CRADD (RAIDD) is a nonenzymatic signaling adaptor that links death-domain-containing PIDD1 to caspase-2. Its C-terminal death domain assembles with the processed PIDD1 death-domain region, while its N-terminal CARD recruits caspase-2 through prodomain interactions. These contacts organize caspase-2 activation platforms involved in apoptotic signaling. Cytoplasmic and, after genotoxic stress, nucleolar platforms have distinct requirements for PIDD1. CRADD-dependent caspase-2 activation can also reinforce p53 signaling through MDM2 cleavage. Disruptive human CRADD variants impair neuronal apoptotic signaling and cause a cortical malformation syndrome. The shorter alternative product retains the CARD region but lacks the canonical death domain; its cellular function is unresolved.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002020 protease binding | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically conserved protease binding. Reason: The current IBD at PTN000385750 lies on the human CRADD path in the 106-node PTHR15034 tree; the human MSA sequence is exactly the official 199-residue product. Human CASP2 interaction is genuine descendant evidence, not circular support. Retain this conservative ancestral protease-binding claim; individual experimental rows can be refined to caspase binding. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000385750 SUPPORTS TRANSFER Current IBD for protease binding is on the human CRADD path; direct human descendant evidence supports transfer. |
| GO:0002020 protease binding | IEA GO_REF:0000002 | ACCEPT | Summary: CRADD-family mapping supports protease binding. Reason: The actual InterPro IPR037939 mapping emits protease binding for the CRADD family. Direct human CASP2 recruitment independently supports this broader electronic annotation. It does not assign protease catalysis to CRADD. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR037939 SUPPORTS TRANSFER The exact current InterPro-to-GO mapping is present and corroborated by the target-specific experiments described in this row. |
| GO:0002020 protease binding | IPI PMID:9044836 CRADD, a novel human apoptotic adaptor molecule for caspase-... | MODIFY | Summary: CRADD directly recruits caspase-2. Reason: The original human CRADD domain experiments identify CASP2 as the bound protease. Refine to the current child caspase binding. CRADD is the adaptor; the paper’s separate cleavage experiment uses the caspase, not CRADD as an enzyme. Proposed replacements: caspase binding Supporting Evidence: PMID:9044836 interacts with caspase-2 |
| GO:0005515 protein binding | IPI PMID:11156409 Identification of a caspase-2 isoform that behaves as an end... | MODIFY | Summary: Binding to a CASP2 prodomain product is retained. Reason: The authentic abstract reports Y2H and immunoprecipitation binding of CASP2L-Pro to RAIDD/CRADD, and the literal interaction record identifies a CASP2 18–106 sufficient-binding region. This prodomain product lacks the last CARD helix; it is not a demonstration of binding an active, full-length protease. Caspase binding identifies the experimentally bound CASP2 class without assigning catalytic activity to that fragment or asserting an intact CARD interface. Full original Methods remain unavailable. Proposed replacements: caspase binding Supporting Evidence: PMID:11156409 caspase-2L-Pro can interact with procaspase-2L and the adaptor protein RAIDD/CRADD |
| GO:0005515 protein binding | IPI PMID:15073321 The PIDDosome, a protein complex implicated in activation of... | MODIFY | Summary: CASP2 association in the PIDDosome. Reason: The complete original abstract identifies a CASP2–PIDD–RAIDD complex, and literal affinity/co-immunoprecipitation records preserve the CASP2 participant and construct annotations. Refine by the identified caspase class, supported independently by the actual domain experiments in 8985253 and 9044836. The original 15073321 full Methods were not recovered. Proposed replacements: caspase binding |
| GO:0005515 protein binding | IPI PMID:15073321 The PIDDosome, a protein complex implicated in activation of... | MODIFY | Summary: PIDD1 association has death-domain specificity. Reason: The original abstract and literal interaction records support PIDD1–CRADD complex association. Independent PIDD-CC recruitment experiments and the purified PIDD/RAIDD death-domain structure establish the appropriate domain-specific binding term. This does not attribute the later Methods to the unavailable full text of 15073321. Proposed replacements: death domain binding |
| GO:0005515 protein binding | IPI PMID:16652156 Functional connection between p53 and caspase-2 is essential... | MODIFY | Summary: CASP2 association in human colon carcinoma cells. Reason: The complete abstract and literal CASP2 records support a RAIDD/PIDD/CASP2 complex in p53-positive and p53-deficient human colon carcinoma cells, including untreated cells. Refine the interaction by the identified caspase class. The paper questions whether this complex is the sole route to CASP2 activation; it does not negate the association. Full Methods were not available. Proposed replacements: caspase binding |
| GO:0005515 protein binding | IPI PMID:16652156 Functional connection between p53 and caspase-2 is essential... | MODIFY | Summary: PIDD1 association in the same cellular complex. Reason: The original abstract verifies RAIDD/PIDD/CASP2 complex formation independently of p53 status or 5-FU treatment. PIDD1 death-domain specificity is established by the separate 17159900 and 17289572 originals. Retain the positive interaction while avoiding a claim that this platform is the only activator of CASP2 in the tested cells. Proposed replacements: death domain binding |
| GO:0005515 protein binding | IPI PMID:17159900 Autoproteolysis of PIDD marks the bifurcation between pro-de... | MODIFY | Summary: CRADD recruits processed PIDD-CC through death-domain assembly. Reason: Human-cell anti-Flag/VSV co-immunoprecipitation distinguishes RAIDD-associated PIDD-CC from PIDD-C. The S588A cleavage mutant loses recruitment and CASP2 activation. Together with the purified death-domain interface, this supports death domain binding. The PIDD-C/RIP1/NEMO NF-kappaB branch is not assigned to CRADD. Proposed replacements: death domain binding Supporting Evidence: PMID:17159900 the PIDD-CC fragment, but not PIDD-C, was detectable in the complex |
| GO:0005515 protein binding | IPI PMID:22458338 Host-pathogen interactome mapping for HTLV-1 and -2 retrovir... | KEEP AS NON CORE | Summary: Positive viral Tax interaction; E3-class precision remains disputed. Reason: The actual HTLV interactome records preserve CRADD association with Tax P14079 in binary Y2H/MAPPIT assays. A more specific ubiquitin-ligase-binding term is not secure: the P14079 E3 annotation is inferred from the P03409 Tax record, and the original biochemical papers disagree. PMID27082114 reports Tax-dependent ubiquitination and E2 discharge, whereas PMID28103322 could not demonstrate Tax E3 activity using active E. coli/Sf9 preparations and an E3 positive control. Retain the positive generic interaction as non-core without dismissing it on compartment grounds or assigning either disputed catalytic mechanism to CRADD. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Positive CRADD–CASP2 interaction. Reason: The exact human binary interactome record identifies CRADD and CASP2; participant identifiers, tags, features and all 42 literal fields are retained in the evidence index. Refine to caspase binding on the measured partner class, corroborated by independent human recruitment experiments. A reference-sequence checksum does not by itself prove that the experimental construct was untagged or full length. This molecular interaction does not assign CRADD caspase catalysis. Proposed replacements: caspase binding |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Positive KCTD9 interaction without a secure functional refinement. Reason: The literal binary interaction record and participant sequence identity support the reported association. The partner is a substrate-recognition component associated with a CUL3 complex; that does not establish that the assayed KCTD9 protein itself is the E3 enzyme. Retain generic binding as non-core under the standing campaign policy; absence of an established native compartmental encounter is not grounds to erase a positive assay. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Positive BBS5 interaction without a secure functional refinement. Reason: The literal binary interaction record and participant sequence identity support the reported association. Membership of the partner in the BBSome does not make CRADD a BBSome component or establish a ciliary function. Retain generic binding as non-core under the standing campaign policy; absence of an established native compartmental encounter is not grounds to erase a positive assay. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Positive APPL2 interaction without a secure functional refinement. Reason: The literal binary interaction record and participant sequence identity support the reported association. The partner’s signaling-adaptor and phosphoinositide-binding roles do not identify a more specific CRADD molecular activity in this binary experiment. Retain generic binding as non-core under the standing campaign policy; absence of an established native compartmental encounter is not grounds to erase a positive assay. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Positive TRIM54 interaction without a secure functional refinement. Reason: The literal binary interaction record and participant sequence identity support the reported association. The reviewed partner record and the assayed construct do not independently establish the E3 class needed for a ligase-binding refinement; a RING-family name alone is insufficient. Retain generic binding as non-core under the standing campaign policy; absence of an established native compartmental encounter is not grounds to erase a positive assay. |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | MODIFY | Summary: CRADD binds muscle alpha-actinin ACTN2. Reason: The literal interaction and variant records identify human ACTN2 P35609, an alpha-actinin-2 muscle isoform. The current GO:0051371 definition and synonyms explicitly cover muscle alpha-actinins including alpha-actinin-2; this is more precise than generic actinin binding. The finding remains a measured interaction, not evidence that CRADD itself crosslinks actin or performs a sarcomeric role. Proposed replacements: muscle alpha-actinin binding |
| GO:0005515 protein binding | IPI PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusi... | MODIFY | Summary: Positive CRADD–CASP2 interaction. Reason: The exact Barcode Fusion Genetics pooled-matrix screening record identifies CRADD and CASP2; participant identifiers, tags, features and all 42 literal fields are retained in the evidence index. Refine to caspase binding on the measured partner class, corroborated by independent human recruitment experiments. A reference-sequence checksum does not by itself prove that the experimental construct was untagged or full length. This molecular interaction does not assign CRADD caspase catalysis. Proposed replacements: caspase binding |
| GO:0005515 protein binding | IPI PMID:27773430 Mutations in CRADD Result in Reduced Caspase-2-Mediated Neur... | MODIFY | Summary: PIDD1 death-domain association survives some disease variants. Reason: Actual human CRADD constructs were tested with the PIDD death-domain region by co-immunoprecipitation. Several variants retain detectable association despite impaired CASP2 activation, while unstable G128R differs. Thus binding and productive signaling must be distinguished; the positive WT domain interaction supports death domain binding. Proposed replacements: death domain binding Supporting Evidence: PMID:27773430 a platform for interaction with other death-domain-containing proteins including PIDD |
| GO:0005515 protein binding | IPI PMID:31467278 Maximizing binary interactome mapping with a minimal number ... | MODIFY | Summary: Positive CRADD–CASP2 interaction. Reason: The exact multi-assay binary interaction benchmark record identifies CRADD and CASP2; participant identifiers, tags, features and all 42 literal fields are retained in the evidence index. Refine to caspase binding on the measured partner class, corroborated by independent human recruitment experiments. A reference-sequence checksum does not by itself prove that the experimental construct was untagged or full length. This molecular interaction does not assign CRADD caspase catalysis. Proposed replacements: caspase binding |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MODIFY | Summary: Positive CRADD–CASP2 interaction. Reason: The exact human variant-interaction study record identifies CRADD and CASP2; participant identifiers, tags, features and all 42 literal fields are retained in the evidence index. Refine to caspase binding on the measured partner class, corroborated by independent human recruitment experiments. A reference-sequence checksum does not by itself prove that the experimental construct was untagged or full length. This molecular interaction does not assign CRADD caspase catalysis. Proposed replacements: caspase binding |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | KEEP AS NON CORE | Summary: Positive APPL2 interaction without a secure functional refinement. Reason: The literal binary interaction record and participant sequence identity support the reported association. The variant-interaction record supports association; no CRADD membrane-trafficking mechanism follows from the partner’s normal role. Retain generic binding as non-core under the standing campaign policy; absence of an established native compartmental encounter is not grounds to erase a positive assay. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: Positive CRADD–CASP2 interaction. Reason: The exact HuRI binary interaction mapping record identifies CRADD and CASP2; participant identifiers, tags, features and all 42 literal fields are retained in the evidence index. Refine to caspase binding on the measured partner class, corroborated by independent human recruitment experiments. A reference-sequence checksum does not by itself prove that the experimental construct was untagged or full length. This molecular interaction does not assign CRADD caspase catalysis. Proposed replacements: caspase binding |
| GO:0005515 protein binding | IPI PMID:37398436 AI-guided pipeline for protein-protein interaction drug disc... | MODIFY | Summary: Positive CRADD–CASP2 interaction. Reason: The exact interaction-assay study accompanying the AI-guided pipeline record identifies CRADD and CASP2; participant identifiers, tags, features and all 42 literal fields are retained in the evidence index. Refine to caspase binding on the measured partner class, corroborated by independent human recruitment experiments. A reference-sequence checksum does not by itself prove that the experimental construct was untagged or full length. This molecular interaction does not assign CRADD caspase catalysis. Proposed replacements: caspase binding |
| GO:0005515 protein binding | IPI PMID:8985253 RAIDD is a new 'death' adaptor molecule. | KEEP AS NON CORE | Summary: Engineered TNFR1 complex association is retained. Reason: Original Nature Figure 4b detects RAIDD with TNFR1 only when TRADD and RIP are coexpressed. This is a positive complex-association result with defined bridging requirements, not direct pairwise TNFR1 recognition or proof of ligand-triggered endogenous death-receptor signaling. Retain generic association without a receptor-binding refinement. |
| GO:0005515 protein binding | IPI PMID:8985253 RAIDD is a new 'death' adaptor molecule. | MODIFY | Summary: CASP2 prodomain recruitment by RAIDD. Reason: The original Nature binding and mutation experiments link the RAIDD N-terminal region to the CASP2/ICH-1 prodomain. Refine by the identified caspase class. Historical 200-residue construct numbering is kept distinct from the current official 199-residue product. Proposed replacements: caspase binding Supporting Evidence: PMID:8985253 mediates the binding of RAIDD to ICH-1 |
| GO:0005515 protein binding | IPI PMID:8985253 RAIDD is a new 'death' adaptor molecule. | KEEP AS NON CORE | Summary: RIP-dependent association with TRADD. Reason: Original Nature Figure 4a shows that RAIDD does not bind TRADD alone; TRADD joins when RIP is present. Preserve the experimentally positive engineered complex association as non-core, without describing it as direct TRADD death-domain binding. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Nuclear localization is a supported contextual assignment. Reason: The combined source includes mouse Cradd O88843, its Ensembl protein identifier and UniProt nuclear location. Actual mouse FLAG-Cradd localization in mIMCD3 cells supports the donor, and human RAIDD-dependent nucleolar activation platforms provide separate biological consistency. Keep nuclear localization at that contextual scope, rather than claiming the mouse image directly localizes endogenous human CRADD. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:O88843 SUPPORTS TRANSFER Mouse Cradd donor localization is grounded in tagged mIMCD3-cell experiments; this is not direct human-protein imaging. ensembl:ENSMUSP00000151735 SUPPORTS TRANSFER The actual Ensembl protein resolves to the same mouse Cradd O88843, preserving identifier equivalence without inventing separate evidence. UniProtKB-SubCell:SL-0191 SUPPORTS TRANSFER The actual UniProt location mapping is consistent with the separately documented localization evidence. |
| GO:0005634 nucleus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ortholog-supported nuclear localization. Reason: The literal O88843 donor annotation is experimentally grounded in tagged mouse Cradd in mIMCD3 cells in PMID22279524. Human-cell nucleolar platform experiments independently fit a nuclear pool but primarily image CASP2 proximity, not CRADD itself. Retain the curator’s ortholog transfer as non-core with these assay limits. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:O88843 SUPPORTS TRANSFER Mouse Cradd donor localization is grounded in tagged mIMCD3-cell experiments; this is not direct human-protein imaging. |
| GO:0005730 nucleolus | NAS PMID:28432080 NPM1 directs PIDDosome-dependent caspase-2 activation in the... | KEEP AS NON CORE | Summary: A genotoxic-stress nucleolar activation platform requires CRADD. Reason: The original distinguishes a cytoplasmic RAIDD-dependent/PIDD-independent platform from a nucleolar platform requiring both proteins. Human HeLa CRISPR and mouse knockout experiments support the platform requirement; CASP2 BiFC and fractionation are not direct fluorescence imaging of CRADD. The existing NAS nucleolar assignment is defensible for the assembled platform under DNA damage, rather than a constitutive distribution claim. Supporting Evidence: PMID:28432080 a nucleolar platform that requires both PIDD and RAIDD |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Inherited cytoplasmic localization. Reason: The actual IBD at PTN001030467 lies on the CRADD target path. Mouse Cradd localization and the fly Dronc cytoplasmic assay are genuine descendant evidence; the latter used GFP-Dronc in NIH3T3 cells and is not an assay of human CRADD. Human cytoplasmic activation platforms independently support the ancestral location. Retain the broad IBA rather than treating donor count as an objection. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001030467 SUPPORTS TRANSFER Current IBD for cytoplasm is on the target path; mouse Cradd and fly Dronc localization evidence is preserved with species/host limits. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Convergent electronic cytoplasmic annotation. Reason: All current rule conditions were evaluated: ARBA00026971 branch 1480 matches the actual CRADD features and taxonomy. Mouse/Ensembl and UniProt location routes independently support cytoplasm. Human cytoplasmic RAIDD-dependent activation provides direct biological compatibility; the broad location does not exclude a stress-induced nucleolar pool. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00026971 SUPPORTS TRANSFER Current ARBA00026971 branch 1480 matches the actual target features and taxon. UniProtKB:O88843 SUPPORTS TRANSFER Mouse Cradd donor localization is grounded in tagged mIMCD3-cell experiments; this is not direct human-protein imaging. ensembl:ENSMUSP00000151735 SUPPORTS TRANSFER The actual Ensembl protein resolves to the same mouse Cradd O88843, preserving identifier equivalence without inventing separate evidence. UniProtKB-SubCell:SL-0086 SUPPORTS TRANSFER The actual UniProt location mapping is consistent with the separately documented localization evidence. |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | ACCEPT | Summary: Ortholog-supported cytoplasmic localization. Reason: The exact mouse O88843 donor has an IDA cytoplasmic annotation from tagged Cradd localization. Human cytoplasmic CASP2 activation platforms requiring RAIDD and the curated cytosolic PIDDosome reactions independently support transfer. Retain the source’s broad cytoplasm term without claiming exclusive cytosolic localization. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:O88843 SUPPORTS TRANSFER Mouse Cradd donor localization is grounded in tagged mIMCD3-cell experiments; this is not direct human-protein imaging. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6800794 | ACCEPT | Summary: Cytosolic participation in the PIDDosome reaction. Reason: The current Reactome R-HSA-6800794 event and its explicit input/output complex path reach P78560 CRADD (residues 1–199) in cytosol. The event represents assembly of PIDD1 with CRADD. This is participant-specific membership, not merely proximity to a pathway title; CRADD is the nonenzymatic scaffold and CASP2 performs proteolysis. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6800797 | ACCEPT | Summary: Cytosolic participation in the PIDDosome reaction. Reason: The current Reactome R-HSA-6800797 event and its explicit input/output complex path reach P78560 CRADD (residues 1–199) in cytosol. The event represents CASP2 processing within the assembled PIDDosome. This is participant-specific membership, not merely proximity to a pathway title; CRADD is the nonenzymatic scaffold and CASP2 performs proteolysis. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6800798 | ACCEPT | Summary: Cytosolic participation in the PIDDosome reaction. Reason: The current Reactome R-HSA-6800798 event and its explicit input/output complex path reach P78560 CRADD (residues 1–199) in cytosol. The event represents recruitment of CASP2 to the PIDDosome. This is participant-specific membership, not merely proximity to a pathway title; CRADD is the nonenzymatic scaffold and CASP2 performs proteolysis. |
| GO:0006974 DNA damage response | NAS PMID:15073321 The PIDDosome, a protein complex implicated in activation of... | KEEP AS NON CORE | Summary: Contextual DNA-damage signaling through the PIDDosome. Reason: The authentic 15073321 abstract reports sensitization to genotoxic stimuli and the RAIDD-containing CASP2 complex. Independent human-cell studies establish RAIDD-dependent CASP2/MDM2 signaling and stress-induced activation platforms. Retain the broad response annotation as non-core; it does not mean CRADD repairs DNA. The original 15073321 full Methods remain unavailable. |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | ACCEPT | Summary: Death-domain mapping agrees with signaling-adaptor activity. Reason: IPR000488 is the actual death-domain source of the signal-transduction mapping. Generic death domains need not specify a particular output, but CRADD’s independently demonstrated PIDD1/CASP2 bridge performs a signaling step. Retain the broad electronic process; do not infer receptor initiation from the domain alone. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR000488 SUPPORTS TRANSFER The exact current InterPro-to-GO mapping is present and corroborated by the target-specific experiments described in this row. |
| GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors | IC PMID:9044836 CRADD, a novel human apoptotic adaptor molecule for caspase-... | MARK AS OVER ANNOTATED | Summary: The specific death-receptor pathway exceeds the cited inference. Reason: GO:0008625 starts with ligand binding to a cell-surface death-domain receptor. The cited 9044836 original demonstrates CRADD domain interactions and overexpression-induced apoptosis, while receptor involvement is proposed. Its GO:0030674 adaptor premise does not establish that receptor-initiated process. The separate positive engineered TNFR1/TRADD complexes remain valid, and mouse RAIDD-null MEFs retained TNF sensitivity in 16183742. These scoped observations justify overannotation, not a universal claim that CRADD can never affect receptor responses. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: GO:0030674 UNRESOLVED The adaptor activity is supported, but that premise alone does not establish the specified ligand-triggered death-receptor process. |
| GO:0030330 DNA damage response, signal transduction by p53 class mediator | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Conserved but contextual p53-response signaling. Reason: The actual PTN008354075 IBD is ancestral to human CRADD and includes genuine human experimental support. PMID21726810 directly tests RAIDD knockdown in damaged U2OS cells and connects the PIDDosome to CASP2-mediated MDM2 cleavage. Retain the propagated p53-response process as non-core, without calling target descendant evidence circular or assigning proteolysis to CRADD. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN008354075 SUPPORTS TRANSFER Current IBD for the p53-response process is on the target path; direct human RAIDD/PIDDosome experiments support the contextual process. |
| GO:0030330 DNA damage response, signal transduction by p53 class mediator | IMP PMID:21726810 Caspase-2-mediated cleavage of Mdm2 creates a p53-induced po... | KEEP AS NON CORE | Summary: RAIDD contributes to p53 reinforcement after DNA damage. Reason: In human U2OS cells, RAIDD knockdown reduces DNA-damage-induced MDM2 cleavage; RAIDD expression and CASP2 controls in human 293T cells place the adaptor upstream of the protease. This supports the existing p53-class response process at the measured cell contexts. It is not direct MDM2 catalysis by CRADD or evidence that every CASP2 platform is apoptotic. Supporting Evidence: file:human/CRADD/CRADD-primary-excerpts.md inhibition of PIDD or RAIDD file:human/CRADD/CRADD-primary-excerpts.md reduction in Mdm2 cleavage |
| GO:0030674 protein-macromolecule adaptor activity | IPI PMID:9044836 CRADD, a novel human apoptotic adaptor molecule for caspase-... | MODIFY | Summary: Noncatalytic signaling-adaptor activity. Reason: Original domain-controlled interactions connect CRADD’s CASP2-binding N terminus and RIP-binding death domain; subsequent PIDD-CC recruitment and purified PIDD/RAIDD assembly establish the signaling bridge. Refine to the verified signaling-adaptor descendant of GO:0030674. CRADD organizes partners rather than cleaving a substrate. Proposed replacements: signaling adaptor activity |
| GO:0042981 regulation of apoptotic process | IEA GO_REF:0000002 | ACCEPT | Summary: CARD mapping is consistent with regulation of apoptosis. Reason: IPR001315 is the actual CARD-domain mapping source. CRADD’s target-specific recruitment, overexpression and loss-of-function experiments independently establish regulation of apoptotic signaling. Retain the broad electronic term; the CARD mapping alone is not used to infer the sign for every CARD protein. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR001315 SUPPORTS TRANSFER The exact current InterPro-to-GO mapping is present and corroborated by the target-specific experiments described in this row. |
| GO:0043065 positive regulation of apoptotic process | IDA PMID:11821383 CARD-8 protein, a new CARD family member that regulates casp... | ACCEPT | Summary: CRADD is an actual apoptotic positive control in the CARD8 paper. Reason: The complete indexed original, not its CARD8-focused abstract, was examined. Figure 7C and the apoptosis Methods include CRADD alongside FADD, Bcl-10, CARD8 and empty vector in transfected MCF-7 cells; dead GFP-positive cells were counted after 36 hours. This directly supports the existing positive-apoptosis assignment. CARD8-specific caspase-1 and NF-kappaB results are not transferred to CRADD. Supporting Evidence: file:human/CRADD/CRADD-primary-excerpts.md vector or FADD, CRADD, Bcl-10, and CARD-8FL expression vectors. |
| GO:0043065 positive regulation of apoptotic process | IEA GO_REF:0000117 | ACCEPT | Summary: Matched ARBA branch supports positive apoptotic regulation. Reason: Current ARBA00027745 branch 25 exactly matches the target’s actual feature/taxon combination and emits this process. Target-specific original overexpression, CASP2 recruitment and neuronal functional assays independently support the sign. No unmatched or historical branch was substituted. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00027745 SUPPORTS TRANSFER Current branch 25 matches the actual target features and taxon; target-specific apoptosis experiments support its emitted process. |
| GO:0043065 positive regulation of apoptotic process | NAS PMID:15073321 The PIDDosome, a protein complex implicated in activation of... | ACCEPT | Summary: PIDDosome assembly positively regulates apoptotic signaling. Reason: The complete original abstract identifies the RAIDD-containing CASP2 complex and increased sensitivity to genotoxic stimuli. Independently read recruitment, assembly and neuronal assays support CRADD’s positive signaling role. Original 15073321 full Methods are unavailable; this acceptance does not invent their details or make the pathway universally necessary. |
| GO:0070513 death domain binding | IEA GO_REF:0000002 | ACCEPT | Summary: CRADD-specific death-domain mappings are supported. Reason: Both literal mapping sources, IPR037926 and IPR037939, map to death domain binding. Human RIP domain controls and PIDD/RAIDD structural and mutational data independently establish the relevant interaction, beyond a prediction from domain presence. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR037926 SUPPORTS TRANSFER The exact current InterPro-to-GO mapping is present and corroborated by the target-specific experiments described in this row. InterPro:IPR037939 SUPPORTS TRANSFER The exact current InterPro-to-GO mapping is present and corroborated by the target-specific experiments described in this row. |
| GO:0070513 death domain binding | IPI PMID:9044836 CRADD, a novel human apoptotic adaptor molecule for caspase-... | ACCEPT | Summary: Direct RIP death-domain binding. Reason: The original human CRADD GST/domain controls show that its C-terminal death domain recognizes the RIP death-domain region. Retain the precise existing function. This molecular interaction alone does not establish ligand-triggered receptor-pathway necessity. Supporting Evidence: PMID:9044836 DD that interacts with RIP |
| GO:0071260 cellular response to mechanical stimulus | IEP PMID:19593445 Expression of the Bcl-2 protein BAD promotes prostate cancer... | REMOVE | Summary: The complete cited original does not support this CRADD assertion. Reason: The source ID and IEP assertion are preserved as provenance. The independently recovered complete original PMID19593445 reports targeted BAD expression/knockdown in human LNCaP/C4-2 prostate-cancer models and nude-mouse xenografts, with BAD, ERK and proliferation measurements. Its complete Methods, Results, Discussion and figure captions contain neither a CRADD experiment nor a broad screen that could supply this annotation, and no mechanical-stimulus experiment. The current GO:0071260 definition does include expression responses; the problem is this specific citation-to-assertion mapping, not a requirement for protective signaling output or a claim that CRADD cannot respond to mechanical stimuli. |
| GO:0097190 apoptotic signaling pathway | IMP PMID:8985253 RAIDD is a new 'death' adaptor molecule. | ACCEPT | Summary: CRADD directly organizes apoptotic signaling. Reason: The original human RAIDD overexpression experiments induce apoptosis, with inhibition by zVAD, CrmA and inactive ICH-1/CASP2 controls. Together with partner recruitment, these support a performed adaptor step in apoptotic signaling rather than mere expression correlation. Engineered conditions do not establish universal endogenous necessity. Supporting Evidence: PMID:8985253 serving as a direct link to the death proteases |
| GO:1905369 endopeptidase complex | IPI PMID:15073321 The PIDDosome, a protein complex implicated in activation of... | MODIFY | Summary: A CASP2-containing caspase complex. Reason: The original abstract identifies the RAIDD/PIDD/CASP2 complex. Later human-cell recruitment and purified DD-core experiments establish its adaptor architecture and connection to CASP2 activation. Refine endopeptidase complex to the current, reinstated child caspase complex. This neither makes CRADD catalytic nor fixes the full intact-cell stoichiometry at the 5:7 DD-crystal ratio. Proposed replacements: caspase complex Supporting Evidence: PMID:15073321 complex that contains the death domain-containing protein PIDD |
| GO:2001235 positive regulation of apoptotic signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Inherited positive regulation of apoptotic signaling. Reason: The actual PTN001030467 IBD lies on the target path. The literal MGI:1336168 donor is mouse Cradd O88843; the source IGI experiment in 16183742 tests PIDD overexpression in RAIDD-null versus wild-type embryonic fibroblasts. That genuine context and human target recruitment/functional evidence support the positive signaling claim. This is not a donor-count argument or a claim of requirement for every apoptotic stimulus. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001030467 SUPPORTS TRANSFER Current IBD for positive apoptotic signaling is on the target path; mouse PIDD/RAIDD genetics and human target experiments are compatible. |
Loading supporting content…
Download this section (compressed HTML)Q: What is the endogenous cellular role of the 103-residue CRADD alternative product, which retains the CARD region but lacks the canonical death domain?
Q: Which physiological stimuli recruit endogenous CRADD to cytoplasmic versus nucleolar CASP2 platforms, and when is PIDD1 required?
Q: Does the binary interaction with HTLV Tax occur in infection, and how should the conflicting Tax E3-activity experiments constrain partner-class annotation?
Q: Which source record generated the CRADD mechanical-response annotation linked to PMID19593445, whose complete original instead assays BAD in prostate-cancer models?
Experiment: Measure endogenous CRADD isoform abundance and localization with isoform-resolved assays, then compare PIDD1 recruitment and CASP2 activation after matched rescue at near-endogenous expression.
Experiment: Use endogenous CRADD perturbation and compartment-resolved CASP2 activation reporters across defined genotoxic and receptor stimuli, separating adaptor recruitment, complex assembly and downstream cell death.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)