that Tube is found to be evenly distributed throughout the cytosol |
| GO:0005829 cytosol | TAS Reactome:R-DME-214847 | ACCEPT | Summary: Reactome places Tube in the cytosol in Toll pathway reactions. Reason: Consistent with experimental evidence; the Toll signalling complex assembles on the cytosolic face of the plasma membrane. Supporting Evidence: PMID:22464168 Expressing Tube in S2 cells revealed that Tube is found to be evenly distributed throughout the cytosol |
| GO:0005829 cytosol | TAS Reactome:R-DME-214853 | ACCEPT | Summary: Reactome places Tube in the cytosol in Toll pathway reactions. Reason: Consistent with experimental evidence; the Toll signalling complex assembles on the cytosolic face of the plasma membrane. Supporting Evidence: PMID:22464168 Expressing Tube in S2 cells revealed that Tube is found to be evenly distributed throughout the cytosol |
| GO:0005829 cytosol | TAS Reactome:R-DME-214857 | ACCEPT | Summary: Reactome places Tube in the cytosol in Toll pathway reactions. Reason: Consistent with experimental evidence; the Toll signalling complex assembles on the cytosolic face of the plasma membrane. Supporting Evidence: PMID:22464168 Expressing Tube in S2 cells revealed that Tube is found to be evenly distributed throughout the cytosol |
| GO:0005829 cytosol | TAS Reactome:R-DME-214859 | ACCEPT | Summary: Reactome places Tube in the cytosol in Toll pathway reactions. Reason: Consistent with experimental evidence; the Toll signalling complex assembles on the cytosolic face of the plasma membrane. Supporting Evidence: PMID:22464168 Expressing Tube in S2 cells revealed that Tube is found to be evenly distributed throughout the cytosol |
| GO:0005829 cytosol | TAS Reactome:R-DME-214860 | ACCEPT | Summary: Reactome places Tube in the cytosol in Toll pathway reactions. Reason: Consistent with experimental evidence; the Toll signalling complex assembles on the cytosolic face of the plasma membrane. Supporting Evidence: PMID:22464168 Expressing Tube in S2 cells revealed that Tube is found to be evenly distributed throughout the cytosol |
| GO:0005829 cytosol | TAS Reactome:R-DME-214864 | ACCEPT | Summary: Reactome places Tube in the cytosol in Toll pathway reactions. Reason: Consistent with experimental evidence; the Toll signalling complex assembles on the cytosolic face of the plasma membrane. Supporting Evidence: PMID:22464168 Expressing Tube in S2 cells revealed that Tube is found to be evenly distributed throughout the cytosol |
| GO:0005829 cytosol | TAS Reactome:R-DME-214878 | ACCEPT | Summary: Reactome places Tube in the cytosol in Toll pathway reactions. Reason: Consistent with experimental evidence; the Toll signalling complex assembles on the cytosolic face of the plasma membrane. Supporting Evidence: PMID:22464168 Expressing Tube in S2 cells revealed that Tube is found to be evenly distributed throughout the cytosol |
| GO:0005829 cytosol | TAS Reactome:R-DME-214880 | ACCEPT | Summary: Reactome places Tube in the cytosol in Toll pathway reactions. Reason: Consistent with experimental evidence; the Toll signalling complex assembles on the cytosolic face of the plasma membrane. Supporting Evidence: PMID:22464168 Expressing Tube in S2 cells revealed that Tube is found to be evenly distributed throughout the cytosol |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for plasma membrane from the Toll-pathway death-domain node including Tube and Pelle. Reason: Tube associates with the plasma membrane in embryos and is recruited there by dMyD88; the node includes Tube's own experimental data. Supporting Evidence: PMID:7635064 We show by immunolocalization that tube protein associates with the plasma membrane during interphase. PMID:22464168 Rather, Tube co-localized with full length dMyD88 at the plasma membrane |
| GO:0005886 plasma membrane | IDA PMID:7635064 Interaction of the pelle kinase with the membrane-associated... | ACCEPT | Summary: Tube associates with the plasma membrane during interphase in syncytial embryos. Reason: Direct immunolocalization. Tube is a peripheral protein at the cytoplasmic face; the more specific cytoplasmic side of plasma membrane is also annotated. Supporting Evidence: PMID:7635064 We show by immunolocalization that tube protein associates with the plasma membrane during interphase. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping to cell membrane. Reason: Consistent with experimental data; Tube is a peripheral, not integral, membrane-associated protein. Supporting Evidence: PMID:7635064 We show by immunolocalization that tube protein associates with the plasma membrane during interphase. |
| GO:0006915 apoptotic process | NAS PMID:10589682 Three-dimensional structure of a complex between the death d... | REMOVE | Summary: Non-traceable author statement from the Pelle-Tube death domain structure paper, based on the death-domain fold. Reason: The death-domain fold is named for apoptotic signalling proteins, but no evidence implicates Tube in apoptosis. The paper describes Tube and Pelle death domains as mediating Dorsal nuclear translocation in dorsoventral patterning and the antifungal response. The annotation reflects domain naming, not function. Supporting Evidence: PMID:10589682 Pelle and Tube also mediate the innate immune response of Drosophila toward fungal infection |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro death domain mapping to signal transduction. Reason: Broad but correct; Tube is a signal-transducing adaptor in the Toll pathway, captured more specifically by Toll signaling pathway. Supporting Evidence: PMID:12351681 Tube recruits MyD88 and Pelle into the heterotrimer by two distinct binding surfaces on the Tube death domain |
| GO:0007526 larval somatic muscle development | IMP PMID:9676200 The Toll pathway is required in the epidermis for muscle dev... | KEEP AS NON CORE | Summary: tube mutants give the same embryonic muscle patterning defects as Toll mutants. Reason: Supported by mutant phenotype; this reflects the Toll pathway acting in epidermal cells for somatic muscle patterning, a secondary developmental role of the pathway. Supporting Evidence: PMID:9676200 We find that spΓ€tzle, tube, and pelle, but not easter, are necessary for muscle development. |
| GO:0008063 Toll signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for Toll signaling pathway from the node grouping Tube and Pelle. Reason: Tube is a core intracellular adaptor of the Drosophila Toll pathway: it bridges MyD88 and the kinase Pelle via its death domain, and is required for both dorsoventral patterning and the Toll-dependent immune response. GO:0008063 (Toll signaling pathway), not the vertebrate toll-like receptor pathway term, is correct for this fly pathway. Supporting Evidence: PMID:8244004 suggesting that tube and pelle act downstream of the membrane protein Toll in the signaling pathway that defines the embryonic dorsal-ventral pattern PMID:12351681 Tube recruits MyD88 and Pelle into the heterotrimer by two distinct binding surfaces on the Tube death domain |
| GO:0008063 Toll signaling pathway | IGI PMID:12559494 Krapfen/dMyd88 is required for the establishment of dorsoven... | ACCEPT | Summary: Epistasis places Krapfen/dMyD88 between Toll and Tube; Tube and MyD88 interact directly. Reason: Tube is a core intracellular adaptor of the Drosophila Toll pathway: it bridges MyD88 and the kinase Pelle via its death domain, and is required for both dorsoventral patterning and the Toll-dependent immune response. GO:0008063 (Toll signaling pathway), not the vertebrate toll-like receptor pathway term, is correct for this fly pathway. Supporting Evidence: PMID:12559494 Epistasis experiments reveal that kra acts between the receptor Toll and the cytoplasmic factor Tube. |
| GO:0008063 Toll signaling pathway | IGI PMID:8244004 Genetic characterization of tube and pelle, genes required f... | ACCEPT | Summary: Double mutants with dominant Toll alleles place tube and pelle downstream of Toll. Reason: Tube is a core intracellular adaptor of the Drosophila Toll pathway: it bridges MyD88 and the kinase Pelle via its death domain, and is required for both dorsoventral patterning and the Toll-dependent immune response. GO:0008063 (Toll signaling pathway), not the vertebrate toll-like receptor pathway term, is correct for this fly pathway. Supporting Evidence: PMID:8244004 suggesting that tube and pelle act downstream of the membrane protein Toll in the signaling pathway that defines the embryonic dorsal-ventral pattern |
| GO:0008063 Toll signaling pathway | IMP PMID:10512628 Formation and biochemical characterization of tube/pelle dea... | ACCEPT | Summary: Tube mutants that fail to bind Pelle do not support signalling in the embryo. Reason: Tube is a core intracellular adaptor of the Drosophila Toll pathway: it bridges MyD88 and the kinase Pelle via its death domain, and is required for both dorsoventral patterning and the Toll-dependent immune response. GO:0008063 (Toll signaling pathway), not the vertebrate toll-like receptor pathway term, is correct for this fly pathway. Supporting Evidence: PMID:10512628 Mutant tube proteins which do not support signaling in the embryo are also unable to bind pelle in the 2-hybrid assay. |
| GO:0008063 Toll signaling pathway | IMP PMID:12351681 A heterotrimeric death domain complex in Toll signaling. | ACCEPT | Summary: RNAi in S2 cells: Tube is required for Toll-induced Drosomycin reporter activation; heterotrimer formation is critical. Reason: Tube is a core intracellular adaptor of the Drosophila Toll pathway: it bridges MyD88 and the kinase Pelle via its death domain, and is required for both dorsoventral patterning and the Toll-dependent immune response. GO:0008063 (Toll signaling pathway), not the vertebrate toll-like receptor pathway term, is correct for this fly pathway. Supporting Evidence: PMID:12351681 RNAi against Pelle, Tube, or Dorsal significantly inhibited the activation of the Drosomycin reporter PMID:12351681 Tube recruits MyD88 and Pelle into the heterotrimer by two distinct binding surfaces on the Tube death domain |
| GO:0008063 Toll signaling pathway | IMP PMID:12431377 Sequential activation of signaling pathways during innate im... | ACCEPT | Summary: Genome-wide expression profiling of Toll pathway mutants after immune challenge. Reason: Tube is a core intracellular adaptor of the Drosophila Toll pathway: it bridges MyD88 and the kinase Pelle via its death domain, and is required for both dorsoventral patterning and the Toll-dependent immune response. GO:0008063 (Toll signaling pathway), not the vertebrate toll-like receptor pathway term, is correct for this fly pathway. Supporting Evidence: PMID:12431377 We demonstrate that, in addition to signaling through the Toll and Imd pathways, signaling through the JNK and JAK/STAT pathways controls distinct subsets of targets induced by microbial agents. |
| GO:0008063 Toll signaling pathway | IMP PMID:8808632 The dorsoventral regulatory gene cassette spΓ€tzle/Toll/cactu... | ACCEPT | Summary: tube is required for the Toll-dependent antifungal response in adults. Reason: Tube is a core intracellular adaptor of the Drosophila Toll pathway: it bridges MyD88 and the kinase Pelle via its death domain, and is required for both dorsoventral patterning and the Toll-dependent immune response. GO:0008063 (Toll signaling pathway), not the vertebrate toll-like receptor pathway term, is correct for this fly pathway. Supporting Evidence: PMID:8808632 the intracellular components of the dorsoventral signaling pathway (except for dorsal) and the extracellular Toll ligand |
| GO:0008063 Toll signaling pathway | TAS PMID:10589682 Three-dimensional structure of a complex between the death d... | ACCEPT | Summary: Structural paper stating that the Pelle-Tube death domain interaction transduces the Toll signal. Reason: Tube is a core intracellular adaptor of the Drosophila Toll pathway: it bridges MyD88 and the kinase Pelle via its death domain, and is required for both dorsoventral patterning and the Toll-dependent immune response. GO:0008063 (Toll signaling pathway), not the vertebrate toll-like receptor pathway term, is correct for this fly pathway. Supporting Evidence: PMID:10589682 In vivo assays of Pelle and Tube mutants confirmed that the integrity of the major heterodimer interface is critical to the activity of these molecules. |
| GO:0009620 response to fungus | TAS PMID:11104525 Fly immunity: great expectations. | MODIFY | Summary: Review describing Tube as a component of the Toll pathway activated by fungal infection. Reason: Tube participates in the Toll pathway that mounts the antifungal defence, and tube mutants are susceptible to fungal infection. The more specific and informative term is defense response to fungus. Proposed replacements: defense response to fungus Supporting Evidence: PMID:11104525 Ligation of Toll leads to the activation of a signaling pathway that involves the adaptor protein Tube, the protein kinase Pelle, and the Rel/NF-ΞΊB family of transcription factors PMID:8808632 We also show that mutations in the Toll signaling pathway dramatically reduce survival after fungal infection. |
| GO:0009898 cytoplasmic side of plasma membrane | IDA PMID:22464168 Phosphoinositide binding by the Toll adaptor dMyD88 controls... | ACCEPT | Summary: Tube is recruited by dMyD88 to the plasma membrane in S2 cells in a death-domain-dependent manner. Reason: Precise location of Tube when signalling: the cytoplasmic face of the plasma membrane, in the Toll-MyD88-Tube-Pelle complex. Supporting Evidence: PMID:22464168 Rather, Tube co-localized with full length dMyD88 at the plasma membrane |
| GO:0009953 dorsal/ventral pattern formation | IGI PMID:8244004 Genetic characterization of tube and pelle, genes required f... | ACCEPT | Summary: Maternal tube is required for ventral and lateral embryonic pattern. Reason: Strong genetic evidence; tube is a maternal dorsal-group gene. Supporting Evidence: PMID:8244004 Females homozygous for strong alleles of tube or pelle produce embryos that lack all ventral and lateral embryonic pattern elements. |
| GO:0009953 dorsal/ventral pattern formation | IMP PMID:10512628 Formation and biochemical characterization of tube/pelle dea... | ACCEPT | Summary: Maternal tube is required for ventral and lateral embryonic pattern. Reason: Strong genetic evidence; tube is a maternal dorsal-group gene. Supporting Evidence: PMID:10512628 Mutant tube proteins which do not support signaling in the embryo are also unable to bind pelle in the 2-hybrid assay. |
| GO:0019904 protein domain specific binding | IPI PMID:10589682 Three-dimensional structure of a complex between the death d... | MODIFY | Summary: Crystal structure of the Tube-Pelle death domain heterodimer. Reason: The specific domain bound is the Pelle death domain; death domain binding (a child of protein domain specific binding) is more precise. Proposed replacements: death domain binding Supporting Evidence: PMID:10589682 Crystal structure of the Pelle and Tube death domain heterodimer reveals that the two death domains adopt a six-helix bundle fold |
| GO:0031663 lipopolysaccharide-mediated signaling pathway | IBA GO_REF:0000033 | REMOVE | Summary: IBA for lipopolysaccharide-mediated signaling pathway propagated from mammalian IRAK-family members. Reason: LPS-mediated signalling is a mammalian TLR4-lineage function, and the fly Toll pathway is not an LPS pathway. In S2 cells Tube, like MyD88 and Pelle, is required for the Toll-dependent Drosomycin reporter but not for the Attacin reporter used as the LPS-pathway readout (PMID:12351681). The ligand-specific process term should not reach Tube. Propagation Review Root cause: PROPAGATION BAD Failure modes: LINEAGE OR TAXON MISMATCH Sources checked: PANTHER:PTN000701353 SUPPORTS SOURCE BUT NOT TARGET Node grouping Pelle/IRAK-family and Tube; the LPS-pathway assertion rests on mammalian IRAK evidence tied to TLR4 ligand specificity, which does not apply to the Spaetzle-activated fly Toll pathway. Supporting Evidence: PMID:12351681 Drosophila MyD88, like Tube and Pelle, was required for activation of the Drosomycin, but not the Attacin, reporter |
| GO:0035172 hemocyte proliferation | TAS PMID:14602069 Thicker than blood: conserved mechanisms in Drosophila and v... | UNDECIDED | Summary: Traceable author statement from a review of Drosophila hematopoiesis. Reason: Only the abstract of this review is cached and it does not mention Tube. Toll pathway gain-of-function is known to affect hemocyte numbers, but the specific statement about tube cannot be checked, so this is left undecided. Supporting Evidence: PMID:14602069 the molecular genetic mechanisms of hematopoietic cell fate determination and commitment within Drosophila blood cell lineages are discussed |
| GO:0045087 innate immune response | IMP PMID:12351681 A heterotrimeric death domain complex in Toll signaling. | ACCEPT | Summary: RNAi of Tube blocks Toll-induced Drosomycin reporter activation in S2 cells. Reason: Tube is required for the Toll-dependent innate immune response to fungi and Gram-positive bacteria. Supporting Evidence: PMID:12351681 RNAi against Pelle, Tube, or Dorsal significantly inhibited the activation of the Drosomycin reporter |
| GO:0045087 innate immune response | TAS PMID:10589682 Three-dimensional structure of a complex between the death d... | ACCEPT | Summary: Statement that Pelle and Tube mediate the innate immune response toward fungal infection. Reason: Consistent with genetic evidence (PMID:8808632). Supporting Evidence: PMID:10589682 Pelle and Tube also mediate the innate immune response of Drosophila toward fungal infection |
| GO:0048262 determination of dorsal/ventral asymmetry | IMP PMID:10512628 Formation and biochemical characterization of tube/pelle dea... | ACCEPT | Summary: Tube is required for determination of ventral fates along the embryonic dorsoventral axis. Reason: Term definition (determination of asymmetry from the dorsal to the ventral side) fits the maternal dorsoventral patterning role of tube. Supporting Evidence: PMID:10512628 Mutant tube proteins which do not support signaling in the embryo are also unable to bind pelle in the 2-hybrid assay. |
| GO:0048262 determination of dorsal/ventral asymmetry | IMP PMID:7635064 Interaction of the pelle kinase with the membrane-associated... | ACCEPT | Summary: Tube is required for determination of ventral fates along the embryonic dorsoventral axis. Reason: Term definition (determination of asymmetry from the dorsal to the ventral side) fits the maternal dorsoventral patterning role of tube. Supporting Evidence: PMID:7635064 This signal directs import of the rel-related protein dorsal into ventral and ventrolateral nuclei, thereby establishing dorsoventral polarity. |
| GO:1990782 protein tyrosine kinase binding | IPI PMID:10512628 Formation and biochemical characterization of tube/pelle dea... | MODIFY | Summary: IPI for binding Pelle recorded as protein tyrosine kinase binding. Reason: Pelle is a serine/threonine kinase of the IRAK family, not a tyrosine kinase, so tyrosine kinase binding is incorrect in its specificity. The interaction itself is well established, via the death domains. Replace with death domain binding (or the parent protein kinase binding). Proposed replacements: death domain binding protein kinase binding Supporting Evidence: PMID:10512628 we show using the yeast two-hybrid system that the wild-type tube and pelle death domains bind together |
| GO:0035591 signaling adaptor activity | IDA PMID:12351681 A heterotrimeric death domain complex in Toll signaling. | NEW | Summary: Tube bridges MyD88 and the kinase Pelle in the Toll receptor signalling complex through two distinct death-domain surfaces. Reason: Tube has no catalytic activity; its molecular role is to assemble the MyD88-Tube-Pelle death-domain heterotrimer and recruit Pelle to the membrane, which is what signaling adaptor activity describes. Tube performs this bridging step itself, so it passes the participation test. Comparator check: MYD88 and TIRAP in human, and Drosophila Myd88, carry GO:0035591 in GOA. None of the existing Tube MF annotations capture the adaptor activity. Supporting Evidence: PMID:12351681 Tube recruits MyD88 and Pelle into the heterotrimer by two distinct binding surfaces on the Tube death domain PMID:7635064 We propose a model wherein tube activates pelle by recruiting it to the plasma membrane, thereby propagating the axis-determining signal. |
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Download this section (compressed HTML)Q: Is Tube a highly diverged orthologue of vertebrate IRAK4 (the proposed functional counterpart), and does the PANTHER placement of Tube within the IRAK/Pelle family reflect true homology of the death domain?
Q: What is the function of Tube binding to Dorsal via the Tube repeats: does it position Dorsal/Cactus near Pelle for phosphorylation?
Q: Do other Drosophila Toll-family receptors (e.g. Toll-7, 18w) signal through Tube, or is Tube specific to the Toll-Spaetzle pathway?
Experiment: Structural determination of the full MyD88-Tube-Pelle death-domain assembly (cryo-EM) to compare its stoichiometry with the vertebrate Myddosome.
Experiment: Rescue of tube null embryos and adults with Tube repeat-deleted constructs to test whether Dorsal binding by Tube is required for signalling in development and immunity.
Experiment: Tissue-specific tube knockdown in fat body versus hemocytes to separate its roles in humoral immunity and hematopoiesis.
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Download this section (compressed HTML)tube (tub) encodes an adaptor protein, which functions downstream of the product of Myd88 in the Toll pathway. Toll pathway is a signaling cascade that plays a key role in various developmental and immune processes, notably embryonic dorsoventral patterning and regulation of antimicrobial peptides.
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