hid encodes Head involution defective, a Drosophila RHG-family IAP antagonist that promotes apoptotic caspase activation. Hid is a mitochondrial tail-anchored protein whose N-terminal IAP-binding motif binds DIAP1 and DIAP2 BIR domains, displacing Dronc and DrICE from IAP control and cooperating with Reaper and Grim to drive apoptotic signaling during development, steroid-triggered tissue remodeling, cell competition, and genotoxic stress responses. Hid is also a direct target of Ras-dependent survival signaling; MAPK phosphorylation sites in Hid are required for Ras/MAPK activity to inhibit its proapoptotic function, in addition to Ras-mediated down-regulation of hid transcription.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002165 instar larval or pupal development | IMP PMID:1752422 Embryonic head involution and rotation of male terminalia re... | MARK AS OVER ANNOTATED | Summary: The old hid locus paper links hid loss to pupal and adult morphogenesis. Reason: hid has strong developmental phenotypes, but this broad larval/pupal-development row describes downstream patterning outcomes of failed cell elimination rather than a discrete activity of the Hid protein. Supporting Evidence: PMID:1752422 required during pupal development |
| GO:0005515 protein binding | IPI PMID:10481910 The Drosophila caspase inhibitor DIAP1 is essential for cell... | MODIFY | Summary: Hid binds the DIAP1 IAP-family ubiquitin ligase in its pro-apoptotic pathway. Reason: The source supports Hid antagonism of DIAP1 rather than an uninformative protein-binding assertion; DIAP1 is a RING-containing IAP E3, so ubiquitin protein ligase binding is more informative. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:10481910 HID blocks DIAP1's ability |
| GO:0005515 protein binding | IPI PMID:10481910 The Drosophila caspase inhibitor DIAP1 is essential for cell... | MODIFY | Summary: Hid binds the DIAP1 IAP-family ubiquitin ligase in its pro-apoptotic pathway. Reason: This is the UniProt-accession version of the same DIAP1 partner row. The assertion should be narrowed from generic protein binding to ubiquitin protein ligase binding. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:10481910 HID blocks DIAP1's ability |
| GO:0005515 protein binding | IPI PMID:10675328 Induction of apoptosis by Drosophila reaper, hid and grim th... | MODIFY | Summary: Hid forms a complex with DIAP1 through the BIR-domain IAP-antagonist interface. Reason: The DIAP1 modifier study ties Hid-DIAP1 complex formation to death induction; the partner is an IAP-family E3 ligase rather than an anonymous binding partner. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:10675328 forming a complex with DIAP1 |
| GO:0005515 protein binding | IPI PMID:12021769 Regulation of Drosophila IAP1 degradation and apoptosis by r... | UNDECIDED | Summary: The cached abstract verifies Reaper-driven DIAP1 turnover but not a Hid-DIAP1 IPI assay. Reason: PMID:12021769 explicitly reports that Reaper, but not Hid, promotes major DIAP1 degradation. Full text may include Hid-DIAP1 binding controls, but the local abstract is not enough to adjudicate this Hid IPI row. Supporting Evidence: PMID:12021769 Rpr, but not Hid |
| GO:0005515 protein binding | IPI PMID:12021771 The DIAP1 RING finger mediates ubiquitination of Dronc and i... | MODIFY | Summary: Hid binding to DIAP1 is retained when the DIAP1 RING finger is disrupted. Reason: The source verifies Hid-DIAP1 binding in a DIAP1 ubiquitination study; ubiquitin protein ligase binding captures the DIAP1 E3 context better than generic protein binding. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:12021771 binding to Rpr, Hid or Dronc |
| GO:0005515 protein binding | IPI PMID:14517550 Molecular mechanism of Reaper-Grim-Hid-mediated suppression ... | MODIFY | Summary: Hid binds the DIAP1 BIR2 surface that overlaps the Dronc interface. Reason: This structural/biochemical paper localizes RHG antagonism to BIR surfaces of DIAP1, so BIR domain binding is the precise replacement for protein binding. Proposed replacements: BIR domain binding Supporting Evidence: PMID:14517550 Dronc-binding surface on BIR2 |
| GO:0005515 protein binding | IPI PMID:18166655 DIAP2 functions as a mechanism-based regulator of drICE that... | MODIFY | Summary: The DIAP2 paper assayed Hid competition with the DIAP2-drICE complex, but this generic IPI row should be resolved cautiously. Reason: PMID:18166655 shows that Hid binds DIAP2 through BIR2/BIR3 and outcompetes drICE for free DIAP2; the better function is BIR domain binding rather than generic protein binding. Proposed replacements: BIR domain binding Supporting Evidence: PMID:18166655 Hid blocks DIAP2 from binding to drICE |
| GO:0005634 nucleus | IDA PMID:21035895 Differential localization and processing of apoptotic protei... | KEEP AS NON CORE | Summary: Hid is detected in nuclei of Malpighian tubule cells that survive metamorphosis. Reason: The location appears real, but nuclear sequestration in Malpighian tubules is a tissue-specific restraint context rather than the core mitochondrial/IAP-antagonist site of Hid action. Supporting Evidence: PMID:21035895 sequestered in the nucleus |
| GO:0005737 cytoplasm | IDA PMID:21035895 Differential localization and processing of apoptotic protei... | UNDECIDED | Summary: The cached Malpighian-tubule abstract does not verify cytoplasmic Hid localization. Reason: The available abstract reports nuclear sequestration of HID, GRIM, DRONC, and DRICE but does not expose the cytoplasmic staining that may have supported this IDA row. Supporting Evidence: PMID:21035895 sequestered in the nucleus |
| GO:0005739 mitochondrion | IDA PMID:10220397 The proapoptotic function of Drosophila Hid is conserved in ... | ACCEPT | Summary: Hid localizes to mitochondria through a C-terminal hydrophobic/tail-anchor region. Reason: Haining et al. directly localized Hid to mitochondria and mapped the C-terminal region needed for that targeting in insect and mammalian cells. Supporting Evidence: PMID:10220397 Hid is localized to the mitochondria |
| GO:0005741 mitochondrial outer membrane | IDA PMID:41576035 The conserved outer mitochondrial membrane protein Mtch regu... | ACCEPT | Summary: Hid behaves as an outer-mitochondrial tail-anchored protein in the Drosophila intestine. Reason: The Mtch study is primarily about mitochondrial tail-anchored insertion and mitophagy, but its supplemental data directly stain endogenous Hid and classify it with Zucchini as a mitochondrial tail-anchored protein whose steady-state level falls in Mtch mutant intestinal cells. Supporting Evidence: PMID:41576035 Mtch mutant cells have reduced Hid and Zucchini levels |
| GO:0005886 plasma membrane | IDA PMID:21035895 Differential localization and processing of apoptotic protei... | UNDECIDED | Summary: The cached Malpighian-tubule abstract does not verify a plasma-membrane Hid staining pattern. Reason: Full-text figures may contain the IDA evidence, but the local abstract only exposes nuclear sequestration of apoptotic proteins in Malpighian tubules. Supporting Evidence: PMID:21035895 sequestered in the nucleus |
| GO:0006915 apoptotic process | IMP PMID:16280349 Mis-specified cells die by an active gene-directed process, ... | MODIFY | Summary: Mis-specified embryonic cells up-regulate hid and then die by an active cell-death program. Reason: Hid is the pro-death signal in these patterning mutants; apoptotic signaling pathway is more specific than top-level apoptotic process. Proposed replacements: apoptotic signaling pathway Supporting Evidence: PMID:16280349 upregulation of the cell death inducer hid |
| GO:0006915 apoptotic process | IMP PMID:20563308 Drosophila microRNAs 263a/b confer robustness during develop... | MODIFY | Summary: miR-263a/b protect mechanosensory bristles by down-regulating the pro-apoptotic hid gene. Reason: The evidence places Hid as the apoptosis-inducing signal downstream of miRNA buffering, not as the entire apoptotic process. Proposed replacements: apoptotic signaling pathway Supporting Evidence: PMID:20563308 down-regulating the pro-apoptotic gene head |
| GO:0006915 apoptotic process | IMP PMID:20837774 Drosophila IAP antagonists form multimeric complexes to prom... | MODIFY | Summary: Hid cooperates with Reaper in a multimeric mitochondrial IAP-antagonist complex. Reason: The direct role tested is RHG apoptotic signaling and Reaper recruitment, so this top-level apoptosis row should be narrowed to apoptotic signaling pathway. Proposed replacements: apoptotic signaling pathway Supporting Evidence: PMID:20837774 Rpr requires Hid for recruitment |
| GO:0007424 open tracheal system development | IMP PMID:16198330 Tracheal branch repopulation precedes induction of the Droso... | KEEP AS NON CORE | Summary: Hid-dependent programmed cell death clears larval Tr2 tracheal cells before air-sac primordium induction. Reason: This is a valid developmental use of Hid-mediated cell death but is a tissue remodeling outcome rather than a separate core molecular function. Supporting Evidence: PMID:16198330 hid)-dependent programmed cell death |
| GO:0007548 sex differentiation | IMP PMID:12919673 Sex-specific apoptosis regulates sexual dimorphism in the Dr... | UNDECIDED | Summary: The cached embryonic-gonad abstract supports doublesex-dependent PCD but not a visible hid perturbation. Reason: Because the local cache lacks the full text, it is not possible to verify whether FlyBase curated hid from a figure or genetic control in the full embryonic-gonad paper. Supporting Evidence: PMID:12919673 Male-specific somatic gonadal precursors |
| GO:0008258 head involution | IMP PMID:1752422 Embryonic head involution and rotation of male terminalia re... | KEEP AS NON CORE | Summary: hid mutations cause the eponymous head-involution phenotype. Reason: The morphogenetic phenotype is correct and historically important, but it is a developmental consequence of altered cell death rather than the core Hid/IAP-antagonist activity. Supporting Evidence: PMID:1752422 hid+ function is necessary |
| GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage | IMP PMID:18688282 E2F and p53 induce apoptosis independently during Drosophila... | KEEP AS NON CORE | Summary: Hid contributes to the DNA-damage-sensitive apoptosis of rbf1 mutant eye discs. Reason: The term is specific and supported, but this is a stress/developmental branch that reuses Hid as a pro-apoptotic effector. Supporting Evidence: PMID:18688282 dependent on both hid and reaper |
| GO:0009267 cellular response to starvation | IMP PMID:18794330 Effector caspase Dcp-1 and IAP protein Bruce regulate starva... | KEEP AS NON CORE | Summary: Hid scored as a regulator in a starvation-induced autophagy screen. Reason: The result supports a peripheral starvation/autophagy role in cultured Drosophila hemocyte-like cells, not the central RHG/IAP antagonist function. Supporting Evidence: PMID:18794330 hid, Bruce, Buffy, debcl, and p53 |
| GO:0010114 response to red light | IMP PMID:14960620 Novel features of cryptochrome-mediated photoreception in th... | UNDECIDED | Summary: The cached cryptochrome photoreception abstract does not expose a hid assay. Reason: The visible abstract focuses on cry and PER-expressing brain neurons; a hid perturbation may be present only in full text. Supporting Evidence: PMID:14960620 cryptochrome (cry), expressed |
| GO:0012501 programmed cell death | IGI PMID:9144202 Cooperative functions of the reaper and head involution defe... | MODIFY | Summary: rpr and hid cooperate to kill embryonic CNS midline cells. Reason: The source describes rpr/hid-driven caspase-dependent apoptotic signaling in CNS midline cells, so apoptotic signaling pathway is a tighter term than programmed cell death. Proposed replacements: apoptotic signaling pathway Supporting Evidence: PMID:9144202 cooperate to induce programmed cell death |
| GO:0012501 programmed cell death | IMP PMID:16168982 Genetic dissection of trophic interactions in the larval opt... | UNDECIDED | Summary: The cached larval optic-neuropil abstract does not mention hid. Reason: This abstract-only source describes trophic interactions in larval optic neuropil development but does not expose the hid evidence for this PCD row. Supporting Evidence: PMID:16168982 Genetic dissection of trophic interactions |
| GO:0012501 programmed cell death | IMP PMID:7622034 The head involution defective gene of Drosophila melanogaste... | MODIFY | Summary: The foundational hid paper establishes Hid as a caspase-upstream death inducer. Reason: The original programmed-cell-death row is correct in spirit but can be narrowed to apoptotic signaling pathway because Hid functions upstream of effector caspases. Proposed replacements: apoptotic signaling pathway Supporting Evidence: PMID:7622034 decreased levels of cell death |
| GO:0012501 programmed cell death | IMP PMID:9144202 Cooperative functions of the reaper and head involution defe... | MODIFY | Summary: Hid is required for and can cooperate with Reaper to induce CNS midline cell death. Reason: As for the paired IGI row, apoptotic signaling pathway captures the RHG role better than the broader programmed cell death parent. Proposed replacements: apoptotic signaling pathway Supporting Evidence: PMID:9144202 cooperate to induce programmed cell death |
| GO:0016239 positive regulation of macroautophagy | IMP PMID:18794330 Effector caspase Dcp-1 and IAP protein Bruce regulate starva... | KEEP AS NON CORE | Summary: Hid scored as a positive regulator of starvation-induced autophagy in Drosophila cells. Reason: The phenotype is supported by a starvation autophagy screen and fits crosstalk between death regulators and autophagy, but it is peripheral to the IAP-antagonist apoptosis function. Supporting Evidence: PMID:18794330 hid, Bruce, Buffy, debcl, and p53 |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:12021769 Regulation of Drosophila IAP1 degradation and apoptosis by r... | UNDECIDED | Summary: The cached abstract does not verify Hid binding in this Reaper/UbcD1 DIAP1-turnover paper. Reason: Although the term is appropriate for a Hid-DIAP1 interaction if the full text assayed it, the local abstract instead emphasizes that Reaper, but not Hid, promotes significant DIAP1 degradation. Supporting Evidence: PMID:12021769 Rpr, but not Hid |
| GO:0035075 response to ecdysone | IMP PMID:10882130 A steroid-triggered transcriptional hierarchy controls saliv... | MARK AS OVER ANNOTATED | Summary: hid transcription is induced by an ecdysone-triggered salivary-gland death hierarchy. Reason: Hid is an induced downstream death activator, not itself part of hormone reception or the transcriptional ecdysone-response cascade. Supporting Evidence: PMID:10882130 E74A is required for maximal levels of hid induction |
| GO:0035096 larval midgut cell programmed cell death | IGI PMID:15150408 A balance between the diap1 death inhibitor and reaper and h... | KEEP AS NON CORE | Summary: rpr and hid redundantly drive steroid-triggered larval midgut cell death. Reason: The tissue-specific process is supported, but it is a developmental deployment of Hid apoptotic signaling. Supporting Evidence: PMID:15150408 rpr and hid acting in a redundant manner in the midguts |
| GO:0043028 cysteine-type endopeptidase regulator activity involved in apoptotic process | IDA PMID:10481910 The Drosophila caspase inhibitor DIAP1 is essential for cell... | MODIFY | Summary: Hid antagonizes DIAP1-mediated caspase inhibition. Reason: Hid does not bind or modulate caspases itself, which GO:0043028 requires ("binds to and modulates the activity of a cysteine-type endopeptidase"). It binds DIAP1 and blocks DIAP1's caspase-inhibitor activity (PMID:10481910), so its molecular function is to sequester DIAP1's BIR surfaces away from caspases. The replacement is GO:0140311 protein sequestering activity, which hid already carries by IDA (PMID:15107838) and as a core function. The genetic interactions with DrICE, Dronc, Strica, Decay and Dark (PMID:16485033) place Hid upstream of those caspases; the same study proposes an additional DIAP1-independent route whose molecular mechanism is not established, so none of these rows shows Hid binding a caspase, and they move with the IDA row. Earlier reasoning: This molecular-function row accurately captures Hid as a cysteine-type endopeptidase regulator in apoptosis. Proposed replacements: protein sequestering activity Context of precomposed term: module dmel_rhg_apoptosome_caspase_activation / rhg_iap_antagonists_hid Decomposed from the precomposed GO:0043028 (projects/INVOLVED_IN_PRECOMPOSITION.md). The apoptotic context is carried by the RHG IAP-antagonist step of the module. Supporting Evidence: PMID:10481910 HID blocks DIAP1's ability |
| GO:0043028 cysteine-type endopeptidase regulator activity involved in apoptotic process | IGI PMID:16485033 Systematic in vivo RNAi analysis of putative components of t... | MODIFY | Summary: Hid-mediated apoptosis requires DrICE as a downstream effector caspase. Reason: Hid does not bind or modulate caspases itself, which GO:0043028 requires ("binds to and modulates the activity of a cysteine-type endopeptidase"). It binds DIAP1 and blocks DIAP1's caspase-inhibitor activity (PMID:10481910), so its molecular function is to sequester DIAP1's BIR surfaces away from caspases. The replacement is GO:0140311 protein sequestering activity, which hid already carries by IDA (PMID:15107838) and as a core function. The genetic interactions with DrICE, Dronc, Strica, Decay and Dark (PMID:16485033) place Hid upstream of those caspases; the same study proposes an additional DIAP1-independent route whose molecular mechanism is not established, so none of these rows shows Hid binding a caspase, and they move with the IDA row. Earlier reasoning: The systematic in vivo RNAi study placed DrICE in the caspase requirement set for Hid killing. Proposed replacements: protein sequestering activity Context of precomposed term: module dmel_rhg_apoptosome_caspase_activation / rhg_iap_antagonists_hid Decomposed from the precomposed GO:0043028 (projects/INVOLVED_IN_PRECOMPOSITION.md). The apoptotic context is carried by the RHG IAP-antagonist step of the module. Supporting Evidence: PMID:16485033 Dronc/Dark and drICE |
| GO:0043028 cysteine-type endopeptidase regulator activity involved in apoptotic process | IGI PMID:16485033 Systematic in vivo RNAi analysis of putative components of t... | MODIFY | Summary: Hid-mediated apoptosis requires the Dronc initiator caspase. Reason: Hid does not bind or modulate caspases itself, which GO:0043028 requires ("binds to and modulates the activity of a cysteine-type endopeptidase"). It binds DIAP1 and blocks DIAP1's caspase-inhibitor activity (PMID:10481910), so its molecular function is to sequester DIAP1's BIR surfaces away from caspases. The replacement is GO:0140311 protein sequestering activity, which hid already carries by IDA (PMID:15107838) and as a core function. The genetic interactions with DrICE, Dronc, Strica, Decay and Dark (PMID:16485033) place Hid upstream of those caspases; the same study proposes an additional DIAP1-independent route whose molecular mechanism is not established, so none of these rows shows Hid binding a caspase, and they move with the IDA row. Earlier reasoning: The systematic in vivo RNAi study placed the Dronc/Dark arm in the caspase requirement set for Hid killing. Proposed replacements: protein sequestering activity Context of precomposed term: module dmel_rhg_apoptosome_caspase_activation / rhg_iap_antagonists_hid Decomposed from the precomposed GO:0043028 (projects/INVOLVED_IN_PRECOMPOSITION.md). The apoptotic context is carried by the RHG IAP-antagonist step of the module. Supporting Evidence: PMID:16485033 Dronc/Dark and drICE |
| GO:0043028 cysteine-type endopeptidase regulator activity involved in apoptotic process | IGI PMID:16485033 Systematic in vivo RNAi analysis of putative components of t... | MODIFY | Summary: Hid-mediated apoptosis requires Strica in the tested RNAi paradigms. Reason: Hid does not bind or modulate caspases itself, which GO:0043028 requires ("binds to and modulates the activity of a cysteine-type endopeptidase"). It binds DIAP1 and blocks DIAP1's caspase-inhibitor activity (PMID:10481910), so its molecular function is to sequester DIAP1's BIR surfaces away from caspases. The replacement is GO:0140311 protein sequestering activity, which hid already carries by IDA (PMID:15107838) and as a core function. The genetic interactions with DrICE, Dronc, Strica, Decay and Dark (PMID:16485033) place Hid upstream of those caspases; the same study proposes an additional DIAP1-independent route whose molecular mechanism is not established, so none of these rows shows Hid binding a caspase, and they move with the IDA row. Earlier reasoning: Strica was one of the rate-limiting caspases identified for Hid-mediated killing. Proposed replacements: protein sequestering activity Context of precomposed term: module dmel_rhg_apoptosome_caspase_activation / rhg_iap_antagonists_hid Decomposed from the precomposed GO:0043028 (projects/INVOLVED_IN_PRECOMPOSITION.md). The apoptotic context is carried by the RHG IAP-antagonist step of the module. Supporting Evidence: PMID:16485033 Hid killing requires Strica, Decay |
| GO:0043028 cysteine-type endopeptidase regulator activity involved in apoptotic process | IGI PMID:16485033 Systematic in vivo RNAi analysis of putative components of t... | MODIFY | Summary: Hid-mediated apoptosis requires Decay in the tested RNAi paradigms. Reason: Hid does not bind or modulate caspases itself, which GO:0043028 requires ("binds to and modulates the activity of a cysteine-type endopeptidase"). It binds DIAP1 and blocks DIAP1's caspase-inhibitor activity (PMID:10481910), so its molecular function is to sequester DIAP1's BIR surfaces away from caspases. The replacement is GO:0140311 protein sequestering activity, which hid already carries by IDA (PMID:15107838) and as a core function. The genetic interactions with DrICE, Dronc, Strica, Decay and Dark (PMID:16485033) place Hid upstream of those caspases; the same study proposes an additional DIAP1-independent route whose molecular mechanism is not established, so none of these rows shows Hid binding a caspase, and they move with the IDA row. Earlier reasoning: Decay was one of the rate-limiting caspases identified for Hid-mediated killing. Proposed replacements: protein sequestering activity Context of precomposed term: module dmel_rhg_apoptosome_caspase_activation / rhg_iap_antagonists_hid Decomposed from the precomposed GO:0043028 (projects/INVOLVED_IN_PRECOMPOSITION.md). The apoptotic context is carried by the RHG IAP-antagonist step of the module. Supporting Evidence: PMID:16485033 Hid killing requires Strica, Decay |
| GO:0043028 cysteine-type endopeptidase regulator activity involved in apoptotic process | IGI PMID:16485033 Systematic in vivo RNAi analysis of putative components of t... | MODIFY | Summary: Hid-mediated apoptosis requires the Dark apoptosome adaptor. Reason: Hid does not bind or modulate caspases itself, which GO:0043028 requires ("binds to and modulates the activity of a cysteine-type endopeptidase"). It binds DIAP1 and blocks DIAP1's caspase-inhibitor activity (PMID:10481910), so its molecular function is to sequester DIAP1's BIR surfaces away from caspases. The replacement is GO:0140311 protein sequestering activity, which hid already carries by IDA (PMID:15107838) and as a core function. The genetic interactions with DrICE, Dronc, Strica, Decay and Dark (PMID:16485033) place Hid upstream of those caspases; the same study proposes an additional DIAP1-independent route whose molecular mechanism is not established, so none of these rows shows Hid binding a caspase, and they move with the IDA row. Earlier reasoning: The Dronc/Dark apoptosome arm was required for Hid-mediated apoptosis in the systematic RNAi study. Proposed replacements: protein sequestering activity Context of precomposed term: module dmel_rhg_apoptosome_caspase_activation / rhg_iap_antagonists_hid Decomposed from the precomposed GO:0043028 (projects/INVOLVED_IN_PRECOMPOSITION.md). The apoptotic context is carried by the RHG IAP-antagonist step of the module. Supporting Evidence: PMID:16485033 Dronc/Dark and drICE |
| GO:0043065 positive regulation of apoptotic process | IDA PMID:15107838 Molecular mechanisms of DrICE inhibition by DIAP1 and remova... | ACCEPT | Summary: Hid promotes apoptosis by relieving DIAP1-mediated DrICE inhibition. Reason: RHG IAP-binding motifs occupy the same DIAP1 BIR1 groove needed to inhibit DrICE, directly releasing an effector caspase. Supporting Evidence: PMID:15107838 same surface groove |
| GO:0043065 positive regulation of apoptotic process | IDA PMID:18166655 DIAP2 functions as a mechanism-based regulator of drICE that... | ACCEPT | Summary: Hid blocks DIAP2 from binding drICE and thereby promotes apoptotic caspase amplification. Reason: Ribeiro et al. directly assayed Hid competition with DIAP2-drICE binding and Hid-triggered cell killing in S2 cells. Supporting Evidence: PMID:18166655 Hid blocks DIAP2 from binding to drICE |
| GO:0043065 positive regulation of apoptotic process | IMP PMID:16485033 Systematic in vivo RNAi analysis of putative components of t... | ACCEPT | Summary: Hid drives apoptosis in vivo upstream of the fly caspase cascade. Reason: The systematic in vivo RNAi study used Hid-mediated apoptosis to define the caspases needed downstream of Hid. Supporting Evidence: PMID:16485033 Hid-mediated apoptosis requires |
| GO:0043065 positive regulation of apoptotic process | IMP PMID:19100727 Regulation of apoptosis of rbf mutant cells during Drosophil... | KEEP AS NON CORE | Summary: Hid up-regulation mediates apoptosis after RBF pathway deregulation. Reason: This is a genuine developmental and cell-cycle-surveillance context for Hid, but it is not a distinct core activity beyond activating apoptosis through IAP antagonism. Supporting Evidence: PMID:19100727 apoptosis of rbf mutant cells is mediated by an upregulation of hid |
| GO:0043153 entrainment of circadian clock by photoperiod | IMP PMID:14960620 Novel features of cryptochrome-mediated photoreception in th... | UNDECIDED | Summary: The cached cryptochrome photoreception abstract does not expose a hid assay. Reason: The visible abstract centers on CRY-dependent photoreception and PER cycling, not Hid; the full text should be checked before accepting or removing this circadian row. Supporting Evidence: PMID:14960620 cryptochrome (cry), expressed |
| GO:0046620 regulation of organ growth | IMP PMID:15066286 Drosophila myc regulates organ size by inducing cell competi... | MARK AS OVER ANNOTATED | Summary: dMyc-induced cell competition uses hid-dependent killing of loser cells to shape wing size. Reason: Hid executes the death arm of cell competition, while dMyc and the competitive interaction regulate organ growth upstream. Supporting Evidence: PMID:15066286 cell competition is executed via induction of the proapoptotic gene hid |
| GO:0048102 autophagic cell death | IEP PMID:10882130 A steroid-triggered transcriptional hierarchy controls saliv... | UNDECIDED | Summary: hid is induced during ecdysone-triggered salivary-gland death, but the local cache does not verify autophagic cell death. Reason: The abstract supports steroid-triggered PCD and hid transcription; it does not distinguish autophagic cell death from caspase-dependent apoptosis. Supporting Evidence: PMID:10882130 larval salivary glands during Drosophila metamorphosis |
| GO:0048102 autophagic cell death | IGI PMID:15150408 A balance between the diap1 death inhibitor and reaper and h... | UNDECIDED | Summary: rpr and hid are required for steroid-triggered larval tissue death, but the cache does not verify this autophagic-cell-death IGI row. Reason: The visible abstract supports larval midgut and salivary-gland destruction but not the autophagic subclass specifically. Supporting Evidence: PMID:15150408 required for destruction of the larval midgut and salivary glands |
| GO:0048102 autophagic cell death | IMP PMID:15150408 A balance between the diap1 death inhibitor and reaper and h... | UNDECIDED | Summary: rpr and hid are required for steroid-triggered larval tissue death, but the cache does not verify this autophagic-cell-death IMP row. Reason: The visible abstract supports larval midgut and salivary-gland destruction but not the autophagic subclass specifically. Supporting Evidence: PMID:15150408 required for destruction of the larval midgut and salivary glands |
| GO:0048800 antennal morphogenesis | IMP PMID:15464574 Role of programmed cell death in patterning the Drosophila a... | KEEP AS NON CORE | Summary: hid-dependent cell death patterns antennal arista branching. Reason: Mutations in hid produce extra arista branches by changing developmental cell survival, a real but contextual morphogenetic output. Supporting Evidence: PMID:15464574 mutations in the proapoptotic gene hid |
| GO:0048813 dendrite morphogenesis | IMP PMID:16980964 Local caspase activity directs engulfment of dendrites durin... | UNDECIDED | Summary: The cached dendrite-pruning abstract supports local caspase activity but not a visible hid perturbation. Reason: Because Hid is not named in the local abstract, the full text is needed to verify whether Hid affects pruning dendrite morphogenesis directly. Supporting Evidence: PMID:16980964 directed by local caspase activity |
| GO:0071480 cellular response to gamma radiation | IMP PMID:24265704 Drosophila UTX coordinates with p53 to regulate ku80 express... | MARK AS OVER ANNOTATED | Summary: Hid is induced by gamma/ionizing radiation independently of UTX. Reason: This control shows that loss of utx has little impact on hid induction. It supports Hid as a radiation-induced apoptotic effector, not as a participant in the generic cellular response to gamma radiation. Supporting Evidence: PMID:24265704 loss of utx has little impact |
| GO:0097190 apoptotic signaling pathway | IDA PMID:10220397 The proapoptotic function of Drosophila Hid is conserved in ... | ACCEPT | Summary: Hid expression induces caspase-dependent apoptotic signaling. Reason: Heterologous Hid expression triggers caspase-dependent apoptosis and requires the N-terminal IAP-binding region. Supporting Evidence: PMID:10220397 Expression of Hid Induces Apoptosis in Mammalian Cells |
| GO:0097190 apoptotic signaling pathway | IGI PMID:10481910 The Drosophila caspase inhibitor DIAP1 is essential for cell... | ACCEPT | Summary: The DIAP1 interaction is a canonical RHG/IAP apoptotic-signaling mechanism. Reason: Hid blocks the anti-apoptotic DIAP1-caspase interaction, directly connecting Hid-DIAP1 binding to apoptotic signaling. Supporting Evidence: PMID:10481910 HID blocks DIAP1's ability |
| GO:0097190 apoptotic signaling pathway | IMP PMID:30379844 EGFR signaling coordinates patterning with cell survival dur... | ACCEPT | Summary: Loss of EGFR survival signaling causes Hid-dependent epidermal apoptosis. Reason: The source shows that hid is up-regulated in EGFR mutants and that removing hid blocks the elevated cleaved-Dcp1 signal. Supporting Evidence: PMID:30379844 hid is up-regulated in most epidermal cells upon loss of EGFR signaling |
| GO:0097190 apoptotic signaling pathway | IMP PMID:7622034 The head involution defective gene of Drosophila melanogaste... | ACCEPT | Summary: hid loss- and gain-of-function evidence places Hid upstream of apoptosis. Reason: The foundational hid cloning paper showed less cell death in hid mutants and p35-suppressible eye ablation after ectopic hid expression. Supporting Evidence: PMID:7622034 decreased levels of cell death |
| GO:0097190 apoptotic signaling pathway | IMP PMID:9814703 Ras promotes cell survival in Drosophila by downregulating h... | ACCEPT | Summary: Ras/MAPK survival signaling suppresses apoptosis by reducing hid expression. Reason: The source genetically links Ras anti-apoptotic activity to down-regulation of hid. Supporting Evidence: PMID:9814703 downregulation of hid is an important mechanism |
| GO:0140311 protein sequestering activity | IDA PMID:15107838 Molecular mechanisms of DrICE inhibition by DIAP1 and remova... | ACCEPT | Summary: Hid sequesters IAP BIR grooves from their caspase substrates. Reason: RHG peptides occupy the same DIAP1 BIR1 groove needed for DrICE inhibition, explaining how Hid relieves IAP-caspase binding. Supporting Evidence: PMID:15107838 same surface groove |
| GO:1904747 positive regulation of apoptotic process involved in development | IMP PMID:22615583 Drosophila activated Cdc42 kinase has an anti-apoptotic func... | ACCEPT | Summary: Hid is a pro-apoptotic developmental effector whose activity can be suppressed by Ack signaling. Reason: The Ack study used Hid-induced developmental apoptosis as a readout and showed that Ack signaling suppresses that death. Supporting Evidence: PMID:22615583 Ack overexpression suppresses hid induced PCD |
| GO:1990525 BIR domain binding | IPI PMID:16485033 Systematic in vivo RNAi analysis of putative components of t... | ACCEPT | Summary: Hid binds DIAP2 BIR domains. Reason: The DIAP2 paper maps Hid binding to DIAP2 BIR2/BIR3 and shows that Hid competes with drICE for free DIAP2. Supporting Evidence: PMID:18166655 Hid binding appeared to be mediated by both BIR2 and 3 domains |
| GO:1990525 BIR domain binding | IPI PMID:16485033 Systematic in vivo RNAi analysis of putative components of t... | ACCEPT | Summary: Hid binds IAP BIR domains as the core RHG antagonist interface. Reason: The 2006 systematic RNAi paper is consistent with direct DIAP1/BIR antagonism; this row is supported by the structural DIAP1 BIR evidence for RHG proteins. Supporting Evidence: PMID:14517550 Dronc-binding surface on BIR2 |
| GO:2000685 positive regulation of cellular response to X-ray | IMP PMID:14729967 Drosophila melanogaster MNK/Chk2 and p53 regulate multiple D... | MODIFY | Summary: Hid contributes to ionizing-radiation-induced apoptosis downstream of p53/MNK. Reason: The paper supports Hid as a dosage-sensitive IR-induced apoptotic effector, not as a general positive regulator of every cellular X-ray response. Proposed replacements: intrinsic apoptotic signaling pathway in response to DNA damage Supporting Evidence: PMID:14729967 hid plays a central, dosage-sensitive role |
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Download this section (compressed HTML)Q: Which developmental apoptosis contexts require Hid-DIAP2 antagonism in addition to the genetically dominant Hid-DIAP1 axis?
Q: How do Hid mitochondrial insertion, RHG oligomerization, and BIR binding combine at endogenous protein levels to set the threshold for DIAP1 and DIAP2 inhibition?
Q: Which upstream survival pathways phosphorylate or otherwise restrain Hid directly in tissues where EGFR/Ras, Ack, or microRNAs buffer developmental apoptosis?
Experiment: Generate endogenous hid alleles that selectively disrupt the IAP-binding motif, predicted tail anchor, and candidate oligomerization or Reaper-binding surfaces, then quantify DIAP1/DIAP2 occupancy, Dronc and DrICE reporter activity, and cell survival in embryos, eye discs, larval midgut, and salivary glands.
Hypothesis: Hid requires separable N-terminal BIR-binding and C-terminal mitochondrial-tail-anchor surfaces for efficient IAP antagonism in vivo.
Type: endogenous separation-of-function allele series with live caspase reporters and IAP co-immunoprecipitation
Experiment: Combine Hid reporters with Diap2 BIR2, BIR3, and RING point mutants at the endogenous locus under weak genotoxic stress, steroid-triggered larval tissue death, and EGFR-loss epidermal apoptosis, then compare SCAT3/drICE activity and cell loss against Diap1 sensitized backgrounds.
Hypothesis: DIAP2 buffering of Hid is context-specific and is only visible when the DIAP1-controlled Dronc threshold is partially compromised.
Type: structure-guided endogenous DIAP2 mutant rescue in Hid-dependent apoptosis assays
head involution defective (hid) encodes a member of the RHG (Reaper-Hid-Grim) family that promotes apoptosis by binding to and inhibiting the inhibitor of apoptosis protein Diap1, thereby enabling caspase activation and cell death. Hid functions within the intrinsic apoptotic pathway and is a key effector of developmental and stress-induced apoptosis throughout Drosophila development. Its activity is negatively regulated by the Ras/MAPK signaling pathway through direct phosphorylation, which suppresses Hid-mediated apoptosis and promotes cell survival.
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