Diap2 encodes Drosophila inhibitor of apoptosis protein 2, a cytoplasmic and contextual nuclear BIR-domain RING E3 ubiquitin ligase that acts mainly in the Imd innate immune pathway downstream of peptidoglycan recognition. Its RING-dependent K63-linked ubiquitination of IMD-pathway components including Dredd, Imd, and Kenny promotes Relish/NF-kappaB activation and antimicrobial peptide induction after Gram-negative bacterial challenge; DIAP2 can also bind and ubiquitinate the effector caspase DrICE, raising the apoptotic threshold without serving as the essential canonical caspase brake performed by DIAP1. In the Malpighian tubules Diap2 is needed for the local epithelial immune response, and its loss lowers expression of the Na+/K+-ATPase and V-ATPase ion pumps, which the tubule immune response also requires.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004842 ubiquitin-protein transferase activity | TAS Reactome:R-DME-209179 | MODIFY | Summary: DIAP2 is a RING E3 ubiquitin ligase; the old transferase term should be updated. Reason: Reactome captures the cytosolic IAP2:BEN:UEV1A E3 ligase complex, but GO:0061630 is the current specific molecular-function term for RING-dependent ubiquitin transfer. Proposed replacements: ubiquitin protein ligase activity Supporting Evidence: Reactome:R-DME-209179 IAP2:BEN:UEV1A E3 ubiquitin ligase complex autoubiquitinates, forming Lys63-linked ubiquitin chains PMID:22549468 DIAP2 promoted the conjugation of K63-linked Ub chains on DREDD |
| GO:0004869 cysteine-type endopeptidase inhibitor activity | IDA PMID:18166655 DIAP2 functions as a mechanism-based regulator of drICE that... | ACCEPT | Summary: Diap2 directly inhibits cysteine-type endopeptidases (caspases). The genus term is correct as it stands; the apoptotic context is carried by the module and core functions, not by a precomposed term. Reason: The genus GO:0004869 is the right term. An earlier pass proposed MODIFY to the precomposed GO:0043027; per projects/INVOLVED_IN_PRECOMPOSITION.md that adds only the apoptotic context, which is carried by the core functions. Superseded reasoning (it argued for the precomposed term), retained only for its evidence: The cited work demonstrates DIAP2 binding, mechanism-based trapping, and RING-dependent ubiquitination of DrICE, so the apoptosis-qualified child term is more informative than the generic cysteine-type endopeptidase inhibitor parent. Supporting Evidence: PMID:18166655 DIAP2 regulates the effector caspase drICE PMID:18166655 target drICE for ubiquitylation |
| GO:0005515 protein binding | IPI PMID:18166655 DIAP2 functions as a mechanism-based regulator of drICE that... | MODIFY | Summary: The DrICE interaction should be represented as caspase binding. Reason: PMID:18166655 maps the BIR3-dependent DIAP2-DrICE interaction and its requirement for DrICE ubiquitylation; GO:0089720 captures the interaction more informatively than generic protein binding. Proposed replacements: caspase binding Supporting Evidence: PMID:18166655 DIAP2 regulates the effector caspase drICE |
| GO:0005515 protein binding | IPI PMID:18166655 DIAP2 functions as a mechanism-based regulator of drICE that... | REMOVE | Summary: Hid binds DIAP2, but this row is only a generic binding assertion. Reason: The interaction is real and mediated by DIAP2 BIR2/BIR3 domains, but no specific GO molecular-function term captures IAP-antagonist binding; a generic protein-binding annotation is uninformative by itself. Supporting Evidence: PMID:18166655 Hid binding appeared to be mediated by both BIR2 and 3 domains |
| GO:0005515 protein binding | IPI PMID:18166655 DIAP2 functions as a mechanism-based regulator of drICE that... | REMOVE | Summary: Reaper binds DIAP2, but this row is only a generic binding assertion. Reason: Reaper physically engages the DIAP2 BIR2 domain, but GO:0005515 does not distinguish this antagonist contact from arbitrary protein binding and should not be retained as a function. Supporting Evidence: PMID:18166655 Rpr and Grim preferentially bound to the BIR2 domain of DIAP2 |
| GO:0005515 protein binding | IPI PMID:18166655 DIAP2 functions as a mechanism-based regulator of drICE that... | REMOVE | Summary: Grim binds DIAP2, but this row is only a generic binding assertion. Reason: Grim physically engages the DIAP2 BIR2 domain; because no better GO activity term exists for this IAP-antagonist interaction, the generic binding row should be removed rather than upgraded. Supporting Evidence: PMID:18166655 Rpr and Grim preferentially bound to the BIR2 domain of DIAP2 |
| GO:0005515 protein binding | IPI PMID:9294184 Inhibition of reaper-induced apoptosis by interaction with i... | REMOVE | Summary: The older Reaper-DIAP2 interaction row is real but generic. Reason: PMID:9294184 shows Reaper coimmunoprecipitation with D-IAP2 and IAP-dependent perinuclear relocalization, but the row asserts only generic protein binding and has no more informative replacement term. Supporting Evidence: PMID:9294184 both baculovirus and Drosophila IAPs physically interact with RPR |
| GO:0005634 nucleus | EXP PMID:24374974 Epithelial immune response in Drosophila malpighian tubules:... | KEEP AS NON CORE | Summary: A UniProt-curated full-text read supports nuclear DIAP2 in the Malpighian-tubule study. Reason: The cached PMID:24374974 abstract centers on Relish nuclear translocation rather than a visible DIAP2-localization assay, but the UniProt record records nucleus and cytoplasm from that full text; keep nucleus as contextual rather than the main IMD signaling compartment. Supporting Evidence: file:DROME/Diap2/Diap2-uniprot.txt SUBCELLULAR LOCATION: Nucleus |
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The IBA nuclear-localization transfer is compatible with curated nuclear DIAP2 evidence. Reason: Nuclear localization is reported for DIAP2, but the best-defined IMD and DrICE functions are cytoplasmic; retain this propagated location as contextual. Supporting Evidence: file:DROME/Diap2/Diap2-uniprot.txt SUBCELLULAR LOCATION: Nucleus |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The UniProt subcellular-location mapping reflects a curated nuclear DIAP2 location. Reason: UniProt imports the nucleus assignment from the Malpighian-tubule literature; this location is plausible and curated but secondary to cytoplasmic IMD signaling. Supporting Evidence: file:DROME/Diap2/Diap2-uniprot.txt SUBCELLULAR LOCATION: Nucleus |
| GO:0005737 cytoplasm | EXP PMID:24374974 Epithelial immune response in Drosophila malpighian tubules:... | ACCEPT | Summary: DIAP2 is cytoplasmic. Reason: The UniProt full-text curation from PMID:24374974 places DIAP2 in the cytoplasm, and the DREDD/IMD ubiquitination mechanism is a cytoplasmic immune-signaling role. Supporting Evidence: file:DROME/Diap2/Diap2-uniprot.txt Cytoplasm {ECO:0000269|PubMed:24374974} PMID:22549468 DIAP2 promoted the conjugation of K63-linked Ub chains on DREDD |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: The cytoplasm is the main compartment for DIAP2 IMD signaling. Reason: DIAP2 acts on cleaved IMD and DREDD in the PGRP/IMD signaling complex before Relish enters the nucleus, so the IBA cytoplasm transfer agrees with direct fly evidence. Supporting Evidence: PMID:22549468 DIAP2 promoted the conjugation of K63-linked Ub chains on DREDD |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: The UniProt subcellular-location mapping to cytoplasm is correct. Reason: DIAP2 is curated by UniProt as cytoplasmic and uses its RING to ubiquitinate cytoplasmic IMD-pathway substrates. Supporting Evidence: file:DROME/Diap2/Diap2-uniprot.txt Cytoplasm {ECO:0000269|PubMed:24374974} PMID:20122400 DIAP2 is the E3 for IMD K63-Ubiquitination in vivo |
| GO:0005829 cytosol | IEA GO_REF:0000117 | UNDECIDED | Summary: The ARBA cytosol projection is plausible but not locally verifiable. Reason: DIAP2 is cytoplasmic, but the specific cytosol assignment from ARBA has no inspected primary source in this row, and the local cytoplasmic literature does not explicitly distinguish cytosol from other cytoplasmic compartments. Supporting Evidence: file:DROME/Diap2/Diap2-uniprot.txt SUBCELLULAR LOCATION: Nucleus |
| GO:0005829 cytosol | TAS Reactome:R-DME-209179 | UNDECIDED | Summary: Reactome places the IAP2 E3 complex in the IMD pathway, but the cached event does not expose compartment evidence. Reason: R-DME-209179 directly names an IAP2-containing E3 ligase complex, yet the cached Reactome record is a one-sentence event summary that does not itself document cytosolic localization. Supporting Evidence: Reactome:R-DME-209179 IAP2:BEN:UEV1A E3 ubiquitin ligase complex autoubiquitinates |
| GO:0005829 cytosol | TAS Reactome:R-DME-209240 | UNDECIDED | Summary: This Reactome event is downstream TAK1-to-IRD5 phosphorylation rather than an exposed DIAP2 localization record. Reason: R-DME-209240 describes IRD5 phosphorylation by activated TAK1; the local cache does not show DIAP2 as an entity in the reaction or state that DIAP2 is cytosolic there. Supporting Evidence: Reactome:R-DME-209240 IRD5 is phosphorylated and activated by phosphorylated TAK1 kinase |
| GO:0005829 cytosol | TAS Reactome:R-DME-209289 | UNDECIDED | Summary: Reactome has TAB2 bind ubiquitinated IAP2 complex, but the cached event is too thin for a compartment check. Reason: R-DME-209289 includes ubiquitinated Apoptosis 2 Inhibitor in a TAK1/TAB2 activation event, but the local summary does not expose the entity compartments underlying the GO cytosol projection. Supporting Evidence: Reactome:R-DME-209289 ubiquitin chains emanating from the Apoptosis 2 Inhibitor |
| GO:0005829 cytosol | TAS Reactome:R-DME-209320 | UNDECIDED | Summary: This Reactome event summarizes TAK1 autophosphorylation without visible DIAP2 evidence. Reason: R-DME-209320 may lie downstream of the IAP2 E3 ligase complex in Reactome, but the cached event only states that TAK1 autophosphorylates, so it does not verify DIAP2 cytosolic localization. Supporting Evidence: Reactome:R-DME-209320 TAK1 kinase is phosphorylated at Thr171 |
| GO:0006511 ubiquitin-dependent protein catabolic process | IMP PMID:17205079 Regulation of the Drosophila ubiquitin ligase DIAP1 is media... | UNDECIDED | Summary: DIAP2 may contribute to DIAP1 degradation, but the row needs full-text confirmation. Reason: The abstract-only cache reports only preliminary evidence that DIAP2 mediates DIAP1 degradation; it does not expose the IMP assay or enough mechanism to verify a ubiquitin-dependent protein-catabolic-process assertion. Supporting Evidence: PMID:17205079 Our preliminary data suggest that DIAP2 mediates DIAP1 degradation |
| GO:0006964 positive regulation of biosynthetic process of antibacterial peptides active against Gram-negative bacteria | HMP PMID:16163390 Inhibitor of apoptosis 2 and TAK1-binding protein are compon... | MODIFY | Summary: The HMP peptide-biosynthesis row should be narrowed to the IMD pathway. Reason: Iap2 acts as a component of peptidoglycan/Imd signaling that drives Attacin and Diptericin expression, not as a direct participant in antibacterial peptide translation or maturation. Proposed replacements: peptidoglycan recognition protein signaling pathway Supporting Evidence: PMID:16163390 Iap2 is required for antimicrobial peptide response also by the fat body in vivo |
| GO:0006964 positive regulation of biosynthetic process of antibacterial peptides active against Gram-negative bacteria | IMP PMID:16163390 Inhibitor of apoptosis 2 and TAK1-binding protein are compon... | MODIFY | Summary: The IMP peptide-biosynthesis row should be narrowed to the IMD pathway. Reason: PMID:16163390 placed Iap2 genetically downstream of Imd; GO:0061057 captures that signaling role more precisely than a broad downstream antimicrobial-peptide biosynthetic output. Proposed replacements: peptidoglycan recognition protein signaling pathway Supporting Evidence: PMID:16163390 Iap2 functions, genetically, downstream of Imd in the fat body in vivo |
| GO:0008270 zinc ion binding | ISM PMID:21912646 Comprehensively surveying structure and function of RING dom... | ACCEPT | Summary: DIAP2 contains zinc-coordinating BIR/RING features. Reason: The ISM row reflects the zinc-binding BIR/RING architecture of DIAP2, including the curated RING-type zinc finger and Zn(2+) ligand sites in UniProt. Supporting Evidence: PMID:21912646 conserved Cys/His chelating zinc ions file:DROME/Diap2/Diap2-uniprot.txt RING-type |
| GO:0016567 protein ubiquitination | IDA PMID:23940367 Caspase-dependent regulation of the ubiquitin-proteasome sys... | UNDECIDED | Summary: The PMID:23940367 Diap2 ubiquitination row is not visible in the local abstract. Reason: The cached record is abstract-only and describes DIAP1-dependent Grim ubiquitination; leave this Diap2 process row unresolved until its full-text Diap2 assay is checked against the FlyBase evidence. Supporting Evidence: PMID:23940367 Caspase-dependent regulation of the ubiquitin-proteasome system through direct substrate targeting |
| GO:0016755 aminoacyltransferase activity | IEA GO_REF:0000117 | MODIFY | Summary: The ARBA aminoacyltransferase parent should be replaced by the demonstrated E3 ligase activity. Reason: DIAP2 is a RING-dependent ubiquitin protein ligase; GO:0061630 is the specific catalytic activity rather than the high-level transferase parent imported by ARBA. Proposed replacements: ubiquitin protein ligase activity Supporting Evidence: PMID:22549468 DIAP2 promoted the conjugation of K63-linked Ub chains on DREDD |
| GO:0022416 chaeta development | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: The ARBA chaeta-development projection overstates the physiological role of DIAP2. Reason: The available Diap2-specific evidence is an ectopic caspase-blockade phenotype in the scutellum; as with the FlyBase IMP row, that overexpression result does not establish chaeta development as an endogenous DIAP2 function. Supporting Evidence: PMID:16222340 DIAP1 and DIAP2 expression also resulted in additional macrochaetes |
| GO:0022416 chaeta development | IMP PMID:16222340 Drosophila caspase transduces Shaggy/GSK-3beta kinase activi... | MARK AS OVER ANNOTATED | Summary: This IMP row overstates a caspase-blockade overexpression phenotype. Reason: Ectopic DIAP2 phenocopied p35 and DIAP1 overexpression in the scutellum, showing that broad caspase inhibition can alter macrochaete number; that does not establish chaeta development as an endogenous DIAP2 function. Supporting Evidence: PMID:16222340 DIAP1 and DIAP2 expression also resulted in additional macrochaetes |
| GO:0031398 positive regulation of protein ubiquitination | IBA GO_REF:0000033 | ACCEPT | Summary: The positive-regulation row is broad but reflects a real IAP-family E3 role. Reason: DIAP2 directly catalyzes K63-linked ubiquitination of IMD-pathway substrates, so an inherited positive regulation of protein ubiquitination process is biologically sound even though the core activity is the E3 molecular function. Supporting Evidence: PMID:20122400 DIAP2 is the E3 for IMD K63-Ubiquitination in vivo PMID:22549468 DIAP2 promoted the conjugation of K63-linked Ub chains on DREDD |
| GO:0031625 ubiquitin protein ligase binding | IEA GO_REF:0000117 | UNDECIDED | Summary: The ARBA ubiquitin-ligase-binding prediction is unsupported here. Reason: The electronic row lacks a gene-specific source; DIAP2 works with E2 enzymes and may contact E3 partners, but this ARBA assertion cannot be tied to a visible endogenous ubiquitin protein ligase binding activity. Supporting Evidence: PMID:22549468 DIAP2 promoted the conjugation of K63-linked Ub chains on DREDD |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:17205079 Regulation of the Drosophila ubiquitin ligase DIAP1 is media... | UNDECIDED | Summary: DIAP1 binding and degradation by DIAP2 need full-text confirmation. Reason: The PMID:17205079 abstract mentions preliminary DIAP2-mediated DIAP1 degradation but does not expose the IPI assay behind this partner-specific row. Supporting Evidence: PMID:17205079 Our preliminary data suggest that DIAP2 mediates DIAP1 degradation |
| GO:0043027 cysteine-type endopeptidase inhibitor activity involved in apoptotic process | IBA GO_REF:0000033 | MODIFY | Summary: The inherited caspase-inhibitory activity is supported by Diap2-specific DrICE experiments. Reason: DIAP2 binds active DrICE and requires both BIR3 and its RING to restrain DrICE-mediated death, matching the PAINT IAP-family inhibitor annotation. Proposed replacements: cysteine-type endopeptidase inhibitor activity Context of precomposed term: in core functions Decomposed from the precomposed GO:0043027 (projects/INVOLVED_IN_PRECOMPOSITION.md) to its genus GO:0004869; the claim is unchanged and the apoptotic context is carried by this review's core functions. Supporting Evidence: PMID:18166655 DIAP2 regulates the effector caspase drICE PMID:18166655 target drICE for ubiquitylation |
| GO:0043027 cysteine-type endopeptidase inhibitor activity involved in apoptotic process | IDA PMID:11337486 Characterization of the Drosophila caspase, DAMM. | MODIFY | Summary: DIAP2 has a verified apoptosis-linked caspase-inhibitor activity. Reason: The PMID:11337486 cache is abstract-only and does not expose the Diap2 assay, but the molecular function asserted by the row is directly supported by later BIR3/DrICE and RING-dependent DrICE-ubiquitylation evidence; keep the FlyBase row rather than second-guessing the full-text curation. Proposed replacements: cysteine-type endopeptidase inhibitor activity Context of precomposed term: in core functions Decomposed from the precomposed GO:0043027 (projects/INVOLVED_IN_PRECOMPOSITION.md) to its genus GO:0004869; the claim is unchanged and the apoptotic context is carried by this review's core functions. Supporting Evidence: PMID:11337486 Characterization of the Drosophila caspase, DAMM PMID:18166655 DIAP2 regulates the effector caspase drICE PMID:18166655 target drICE for ubiquitylation |
| GO:0043027 cysteine-type endopeptidase inhibitor activity involved in apoptotic process | IEA GO_REF:0000117 | MODIFY | Summary: The electronic caspase-inhibitor import mirrors a real DIAP2 activity. Reason: DIAP2 directly regulates the effector caspase DrICE through a BIR3/caspase-cleavage-site mechanism and RING-dependent ubiquitylation. Proposed replacements: cysteine-type endopeptidase inhibitor activity Context of precomposed term: in core functions Decomposed from the precomposed GO:0043027 (projects/INVOLVED_IN_PRECOMPOSITION.md) to its genus GO:0004869; the claim is unchanged and the apoptotic context is carried by this review's core functions. Supporting Evidence: PMID:18166655 DIAP2 regulates the effector caspase drICE PMID:18166655 target drICE for ubiquitylation |
| GO:0043028 cysteine-type endopeptidase regulator activity involved in apoptotic process | IMP PMID:16485033 Systematic in vivo RNAi analysis of putative components of t... | MODIFY | Summary: DIAP2 regulates active DrICE in apoptosis assays. Reason: The RNAi-screen paper found that overexpressed DIAP2 can rescue apoptosis caused by DIAP1 depletion and binds active DrICE, matching the cysteine endopeptidase regulator term. Proposed replacements: cysteine-type endopeptidase inhibitor activity Context of precomposed term: in core functions Decomposed from the precomposed GO:0043028 (projects/INVOLVED_IN_PRECOMPOSITION.md) to its genus GO:0004869; the claim is unchanged and the apoptotic context is carried by this review's core functions. The regulator row is narrowed to inhibitor: DIAP2 binds active DrICE and restrains it. Supporting Evidence: PMID:16485033 overexpression of DIAP2 can rescue diap1-RNAi-mediated apoptosis PMID:16485033 DIAP2 binds active drICE |
| GO:0043066 negative regulation of apoptotic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: DIAP2 can raise the apoptotic threshold through DrICE restraint, but this is not its dominant endogenous process. Reason: The PAINT transfer is defensible because DIAP2 directly binds and regulates DrICE; nevertheless Diap2 null flies are viable and lack gross developmental apoptosis defects, whereas their major phenotype is loss of IMD innate immune signaling. Supporting Evidence: PMID:18166655 diap2 mutant cells are sensitized to apoptosis after exposure to sublethal doses of x-ray irradiation PMID:17068333 These flies are viable and show no defects in developmental or stress-induced apoptosis |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:10200511 Anti-apoptotic potential of insect cellular and viral IAPs i... | KEEP AS NON CORE | Summary: Drosophila IAPs suppress mammalian caspase-induced apoptosis in a heterologous assay. Reason: The cited abstract supports anti-apoptotic potential of Drosophila cellular IAPs against overexpressed mammalian caspases; that agrees with DIAP2 being able to restrain caspases but is not the core in-vivo IMD pathway role. Supporting Evidence: PMID:10200511 Drosophila cellular IAPs and two baculoviral IAPs (OpIAP and CpIAP) can inhibit mammalian cell death induced by overexpression of Caspases 1 and 2 |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:9294184 Inhibition of reaper-induced apoptosis by interaction with i... | KEEP AS NON CORE | Summary: DIAP2 can inhibit Reaper-induced apoptosis when coexpressed. Reason: The older transfection study shows Drosophila IAPs bind Reaper and block Reaper-induced death; retain the broad apoptosis-regulation row as a contextual overexpression activity. Supporting Evidence: PMID:9294184 Expression of IAPs blocked RPR-induced apoptosis |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:18166655 DIAP2 functions as a mechanism-based regulator of drICE that... | KEEP AS NON CORE | Summary: DIAP2 loss sensitizes cells to apoptotic stress through DrICE derepression. Reason: PMID:18166655 demonstrates an endogenous increase in DrICE activity and x-ray sensitivity in diap2 mutants, but also frames this as a threshold role that does not by itself cause spontaneous apoptosis. Supporting Evidence: PMID:18166655 diap2 mutant cells are sensitized to apoptosis after exposure to sublethal doses of x-ray irradiation |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:9294184 Inhibition of reaper-induced apoptosis by interaction with i... | KEEP AS NON CORE | Summary: DIAP2-dependent perinuclear Reaper relocalization was observed in a coexpression system. Reason: The location is supported by the RPR/IAP coexpression paper, but it is tied to ectopic Reaper antagonism rather than to the main PGRP/IMD signaling role. Supporting Evidence: PMID:9294184 punctate perinuclear locations which coincided with IAP localization |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: The electronic perinuclear import is plausible but contextual. Reason: Perinuclear relocalization is documented for DIAP2 with Reaper coexpression; keep the electronic row as a non-core copy of that contextual localization. Supporting Evidence: PMID:9294184 punctate perinuclear locations which coincided with IAP localization |
| GO:0050829 defense response to Gram-negative bacterium | IMP PMID:16894030 The Drosophila inhibitor of apoptosis protein DIAP2 function... | KEEP AS NON CORE | Summary: DIAP2 is required for the organismal defense response to Gram-negative infection. Reason: The row is broader than the proximal E3-ligase step, but diap2 null flies fail to induce antibacterial peptide genes and die after Gram-negative infection. Supporting Evidence: PMID:16894030 acutely sensitive to infection by gram-negative bacteria PMID:16894030 diap2 mutant flies failed to activate NF-kappaB-mediated expression of antibacterial peptide genes |
| GO:0050829 defense response to Gram-negative bacterium | IMP PMID:17068333 The Drosophila inhibitor of apoptosis (IAP) DIAP2 is dispens... | KEEP AS NON CORE | Summary: DIAP2 is required for Gram-negative antibacterial immunity but not cell survival. Reason: Huh et al. independently found that diap2 null mutants are viable but require DIAP2 for Gram-negative infection resistance and Relish activation. Supporting Evidence: PMID:17068333 DIAP2 is required for the innate immune response to Gram-negative bacterial infection |
| GO:0050829 defense response to Gram-negative bacterium | IMP PMID:22549468 Ubiquitylation of the initiator caspase DREDD is required fo... | KEEP AS NON CORE | Summary: DREDD ubiquitylation by DIAP2 is required for Gram-negative infection resistance. Reason: PMID:22549468 ties the organismal defense phenotype to signal-dependent DIAP2-mediated DREDD ubiquitination in the IMD pathway. Supporting Evidence: PMID:22549468 loss of the Ub-E3 ligase for DREDD, or loss of signal-dependent ubiquitylation of DREDD |
| GO:0051726 regulation of cell cycle | IBA GO_REF:0000033 | REMOVE | Summary: The cell-cycle IBA is overpropagated from the IAP family. Reason: No Diap2-specific cached paper or UniProt curation supports a normal cell-cycle role; this looks like a PANTHER family-level propagation from other IAP subfamilies such as chromosomal-passenger BIRC5/Bir1-like proteins. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN000005168 SUPPORTS SOURCE BUT NOT TARGET The IAP family contains cell-cycle regulators, but Diap2-specific evidence points to IMD signaling and DrICE restraint rather than cell-cycle control. Supporting Evidence: PMID:20122400 DIAP2 is the E3 for IMD K63-Ubiquitination in vivo |
| GO:0061057 peptidoglycan recognition protein signaling pathway | HMP PMID:16163390 Inhibitor of apoptosis 2 and TAK1-binding protein are compon... | ACCEPT | Summary: Iap2 acts in the Drosophila Imd/peptidoglycan-response pathway. Reason: The HMP row correctly captures the RNAi screen and in-vivo fat-body evidence that Iap2 is a downstream component of Imd signaling. Supporting Evidence: PMID:16163390 Iap2 functions, genetically, downstream of Imd in the fat body in vivo |
| GO:0061057 peptidoglycan recognition protein signaling pathway | IDA PMID:34262145 Drice restrains Diap2-mediated inflammatory signalling and i... | ACCEPT | Summary: Diap2 drives Relish/Imd inflammatory signaling in epithelia and fat body. Reason: The Drice-Diap2 study directly manipulates Diap2 and shows that unrestrained Diap2 ubiquitinates multiple Imd-pathway targets. Supporting Evidence: PMID:34262145 Unrestrained Diap2 drives Imd sigalling by ubiquitinating Imd, Dredd and Kenny |
| GO:0061057 peptidoglycan recognition protein signaling pathway | IMP PMID:16163390 Inhibitor of apoptosis 2 and TAK1-binding protein are compon... | ACCEPT | Summary: Iap2 is required for Imd signaling in cells and in the fat body. Reason: The same PMID:16163390 genetic evidence places Iap2 downstream of Imd in the antimicrobial-peptide response. Supporting Evidence: PMID:16163390 Iap2 is required for antimicrobial peptide response also by the fat body in vivo |
| GO:0061057 peptidoglycan recognition protein signaling pathway | IMP PMID:16894030 The Drosophila inhibitor of apoptosis protein DIAP2 function... | ACCEPT | Summary: DIAP2 is an essential component of the Imd signaling cascade in vivo. Reason: Null mutants fail to activate NF-kappaB-dependent antibacterial peptide expression after Gram-negative challenge, directly supporting the peptidoglycan-response pathway row. Supporting Evidence: PMID:16894030 DIAP2 as an essential component of the Imd signaling cascade |
| GO:0061057 peptidoglycan recognition protein signaling pathway | IMP PMID:17343912 Iap2 is required for a sustained response in the Drosophila ... | ACCEPT | Summary: Iap2 sustains Imd-pathway antimicrobial gene expression and microbial resistance. Reason: Genome-wide kinetic RNAi analysis found a specific Iap2 requirement in S2 immune responses and in vivo microbial resistance. Supporting Evidence: PMID:17343912 Iap2 is required to sustain antimicrobial peptide gene expression in S2 cells PMID:17343912 inactivation of Iap2 by RNAi resulted in impaired microbial resistance in Drosophila in vivo |
| GO:0061057 peptidoglycan recognition protein signaling pathway | IMP PMID:19497884 Two roles for the Drosophila IKK complex in the activation o... | ACCEPT | Summary: DIAP2 is required upstream of Relish phosphorylation in the Imd pathway. Reason: The Relish phosphorylation paper used RNAi epistasis and found DIAP2 was required for signal-dependent Relish phosphorylation downstream of peptidoglycan recognition. Supporting Evidence: PMID:19497884 Uev1a/Ubc13, DIAP2, TAB2, TAK1, and IKKΞ³ were all required for phosphorylation of Relish |
| GO:0061057 peptidoglycan recognition protein signaling pathway | IMP PMID:20122400 Caspase-mediated cleavage, IAP binding, and ubiquitination: ... | ACCEPT | Summary: DIAP2 acts between IMD and TAK1 and ubiquitinates IMD. Reason: PMID:20122400 shows DIAP2 is needed for DAP-type PGN stimulation and then identifies DIAP2 as the RING-dependent E3 for IMD K63 ubiquitination in flies. Supporting Evidence: PMID:20122400 DIAP2 RNAi markedly inhibited the induction of the antimicrobial peptide gene Diptericin following immune stimulation with DAP-type peptidoglycan PMID:20122400 DIAP2 is the E3 for IMD K63-Ubiquitination in vivo |
| GO:0061057 peptidoglycan recognition protein signaling pathway | IMP PMID:22549468 Ubiquitylation of the initiator caspase DREDD is required fo... | ACCEPT | Summary: DIAP2-dependent K63 ubiquitination of DREDD is required in IMD signaling. Reason: The DREDD ubiquitylation paper shows that DIAP2 binds DREDD, promotes K63-linked DREDD ubiquitination, and is required for IMD/Relish processing after Gram-negative infection. Supporting Evidence: PMID:22549468 DIAP2 promoted the conjugation of K63-linked Ub chains on DREDD PMID:22549468 DIAP2-mediated ubiquitylation of DREDD is required for innate immune signalling |
| GO:0061057 peptidoglycan recognition protein signaling pathway | IMP PMID:28377500 Innate immune signaling in Drosophila is regulated by transf... | ACCEPT | Summary: Diap2 is required for rapid K63 ubiquitination of Imd in the peptidoglycan response. Reason: Ubiquitin-editing experiments showed that Diap2 is needed for Imd Lys-63 polyubiquitination and Diptericin induction downstream of DAP-type peptidoglycan. Supporting Evidence: PMID:28377500 Imd Lys-63-polyubiquitination is prevented by knocking down Diap2 |
| GO:0061630 ubiquitin protein ligase activity | IBA GO_REF:0000033 | ACCEPT | Summary: The PANTHER E3-ligase transfer is correct for DIAP2. Reason: Direct fly experiments place DIAP2 RING activity on DREDD and IMD in IMD signaling and on DrICE in the apoptotic-threshold branch. Supporting Evidence: PMID:22549468 DIAP2 promoted the conjugation of K63-linked Ub chains on DREDD PMID:20122400 DIAP2 is the E3 for IMD K63-Ubiquitination in vivo PMID:18166655 target drICE for ubiquitylation |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:17205079 Regulation of the Drosophila ubiquitin ligase DIAP1 is media... | UNDECIDED | Summary: The DIAP1-degradation E3 assay is unresolved without full text. Reason: The abstract-only PMID:17205079 cache names DIAP2-mediated DIAP1 degradation only as preliminary data and does not expose the IDA evidence for DIAP2 ubiquitin ligase activity. Supporting Evidence: PMID:17205079 Our preliminary data suggest that DIAP2 mediates DIAP1 degradation |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:18166655 DIAP2 functions as a mechanism-based regulator of drICE that... | ACCEPT | Summary: DIAP2 uses its RING to ubiquitinate DrICE. Reason: The DrICE mechanism paper directly demonstrates DIAP2 RING-dependent ubiquitylation of DrICE. Supporting Evidence: PMID:18166655 target drICE for ubiquitylation |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:20122400 Caspase-mediated cleavage, IAP binding, and ubiquitination: ... | ACCEPT | Summary: DIAP2 is the RING E3 for IMD K63 ubiquitination. Reason: Wild-type DIAP2, but not a RING mutant, rescues IMD ubiquitination in diap2 null flies, supporting direct ubiquitin ligase activity. Supporting Evidence: PMID:20122400 DIAP2 is the E3 for IMD K63-Ubiquitination in vivo |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:23940367 Caspase-dependent regulation of the ubiquitin-proteasome sys... | UNDECIDED | Summary: The PMID:23940367 Diap2 E3 row is not visible in the local abstract. Reason: The cached abstract focuses on DIAP1-mediated Grim ubiquitination; do not second-guess the FlyBase IDA row, but leave it unresolved until the full Diap2 evidence in the paper is curated. Supporting Evidence: PMID:23940367 Grim is a caspase substrate whose cleavage promotes apoptosis by limiting, in a target-specific fashion, its ubiquitinylation and turnover by the proteasome |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:30026495 M1-linked ubiquitination by LUBEL is required for inflammato... | ACCEPT | Summary: DIAP2 catalyzes K63-linked ubiquitination of Kenny. Reason: The LUBEL/Kenny study shows DIAP2-dependent K63 ubiquitination of Kenny, a regulatory IKK component in the Imd pathway. Supporting Evidence: PMID:30026495 K63-linked ubiquitin chains conjugated to Kenny by DIAP2 |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:34262145 Drice restrains Diap2-mediated inflammatory signalling and i... | ACCEPT | Summary: Diap2 ubiquitinates Imd-pathway targets in the Drice intestinal-inflammation branch. Reason: The 2021 study confirms that Diap2 abundance controls ubiquitination of Dredd and Kenny and therefore inflammatory Imd signaling in the gut. Supporting Evidence: PMID:34262145 Unrestrained Diap2 drives Imd sigalling by ubiquitinating Imd, Dredd and Kenny |
| GO:0070534 protein K63-linked ubiquitination | IDA PMID:22549468 Ubiquitylation of the initiator caspase DREDD is required fo... | ACCEPT | Summary: DIAP2 mediates K63-linked ubiquitination of DREDD. Reason: DIAP2 binds DREDD and conjugates K63-linked Ub chains in a signal-dependent manner. Supporting Evidence: PMID:22549468 DIAP2 promoted the conjugation of K63-linked Ub chains on DREDD |
| GO:0070534 protein K63-linked ubiquitination | IDA PMID:30026495 M1-linked ubiquitination by LUBEL is required for inflammato... | ACCEPT | Summary: DIAP2 mediates K63-linked ubiquitination of Kenny. Reason: Kenny is modified by mixed M1/K63 ubiquitin chains, and DIAP2 drives the K63-linked arm of that modification. Supporting Evidence: PMID:30026495 K63-linked ubiquitin chains conjugated to Kenny by DIAP2 |
| GO:0070534 protein K63-linked ubiquitination | IDA PMID:34262145 Drice restrains Diap2-mediated inflammatory signalling and i... | ACCEPT | Summary: Diap2-dependent K63 ubiquitination of Dredd and Kenny is regulated by Drice in the intestine. Reason: Unrestrained Diap2 in Drice-deficient guts increases K63-dependent Imd signaling through Dredd and Kenny ubiquitination. Supporting Evidence: PMID:34262145 Unrestrained Diap2 drives Imd sigalling by ubiquitinating Imd, Dredd and Kenny |
| GO:0070936 protein K48-linked ubiquitination | IDA PMID:17205079 Regulation of the Drosophila ubiquitin ligase DIAP1 is media... | UNDECIDED | Summary: K48-linked DIAP1 turnover by DIAP2 needs full-text support. Reason: The abstract-only cache alludes to DIAP2-mediated DIAP1 degradation but does not expose the assay or show a K48 linkage, so the K48-specific process row remains unresolved. Supporting Evidence: PMID:17205079 Our preliminary data suggest that DIAP2 mediates DIAP1 degradation |
| GO:0070936 protein K48-linked ubiquitination | IEA GO_REF:0000117 | UNDECIDED | Summary: The ARBA K48-linked ubiquitination projection cannot be verified. Reason: Direct curated Diap2 evidence mainly supports K63-linked ubiquitination of IMD-pathway substrates; no inspected source validates this electronic K48-linked ubiquitination assertion. Supporting Evidence: PMID:22549468 DIAP2 promoted the conjugation of K63-linked Ub chains on DREDD |
| GO:0089720 caspase binding | IEA GO_REF:0000117 | ACCEPT | Summary: The electronic caspase-binding row mirrors the direct DrICE interaction. Reason: DIAP2 physically binds active DrICE through its BIR3 domain and the DrICE IAP-binding motif. Supporting Evidence: PMID:18166655 DIAP2 regulates the effector caspase drICE PMID:18166655 The BIR3 domain of DIAP2 was indispensable for drICE binding |
| GO:0089720 caspase binding | IPI PMID:16485033 Systematic in vivo RNAi analysis of putative components of t... | ACCEPT | Summary: DIAP2 binds active DrICE. Reason: The RNAi-screen abstract directly states that DIAP2 binds active DrICE, supporting this partner-specific caspase-binding row. Supporting Evidence: PMID:16485033 DIAP2 binds active drICE |
| GO:0140096 catalytic activity, acting on a protein | IEA GO_REF:0000117 | MODIFY | Summary: The ARBA catalytic-activity parent should be replaced by ubiquitin protein ligase activity. Reason: DIAP2 does not merely have unspecified catalytic activity on a protein; it is a RING E3 that catalyzes ubiquitin transfer to IMD, DREDD, Kenny, and DrICE. Proposed replacements: ubiquitin protein ligase activity Supporting Evidence: PMID:22549468 DIAP2 promoted the conjugation of K63-linked Ub chains on DREDD PMID:20122400 DIAP2 is the E3 for IMD K63-Ubiquitination in vivo |
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Download this section (compressed HTML)Q: Which endogenous DIAP2 substrates besides Dredd, Imd, and Kenny are ubiquitinated during acute systemic infection versus chronic gut exposure to commensal peptidoglycan?
Q: Does endogenous DIAP2 restrain apoptotic DrICE in a defined developmental or stress context, or is the DrICE branch mainly an overexpression and sensitized-stress activity secondary to the IMD-pathway role?
Q: What mechanism links Diap2 to Malpighian-tubule ion-channel expression, and does that epithelial branch require DIAP2 RING activity on the same substrates used in fat-body IMD signaling?
Experiment: Generate endogenous Diap2 alleles that selectively disrupt Dredd/Imd binding or the RING E2 interface, infect larvae and adults with Ecc15 or stimulate dissected guts with DAP-type peptidoglycan, and quantify ubiquitin remnants on Dredd, Imd, and Kenny together with Relish cleavage and AMP transcript induction.
Hypothesis: DIAP2 uses separable BIR2/BIR3 and RING interfaces to place K63-linked ubiquitin on distinct Imd-pathway substrates in vivo.
Type: endogenous separation-of-function allelic series with ubiquitin-remnant proteomics
Experiment: Introduce DIAP2 Asp100 and BIR3 point mutants at the endogenous locus and compare basal gut inflammation, SCAT3 DrICE reporter activity, x-ray sensitization, and canonical developmental apoptosis against wild-type and RING-mutant rescue alleles.
Hypothesis: The DIAP2-DrICE covalent-trapping branch limits sublethal DrICE activity without being sufficient to replace DIAP1 as the canonical apoptosis inhibitor.
Type: structure-guided endogenous mutant rescue with live caspase reporters
Death-associated inhibitor of apoptosis 2 (Diap2) encodes a protein with ubiquitin E3-ligase activity that functions in the Imd pathway by conjugating the product of imd with K63-polyubiquitin chains.
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