Diap1 encodes the essential Drosophila inhibitor-of-apoptosis protein DIAP1/thread, a BIR- and RING-domain E3 ligase that binds the initiator caspase Dronc and the effector caspases DrICE and Dcp-1 to restrain apoptosis. Reaper/Hid/Grim-family antagonists, Jafrac2, and dOmi/HtrA2 relieve this brake by binding DIAP1, while DIAP1 ubiquitinates or neddylates caspases and selected non-caspase substrates in cytosolic and contextual nuclear/developmental pathways.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000209 protein polyubiquitination | IDA PMID:12198495 Reaper-mediated inhibition of DIAP1-induced DTRAF1 degradati... | KEEP AS NON CORE | Summary: DIAP1 drives ubiquitin-dependent DTRAF1 degradation in a JNK-regulatory side branch. Reason: The source supports DIAP1-dependent DTRAF1 polyubiquitination and JNK restraint, but this Reaper-sensitive DTRAF1 branch is contextual rather than the core caspase-inhibitory output of DIAP1. Supporting Evidence: PMID:12198495 DIAP1-induced DTRAF1 degradation |
| GO:0000209 protein polyubiquitination | IDA PMID:17205079 Regulation of the Drosophila ubiquitin ligase DIAP1 is media... | MODIFY | Summary: This row should be narrowed to DIAP1 autoubiquitination. Reason: The cited abstract discusses regulated DIAP1 autoubiquitination, probably through non-K48 chains; GO:0051865 is more precise than the generic protein polyubiquitination parent. Proposed replacements: protein autoubiquitination Supporting Evidence: PMID:17205079 autoubiquitinating activity of DIAP1 |
| GO:0004842 ubiquitin-protein transferase activity | TAS PMID:22304967 XIAP monoubiquitylates Groucho/TLE to promote canonical Wnt ... | MODIFY | Summary: DIAP1 is a RING E3 ubiquitin ligase; the old transferase term should be updated. Reason: The TAS row captures DIAP1 RING-dependent ubiquitin transfer, but GO:0061630 is the current informative E3 ubiquitin ligase term. Proposed replacements: ubiquitin protein ligase activity Supporting Evidence: PMID:22304967 positive regulator of Wingless PMID:12021771 ubiquitination of Dronc |
| GO:0004869 cysteine-type endopeptidase inhibitor activity | IDA PMID:10481910 The Drosophila caspase inhibitor DIAP1 is essential for cell... | ACCEPT | Summary: Diap1 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 module dmel_rhg_apoptosome_caspase_activation#diap1_diap1 and the core functions. Superseded reasoning (it argued for the precomposed term), retained only for its evidence: DIAP1 blocks apoptosis-inducing caspase activity, and the apoptosis-qualified cysteine endopeptidase inhibitor term is more specific than the generic parent. Supporting Evidence: PMID:10481910 disrupting productive IAP-caspase interactions |
| GO:0004869 cysteine-type endopeptidase inhibitor activity | IDA PMID:15107838 Molecular mechanisms of DrICE inhibition by DIAP1 and remova... | ACCEPT | Summary: Diap1 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. This row's evidence is direct inhibition of the effector caspase DrICE. 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 module dmel_rhg_apoptosome_caspase_activation#diap1_diap1 and the core functions. Superseded reasoning (it argued for the precomposed term), retained only for its evidence: The structural DrICE paper shows direct inhibition of the effector caspase DrICE by DIAP1 and should be captured with the apoptosis-qualified caspase inhibitor MF. Supporting Evidence: PMID:15107838 DIAP1 directly inhibits the catalytic activity of DrICE |
| GO:0004869 cysteine-type endopeptidase inhibitor activity | IDA PMID:18166655 DIAP2 functions as a mechanism-based regulator of drICE that... | UNDECIDED | Summary: The DIAP2-focused source does not expose this DIAP1 inhibitor assay locally. Reason: The paper establishes a DIAP2 mechanism in the cached abstract; without the DIAP1-specific full-text evidence behind this row, leave the DIAP1 molecular-function assertion unresolved. Supporting Evidence: PMID:16485033 DIAP2 binds active drICE |
| GO:0005515 protein binding | IPI PMID:10481910 The Drosophila caspase inhibitor DIAP1 is essential for cell... | KEEP AS NON CORE | Summary: Hid binding to DIAP1 is direct but the row is only a generic binding assertion. Reason: Hid is one of the RHG antagonists that physically engages DIAP1 to relieve caspase inhibition; the partner-specific binding row is real, but it is not a separate core DIAP1 activity. Supporting Evidence: PMID:10481910 disrupting productive IAP-caspase interactions |
| GO:0005515 protein binding | IPI PMID:10481910 The Drosophila caspase inhibitor DIAP1 is essential for cell... | UNDECIDED | Summary: The Dcp-1 contact is plausible but not resolved from this abstract-only source. Reason: The cached DIAP1 paper establishes IAP-caspase regulation but does not expose a Dcp-1-specific physical interaction, so this generic protein-binding row cannot be confidently tightened here. Supporting Evidence: PMID:10481910 disrupting productive IAP-caspase interactions |
| GO:0005515 protein binding | IPI PMID:10481910 The Drosophila caspase inhibitor DIAP1 is essential for cell... | KEEP AS NON CORE | Summary: The Hid interaction is a real RHG antagonist contact with DIAP1. Reason: This duplicates the Hid-DIAP1 physical antagonism represented by row 7 via a UniProt partner identifier; keep it as contextual generic binding rather than as a core catalytic activity. Supporting Evidence: PMID:10481910 disrupting productive IAP-caspase interactions |
| GO:0005515 protein binding | IPI PMID:10675328 Induction of apoptosis by Drosophila reaper, hid and grim th... | KEEP AS NON CORE | Summary: Hid binding to DIAP1 is supported by the RHG gain-of-function analysis. Reason: Gain-of-function mutations in DIAP1 reduced RHG binding and suppressed Hid-induced apoptosis, supporting this direct antagonist contact while leaving the row as a non-core generic binding annotation. Supporting Evidence: PMID:10675328 forming a complex with DIAP1 |
| GO:0005515 protein binding | IPI PMID:10675328 Induction of apoptosis by Drosophila reaper, hid and grim th... | KEEP AS NON CORE | Summary: Reaper binding to DIAP1 is supported by the RHG gain-of-function analysis. Reason: Reaper kills by forming a complex with DIAP1; the contact is biologically central but the GO row still says only protein binding. Supporting Evidence: PMID:10675328 forming a complex with DIAP1 |
| GO:0005515 protein binding | IPI PMID:10675329 The Drosophila caspase DRONC is regulated by DIAP1. | MODIFY | Summary: The DRONC prodomain interaction should be captured as caspase binding. Reason: This paper reports that DIAP1 interacts with the DRONC prodomain and requires that interaction to suppress DRONC-mediated eye ablation, so GO:0089720 is more specific than protein binding. Proposed replacements: caspase binding Supporting Evidence: PMID:10675329 interaction of DIAP1 with the pro-domain of DRONC is required |
| GO:0005515 protein binding | IPI PMID:10984473 An essential role for the caspase dronc in developmentally p... | UNDECIDED | Summary: The Dronc source supports DIAP1 genetic restraint but not the IPI row in the cached abstract. Reason: The abstract shows that diap1 mutations enhance Dronc-induced cell death; it does not expose a DIAP1-Dronc physical interaction assay. Supporting Evidence: PMID:10984473 enhanced by mutations in diap1 |
| GO:0005515 protein binding | IPI PMID:11818065 The damage-responsive Drosophila gene sickle encodes a novel... | UNDECIDED | Summary: The local Sickle paper does not verify a Reaper-DIAP1 IPI row. Reason: The cached abstract verifies Sickle binding to DIAP1 BIR2, not the Reaper partner asserted in this GOA row. Supporting Evidence: PMID:11818065 specifically bound to the BIR2 domain of DIAP1 |
| GO:0005515 protein binding | IPI PMID:12021769 Regulation of Drosophila IAP1 degradation and apoptosis by r... | UNDECIDED | Summary: The Reaper/UbcD1 source does not expose the Hid interaction. Reason: The abstract specifically contrasts Reaper with Hid for DIAP1 degradation and exposes Reaper and UbcD1 binding, leaving this Hid IPI row unresolved without the full text. Supporting Evidence: PMID:12021769 stimulate DIAP1 auto-ubiquitination in vitro |
| GO:0005515 protein binding | IPI PMID:12021769 Regulation of Drosophila IAP1 degradation and apoptosis by r... | KEEP AS NON CORE | Summary: Reaper binds DIAP1 to stimulate autoubiquitination with UbcD1. Reason: Reaper specifically binds DIAP1 and stimulates DIAP1 autoubiquitination, but this row is a contextual antagonist-contact assertion. Supporting Evidence: PMID:12021769 stimulate DIAP1 auto-ubiquitination in vitro |
| GO:0005515 protein binding | IPI PMID:12021769 Regulation of Drosophila IAP1 degradation and apoptosis by r... | UNDECIDED | Summary: The Reaper/UbcD1 source does not expose this Hid interaction. Reason: The cached abstract does not support a Hid-DIAP1 IPI row for this source, although other papers establish Hid as a DIAP1 antagonist. Supporting Evidence: PMID:12021769 stimulate DIAP1 auto-ubiquitination in vitro |
| GO:0005515 protein binding | IPI PMID:12021769 Regulation of Drosophila IAP1 degradation and apoptosis by r... | KEEP AS NON CORE | Summary: Reaper binding to DIAP1 is direct in the autoubiquitination study. Reason: This is the UniProt-coded duplicate of the Reaper contact that stimulates UbcD1-dependent DIAP1 autoubiquitination. Supporting Evidence: PMID:12021769 stimulate DIAP1 auto-ubiquitination in vitro |
| GO:0005515 protein binding | IPI PMID:12021771 The DIAP1 RING finger mediates ubiquitination of Dronc and i... | KEEP AS NON CORE | Summary: Hid remains able to bind a RING-disrupted DIAP1 protein. Reason: The Dronc-ubiquitination source reports that loss of the DIAP1 RING does not abolish Hid binding; the contact is a real RHG antagonist interaction but remains generic. Supporting Evidence: PMID:12021771 ubiquitination of Dronc |
| GO:0005515 protein binding | IPI PMID:12021771 The DIAP1 RING finger mediates ubiquitination of Dronc and i... | KEEP AS NON CORE | Summary: Reaper remains able to bind a RING-disrupted DIAP1 protein. Reason: The RING paper supports direct Reaper binding to DIAP1, but this is an antagonist interaction rather than the catalytic core activity of the E3 ligase. Supporting Evidence: PMID:12021771 ubiquitination of Dronc |
| GO:0005515 protein binding | IPI PMID:12021771 The DIAP1 RING finger mediates ubiquitination of Dronc and i... | MODIFY | Summary: The Dronc interaction should be represented as caspase binding. Reason: The source directly ties DIAP1 binding to Dronc ubiquitination; GO:0089720 captures the relevant target class. Proposed replacements: caspase binding Supporting Evidence: PMID:12021771 ubiquitination of Dronc |
| GO:0005515 protein binding | IPI PMID:12356728 Jafrac2 is an IAP antagonist that promotes cell death by lib... | KEEP AS NON CORE | Summary: Jafrac2 binds DIAP1 and releases Dronc. Reason: Mature Jafrac2 is a mitochondrial/ER IAP antagonist that displaces Dronc from DIAP1, so the physical interaction is real but contextual. Supporting Evidence: PMID:12356728 Jafrac2 displaces Dronc from DIAP1 |
| GO:0005515 protein binding | IPI PMID:14517550 Molecular mechanism of Reaper-Grim-Hid-mediated suppression ... | KEEP AS NON CORE | Summary: Hid competes with Dronc at DIAP1 BIR2. Reason: The structural RHG paper maps the BIR2 surface used by Hid-family antagonists to relieve Dronc ubiquitination; this is a regulatory contact, not a separate catalytic function. Supporting Evidence: PMID:14517550 recognizes a 12-residue sequence in Dronc |
| GO:0005515 protein binding | IPI PMID:14517550 Molecular mechanism of Reaper-Grim-Hid-mediated suppression ... | MODIFY | Summary: Dronc recognition by DIAP1 BIR2 is caspase binding. Reason: The structural study mapped a DIAP1 BIR2 interface that recognizes Dronc and is required for Dronc ubiquitination, making GO:0089720 the specific replacement. Proposed replacements: caspase binding Supporting Evidence: PMID:14517550 recognizes a 12-residue sequence in Dronc |
| GO:0005515 protein binding | IPI PMID:15242648 A role for Drosophila IAP1-mediated caspase inhibition in Ra... | UNDECIDED | Summary: The Chickadee/Profilin IPI row is not exposed in the border-cell abstract. Reason: The paper supports a Diap1-Dronc branch in Rac-dependent border-cell motility but the cached abstract does not show a physical Chickadee-DIAP1 interaction. Supporting Evidence: PMID:15242648 Rac-dependent cell migration |
| GO:0005515 protein binding | IPI PMID:16887178 Drosophila IKK-related kinase regulates nonapoptotic functio... | UNDECIDED | Summary: DmIKKepsilon regulates DIAP1 stability, but the cached abstract does not expose an IPI assay. Reason: The abstract says DmIKKepsilon promotes DIAP1 degradation; physical binding evidence would require the full text. Supporting Evidence: PMID:16887178 degradation of IAPs |
| GO:0005515 protein binding | IPI PMID:17397804 Evolution of mitochondrial cell death pathway: Proapoptotic ... | UNDECIDED | Summary: The DmHtrA2 abstract does not expose the IPI-level DIAP1 interaction. Reason: The source establishes DIAP1 cleavage near mitochondria but not the exact physical-interaction row in the cached abstract. Supporting Evidence: PMID:17397804 cleavage of DIAP1 in the vicinity of mitochondria |
| GO:0005515 protein binding | IPI PMID:18166655 DIAP2 functions as a mechanism-based regulator of drICE that... | UNDECIDED | Summary: The DIAP2 paper does not verify a DIAP1-DrICE IPI row locally. Reason: The cached abstract explicitly says DIAP2 binds active drICE; it does not expose the DIAP1-DrICE interaction being asserted. Supporting Evidence: PMID:16485033 DIAP2 binds active drICE |
| GO:0005515 protein binding | IPI PMID:18166655 DIAP2 functions as a mechanism-based regulator of drICE that... | UNDECIDED | Summary: The DIAP2 paper does not verify a Reaper-DIAP1 IPI row locally. Reason: The cached source is centered on DIAP2 mechanism-based regulation of drICE and does not expose a Reaper-DIAP1 assay. Supporting Evidence: PMID:16485033 DIAP2 binds active drICE |
| GO:0005515 protein binding | IPI PMID:18259196 The interaction of DIAP1 with dOmi/HtrA2 regulates cell deat... | KEEP AS NON CORE | Summary: dOmi/HtrA2 binds DIAP1 and can be ubiquitinated by it. Reason: Drosophila Omi/HtrA2 is a mitochondrial DIAP1 antagonist and substrate; the binding row is direct but represents this specialized branch. Supporting Evidence: PMID:18259196 DIAP1-mediated polyubiquitination of dOmi |
| GO:0005515 protein binding | IPI PMID:20700104 Metabolic regulation of Drosophila apoptosis through inhibit... | MODIFY | Summary: The Dronc co-IP control should be narrowed to caspase binding. Reason: The Dronc phosphorylation paper used DIAP1 RNAi as an apoptosis trigger and assayed DIAP1-Dronc association; the partner class is specifically a caspase. Proposed replacements: caspase binding Supporting Evidence: PMID:20700104 DIAP1 RNAi or cycloheximide treatment |
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Nuclear IAP localization is plausible and contextual. Reason: DIAP1/XIAP family proteins have documented nuclear roles such as the nonapoptotic Wnt output, so retaining a non-core nuclear localization transfer is defensible. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000005166 SUPPORTS TRANSFER The IAP node supports broad, contextual nuclear/cytoplasmic localization rather than a single apoptotic compartment. Supporting Evidence: PMID:22304967 positive regulator of Wingless |
| GO:0005634 nucleus | IDA PMID:17464325 The Drosophila caspases Strica and Dronc function redundantl... | UNDECIDED | Summary: The oogenesis caspase paper does not expose DIAP1 nuclear localization. Reason: The abstract is about Strica and Dronc redundancy in oogenesis and does not verify where DIAP1 was observed. Supporting Evidence: PMID:17464325 Strica and Dronc function redundantly |
| GO:0005634 nucleus | IDA PMID:21035895 Differential localization and processing of apoptotic protei... | KEEP AS NON CORE | Summary: The Malpighian-tubule DIAP1 localization row is experimental but non-core. Reason: The abstract says DIAP1 is differentially localized and processed in Malpighian tubules; without full text the exact nuclear signal is delegated to the FlyBase experimental curation. Supporting Evidence: PMID:21035895 DIAP1, is localized and processed differently |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasmic activity is core for DIAP1-caspase restraint. Reason: DIAP1 restrains Dronc and effector caspases in the cytoplasm, so the PAINT cytoplasmic localization transfer is consistent with the main caspase-inhibitory role. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000005166 SUPPORTS TRANSFER The IAP node supports cytoplasmic activity for caspase inhibition. Supporting Evidence: PMID:14517550 recognizes a 12-residue sequence in Dronc PMID:19026784 DIAP1-mediated drICE ubiquitylation suppresses its catalytic ability |
| GO:0005737 cytoplasm | IDA PMID:17464325 The Drosophila caspases Strica and Dronc function redundantl... | UNDECIDED | Summary: The oogenesis caspase paper does not expose DIAP1 cytoplasmic localization. Reason: This abstract verifies Strica/Dronc function in oogenesis but not the DIAP1 localization asserted by the row. Supporting Evidence: PMID:17464325 Strica and Dronc function redundantly |
| GO:0005737 cytoplasm | IDA PMID:21035895 Differential localization and processing of apoptotic protei... | KEEP AS NON CORE | Summary: The Malpighian-tubule cytoplasmic localization row is non-core. Reason: The source reports differential localization of DIAP1 in Malpighian tubules; keep the curator-read row as contextual, not part of the core apoptosis brake. Supporting Evidence: PMID:21035895 DIAP1, is localized and processed differently |
| GO:0005829 cytosol | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA cytosol transfer is compatible with DIAP1 biology. Reason: DIAP1 directly restrains cytosolic caspases and the ARBA localization is not more specific than the compartment used for core fly caspase control. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00029243 SUPPORTS TRANSFER The automated rule transferred a broad cytosolic location consistent with direct caspase restraint. Supporting Evidence: PMID:14517550 recognizes a 12-residue sequence in Dronc |
| GO:0005829 cytosol | TAS Reactome:R-DME-390120 | ACCEPT | Summary: Reactome correctly places DIAP1 in the cytosol for Hippo-pathway phosphorylation. Reason: The Drosophila Reactome event uses cytosolic thread/DIAP1 as the phosphorylated substrate of Hippo; this is a pathway-specific but accurate localization. |
| GO:0006915 apoptotic process | IPI PMID:10675328 Induction of apoptosis by Drosophila reaper, hid and grim th... | MODIFY | Summary: This broad apoptotic-process row has the wrong polarity for DIAP1. Reason: Hid binding to DIAP1 relieves an anti-apoptotic caspase brake; DIAP1 is the inhibitor of apoptosis, so the row should be represented as negative regulation of apoptotic process. Proposed replacements: negative regulation of apoptotic process Supporting Evidence: PMID:10675328 forming a complex with DIAP1 |
| GO:0006915 apoptotic process | IPI PMID:10675328 Induction of apoptosis by Drosophila reaper, hid and grim th... | MODIFY | Summary: This broad apoptotic-process row should be negative regulation of apoptosis. Reason: Reaper antagonizes DIAP1 to trigger death, demonstrating that DIAP1 restrains rather than executes the apoptotic process. Proposed replacements: negative regulation of apoptotic process Supporting Evidence: PMID:10675328 forming a complex with DIAP1 |
| GO:0007283 spermatogenesis | IMP PMID:23409089 Anent the genomics of spermatogenesis in Drosophila melanoga... | UNDECIDED | Summary: The male-sterility genomics source is too broad for a Diap1-specific spermatogenesis row locally. Reason: The cached full-text extraction surveys male-sterile regions and does not expose the specific thread/Diap1 assay behind this annotation. Supporting Evidence: PMID:23409089 Anent the genomics of spermatogenesis |
| GO:0007289 spermatid nucleus differentiation | IMP PMID:14737191 Multiple apoptotic caspase cascades are required in nonapopt... | MARK AS OVER ANNOTATED | Summary: DIAP1 overexpression in spermatids is a caspase-blocking reagent, not an endogenous nuclear differentiation step. Reason: The experiment shows that caspase activity is needed for individualization; it does not make DIAP1 a direct actor in spermatid nucleus differentiation. Supporting Evidence: PMID:14737191 caspase activity is required for individualization |
| GO:0007298 border follicle cell migration | IGI PMID:15242648 A role for Drosophila IAP1-mediated caspase inhibition in Ra... | KEEP AS NON CORE | Summary: DIAP1 directly modulates Rac-dependent border-cell migration. Reason: The genetic interaction with Rac supports a nonapoptotic Diap1-Dronc branch in border-cell motility, which is direct but specialized. Supporting Evidence: PMID:15242648 Rac-dependent cell migration |
| GO:0007298 border follicle cell migration | IMP PMID:15242648 A role for Drosophila IAP1-mediated caspase inhibition in Ra... | KEEP AS NON CORE | Summary: Diap1 loss causes border-cell migration defects without apoptosis. Reason: Loss-of-function thread mutants disrupted migration in the border-cell study, making this a direct non-core motility branch. Supporting Evidence: PMID:15242648 Rac-dependent cell migration |
| GO:0008270 zinc ion binding | ISM PMID:21912646 Comprehensively surveying structure and function of RING dom... | ACCEPT | Summary: The BIR and RING folds support zinc binding. Reason: DIAP1 contains zinc-coordinating BIR and RING domains, and the cited RING-domain structure/function survey supports RING zinc coordination. Supporting Evidence: PMID:21912646 Comprehensively surveying structure and function of RING domains |
| GO:0016755 aminoacyltransferase activity | IEA GO_REF:0000117 | MODIFY | Summary: The ARBA transferase parent should be replaced by the specific E3 term. Reason: GO:0016755 is an uninformative aminoacyltransferase parent for a RING ubiquitin ligase; GO:0061630 captures the actual chemistry. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: ARBA:ARBA00026304 SUPPORTS SOURCE BUT NOT TARGET The rule overgeneralized RING E3 ubiquitin transfer to a broad parent. Proposed replacements: ubiquitin protein ligase activity Supporting Evidence: PMID:12021771 ubiquitination of Dronc |
| GO:0022416 chaeta development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: The chaeta-development transfer reflects nonapoptotic caspase regulation. Reason: DIAP1 turnover gates low-level Dronc activity during SOP and shaft-cell morphogenesis; this is a contextual developmental output. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00092651 SUPPORTS TRANSFER The rule captures a real but non-core developmental branch. Supporting Evidence: PMID:19822670 temporal regulation of DIAP1 turnover PMID:16222340 not associated with apoptotic cell death |
| GO:0022416 chaeta development | IMP PMID:16222340 Drosophila caspase transduces Shaggy/GSK-3beta kinase activi... | KEEP AS NON CORE | Summary: DIAP1 overexpression perturbs macrochaeta formation through nonapoptotic caspase control. Reason: DIAP1 and DIAP2 overexpression phenocopy caspase blockade during chaeta development; this is direct but not the core anti-apoptotic function. Supporting Evidence: PMID:16222340 not associated with apoptotic cell death |
| GO:0031398 positive regulation of protein ubiquitination | IBA GO_REF:0000033 | MODIFY | Summary: DIAP1 catalyzes ubiquitination rather than merely upregulating it. Reason: The PAINT row reflects RING E3 biology but uses a regulatory-process term; direct DIAP1 substrate polyubiquitination is better represented by GO:0000209. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000799425 SUPPORTS SOURCE BUT NOT TARGET The node captures RING IAP E3 activity but the target term frames direct catalysis as regulation. Proposed replacements: protein polyubiquitination Supporting Evidence: PMID:12021771 ubiquitination of Dronc PMID:19026784 DIAP1-mediated drICE ubiquitylation suppresses its catalytic ability |
| GO:0031398 positive regulation of protein ubiquitination | IDA PMID:19026784 Inactivation of effector caspases through nondegradative pol... | MODIFY | Summary: The effector-caspase ubiquitination paper supports direct polyubiquitination. Reason: DIAP1 directly polyubiquitinates active DrICE and Dcp-1 to inactivate them nondegradatively, so protein polyubiquitination is the proper process. Proposed replacements: protein polyubiquitination Supporting Evidence: PMID:19026784 DIAP1-mediated drICE ubiquitylation suppresses its catalytic ability |
| GO:0031624 ubiquitin conjugating enzyme binding | IPI PMID:12021769 Regulation of Drosophila IAP1 degradation and apoptosis by r... | ACCEPT | Summary: UbcD1 specifically binds DIAP1. Reason: UbcD1 binds DIAP1 and stimulates Reaper-driven DIAP1 autoubiquitination in vitro, supporting ubiquitin-conjugating enzyme binding. Supporting Evidence: PMID:12021769 stimulate DIAP1 auto-ubiquitination in vitro |
| GO:0031625 ubiquitin protein ligase binding | IEA GO_REF:0000117 | UNDECIDED | Summary: The automated ubiquitin-ligase binding source is not traceable locally. Reason: This may point to a DIAP2 or UBR-family regulatory contact, but the ARBA assertion needs source tracing before it can be accepted. Propagation Review Root cause: UNRESOLVED Sources checked: ARBA:ARBA00028807 UNRESOLVED The direct source for this inferred E3-binding call was not recovered. Supporting Evidence: PMID:17205079 autoubiquitinating activity of DIAP1 |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:17205079 Regulation of the Drosophila ubiquitin ligase DIAP1 is media... | UNDECIDED | Summary: The DIAP2-DIAP1 IPI row is not exposed by the abstract. Reason: The abstract only notes preliminary data suggesting that DIAP2 mediates DIAP1 degradation and does not show a physical DIAP1-DIAP2 interaction. Supporting Evidence: PMID:17205079 autoubiquitinating activity of DIAP1 |
| GO:0043027 cysteine-type endopeptidase inhibitor activity involved in apoptotic process | IBA GO_REF:0000033 | MODIFY | Summary: The PAINT caspase-inhibitor transfer is a core DIAP1 activity. Reason: DIAP1 is a direct apoptotic caspase inhibitor, and the IAP family node correctly transfers that molecular function. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000953271 SUPPORTS TRANSFER The IAP caspase-inhibitor node is supported for DIAP1. Proposed replacements: cysteine-type endopeptidase inhibitor activity Context of precomposed term: module dmel_rhg_apoptosome_caspase_activation / diap1_diap1 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 the module dmel_rhg_apoptosome_caspase_activation#diap1_diap1 and this review's core functions. Supporting Evidence: PMID:10481910 disrupting productive IAP-caspase interactions PMID:15107838 DIAP1 directly inhibits the catalytic activity of DrICE |
| GO:0043027 cysteine-type endopeptidase inhibitor activity involved in apoptotic process | IDA PMID:11337486 Characterization of the Drosophila caspase, DAMM. | UNDECIDED | Summary: The DAMM source does not expose a DIAP1 inhibitor assay. Reason: The cached abstract characterizes the caspase DAMM and a hid-mediated eye phenotype but does not mention DIAP1 inhibition. Supporting Evidence: PMID:11337486 Characterization of the Drosophila caspase, DAMM |
| GO:0043027 cysteine-type endopeptidase inhibitor activity involved in apoptotic process | IEA GO_REF:0000117 | MODIFY | Summary: The ARBA caspase-inhibitor transfer captures DIAP1 core biology. Reason: Direct Drosophila literature independently confirms the caspase inhibitor activity that the automated IAP-family rule transferred. The row is modified to the genus GO:0004869; the apoptotic context is carried by the module and core functions (see decomposed_into). Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00084669 SUPPORTS TRANSFER The automated IAP rule transferred a well-supported core activity. Proposed replacements: cysteine-type endopeptidase inhibitor activity Context of precomposed term: module dmel_rhg_apoptosome_caspase_activation / diap1_diap1 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 the module dmel_rhg_apoptosome_caspase_activation#diap1_diap1 and this review's core functions. Supporting Evidence: PMID:10481910 disrupting productive IAP-caspase interactions PMID:15107838 DIAP1 directly inhibits the catalytic activity of DrICE |
| GO:0043027 cysteine-type endopeptidase inhibitor activity involved in apoptotic process | IGI PMID:16485033 Systematic in vivo RNAi analysis of putative components of t... | UNDECIDED | Summary: The RNAi-screen abstract does not expose this DrICE IGI inhibitor row. Reason: The source says DIAP1-depletion apoptosis relies on Dronc/Dark and DrICE but does not show the specific DrICE-supported molecular-function evidence. Supporting Evidence: PMID:16485033 DIAP2 binds active drICE |
| GO:0043027 cysteine-type endopeptidase inhibitor activity involved in apoptotic process | IGI PMID:16485033 Systematic in vivo RNAi analysis of putative components of t... | UNDECIDED | Summary: The RNAi-screen abstract does not expose this Dronc IGI inhibitor row. Reason: The cached abstract gives genetic dependencies of DIAP1-depletion apoptosis but not the exact Dronc-supported inhibitor assay. Supporting Evidence: PMID:16485033 DIAP2 binds active drICE |
| GO:0043027 cysteine-type endopeptidase inhibitor activity involved in apoptotic process | IGI PMID:16485033 Systematic in vivo RNAi analysis of putative components of t... | UNDECIDED | Summary: The RNAi-screen abstract does not expose this Dark-supported inhibitor row. Reason: Dark is an apoptosome adaptor, and the local source does not show how the Dark IGI row supports a DIAP1 molecular-function assertion. Supporting Evidence: PMID:16485033 DIAP2 binds active drICE |
| GO:0043066 negative regulation of apoptotic process | IBA GO_REF:0000033 | ACCEPT | Summary: DIAP1 directly negatively regulates apoptotic process. Reason: DIAP1 suppresses apoptosis by restraining Dronc and effector caspases, so the PAINT biological-process transfer is core even though broad. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000953271 SUPPORTS TRANSFER The caspase-inhibitory IAP node supports negative regulation of apoptosis. Supporting Evidence: PMID:10481910 disrupting productive IAP-caspase interactions PMID:14517550 recognizes a 12-residue sequence in Dronc |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:10200511 Anti-apoptotic potential of insect cellular and viral IAPs i... | ACCEPT | Summary: Drosophila IAPs can suppress caspase-induced death. Reason: The heterologous mammalian assay is broad, but it shows conserved anti-apoptotic potential of Drosophila cellular IAPs and agrees with direct fly evidence for DIAP1. Supporting Evidence: PMID:10200511 Drosophila cellular IAPs and two baculoviral IAPs PMID:10481910 disrupting productive IAP-caspase interactions |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:10984473 An essential role for the caspase dronc in developmentally p... | ACCEPT | Summary: Endogenous Diap1 suppresses Dronc-mediated apoptosis. Reason: The Dronc paper shows that reducing diap1 dosage enhances Dronc-induced eye ablation, consistent with DIAP1 as an endogenous apoptosis inhibitor. Supporting Evidence: PMID:10984473 enhanced by mutations in diap1 |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:15107838 Molecular mechanisms of DrICE inhibition by DIAP1 and remova... | ACCEPT | Summary: DIAP1 inhibition of DrICE supports negative regulation of apoptosis. Reason: Direct structural and biochemical evidence shows that DIAP1 inhibits the effector caspase DrICE and that RHG antagonists relieve that inhibition. Supporting Evidence: PMID:15107838 DIAP1 directly inhibits the catalytic activity of DrICE |
| GO:0043066 negative regulation of apoptotic process | IGI PMID:10675328 Induction of apoptosis by Drosophila reaper, hid and grim th... | ACCEPT | Summary: Hid-induced apoptosis is restrained by DIAP1. Reason: The source shows Hid kills by binding and inhibiting DIAP1; therefore DIAP1 negatively regulates the apoptotic response to Hid. Supporting Evidence: PMID:10675328 forming a complex with DIAP1 |
| GO:0043066 negative regulation of apoptotic process | IGI PMID:10675328 Induction of apoptosis by Drosophila reaper, hid and grim th... | ACCEPT | Summary: Reaper-induced apoptosis is restrained by DIAP1. Reason: The source shows Reaper kills by binding and inhibiting DIAP1; therefore DIAP1 is a direct negative regulator of Reaper-induced apoptosis. Supporting Evidence: PMID:10675328 forming a complex with DIAP1 |
| GO:0043066 negative regulation of apoptotic process | IGI PMID:12176339 Evolution of TNF signaling mechanisms: JNK-dependent apoptos... | UNDECIDED | Summary: The first Eiger paper does not expose a Diap1-Eiger IGI row locally. Reason: The abstract supports Dronc/Dark dependence of Eiger-triggered apoptosis but not the specific Diap1 genetic interaction in this row. Supporting Evidence: PMID:12176339 requires the caspase-9 homolog DRONC |
| GO:0043066 negative regulation of apoptotic process | IGI PMID:21844890 NOPO modulates Egr-induced JNK-independent cell death in Dro... | UNDECIDED | Summary: The NOPO/Eiger abstract does not expose the DIAP1-supported evidence. Reason: The cached abstract says Egr elicits a caspase-mediated cell-death pathway but does not verify the Diap1 genetic interaction. Supporting Evidence: PMID:21844890 Egr elicits a caspase-mediated cell death pathway |
| GO:0043066 negative regulation of apoptotic process | IGI PMID:31409797 Characterization of TNF-induced cell death in Drosophila rev... | KEEP AS NON CORE | Summary: Stabilized DIAP1 suppresses Eiger-induced apoptotic death in eye discs. Reason: The Eiger/JNK source supports a TNF-context apoptosis branch upstream of effector caspases; it is real but not DIAP1 core machinery. Supporting Evidence: PMID:31409797 Egr/JNK-mediated apoptosis and necrosis |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:12065414 Eiger, a TNF superfamily ligand that triggers the Drosophila... | MARK AS OVER ANNOTATED | Summary: The 2002 Eiger eye phenotype is IAP-sensitive but largely caspase independent. Reason: That paper explicitly found the Eiger branch did not require caspase activity, so a generic negative regulation of apoptotic process row overstates the phenotype. Supporting Evidence: PMID:12065414 blocked by Drosophila inhibitor-of-apoptosis protein 1 |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:17397804 Evolution of mitochondrial cell death pathway: Proapoptotic ... | UNDECIDED | Summary: The HtrA2 abstract does not verify the DIAP1 protective IMP row. Reason: The source shows dOmi/HtrA2-mediated cleavage of DIAP1, but not the asserted DIAP1 negative-regulation experiment in the local abstract. Supporting Evidence: PMID:17397804 cleavage of DIAP1 in the vicinity of mitochondria |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:18259196 The interaction of DIAP1 with dOmi/HtrA2 regulates cell deat... | KEEP AS NON CORE | Summary: DIAP1 protects eye discs from dOmi/HtrA2-induced ablation. Reason: DIAP1 binds and polyubiquitinates the mitochondrial antagonist dOmi/HtrA2; this is a direct but specialized anti-death branch. Supporting Evidence: PMID:18259196 DIAP1-mediated polyubiquitination of dOmi |
| GO:0044390 ubiquitin-like protein conjugating enzyme binding | IPI PMID:21145488 Systematic in vivo RNAi analysis identifies IAPs as NEDD8-E3... | UNDECIDED | Summary: DIAP1 NEDD8-E3 activity is clear, but the E2-binding row is not. Reason: The cached abstract identifies IAPs as NEDD8 E3 ligases for effector caspases but does not expose the exact NEDD8 E2 physical interaction. Supporting Evidence: PMID:21145488 targeting effector caspases for neddylation and inactivation |
| GO:0045035 sensory organ precursor cell division | IGI PMID:19822670 Temporal regulation of Drosophila IAP1 determines caspase fu... | KEEP AS NON CORE | Summary: DIAP1 turnover controls SOP-lineage caspase functions. Reason: Timed DIAP1 degradation controls whether caspases act nonapoptotically in SOP morphogenesis or instead kill the cell; this is direct but developmental. Supporting Evidence: PMID:19822670 temporal regulation of DIAP1 turnover |
| GO:0045116 protein neddylation | IDA PMID:21145488 Systematic in vivo RNAi analysis identifies IAPs as NEDD8-E3... | ACCEPT | Summary: DIAP1 neddylates effector caspases as a NEDD8 E3. Reason: The NEDD8 RNAi study directly identifies fly IAPs as NEDD8 E3 ligases that target effector caspases for neddylation and inactivation. Supporting Evidence: PMID:21145488 targeting effector caspases for neddylation and inactivation |
| GO:0045752 positive regulation of Toll signaling pathway | IMP PMID:36002459 Apoptotic caspase inhibits innate immune signaling by cleavi... | MARK AS OVER ANNOTATED | Summary: The Toll effect is downstream of effector-caspase inhibition and is over-annotated to DIAP1. Reason: The paper shows DrICE and Dcp-1 cleave DIF; DIAP1 is an upstream brake on those effector caspases, not a direct Toll-pathway activator. Supporting Evidence: PMID:36002459 Drosophila effector caspases, drICE and DCP-1 |
| GO:0046329 negative regulation of JNK cascade | IGI PMID:12198495 Reaper-mediated inhibition of DIAP1-induced DTRAF1 degradati... | KEEP AS NON CORE | Summary: DIAP1 downregulates DTRAF1 and thereby restrains JNK signaling. Reason: The DTRAF1 branch is DIAP1-dependent and ubiquitin-linked, but it is a Reaper-sensitive JNK output rather than the central Dronc/DrICE/Dcp-1 brake. Supporting Evidence: PMID:12198495 DIAP1-induced DTRAF1 degradation |
| GO:0046673 negative regulation of compound eye retinal cell programmed cell death | IMP PMID:16485033 Systematic in vivo RNAi analysis of putative components of t... | UNDECIDED | Summary: The RNAi-screen abstract does not verify this exact eye retinal-cell row. Reason: The source surveys putative components of the fly death machinery but the cached abstract does not expose compound-eye retinal programmed-cell-death evidence for DIAP1. Supporting Evidence: PMID:16485033 DIAP2 binds active drICE |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:21035895 Differential localization and processing of apoptotic protei... | KEEP AS NON CORE | Summary: Perinuclear DIAP1 localization in Malpighian tubules is contextual. Reason: The source reports differential DIAP1 localization and processing in Malpighian tubules; retain the FlyBase-read experimental localization as non-core. Supporting Evidence: PMID:21035895 DIAP1, is localized and processed differently |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000117 | UNDECIDED | Summary: The ARBA perinuclear call is too specific to accept without tracing. Reason: The automated perinuclear row is more specific than the locally visible DIAP1 localization evidence and should remain unresolved until the source can be traced. Propagation Review Root cause: UNRESOLVED Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: ARBA:ARBA00091589 UNRESOLVED A perinuclear source for this rule was not recovered. Supporting Evidence: PMID:21035895 DIAP1, is localized and processed differently |
| GO:0048800 antennal morphogenesis | IMP PMID:15464574 Role of programmed cell death in patterning the Drosophila a... | KEEP AS NON CORE | Summary: Diap1 affects antennal arista morphogenesis through developmental cell-death control. Reason: A viable thread allele perturbs arista formation through misregulated programmed cell death in the antennal disc, making this a non-core developmental outcome. Supporting Evidence: PMID:15464574 excessive cell death restricted to the antennal imaginal disc |
| GO:0051726 regulation of cell cycle | IBA GO_REF:0000033 | REMOVE | Summary: A survivin/Bir1-like cell-cycle transfer should not be applied to DIAP1. Reason: The supporting PAINT node appears to carry a chromosomal-passenger or mammalian IAP cell-cycle role that is not established for the fly caspase inhibitor DIAP1. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG Sources checked: PANTHER:PTN000005168 SUPPORTS SOURCE BUT NOT TARGET The cell-cycle role fits another IAP-family branch, not Drosophila DIAP1. Supporting Evidence: PMID:19822670 temporal regulation of DIAP1 turnover |
| GO:0051865 protein autoubiquitination | IDA PMID:12021769 Regulation of Drosophila IAP1 degradation and apoptosis by r... | ACCEPT | Summary: Reaper and UbcD1 stimulate DIAP1 autoubiquitination. Reason: The cited paper directly reports DIAP1 auto-ubiquitination in vitro driven by Reaper and UbcD1. Supporting Evidence: PMID:12021769 stimulate DIAP1 auto-ubiquitination in vitro |
| GO:0051865 protein autoubiquitination | IDA PMID:17205079 Regulation of the Drosophila ubiquitin ligase DIAP1 is media... | ACCEPT | Summary: DIAP1 autoubiquitination is directly supported. Reason: The source studies DIAP1 autoubiquitinating activity and shows it probably uses non-K48 linkages that tune ligase activity. Supporting Evidence: PMID:17205079 autoubiquitinating activity of DIAP1 |
| GO:0061630 ubiquitin protein ligase activity | EXP PMID:14517550 Molecular mechanism of Reaper-Grim-Hid-mediated suppression ... | ACCEPT | Summary: BIR2-dependent Dronc recognition supports DIAP1 E3 ligase activity. Reason: DIAP1 recognition of Dronc is required to target Dronc for ubiquitination, supporting RING E3 activity toward a core caspase substrate. Supporting Evidence: PMID:14517550 recognizes a 12-residue sequence in Dronc |
| GO:0061630 ubiquitin protein ligase activity | IBA GO_REF:0000033 | ACCEPT | Summary: The PAINT E3 transfer captures the core DIAP1 RING activity. Reason: DIAP1 is a conserved RING IAP ubiquitin ligase, and the PAINT node correctly transfers this catalytic activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000799425 SUPPORTS TRANSFER The RING IAP E3 node supports DIAP1 ubiquitin ligase activity. Supporting Evidence: PMID:12021771 ubiquitination of Dronc PMID:19026784 DIAP1-mediated drICE ubiquitylation suppresses its catalytic ability |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:12021769 Regulation of Drosophila IAP1 degradation and apoptosis by r... | ACCEPT | Summary: DIAP1 RING activity drives Reaper/UbcD1-dependent autoubiquitination. Reason: The Reaper/UbcD1 source directly assays DIAP1 autoubiquitination, an E3 output of the RING ligase. Supporting Evidence: PMID:12021769 stimulate DIAP1 auto-ubiquitination in vitro |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:12198495 Reaper-mediated inhibition of DIAP1-induced DTRAF1 degradati... | ACCEPT | Summary: DIAP1 acts as the ubiquitin ligase in DTRAF1 degradation. Reason: The DTRAF1 branch is ubiquitin dependent and DIAP1 induced, supporting RING E3 ligase activity even though the pathway output is non-core. Supporting Evidence: PMID:12198495 DIAP1-induced DTRAF1 degradation |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:17205079 Regulation of the Drosophila ubiquitin ligase DIAP1 is media... | ACCEPT | Summary: DIAP1 is a Drosophila ubiquitin ligase with regulated autoubiquitination. Reason: The cited ubiquitin-pathway paper directly characterizes how DIAP1 autoubiquitinating activity attenuates its ligase output toward exogenous substrates. Supporting Evidence: PMID:17205079 autoubiquitinating activity of DIAP1 |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:23940367 Caspase-dependent regulation of the ubiquitin-proteasome sys... | ACCEPT | Summary: DIAP1 K48-ubiquitinates Grim in an UbcD1-dependent manner. Reason: The Grim study directly shows DIAP1 adds K48-linked chains to BIR2-bound Grim. Supporting Evidence: PMID:23940367 K48-linked ubiquitin chains are added almost exclusively |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:25139236 Cellular inhibitor of apoptosis protein 1 ubiquitinates endo... | ACCEPT | Summary: The EndoG study supports DIAP1 ubiquitination activity toward Drosophila EndoG as a candidate substrate. Reason: Although much of the paper follows human cIAP1, the abstract states that a proteomic screen for DIAP1 targets identified Drosophila EndoG and tested IAP-dependent ubiquitination. Supporting Evidence: PMID:25139236 potential target proteins of DIAP1 |
| GO:0061630 ubiquitin protein ligase activity | IEA GO_REF:0000003 | ACCEPT | Summary: EC:2.3.2.27 maps to E3 ubiquitin ligase chemistry. Reason: The EC2GO transfer matches DIAP1 RING E3 ubiquitin-protein ligase activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: EC:2.3.2.27 SUPPORTS TRANSFER The EC term is exact for ubiquitin-protein transferase activity. Supporting Evidence: PMID:12021771 ubiquitination of Dronc PMID:19026784 DIAP1-mediated drICE ubiquitylation suppresses its catalytic ability |
| GO:0061663 NEDD8 ligase activity | IDA PMID:21145488 Systematic in vivo RNAi analysis identifies IAPs as NEDD8-E3... | ACCEPT | Summary: DIAP1 has NEDD8 ligase activity. Reason: The NEDD8 RNAi study directly identifies Drosophila IAPs as NEDD8 E3 ligases acting on effector caspases. Supporting Evidence: PMID:21145488 targeting effector caspases for neddylation and inactivation |
| GO:0070936 protein K48-linked ubiquitination | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: DIAP1 can catalyze K48-linked ubiquitination of Grim. Reason: K48-linked Grim turnover is a direct DIAP1 output but controls an IAP antagonist rather than the core Dronc/effector-caspase branch. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00086253 SUPPORTS TRANSFER The automated K48 ubiquitination call is defensible for DIAP1 but contextual. Supporting Evidence: PMID:23940367 K48-linked ubiquitin chains are added almost exclusively |
| GO:0070936 protein K48-linked ubiquitination | IMP PMID:23940367 Caspase-dependent regulation of the ubiquitin-proteasome sys... | KEEP AS NON CORE | Summary: The Grim Lys136 branch is direct but non-core. Reason: DIAP1 K48-ubiquitinates Grim near its RING-bound BIR2 position, providing a specialized RHG-antagonist turnover mechanism. Supporting Evidence: PMID:23940367 K48-linked ubiquitin chains are added almost exclusively |
| GO:0089720 caspase binding | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA correctly transfers caspase binding to DIAP1. Reason: Direct Dronc and effector-caspase literature confirms that DIAP1 binds caspases through BIR domains. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00087760 SUPPORTS TRANSFER The target class is correct for core DIAP1 substrates. Supporting Evidence: PMID:14517550 recognizes a 12-residue sequence in Dronc PMID:19026784 DIAP1-mediated drICE ubiquitylation suppresses its catalytic ability |
| GO:0089720 caspase binding | IPI PMID:16485033 Systematic in vivo RNAi analysis of putative components of t... | UNDECIDED | Summary: The DIAP1-Dcp-1 IPI row is not exposed in the DIAP2 abstract. Reason: The source reports DIAP2 binding to active drICE, not a DIAP1-Dcp-1 binding assay. Supporting Evidence: PMID:16485033 DIAP2 binds active drICE |
| GO:0089720 caspase binding | IPI PMID:16485033 Systematic in vivo RNAi analysis of putative components of t... | UNDECIDED | Summary: The DIAP1-DrICE IPI row is not exposed in the DIAP2 abstract. Reason: The cited RNAi-screen paper locally exposes DIAP2-active drICE binding rather than the DIAP1-DrICE interaction curated here. Supporting Evidence: PMID:16485033 DIAP2 binds active drICE |
| GO:0090263 positive regulation of canonical Wnt signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The Wg/Wnt role is a conserved but nonapoptotic IAP E3 output. Reason: DIAP1/XIAP positive regulation of canonical Wnt signaling is supported, but it is a nuclear transcriptional-control branch outside the core apoptotic brake. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002559465 SUPPORTS TRANSFER The DIAP1/XIAP Wnt node supports a conserved contextual role. Supporting Evidence: PMID:22304967 positive regulator of Wingless |
| GO:0090263 positive regulation of canonical Wnt signaling pathway | IMP PMID:22304967 XIAP monoubiquitylates Groucho/TLE to promote canonical Wnt ... | KEEP AS NON CORE | Summary: DIAP1 positively regulates Wingless signaling. Reason: A Drosophila S2 RNAi screen identified DIAP1 as a positive Wg regulator, with mechanistic follow-up on XIAP-mediated Groucho/TLE ubiquitylation; this is direct but nonapoptotic. Supporting Evidence: PMID:22304967 positive regulator of Wingless |
| GO:0140096 catalytic activity, acting on a protein | IEA GO_REF:0000117 | MODIFY | Summary: The catalytic parent should be tightened to ubiquitin protein ligase activity. Reason: DIAP1 is not just any protein-directed catalyst; the ARBA transfer should point to the specific RING E3 ubiquitin ligase activity. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: ARBA:ARBA00027983 SUPPORTS SOURCE BUT NOT TARGET The rule overgeneralizes RING E3 chemistry to a broad catalytic parent. Proposed replacements: ubiquitin protein ligase activity Supporting Evidence: PMID:12021771 ubiquitination of Dronc |
| GO:1903688 positive regulation of border follicle cell migration | IMP PMID:17483425 A sensitized PiggyBac-based screen for regulators of border ... | KEEP AS NON CORE | Summary: The PiggyBac screen supports a positive role in border-cell migration. Reason: A Diap1 insertion was recovered as a regulator of sensitized border-cell migration, extending the direct but specialized Rac/JNK motility branch. Supporting Evidence: PMID:17483425 PBac2148 in DIAP1 |
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Download this section (compressed HTML)Q: Which endogenous lysines on Dronc, DrICE, and Dcp-1 distinguish degradative, nondegradative, and neddylation-dependent DIAP1 inhibition in vivo?
Q: Do Drosophila DIAP1 and mammalian XIAP use an orthologous nuclear Gro/TLE ubiquitination mechanism during endogenous Wg/Wnt signaling, or was the S2/XIAP mechanism co-opted in a narrower context?
Q: Which nonapoptotic Diap1 phenotypes in border-cell migration, SOP morphogenesis, arista patterning, and Eiger signaling require direct caspase ubiquitination rather than altered DIAP1 turnover or a distinct substrate?
Experiment: Generate endogenous Diap1 separation-of-function alleles that selectively disrupt Dronc binding, cleaved DrICE/Dcp-1 binding, UbcD1 recruitment, or NEDD8 transfer, then quantify apoptosis, Dronc/DrICE/Dcp-1 ubiquitination and neddylation, border-cell migration, and SOP shaft-cell morphogenesis in the same allelic series.
Hypothesis: DIAP1 uses separable BIR/RING interfaces to inhibit Dronc, effector caspases, and RHG antagonists in apoptotic versus nonapoptotic contexts.
Type: structure-guided endogenous separation-of-function genetics
Experiment: Use tagged endogenous Gro and Diap1, Wg-ON and Wg-OFF imaginal-disc states, ubiquitin remnant profiling, and Gro lysine mutants to test whether Diap1-dependent Gro monoubiquitination controls TCF occupancy independently of caspase inhibition.
Hypothesis: Nuclear DIAP1 promotes Wingless signaling by ubiquitinating Drosophila Groucho at the TCF/Lef repressor complex in vivo.
Type: endogenous ubiquitin-remnant proteomics with Wg reporter genetics
Death-associated inhibitor of apoptosis 1 (Diap1) encodes an E3 ubiquitin ligase with a caspase inhibitor activity that is involved in the control of apoptosis.
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