CASP3 (caspase-3; apopain/CPP32/Yama) is the principal executioner cysteine-aspartic protease of apoptosis in human cells. Synthesized as an inactive zymogen, it is activated by proteolytic cleavage by initiator caspases (CASP8, CASP9, CASP10) and granzyme B into a heterotetramer of two p17/p12 heterodimers with a catalytic cysteine. It is a cysteine-type endopeptidase (EC 3.4.22.56) that cleaves substrates strictly after aspartate residues, with a preferred Asp-X-X-Asp recognition motif. During the execution/demolition phase of apoptosis it cleaves hundreds of cellular substrates, including PARP1, the ICAD/DFF45 inhibitor of the CAD/DFF40 DNA-fragmentation nuclease, cytoskeletal and junctional proteins, and numerous signaling proteins, thereby dismantling the dying cell and promoting phosphatidylserine exposure for efferocytosis. Beyond classical apoptosis, caspase-3 cleaves gasdermin-E (GSDME/DFNA5) to switch cells to pyroptosis, processes cytokines such as IL-18, and restrains innate antiviral signaling by cleaving cGAS, MAVS, IRF3, and NF-kB subunits. It also has non-lethal roles, contributing to differentiation programs (e.g., erythroid, keratinocyte, neuronal) through limited substrate cleavage. Caspase-3 acts mainly in the cytoplasm/cytosol but its active form is also found in the nucleus during apoptosis; its activity is restrained by inhibitors including XIAP and BIRC6 and by S-nitrosylation of the catalytic cysteine.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Caspase-3 acts in the cytoplasm/cytosol, where the procaspase resides and where it is activated and cleaves most substrates. Reason: Cytoplasmic localization is well supported as the principal site of caspase-3 activity; this is the consensus phylogenetic (IBA) cellular component and matches UniProt subcellular location. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm PMID:15003516 Caspase 3 activation is controlled by a sequence located in the N-terminus of its large subunit. |
| GO:0006915 apoptotic process | IBA GO_REF:0000033 | ACCEPT | Summary: Caspase-3 is the principal executioner caspase of apoptosis, a deeply conserved role captured by the IBA annotation. Reason: Involvement in apoptosis is the defining biological process for caspase-3 and is supported by phylogenetic inference and extensive experimental literature. Supporting Evidence: PMID:18723680 Caspase-3 was found to be generally more promiscuous than caspase-7 and appears to be the major executioner caspase during the demolition phase of apoptosis. PMID:7596430 suggesting that apopain/CPP32 is important for the initiation of apoptotic cell death. |
| GO:0004197 cysteine-type endopeptidase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Caspase-3 is a cysteine-type endopeptidase (EC 3.4.22.56) that cleaves substrates after aspartate residues; this is its core molecular function. Reason: This is the central, well-established molecular function of caspase-3, supported by phylogenetic inference, biochemical purification, and crystal structures. It should be retained as a core function. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Strict requirement for an Asp residue at positions P1 and P4. It has a preferred cleavage sequence of Asp-Xaa-Xaa-Asp-|- PMID:7596430 suggesting that apopain/CPP32 is important for the initiation of apoptotic cell death. file:human/CASP3/CASP3-deep-research-falcon.md the most proteolytically proficient executioner of programmed cell death |
| GO:0006508 proteolysis | IBA GO_REF:0000033 | ACCEPT | Summary: Caspase-3 carries out proteolysis of many substrates; proteolysis is the biological process realization of its endopeptidase activity. Reason: Proteolysis is correct and consistent with the cysteine-type endopeptidase molecular function, although it is broad. Retained as a supporting (non-distinguishing) process term. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Strict requirement for an Asp residue at positions P1 and P4. It has a preferred cleavage sequence of Asp-Xaa-Xaa-Asp-|- PMID:7596430 suggesting that apopain/CPP32 is important for the initiation of apoptotic cell death. |
| GO:0031264 death-inducing signaling complex | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: The death-inducing signaling complex (DISC) is the platform that activates initiator caspase-8; caspase-3 is an executioner caspase acting downstream of the DISC rather than a DISC component. Reason: Caspase-3 is activated downstream of the DISC (by caspase-8) and is not generally considered a structural part of the DISC itself. This phylogenetic part_of assignment likely reflects over-propagation across the caspase family; caspase-3's role is as an executioner, not a DISC subunit. Supporting Evidence: PMID:18723680 Caspase-3 was found to be generally more promiscuous than caspase-7 and appears to be the major executioner caspase during the demolition phase of apoptosis. file:human/CASP3/CASP3-uniprot.txt Cleavage by granzyme B, caspase-6, caspase-8 and caspase-10 generates the two active subunits |
| GO:0097194 execution phase of apoptosis | IBA GO_REF:0000033 | ACCEPT | Summary: Caspase-3 is the major executioner caspase responsible for the demolition/execution phase of apoptosis. Reason: This is a precise and core biological process term for caspase-3, supported by phylogenetic inference and experimental evidence that caspase-3 dominates the demolition phase. Supporting Evidence: PMID:18723680 Caspase-3 was found to be generally more promiscuous than caspase-7 and appears to be the major executioner caspase during the demolition phase of apoptosis. |
| GO:0008047 enzyme activator activity | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Caspase-3 activates downstream enzymes by proteolytic cleavage (e.g., caspase-6, -7, -9 and gasdermin-E), but it does so via its endopeptidase activity rather than acting as a classical allosteric enzyme activator. Reason: While caspase-3 cleavage-activates other zymogens, the generic enzyme activator activity term mischaracterizes the mechanism, which is proteolysis. The cysteine-type endopeptidase activity term already captures this function more accurately. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Cleaves and activates caspase-6, -7 and -9 (CASP6, CASP7 and CASP9, respectively) PMID:28459430 GSDME was specifically cleaved by caspase-3 in its linker, generating a GSDME-N fragment that perforates membranes and thereby induces pyroptosis. |
| GO:0043525 positive regulation of neuron apoptotic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: As the executioner caspase, caspase-3 promotes neuronal apoptosis (e.g., developmental neuronal death), a tissue-specific instance of its general apoptotic execution role. Reason: This is a genuine but downstream, tissue-specific manifestation of the core apoptotic execution function rather than a distinct molecular activity. Retained as non-core. Supporting Evidence: PMID:18723680 Caspase-3 was found to be generally more promiscuous than caspase-7 and appears to be the major executioner caspase during the demolition phase of apoptosis. |
| GO:0030182 neuron differentiation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Caspase-3 has non-apoptotic roles in neuronal differentiation/remodeling through limited substrate cleavage, captured by phylogenetic inference. Reason: Differentiation is a real but downstream, non-core role relative to caspase-3's core cysteine-protease and apoptotic-execution functions. Retained as non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Triggers cell adhesion in sympathetic neurons through RET cleavage |
| GO:0030216 keratinocyte differentiation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Caspase-3 contributes to keratinocyte differentiation (cornification), a non-apoptotic tissue-specific role inferred phylogenetically. Reason: This is a genuine but downstream, tissue-specific differentiation role and not the core protease/apoptotic-execution function. Retained as non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Triggers cell adhesion in sympathetic neurons through RET cleavage |
| GO:0030218 erythrocyte differentiation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Caspase-3 is activated during terminal erythroid differentiation; its activity is restrained (e.g., Hsp70 protecting GATA-1) so that differentiation proceeds without apoptosis. Reason: A genuine non-apoptotic role in erythropoiesis, supported experimentally, but downstream of and dependent on the core protease function. Retained as non-core. Supporting Evidence: PMID:17167422 Caspase-3 is activated during both terminal differentiation and erythropoietin-starvation-induced apoptosis of human erythroid precursors. |
| GO:0004197 cysteine-type endopeptidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation of the core cysteine-type endopeptidase activity, consistent with experimental and phylogenetic evidence. Reason: Correct core molecular function; the IEA agrees with the IBA and IDA evidence for the same term. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Strict requirement for an Asp residue at positions P1 and P4. It has a preferred cleavage sequence of Asp-Xaa-Xaa-Asp-|- |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation of cytoplasmic localization, consistent with UniProt and IBA evidence. Reason: Correct cellular component; agrees with experimental subcellular location. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0006508 proteolysis | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation of proteolysis, the process realization of caspase-3's endopeptidase activity. Reason: Correct though broad; consistent with the IBA proteolysis annotation. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Strict requirement for an Asp residue at positions P1 and P4. It has a preferred cleavage sequence of Asp-Xaa-Xaa-Asp-|- |
| GO:0006915 apoptotic process | IEA GO_REF:0000117 | ACCEPT | Summary: Electronic (ARBA) annotation of apoptotic process, the core biological process for caspase-3. Reason: Correct core process; agrees with IBA and experimental evidence. Supporting Evidence: PMID:7596430 suggesting that apopain/CPP32 is important for the initiation of apoptotic cell death. |
| GO:0008234 cysteine-type peptidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Broader parent of cysteine-type endopeptidase activity; correct but less specific. Reason: Correct but more general than GO:0004197. Acceptable as an IEA parent term; the more specific endopeptidase term is the core function. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Strict requirement for an Asp residue at positions P1 and P4. It has a preferred cleavage sequence of Asp-Xaa-Xaa-Asp-|- |
| GO:0051604 protein maturation | IEA GO_REF:0000117 | ACCEPT | Summary: Caspase-3 matures/processes substrate proteins by limited proteolysis (e.g., activating gasdermin-E, processing cytokines). Reason: Protein maturation is a valid process realization of caspase-3 activation-by-cleavage of substrates; supported by experimental gasdermin/cytokine processing. Supporting Evidence: PMID:28459430 GSDME was specifically cleaved by caspase-3 in its linker, generating a GSDME-N fragment that perforates membranes and thereby induces pyroptosis. |
| GO:0072734 cellular response to staurosporine | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Caspase-3 is activated during staurosporine-induced apoptosis (a standard intrinsic-apoptosis trigger). Reason: A stimulus/response context term rather than a core function; caspase-3 acts as the executioner downstream of staurosporine-induced intrinsic apoptosis. Retained as non-core. Supporting Evidence: PMID:22253444 the main processing of pro-caspase-3 takes place in the cytosol of both cells lines analyzed even if caspase-3 active fragments can also be evidenced in the nuclear fractions after STP treatment |
| GO:0005515 protein binding | IPI PMID:11257232 Structural basis for the inhibition of caspase-3 by XIAP. | MARK AS OVER ANNOTATED | Summary: This IPI captures a physical interaction (XIAP (BIR2 domain) binds and inhibits caspase-3 [structural].) but the generic protein binding term is uninformative about caspase-3's molecular function. Reason: Bare protein binding (GO:0005515) does not describe a distinct caspase-3 molecular activity; the functionally meaningful interactions (substrate cleavage, inhibitor binding) are better represented by the endopeptidase activity and protease binding terms. Retained but flagged as uninformative. Supporting Evidence: PMID:11257232 Structural basis for the inhibition of caspase-3 by XIAP. |
| GO:0005515 protein binding | IPI PMID:16227597 A-kinase-anchoring protein 95 functions as a potential carri... | MARK AS OVER ANNOTATED | Summary: This IPI captures a physical interaction (AKAP95 associates with active caspase-3 (nuclear translocation carrier).) but the generic protein binding term is uninformative about caspase-3's molecular function. Reason: Bare protein binding (GO:0005515) does not describe a distinct caspase-3 molecular activity; the functionally meaningful interactions (substrate cleavage, inhibitor binding) are better represented by the endopeptidase activity and protease binding terms. Retained but flagged as uninformative. Supporting Evidence: PMID:16227597 A-kinase-anchoring protein 95 functions as a potential carrier for the nuclear translocation of active caspase 3 through an enzyme-substrate-like association. |
| GO:0005515 protein binding | IPI PMID:16501604 Protein kinase WNK3 increases cell survival in a caspase-3-d... | MARK AS OVER ANNOTATED | Summary: This IPI captures a physical interaction (WNK3 kinase interaction in a caspase-3-dependent survival pathway.) but the generic protein binding term is uninformative about caspase-3's molecular function. Reason: Bare protein binding (GO:0005515) does not describe a distinct caspase-3 molecular activity; the functionally meaningful interactions (substrate cleavage, inhibitor binding) are better represented by the endopeptidase activity and protease binding terms. Retained but flagged as uninformative. Supporting Evidence: PMID:16501604 Protein kinase WNK3 increases cell survival in a caspase-3-dependent pathway. |
| GO:0005515 protein binding | IPI PMID:16530191 N-myristoyltransferase 2 expression in human colon cancer: c... | MARK AS OVER ANNOTATED | Summary: This IPI captures a physical interaction (NMT2/calpain-caspase cross-talk interaction.) but the generic protein binding term is uninformative about caspase-3's molecular function. Reason: Bare protein binding (GO:0005515) does not describe a distinct caspase-3 molecular activity; the functionally meaningful interactions (substrate cleavage, inhibitor binding) are better represented by the endopeptidase activity and protease binding terms. Retained but flagged as uninformative. Supporting Evidence: PMID:16530191 N-myristoyltransferase 2 expression in human colon cancer: cross-talk between the calpain and caspase system. |
| GO:0005515 protein binding | IPI PMID:17167422 Hsp70 regulates erythropoiesis by preventing caspase-3-media... | MARK AS OVER ANNOTATED | Summary: This IPI captures a physical interaction (GATA-1 / Hsp70 interaction context in erythroid precursors.) but the generic protein binding term is uninformative about caspase-3's molecular function. Reason: Bare protein binding (GO:0005515) does not describe a distinct caspase-3 molecular activity; the functionally meaningful interactions (substrate cleavage, inhibitor binding) are better represented by the endopeptidase activity and protease binding terms. Retained but flagged as uninformative. Supporting Evidence: PMID:17167422 Hsp70 regulates erythropoiesis by preventing caspase-3-mediated cleavage of GATA-1. |
| GO:0005515 protein binding | IPI PMID:17544405 Caspase-3-mediated cleavage of Akt: involvement of non-conse... | MARK AS OVER ANNOTATED | Summary: This IPI captures a physical interaction (AKT1 cleavage substrate interaction.) but the generic protein binding term is uninformative about caspase-3's molecular function. Reason: Bare protein binding (GO:0005515) does not describe a distinct caspase-3 molecular activity; the functionally meaningful interactions (substrate cleavage, inhibitor binding) are better represented by the endopeptidase activity and protease binding terms. Retained but flagged as uninformative. Supporting Evidence: PMID:17544405 Caspase-3-mediated cleavage of Akt: involvement of non-consensus sites and influence of phosphorylation. |
| GO:0005515 protein binding | IPI PMID:17606900 Thioredoxin is required for S-nitrosation of procaspase-3 an... | MARK AS OVER ANNOTATED | Summary: This IPI captures a physical interaction (Thioredoxin / procaspase-3 S-nitrosation interaction.) but the generic protein binding term is uninformative about caspase-3's molecular function. Reason: Bare protein binding (GO:0005515) does not describe a distinct caspase-3 molecular activity; the functionally meaningful interactions (substrate cleavage, inhibitor binding) are better represented by the endopeptidase activity and protease binding terms. Retained but flagged as uninformative. Supporting Evidence: PMID:17606900 Thioredoxin is required for S-nitrosation of procaspase-3 and the inhibition of apoptosis in Jurkat cells. |
| GO:0005515 protein binding | IPI PMID:18723680 Executioner caspase-3 and caspase-7 are functionally distinc... | MARK AS OVER ANNOTATED | Summary: This IPI captures a physical interaction (Substrate interactions (Bid, XIAP, gelsolin, caspase-6, p23).) but the generic protein binding term is uninformative about caspase-3's molecular function. Reason: Bare protein binding (GO:0005515) does not describe a distinct caspase-3 molecular activity; the functionally meaningful interactions (substrate cleavage, inhibitor binding) are better represented by the endopeptidase activity and protease binding terms. Retained but flagged as uninformative. Supporting Evidence: PMID:18723680 Executioner caspase-3 and caspase-7 are functionally distinct proteases. |
| GO:0005515 protein binding | IPI PMID:19273858 S-nitrosylation of XIAP compromises neuronal survival in Par... | MARK AS OVER ANNOTATED | Summary: This IPI captures a physical interaction (XIAP S-nitrosylation interaction context.) but the generic protein binding term is uninformative about caspase-3's molecular function. Reason: Bare protein binding (GO:0005515) does not describe a distinct caspase-3 molecular activity; the functionally meaningful interactions (substrate cleavage, inhibitor binding) are better represented by the endopeptidase activity and protease binding terms. Retained but flagged as uninformative. Supporting Evidence: PMID:19273858 S-nitrosylation of XIAP compromises neuronal survival in Parkinson's disease. |
| GO:0005515 protein binding | IPI PMID:21726810 Caspase-2-mediated cleavage of Mdm2 creates a p53-induced po... | MARK AS OVER ANNOTATED | Summary: This IPI captures a physical interaction (MDM2 cleavage interaction context.) but the generic protein binding term is uninformative about caspase-3's molecular function. Reason: Bare protein binding (GO:0005515) does not describe a distinct caspase-3 molecular activity; the functionally meaningful interactions (substrate cleavage, inhibitor binding) are better represented by the endopeptidase activity and protease binding terms. Retained but flagged as uninformative. Supporting Evidence: PMID:21726810 Caspase-2-mediated cleavage of Mdm2 creates a p53-induced positive feedback loop. |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | MARK AS OVER ANNOTATED | Summary: This IPI captures a physical interaction (High-throughput liver interactome screen.) but the generic protein binding term is uninformative about caspase-3's molecular function. Reason: Bare protein binding (GO:0005515) does not describe a distinct caspase-3 molecular activity; the functionally meaningful interactions (substrate cleavage, inhibitor binding) are better represented by the endopeptidase activity and protease binding terms. Retained but flagged as uninformative. Supporting Evidence: PMID:21988832 Toward an understanding of the protein interaction network of the human liver. |
| GO:0005515 protein binding | IPI PMID:23150525 Regulation of co- and post-translational myristoylation of p... | MARK AS OVER ANNOTATED | Summary: This IPI captures a physical interaction (N-myristoyltransferase/caspase interplay during apoptosis.) but the generic protein binding term is uninformative about caspase-3's molecular function. Reason: Bare protein binding (GO:0005515) does not describe a distinct caspase-3 molecular activity; the functionally meaningful interactions (substrate cleavage, inhibitor binding) are better represented by the endopeptidase activity and protease binding terms. Retained but flagged as uninformative. Supporting Evidence: PMID:23150525 Regulation of co- and post-translational myristoylation of proteins during apoptosis: interplay of N-myristoyltransferases and caspases. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | MARK AS OVER ANNOTATED | Summary: This IPI captures a physical interaction (Proximity ligation interactome profiling.) but the generic protein binding term is uninformative about caspase-3's molecular function. Reason: Bare protein binding (GO:0005515) does not describe a distinct caspase-3 molecular activity; the functionally meaningful interactions (substrate cleavage, inhibitor binding) are better represented by the endopeptidase activity and protease binding terms. Retained but flagged as uninformative. Supporting Evidence: PMID:25241761 Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: This IPI captures a physical interaction (Large-scale interactome (protein communities) screen.) but the generic protein binding term is uninformative about caspase-3's molecular function. Reason: Bare protein binding (GO:0005515) does not describe a distinct caspase-3 molecular activity; the functionally meaningful interactions (substrate cleavage, inhibitor binding) are better represented by the endopeptidase activity and protease binding terms. Retained but flagged as uninformative. Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: This IPI captures a physical interaction (Binary protein interactome reference map (HuRI).) but the generic protein binding term is uninformative about caspase-3's molecular function. Reason: Bare protein binding (GO:0005515) does not describe a distinct caspase-3 molecular activity; the functionally meaningful interactions (substrate cleavage, inhibitor binding) are better represented by the endopeptidase activity and protease binding terms. Retained but flagged as uninformative. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: This IPI captures a physical interaction (Neurodegenerative disease interactome screen.) but the generic protein binding term is uninformative about caspase-3's molecular function. Reason: Bare protein binding (GO:0005515) does not describe a distinct caspase-3 molecular activity; the functionally meaningful interactions (substrate cleavage, inhibitor binding) are better represented by the endopeptidase activity and protease binding terms. Retained but flagged as uninformative. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: This IPI captures a physical interaction (Cell-specific interactome remodeling screen.) but the generic protein binding term is uninformative about caspase-3's molecular function. Reason: Bare protein binding (GO:0005515) does not describe a distinct caspase-3 molecular activity; the functionally meaningful interactions (substrate cleavage, inhibitor binding) are better represented by the endopeptidase activity and protease binding terms. Retained but flagged as uninformative. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0005515 protein binding | IPI PMID:38884001 Mapping adipocyte interactome networks by HaloTag-enrichment... | MARK AS OVER ANNOTATED | Summary: This IPI captures a physical interaction (Adipocyte interactome HaloTag-MS screen.) but the generic protein binding term is uninformative about caspase-3's molecular function. Reason: Bare protein binding (GO:0005515) does not describe a distinct caspase-3 molecular activity; the functionally meaningful interactions (substrate cleavage, inhibitor binding) are better represented by the endopeptidase activity and protease binding terms. Retained but flagged as uninformative. Supporting Evidence: PMID:38884001 Mapping adipocyte interactome networks by HaloTag-enrichment-mass spectrometry. |
| GO:0005515 protein binding | IPI PMID:7596430 Identification and inhibition of the ICE/CED-3 protease nece... | MARK AS OVER ANNOTATED | Summary: This IPI captures a physical interaction (PARP / caspase substrate interactions (apopain).) but the generic protein binding term is uninformative about caspase-3's molecular function. Reason: Bare protein binding (GO:0005515) does not describe a distinct caspase-3 molecular activity; the functionally meaningful interactions (substrate cleavage, inhibitor binding) are better represented by the endopeptidase activity and protease binding terms. Retained but flagged as uninformative. Supporting Evidence: PMID:7596430 Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. |
| GO:0001554 luteolysis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to luteolysis. Reason: Luteolysis is a tissue-specific apoptotic process (corpus luteum regression) inferred by ortholog transfer; a downstream context of the core apoptotic-execution role. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0001666 response to hypoxia | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to response to hypoxia. Reason: Response to hypoxia is a stimulus/response context (ortholog-transferred), not a core caspase-3 function. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0002020 protease binding | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to protease binding. Reason: Protease binding is informative and supported because caspase-3 is bound and inhibited by XIAP (and related IAPs) and interacts with upstream proteases. This is a meaningful interaction term, unlike bare protein binding. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0004175 endopeptidase activity | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to endopeptidase activity. Reason: Endopeptidase activity is a correct parent of the cysteine-type endopeptidase activity; acceptable though less specific. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0004190 aspartic-type endopeptidase activity | IEA GO_REF:0000107 | REMOVE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to aspartic-type endopeptidase activity. Reason: Aspartic-type endopeptidase activity is mechanistically incorrect because caspase-3 is a CYSTEINE protease that cleaves after aspartate residues and is not an aspartic protease. This appears to be an erroneous ortholog/keyword transfer. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0004861 cyclin-dependent protein serine/threonine kinase inhibitor activity | IEA GO_REF:0000107 | REMOVE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to cyclin-dependent protein serine/threonine kinase inhibitor activity. Reason: Cyclin-dependent protein kinase inhibitor activity is not a caspase-3 molecular function; this is an implausible ortholog-transferred MF and should be removed. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0005123 death receptor binding | IEA GO_REF:0000107 | REMOVE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to death receptor binding. Reason: Death receptor binding is not an established caspase-3 molecular function; caspase-3 acts downstream of death-receptor signaling (via caspase-8) rather than binding death receptors. Likely an over-propagated transfer. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0005634 nucleus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to nucleus. Reason: Active caspase-3 is found in the nucleus during apoptosis, but this is secondary to its core cytoplasmic site. Kept consistent with the IDA nucleus rows as non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0007413 axonal fasciculation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to axonal fasciculation. Reason: Axonal fasciculation is a tissue/developmental neuronal role inferred by ortholog transfer; downstream and non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0007611 learning or memory | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to learning or memory. Reason: Learning or memory is a high-level organismal phenotype (ortholog-transferred), reflecting non-apoptotic synaptic roles; non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0008233 peptidase activity | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to peptidase activity. Reason: Peptidase activity is a correct broad parent term for caspase-3's protease activity; acceptable though general. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0008627 intrinsic apoptotic signaling pathway in response to osmotic stress | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to intrinsic apoptotic signaling pathway in response to osmotic stress. Reason: Intrinsic apoptotic signaling in response to osmotic stress is a stimulus-specific apoptosis context; caspase-3 is the executioner. Non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0009410 response to xenobiotic stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to response to xenobiotic stimulus. Reason: Response to xenobiotic stimulus is a stimulus/response context (ortholog-transferred); non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0009749 response to glucose | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to response to glucose. Reason: Response to glucose is a stimulus/response context; non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0010038 response to metal ion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to response to metal ion. Reason: Response to metal ion is a stimulus/response context; non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0010165 response to X-ray | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to response to X-ray. Reason: Response to X-ray reflects DNA-damage-induced apoptosis context; caspase-3 acts as executioner. Non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0014069 postsynaptic density | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to postsynaptic density. Reason: Postsynaptic density localization reflects non-apoptotic synaptic roles (e.g., synapse pruning) inferred by transfer; non-core relative to cytoplasmic/nuclear core localization. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0016005 phospholipase A2 activator activity | IEA GO_REF:0000107 | REMOVE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to phospholipase A2 activator activity. Reason: Phospholipase A2 activator activity is not an established caspase-3 molecular function; implausible ortholog-transferred MF and should be removed. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0021766 hippocampus development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to hippocampus development. Reason: Hippocampus development is a developmental/tissue context (ortholog-transferred); non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0030163 protein catabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to protein catabolic process. Reason: Protein catabolic process is consistent with caspase-3 proteolysis of substrates; acceptable as a process term. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0030182 neuron differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to neuron differentiation. Reason: Neuron differentiation is a non-apoptotic, tissue-specific role; non-core (duplicate of the IBA neuron differentiation row). Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0031264 death-inducing signaling complex | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to death-inducing signaling complex. Reason: Caspase-3 acts downstream of the DISC as an executioner and is not a structural DISC component; this part_of assignment is an over-annotation (consistent with the IBA row). Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0031647 regulation of protein stability | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to regulation of protein stability. Reason: Regulation of protein stability reflects substrate-cleavage consequences (e.g., BACE/GGA3); a downstream effect, non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0032025 response to cobalt ion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to response to cobalt ion. Reason: Response to cobalt ion is a stimulus/response context; non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0032355 response to estradiol | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to response to estradiol. Reason: Response to estradiol is a stimulus/response context; non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0032496 response to lipopolysaccharide | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to response to lipopolysaccharide. Reason: Response to lipopolysaccharide is a stimulus/response context; non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0034349 glial cell apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to glial cell apoptotic process. Reason: Glial cell apoptotic process is a cell-type-specific instance of apoptotic execution; non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0035094 response to nicotine | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to response to nicotine. Reason: Response to nicotine is a stimulus/response context; non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0035556 intracellular signal transduction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to intracellular signal transduction. Reason: Intracellular signal transduction is broad; caspase-3 modulates signaling by cleaving signaling proteins, but this term is over-general. Non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0036269 swimming behavior | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to swimming behavior. Reason: Swimming behavior is a zebrafish-derived organismal phenotype transferred by orthology; non-core for human caspase-3. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0042542 response to hydrogen peroxide | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to response to hydrogen peroxide. Reason: Response to hydrogen peroxide (oxidative stress) is a stimulus/response context; non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0043025 neuronal cell body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to neuronal cell body. Reason: Neuronal cell body localization reflects neuronal context; non-core relative to core cytoplasmic/nuclear localization. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0043065 positive regulation of apoptotic process | IEA GO_REF:0000120 | ACCEPT | Summary: As the executioner caspase, caspase-3 positively drives the apoptotic process. Reason: Positive regulation of apoptotic process is consistent with caspase-3's executioner role; acceptable IEA, though the more precise execution-phase term is core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0043200 response to amino acid | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to response to amino acid. Reason: Response to amino acid is a stimulus/response context; non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0043523 regulation of neuron apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to regulation of neuron apoptotic process. Reason: Regulation of neuron apoptotic process is a tissue-specific manifestation of apoptotic execution; non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0043525 positive regulation of neuron apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to positive regulation of neuron apoptotic process. Reason: Positive regulation of neuron apoptotic process is a tissue-specific manifestation of apoptotic execution; non-core (duplicate of the IBA row). Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0044877 protein-containing complex binding | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to protein-containing complex binding. Reason: Protein-containing complex binding is supported (e.g., apoptosome-associated activation, XIAP/BIRC6 complexes); acceptable though general. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0045471 response to ethanol | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to response to ethanol. Reason: Response to ethanol is a stimulus/response context; non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0051146 striated muscle cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to striated muscle cell differentiation. Reason: Striated muscle cell differentiation is a non-apoptotic tissue-specific differentiation role; non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0051384 response to glucocorticoid | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to response to glucocorticoid. Reason: Response to glucocorticoid is a stimulus/response context (e.g., thymocyte apoptosis); non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0071887 leukocyte apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to leukocyte apoptotic process. Reason: Leukocyte apoptotic process is a cell-type-specific instance of apoptotic execution; non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0072347 response to anesthetic | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to response to anesthetic. Reason: Response to anesthetic is a stimulus/response context; non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0098693 regulation of synaptic vesicle cycle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to regulation of synaptic vesicle cycle. Reason: Regulation of synaptic vesicle cycle reflects non-apoptotic synaptic roles inferred by transfer; non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0098883 synapse pruning | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to synapse pruning. Reason: Synapse pruning is a non-apoptotic neuronal role (local caspase activity); genuine but downstream/non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0098978 glutamatergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to glutamatergic synapse. Reason: Glutamatergic synapse localization reflects synaptic roles inferred by transfer; non-core relative to core localization. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:1902004 positive regulation of amyloid-beta formation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to positive regulation of amyloid-beta formation. Reason: Positive regulation of amyloid-beta formation reflects substrate-cleavage effects on APP processing (BACE/GGA3); downstream, non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:1990418 response to insulin-like growth factor stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transferred (Ensembl Compara, GO_REF:0000107) annotation to response to insulin-like growth factor stimulus. Reason: Response to insulin-like growth factor stimulus is a stimulus/response context; non-core. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0032880 regulation of protein localization | IMP PMID:17559062 The most widespread desmosomal cadherin, desmoglein 2, is a ... | KEEP AS NON CORE | Summary: Caspase-3 cleaves desmoglein-2 (DSG2) and JUP at desmosomes, altering junctional protein localization during apoptosis. Reason: Regulation of protein localization here is a downstream consequence of substrate cleavage (desmosomal disassembly) rather than a core function; retained as non-core. Supporting Evidence: PMID:17559062 The most widespread desmosomal cadherin, desmoglein 2, is a novel target of caspase 3-mediated apoptotic machinery. |
| GO:0098883 synapse pruning | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Caspase-3 contributes to synapse pruning, a non-apoptotic local role inferred by sequence similarity. Reason: A genuine but downstream/non-core neuronal role; retained as non-core (mirrors the IEA synapse pruning row). Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis |
| GO:0016485 protein processing | ISS GO_REF:0000024 | ACCEPT | Summary: Caspase-3 processes substrate proteins by limited proteolysis (ISS). Reason: Protein processing is a valid process realization of caspase-3 substrate cleavage; consistent with IDA evidence. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt mediates execution of apoptosis by catalyzing cleavage of many proteins |
| GO:0016485 protein processing | IDA PMID:33725486 Caspase cleavage releases a nuclear protein fragment that st... | ACCEPT | Summary: Caspase-3 processes XRCC4, releasing a C-terminal fragment that activates the Xkr4 scramblase. Reason: Direct evidence of caspase-3 protein processing producing an active fragment; core-adjacent process. Supporting Evidence: PMID:33725486 Upon apoptotic stimuli, XRCC4, contained in the DNA repair complex, is cleaved by caspases, and its C-terminal fragment with an intrinsically disordered region is released into the cytoplasm. |
| GO:0097194 execution phase of apoptosis | IDA PMID:18723680 Executioner caspase-3 and caspase-7 are functionally distinc... | ACCEPT | Summary: Caspase-3 is the major executioner caspase of the demolition phase of apoptosis. Reason: Direct, well-supported core process term. Supporting Evidence: PMID:18723680 Caspase-3 was found to be generally more promiscuous than caspase-7 and appears to be the major executioner caspase during the demolition phase of apoptosis. |
| GO:0097194 execution phase of apoptosis | IDA PMID:33725486 Caspase cleavage releases a nuclear protein fragment that st... | ACCEPT | Summary: Caspase-3 executes apoptosis, including cleavage of XRCC4/scramblases driving PtdSer exposure. Reason: Direct evidence supporting the execution-phase role. Supporting Evidence: PMID:33725486 caspase-mediated cleavage releases a nuclear protein fragment for direct regulation of lipid dynamics on the plasma membrane. |
| GO:0005737 cytoplasm | EXP PMID:15003516 Caspase 3 activation is controlled by a sequence located in ... | ACCEPT | Summary: Caspase-3 localizes to the cytoplasm; activation is controlled by an N-terminal sequence of its large subunit. Reason: Experimental (EXP) cytoplasmic localization; core location. Supporting Evidence: PMID:15003516 Caspase 3 activation is controlled by a sequence located in the N-terminus of its large subunit. |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:17823127 Cytosolic accumulation of HSP60 during apoptosis with or wit... | ACCEPT | Summary: Direct evidence of caspase-3 cysteine-type endopeptidase activity. HSP60 modulates caspase-3 pro/anti-apoptotic activity (cysteine protease assay). Reason: This is the core molecular function of caspase-3, repeatedly demonstrated experimentally on diverse substrates. Retained as a core function. Supporting Evidence: PMID:17823127 Cytosolic accumulation of HSP60 during apoptosis with or without apparent mitochondrial release: evidence that its pro-apoptotic or pro-survival functions involve differential interactions with caspase-3. |
| GO:0097194 execution phase of apoptosis | IGI PMID:12107093 Microinjection of cathepsin d induces caspase-dependent apop... | ACCEPT | Summary: Cathepsin D microinjection induces caspase-dependent apoptosis, with caspase-3 acting in the execution phase (genetic interaction). Reason: Supports caspase-3's execution-phase role via genetic interaction evidence. Supporting Evidence: PMID:12107093 Microinjection of cathepsin d induces caspase-dependent apoptosis in fibroblasts. |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:9334240 Involvement of caspase-1 and caspase-3 in the production and... | ACCEPT | Summary: Direct evidence of caspase-3 cysteine-type endopeptidase activity. Caspase-3 cleaves pro- and mature IL-18 at Asp71/Asp76 (DEVD-inhibitable activity). Reason: This is the core molecular function of caspase-3, repeatedly demonstrated experimentally on diverse substrates. Retained as a core function. Supporting Evidence: PMID:9334240 Involvement of caspase-1 and caspase-3 in the production and processing of mature human interleukin 18 in monocytic THP.1 cells. |
| GO:0016485 protein processing | IDA PMID:9334240 Involvement of caspase-1 and caspase-3 in the production and... | ACCEPT | Summary: Caspase-3 processes IL-18 (cleaving at Asp71/Asp76). Reason: Direct evidence of caspase-3 protein processing of a cytokine substrate. Supporting Evidence: PMID:9334240 the other is caspase-3, which cleaves both precursor and mature hIL-18 at Asp71-Ser72 and Asp76-Asn77 to generate biologically inactive products. |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:37327784 Gasdermin D licenses MHCII induction to maintain food tolera... | ACCEPT | Summary: Direct evidence of caspase-3 cysteine-type endopeptidase activity. Caspase-3 protease activity in gasdermin/IL-18 processing context. Reason: This is the core molecular function of caspase-3, repeatedly demonstrated experimentally on diverse substrates. Retained as a core function. Supporting Evidence: PMID:37327784 Gasdermin D licenses MHCII induction to maintain food tolerance in small intestine. |
| GO:0001818 negative regulation of cytokine production | IMP PMID:36002459 Apoptotic caspase inhibits innate immune signaling by cleavi... | ACCEPT | Summary: Caspase-3 cleaves NF-kB members (p65/RelA, RelB, c-Rel), dampening cytokine production. Reason: Direct functional (IMP) evidence that caspase-3 negatively regulates cytokine production via NF-kB cleavage; a genuine non-apoptotic immunoregulatory role. Supporting Evidence: PMID:36002459 caspase-3 can mediate the cleavage of NF-ΞΊB members p65/RelA, RelB, and c-Rel via its protease activity |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:36002459 Apoptotic caspase inhibits innate immune signaling by cleavi... | ACCEPT | Summary: Direct evidence of caspase-3 cysteine-type endopeptidase activity. Caspase-3 cleaves NF-kB subunits p65/RelA, RelB, c-Rel via its protease activity. Reason: This is the core molecular function of caspase-3, repeatedly demonstrated experimentally on diverse substrates. Retained as a core function. Supporting Evidence: PMID:36002459 Apoptotic caspase inhibits innate immune signaling by cleaving NF-ΞΊBs in both Mammals and Flies. |
| GO:0006915 apoptotic process | IDA PMID:34480022 Endotoxin stabilizes protein arginine methyltransferase 4 (P... | ACCEPT | Summary: Caspase-3 mediates apoptosis (PRMT4/endotoxin-triggered death of lung epithelia). Reason: Direct evidence of caspase-3 in the apoptotic process; core. Supporting Evidence: PMID:34480022 Endotoxin stabilizes protein arginine methyltransferase 4 (PRMT4) protein triggering death of lung epithelia. |
| GO:0070269 pyroptotic inflammatory response | IDA PMID:36426955 TRIM21 Regulates Virus-Induced Cell Pyroptosis through Polyu... | KEEP AS NON CORE | Summary: Caspase-3 participates in pyroptotic inflammatory responses (virus-induced pyroptosis context). Reason: Pyroptosis via gasdermin cleavage is a genuine caspase-3 role; this particular TRIM21/ISG12a context is supportive but the core pyroptosis link is the GSDME cleavage. Retained as non-core context. Supporting Evidence: PMID:36426955 TRIM21 Regulates Virus-Induced Cell Pyroptosis through Polyubiquitination of ISG12a. |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:33852854 Gasdermin E permits interleukin-1 beta release in distinct s... | ACCEPT | Summary: Direct evidence of caspase-3 cysteine-type endopeptidase activity. Caspase-3 cleaves and activates gasdermin-E (GSDME) at its linker. Reason: This is the core molecular function of caspase-3, repeatedly demonstrated experimentally on diverse substrates. Retained as a core function. Supporting Evidence: PMID:33852854 Gasdermin E permits interleukin-1 beta release in distinct sublytic and pyroptotic phases. |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:35594856 Human NLRP1 is a sensor of pathogenic coronavirus 3CL protea... | ACCEPT | Summary: Direct evidence of caspase-3 cysteine-type endopeptidase activity. Caspase-3 protease activity in NLRP1/gasdermin processing context. Reason: This is the core molecular function of caspase-3, repeatedly demonstrated experimentally on diverse substrates. Retained as a core function. Supporting Evidence: PMID:35594856 Human NLRP1 is a sensor of pathogenic coronavirus 3CL proteases in lung epithelial cells. |
| GO:0051604 protein maturation | IDA PMID:33852854 Gasdermin E permits interleukin-1 beta release in distinct s... | ACCEPT | Summary: Caspase-3 matures gasdermin-E (GSDME) by cleavage at its activation site. Reason: Direct evidence of caspase-3 protein maturation of a substrate. Supporting Evidence: PMID:33852854 non-cleavable GSDMED270A variant (altered at the CASP3 cleavage and activation site) |
| GO:0051604 protein maturation | IDA PMID:35594856 Human NLRP1 is a sensor of pathogenic coronavirus 3CL protea... | ACCEPT | Summary: Caspase-3 matures gasdermin substrates in the NLRP1/coronavirus protease context. Reason: Direct evidence of caspase-3 protein maturation activity. Supporting Evidence: PMID:35594856 Human NLRP1 is a sensor of pathogenic coronavirus 3CL proteases in lung epithelial cells. |
| GO:0140639 positive regulation of pyroptotic inflammatory response | IDA PMID:33852854 Gasdermin E permits interleukin-1 beta release in distinct s... | ACCEPT | Summary: Caspase-3 cleavage of GSDME positively regulates pyroptotic IL-1b release. Reason: Direct evidence that caspase-3-GSDME cleavage promotes the pyroptotic inflammatory response. Supporting Evidence: PMID:33852854 Gasdermin E permits interleukin-1 beta release in distinct sublytic and pyroptotic phases. |
| GO:0140639 positive regulation of pyroptotic inflammatory response | IDA PMID:35594856 Human NLRP1 is a sensor of pathogenic coronavirus 3CL protea... | ACCEPT | Summary: Caspase-3 promotes pyroptotic inflammatory responses via gasdermin cleavage in the NLRP1 context. Reason: Direct evidence supporting caspase-3's positive role in pyroptosis. Supporting Evidence: PMID:35594856 Human NLRP1 is a sensor of pathogenic coronavirus 3CL proteases in lung epithelial cells. |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:28459430 Chemotherapy drugs induce pyroptosis through caspase-3 cleav... | ACCEPT | Summary: Direct evidence of caspase-3 cysteine-type endopeptidase activity. Caspase-3 specifically cleaves GSDME in its linker to generate the pore-forming N fragment. Reason: This is the core molecular function of caspase-3, repeatedly demonstrated experimentally on diverse substrates. Retained as a core function. Supporting Evidence: PMID:28459430 Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin. |
| GO:0051604 protein maturation | IDA PMID:28459430 Chemotherapy drugs induce pyroptosis through caspase-3 cleav... | ACCEPT | Summary: Caspase-3 matures gasdermin-E by cleavage in its linker to generate the pore-forming fragment. Reason: Direct evidence of caspase-3 protein maturation of GSDME. Supporting Evidence: PMID:28459430 GSDME was specifically cleaved by caspase-3 in its linker, generating a GSDME-N fragment that perforates membranes and thereby induces pyroptosis. |
| GO:0097194 execution phase of apoptosis | IDA PMID:16374543 Nuclear caspase-3 and caspase-7 activation, and poly(ADP-rib... | ACCEPT | Summary: Active nuclear caspase-3 executes apoptosis (PARP cleavage) early in camptothecin-induced death. Reason: Direct evidence of caspase-3 execution-phase activity. Supporting Evidence: PMID:16374543 the activation of nuclear caspases-7 and -3, and poly(ADP-ribose) polymerase (PARP) cleavage, are early events in camptothecin-induced apoptosis |
| GO:0140639 positive regulation of pyroptotic inflammatory response | IDA PMID:28459430 Chemotherapy drugs induce pyroptosis through caspase-3 cleav... | ACCEPT | Summary: Caspase-3 cleavage of GSDME positively regulates pyroptosis after chemotherapy. Reason: Direct evidence that caspase-3 promotes the pyroptotic inflammatory response. Supporting Evidence: PMID:28459430 caspase-3 activation can trigger necrosis by cleaving GSDME |
| GO:0005737 cytoplasm | IDA PMID:17167422 Hsp70 regulates erythropoiesis by preventing caspase-3-media... | ACCEPT | Summary: Active caspase-3 acts in the cytoplasm of erythroid precursors (and nucleus on GATA-1). Reason: Cytoplasm is the core site of caspase-3 activity; consistent with experimental evidence. Supporting Evidence: PMID:17167422 Caspase-3 is activated during both terminal differentiation and erythropoietin-starvation-induced apoptosis of human erythroid precursors. |
| GO:0097193 intrinsic apoptotic signaling pathway | IMP PMID:15565177 A novel mitochondrial protein DIP mediates E2F1-induced apop... | ACCEPT | Summary: Caspase-3 is activated and executes the intrinsic (mitochondrial) apoptotic pathway (DIP/E2F1). Reason: Caspase-3 acts in intrinsic apoptotic signaling downstream of mitochondrial signals; supported. Supporting Evidence: PMID:15565177 typical apoptotic features such as caspase-3 activation and cleavage of poly(ADP-ribose)-polymerase |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:16374543 Nuclear caspase-3 and caspase-7 activation, and poly(ADP-rib... | ACCEPT | Summary: Direct evidence of caspase-3 cysteine-type endopeptidase activity. Active nuclear caspase-3 cleaves PARP early in camptothecin-induced apoptosis. Reason: This is the core molecular function of caspase-3, repeatedly demonstrated experimentally on diverse substrates. Retained as a core function. Supporting Evidence: PMID:16374543 Nuclear caspase-3 and caspase-7 activation, and poly(ADP-ribose) polymerase cleavage are early events in camptothecin-induced apoptosis. |
| GO:0005634 nucleus | IDA PMID:16374543 Nuclear caspase-3 and caspase-7 activation, and poly(ADP-rib... | KEEP AS NON CORE | Summary: Active caspase-3 is found in the nucleus, cleaving PARP early in apoptosis. Reason: Nuclear localization of active caspase-3 is supported but secondary to its core cytoplasmic site; retained as non-core. Supporting Evidence: PMID:16374543 the activation of nuclear caspases-7 and -3, and poly(ADP-ribose) polymerase (PARP) cleavage, are early events in camptothecin-induced apoptosis |
| GO:0030163 protein catabolic process | IDA PMID:16374543 Nuclear caspase-3 and caspase-7 activation, and poly(ADP-rib... | ACCEPT | Summary: Caspase-3 carries out protein catabolism (PARP cleavage) during apoptosis. Reason: Protein catabolic process is consistent with caspase-3 substrate cleavage; acceptable. Supporting Evidence: PMID:16374543 poly(ADP-ribose) polymerase (PARP) cleavage, are early events in camptothecin-induced apoptosis |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:20566630 Identification of functional regions defining different acti... | ACCEPT | Summary: Direct evidence of caspase-3 cysteine-type endopeptidase activity. Functional regions defining caspase-3 vs caspase-7 cellular protease activity. Reason: This is the core molecular function of caspase-3, repeatedly demonstrated experimentally on diverse substrates. Retained as a core function. Supporting Evidence: PMID:20566630 Identification of functional regions defining different activity in caspase-3 and caspase-7 within cells. |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:23650375 Structural snapshots reveal distinct mechanisms of procaspas... | ACCEPT | Summary: Direct evidence of caspase-3 cysteine-type endopeptidase activity. Structural snapshots of procaspase-3 activation (catalytic mechanism). Reason: This is the core molecular function of caspase-3, repeatedly demonstrated experimentally on diverse substrates. Retained as a core function. Supporting Evidence: PMID:23650375 Structural snapshots reveal distinct mechanisms of procaspase-3 and -7 activation. |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:18723680 Executioner caspase-3 and caspase-7 are functionally distinc... | ACCEPT | Summary: Direct evidence of caspase-3 cysteine-type endopeptidase activity. Caspase-3 cleaves multiple natural substrates (Bid, XIAP, gelsolin, caspase-6, p23). Reason: This is the core molecular function of caspase-3, repeatedly demonstrated experimentally on diverse substrates. Retained as a core function. Supporting Evidence: PMID:18723680 Executioner caspase-3 and caspase-7 are functionally distinct proteases. |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:30878284 Apoptotic Caspases Suppress Type I Interferon Production via... | ACCEPT | Summary: Direct evidence of caspase-3 cysteine-type endopeptidase activity. Caspase-3 cleaves cGAS, MAVS and IRF3 via its protease activity. Reason: This is the core molecular function of caspase-3, repeatedly demonstrated experimentally on diverse substrates. Retained as a core function. Supporting Evidence: PMID:30878284 Apoptotic Caspases Suppress Type I Interferon Production via the Cleavage of cGAS, MAVS, and IRF3. |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:33725486 Caspase cleavage releases a nuclear protein fragment that st... | ACCEPT | Summary: Direct evidence of caspase-3 cysteine-type endopeptidase activity. Caspase-3 cleaves XRCC4 and XKR scramblases (apoptotic PtdSer exposure). Reason: This is the core molecular function of caspase-3, repeatedly demonstrated experimentally on diverse substrates. Retained as a core function. Supporting Evidence: PMID:33725486 Caspase cleavage releases a nuclear protein fragment that stimulates phospholipid scrambling at the plasma membrane. |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:24904167 Caspase-mediated cleavage of phospholipid flippase for apopt... | ACCEPT | Summary: Direct evidence of caspase-3 cysteine-type endopeptidase activity. Caspase-3 cleaves the ATP11C phospholipid flippase for apoptotic PtdSer exposure. Reason: This is the core molecular function of caspase-3, repeatedly demonstrated experimentally on diverse substrates. Retained as a core function. Supporting Evidence: PMID:24904167 Caspase-mediated cleavage of phospholipid flippase for apoptotic phosphatidylserine exposure. |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:19240112 Huntingtin promotes cell survival by preventing Pak2 cleavag... | ACCEPT | Summary: Direct evidence of caspase-3 cysteine-type endopeptidase activity. Caspase-3 cleaves PAK2 (huntingtin modulates this). Reason: This is the core molecular function of caspase-3, repeatedly demonstrated experimentally on diverse substrates. Retained as a core function. Supporting Evidence: PMID:19240112 Huntingtin promotes cell survival by preventing Pak2 cleavage. |
| GO:0008233 peptidase activity | IDA PMID:17167422 Hsp70 regulates erythropoiesis by preventing caspase-3-media... | ACCEPT | Summary: Caspase-3 peptidase activity cleaves GATA-1 in erythroid precursors. Reason: Peptidase activity is correct (broad parent of cysteine-type endopeptidase activity); supported. Supporting Evidence: PMID:17167422 Hsp70 prevents active caspase-3 from cleaving GATA-1 and inducing apoptosis. |
| GO:0005515 protein binding | IPI PMID:15246877 S-nitrosation of thioredoxin in the nitrogen monoxide/supero... | MARK AS OVER ANNOTATED | Summary: This IPI captures a physical interaction (Thioredoxin/ASK1 S-nitrosation interaction context.) but the generic protein binding term is uninformative about caspase-3's molecular function. Reason: Bare protein binding (GO:0005515) does not describe a distinct caspase-3 molecular activity; the functionally meaningful interactions (substrate cleavage, inhibitor binding) are better represented by the endopeptidase activity and protease binding terms. Retained but flagged as uninformative. Supporting Evidence: PMID:15246877 S-nitrosation of thioredoxin in the nitrogen monoxide/superoxide system activates apoptosis signal-regulating kinase 1. |
| GO:0006508 proteolysis | IDA PMID:17553422 Depletion of GGA3 stabilizes BACE and enhances beta-secretas... | ACCEPT | Summary: Caspase-3 cleaves GGA3, stabilizing BACE and enhancing beta-secretase activity (proteolysis). Reason: Proteolysis is correct and consistent with the cysteine-type endopeptidase function; this substrate cleavage is a concrete instance. Kept consistent with the other proteolysis annotations. Supporting Evidence: PMID:17553422 Depletion of GGA3 stabilizes BACE and enhances beta-secretase activity. |
| GO:0031647 regulation of protein stability | IDA PMID:17553422 Depletion of GGA3 stabilizes BACE and enhances beta-secretas... | KEEP AS NON CORE | Summary: Caspase-3 cleavage of GGA3 alters BACE protein stability. Reason: Regulation of protein stability is a downstream consequence of substrate cleavage; non-core. Supporting Evidence: PMID:17553422 Depletion of GGA3 stabilizes BACE and enhances beta-secretase activity. |
| GO:1902004 positive regulation of amyloid-beta formation | IDA PMID:17553422 Depletion of GGA3 stabilizes BACE and enhances beta-secretas... | KEEP AS NON CORE | Summary: Caspase-3-mediated GGA3 cleavage increases BACE/beta-secretase activity, promoting amyloid-beta formation. Reason: A downstream, disease-context effect of substrate cleavage; genuine but non-core. Supporting Evidence: PMID:17553422 Depletion of GGA3 stabilizes BACE and enhances beta-secretase activity. |
| GO:0004197 cysteine-type endopeptidase activity | IMP PMID:21980415 Identification of a conserved anti-apoptotic protein that mo... | ACCEPT | Summary: Direct evidence of caspase-3 cysteine-type endopeptidase activity. Anti-apoptotic protein modulates mitochondrial caspase-3 activation. Reason: This is the core molecular function of caspase-3, repeatedly demonstrated experimentally on diverse substrates. Retained as a core function. Supporting Evidence: PMID:21980415 Identification of a conserved anti-apoptotic protein that modulates the mitochondrial apoptosis pathway. |
| GO:0006915 apoptotic process | IMP PMID:15565177 A novel mitochondrial protein DIP mediates E2F1-induced apop... | ACCEPT | Summary: Caspase-3 is activated and mediates apoptosis in the DIP/E2F1 pathway. Reason: Direct evidence of caspase-3 in the apoptotic process; core. Supporting Evidence: PMID:15565177 typical apoptotic features such as caspase-3 activation and cleavage of poly(ADP-ribose)-polymerase |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:16920334 Protective role of Cop in Rip2/caspase-1/caspase-4-mediated ... | ACCEPT | Summary: Direct evidence of caspase-3 cysteine-type endopeptidase activity. Caspase-3 activity in Rip2/caspase-1/-4-mediated cell death. Reason: This is the core molecular function of caspase-3, repeatedly demonstrated experimentally on diverse substrates. Retained as a core function. Supporting Evidence: PMID:16920334 Protective role of Cop in Rip2/caspase-1/caspase-4-mediated HeLa cell death. |
| GO:0008233 peptidase activity | IDA PMID:19740745 A truncated form of p23 down-regulates telomerase activity v... | ACCEPT | Summary: Caspase-3 peptidase activity generates a truncated p23 that down-regulates telomerase. Reason: Peptidase activity is correct (broad); supported by substrate cleavage evidence. Supporting Evidence: PMID:19740745 A truncated form of p23 down-regulates telomerase activity via disruption of Hsp90 function. |
| GO:0004197 cysteine-type endopeptidase activity | IMP PMID:22253444 Apoptotic DNA degradation into oligonucleosomal fragments, b... | ACCEPT | Summary: Direct evidence of caspase-3 cysteine-type endopeptidase activity. Caspase-3 cleaves ICAD/CAD to enable apoptotic DNA fragmentation. Reason: This is the core molecular function of caspase-3, repeatedly demonstrated experimentally on diverse substrates. Retained as a core function. Supporting Evidence: PMID:22253444 Apoptotic DNA degradation into oligonucleosomal fragments, but not apoptotic nuclear morphology, relies on a cytosolic pool of DFF40/CAD endonuclease. |
| GO:0005829 cytosol | IDA PMID:22253444 Apoptotic DNA degradation into oligonucleosomal fragments, b... | ACCEPT | Summary: Caspase-3 is processed and active in the cytosol (where it cleaves ICAD/CAD). Reason: Cytosol is the core location of caspase-3 activity; directly supported. Supporting Evidence: PMID:22253444 the main processing of pro-caspase-3 takes place in the cytosol of both cells lines analyzed |
| GO:0072734 cellular response to staurosporine | IMP PMID:22253444 Apoptotic DNA degradation into oligonucleosomal fragments, b... | KEEP AS NON CORE | Summary: Caspase-3 is activated in response to staurosporine, cleaving ICAD to enable DNA fragmentation. Reason: A stimulus/response context (intrinsic apoptosis trigger); caspase-3 acts as executioner. Non-core. Supporting Evidence: PMID:22253444 the activation of, at least, caspase-3 is necessary for the proper cleavage of ICAD L/S |
| GO:0016241 regulation of macroautophagy | TAS PMID:19549685 Caspase cleavage of Atg4D stimulates GABARAP-L1 processing a... | KEEP AS NON CORE | Summary: Caspase cleavage of Atg4D stimulates GABARAP-L1 processing, linking caspase-3 to autophagy regulation. Reason: Regulation of macroautophagy is a downstream cross-talk role (TAS) via substrate cleavage; non-core. Supporting Evidence: PMID:19549685 Caspase cleavage of Atg4D stimulates GABARAP-L1 processing and triggers mitochondrial targeting and apoptosis. |
| GO:0048011 neurotrophin TRK receptor signaling pathway | IDA PMID:23954828 Dok5 is involved in the signaling pathway of neurotrophin-3 ... | KEEP AS NON CORE | Summary: Caspase-3 acts within neurotrophin/TrkC (Dok5) signaling, where TrkC can trigger apoptosis. Reason: A signaling-pathway context where caspase-3 acts downstream; non-core relative to the core protease/apoptosis function. Supporting Evidence: PMID:23954828 Dok5 is involved in the signaling pathway of neurotrophin-3 against TrkC-induced apoptosis. |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:23729654 The human papillomavirus-16 E7 oncoprotein exerts antiapopto... | ACCEPT | Summary: Direct evidence of caspase-3 cysteine-type endopeptidase activity. HPV-16 E7/gelsolin context modulating caspase-3 activity. Reason: This is the core molecular function of caspase-3, repeatedly demonstrated experimentally on diverse substrates. Retained as a core function. Supporting Evidence: PMID:23729654 The human papillomavirus-16 E7 oncoprotein exerts antiapoptotic effects via its physical interaction with the actin-binding protein gelsolin. |
| GO:0004197 cysteine-type endopeptidase activity | IMP PMID:10921886 The RET proto-oncogene induces apoptosis: a novel mechanism ... | ACCEPT | Summary: Direct evidence of caspase-3 cysteine-type endopeptidase activity. RET proto-oncogene-induced apoptosis is caspase-3-dependent. Reason: This is the core molecular function of caspase-3, repeatedly demonstrated experimentally on diverse substrates. Retained as a core function. Supporting Evidence: PMID:10921886 The RET proto-oncogene induces apoptosis: a novel mechanism for Hirschsprung disease. |
| GO:0030218 erythrocyte differentiation | IDA PMID:17167422 Hsp70 regulates erythropoiesis by preventing caspase-3-media... | KEEP AS NON CORE | Summary: Caspase-3 is activated during terminal erythroid differentiation; GATA-1 is protected from cleavage by Hsp70. Reason: A genuine non-apoptotic role in erythropoiesis, but downstream of the core protease function. Non-core. Supporting Evidence: PMID:17167422 Caspase-3 is activated during both terminal differentiation and erythropoietin-starvation-induced apoptosis of human erythroid precursors. |
| GO:0030218 erythrocyte differentiation | TAS PMID:18309324 No death without life: vital functions of apoptotic effector... | KEEP AS NON CORE | Summary: Effector caspases including caspase-3 have vital (non-death) functions in erythroid differentiation. Reason: Non-apoptotic differentiation role (TAS review); genuine but non-core. Supporting Evidence: PMID:18309324 No death without life: vital functions of apoptotic effectors. |
| GO:0030220 platelet formation | TAS PMID:18309324 No death without life: vital functions of apoptotic effector... | KEEP AS NON CORE | Summary: Caspase-3 contributes to platelet formation (a non-apoptotic effector-caspase function). Reason: A genuine non-apoptotic tissue role (TAS review); non-core. Supporting Evidence: PMID:18309324 No death without life: vital functions of apoptotic effectors. |
| GO:0097194 execution phase of apoptosis | IMP PMID:11350920 Deficiency of caspase-3 in MCF7 cells blocks Bax-mediated nu... | ACCEPT | Summary: Caspase-3 is required for Bax-mediated nuclear fragmentation in the execution phase (MCF7 deficiency). Reason: Direct functional (IMP) evidence for caspase-3's execution-phase role in nuclear demolition. Supporting Evidence: PMID:11350920 Deficiency of caspase-3 in MCF7 cells blocks Bax-mediated nuclear fragmentation but not cell death. |
| GO:0004197 cysteine-type endopeptidase activity | IMP PMID:17559062 The most widespread desmosomal cadherin, desmoglein 2, is a ... | ACCEPT | Summary: Direct evidence of caspase-3 cysteine-type endopeptidase activity. Caspase-3 cleaves desmoglein-2 (DSG2) and JUP at desmosomes. Reason: This is the core molecular function of caspase-3, repeatedly demonstrated experimentally on diverse substrates. Retained as a core function. Supporting Evidence: PMID:17559062 The most widespread desmosomal cadherin, desmoglein 2, is a novel target of caspase 3-mediated apoptotic machinery. |
| GO:0097194 execution phase of apoptosis | IDA PMID:8689682 Induction of apoptotic program in cell-free extracts: requir... | ACCEPT | Summary: In cell-free extracts, cytochrome c/dATP triggers the apoptotic program that activates executioner caspase-3. Reason: Classic evidence placing caspase-3 in the execution phase downstream of cytochrome c/apoptosome. Supporting Evidence: PMID:8689682 Cells undergoing apoptosis in vivo showed increased release of cytochrome c to their cytosol, suggesting that mitochondria may function in apoptosis by releasing cytochrome c. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-211186 | KEEP AS NON CORE | Summary: Reactome places caspase-3 in the nucleoplasm for nuclear substrate cleavage (e.g., DFF45/ICAD), consistent with active caspase-3 translocating to the nucleus during apoptosis. Reason: Nuclear/nucleoplasm localization of active caspase-3 is supported but secondary to its core cytoplasmic site; retained as non-core location context for nuclear substrate cleavage. Supporting Evidence: PMID:16374543 the activation of nuclear caspases-7 and -3, and poly(ADP-ribose) polymerase (PARP) cleavage, are early events in camptothecin-induced apoptosis |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-211190 | KEEP AS NON CORE | Summary: Reactome places caspase-3 in the nucleoplasm for nuclear substrate cleavage (e.g., DFF45/ICAD), consistent with active caspase-3 translocating to the nucleus during apoptosis. Reason: Nuclear/nucleoplasm localization of active caspase-3 is supported but secondary to its core cytoplasmic site; retained as non-core location context for nuclear substrate cleavage. Supporting Evidence: PMID:16374543 the activation of nuclear caspases-7 and -3, and poly(ADP-ribose) polymerase (PARP) cleavage, are early events in camptothecin-induced apoptosis |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-211219 | KEEP AS NON CORE | Summary: Reactome places caspase-3 in the nucleoplasm for nuclear substrate cleavage (e.g., DFF45/ICAD), consistent with active caspase-3 translocating to the nucleus during apoptosis. Reason: Nuclear/nucleoplasm localization of active caspase-3 is supported but secondary to its core cytoplasmic site; retained as non-core location context for nuclear substrate cleavage. Supporting Evidence: PMID:16374543 the activation of nuclear caspases-7 and -3, and poly(ADP-ribose) polymerase (PARP) cleavage, are early events in camptothecin-induced apoptosis |
| GO:0005829 cytosol | TAS Reactome:R-HSA-114252 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-201595 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-201603 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-201608 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-201611 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-201622 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-201628 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-201629 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-201630 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-201631 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-201636 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-201639 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-201640 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2028692 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2028697 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202917 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202939 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202947 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202960 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202966 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202967 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-202969 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-205117 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-211219 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-212552 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-350651 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-351849 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-351871 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-351876 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-351877 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-351901 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-351913 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-373705 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-418845 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-449073 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9627104 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9647632 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9686088 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005829 cytosol | TAS Reactome:R-NUL-211643 | ACCEPT | Summary: Reactome places caspase-3 (and its substrate-cleavage reactions) in the cytosol, the principal compartment of caspase-3 activity. Reason: Cytosol is the core, well-supported location of caspase-3. These Reactome rows are substrate-cleavage reaction contexts; the cytosolic cellular component is correct. Supporting Evidence: file:human/CASP3/CASP3-uniprot.txt SUBCELLULAR LOCATION; Cytoplasm |
| GO:0005515 protein binding | IPI PMID:9208847 Casper is a FADD- and caspase-related inducer of apoptosis. | MARK AS OVER ANNOTATED | Summary: This IPI captures a physical interaction (Casper/c-FLIP FADD- and caspase-related interaction.) but the generic protein binding term is uninformative about caspase-3's molecular function. Reason: Bare protein binding (GO:0005515) does not describe a distinct caspase-3 molecular activity; the functionally meaningful interactions (substrate cleavage, inhibitor binding) are better represented by the endopeptidase activity and protease binding terms. Retained but flagged as uninformative. Supporting Evidence: PMID:9208847 Casper is a FADD- and caspase-related inducer of apoptosis. |
| GO:0005634 nucleus | IDA PMID:17167422 Hsp70 regulates erythropoiesis by preventing caspase-3-media... | KEEP AS NON CORE | Summary: Active caspase-3 is present in the nucleus of erythroid precursors where it can cleave GATA-1. Reason: Nuclear localization of active caspase-3 is supported but secondary to its core cytoplasmic site; non-core. Supporting Evidence: PMID:17167422 Hsp70 co-localizes and interacts with GATA-1 in the nucleus of erythroid precursors undergoing terminal differentiation. |
| GO:0005829 cytosol | IDA PMID:17167422 Hsp70 regulates erythropoiesis by preventing caspase-3-media... | ACCEPT | Summary: Caspase-3 acts in the cytosol of erythroid precursors. Reason: Cytosol is the core site of caspase-3 activity; supported. Supporting Evidence: PMID:17167422 Caspase-3 is activated during both terminal differentiation and erythropoietin-starvation-induced apoptosis of human erythroid precursors. |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:21726810 Caspase-2-mediated cleavage of Mdm2 creates a p53-induced po... | ACCEPT | Summary: Direct evidence of caspase-3 cysteine-type endopeptidase activity. Caspase-3 cleavage activity in the MDM2/p53 feedback context. Reason: This is the core molecular function of caspase-3, repeatedly demonstrated experimentally on diverse substrates. Retained as a core function. Supporting Evidence: PMID:21726810 Caspase-2-mediated cleavage of Mdm2 creates a p53-induced positive feedback loop. |
| GO:0034612 response to tumor necrosis factor | TAS PMID:10521396 Cleavage of the death domain kinase RIP by caspase-8 prompts... | KEEP AS NON CORE | Summary: Caspase-3 acts downstream of TNF-induced apoptosis (RIP cleavage by caspase-8). Reason: Response to TNF is a stimulus/response signaling context; caspase-3 is the executioner downstream. Non-core. Supporting Evidence: PMID:10521396 Cleavage of the death domain kinase RIP by caspase-8 prompts TNF-induced apoptosis. |
| GO:0097190 apoptotic signaling pathway | TAS PMID:10521396 Cleavage of the death domain kinase RIP by caspase-8 prompts... | ACCEPT | Summary: Caspase-3 acts within the apoptotic signaling pathway (TNF/death-receptor-induced apoptosis). Reason: Apoptotic signaling pathway is a valid process for caspase-3 as the executioner; supported. Supporting Evidence: PMID:10521396 Cleavage of the death domain kinase RIP by caspase-8 prompts TNF-induced apoptosis. |
| GO:0008233 peptidase activity | IDA PMID:9353287 Generation of anti-apoptotic presenilin-2 polypeptides by al... | ACCEPT | Summary: Caspase-3 peptidase activity cleaves presenilin-2 generating anti-apoptotic polypeptides. Reason: Peptidase activity is correct (broad); supported by substrate cleavage evidence. Supporting Evidence: PMID:9353287 Generation of anti-apoptotic presenilin-2 polypeptides by alternative transcription, proteolysis, and caspase-3 cleavage. |
| GO:0005515 protein binding | IPI PMID:17823127 Cytosolic accumulation of HSP60 during apoptosis with or wit... | MARK AS OVER ANNOTATED | Summary: This IPI captures a physical interaction (HSP60 interaction modulating pro/anti-apoptotic functions.) but the generic protein binding term is uninformative about caspase-3's molecular function. Reason: Bare protein binding (GO:0005515) does not describe a distinct caspase-3 molecular activity; the functionally meaningful interactions (substrate cleavage, inhibitor binding) are better represented by the endopeptidase activity and protease binding terms. Retained but flagged as uninformative. Supporting Evidence: PMID:17823127 Cytosolic accumulation of HSP60 during apoptosis with or without apparent mitochondrial release: evidence that its pro-apoptotic or pro-survival functions involve differential interactions with caspase-3. |
| GO:0005829 cytosol | IDA PMID:17823127 Cytosolic accumulation of HSP60 during apoptosis with or wit... | ACCEPT | Summary: Caspase-3 is present in the cytosol, where cytosolic HSP60 modulates its activity during apoptosis. Reason: Cytosol is the core location of caspase-3; directly supported. Supporting Evidence: PMID:17823127 Cytosolic accumulation of HSP60 during apoptosis with or without apparent mitochondrial release |
| GO:0006508 proteolysis | IDA PMID:12888622 Caspase cleavage of tau: linking amyloid and neurofibrillary... | ACCEPT | Summary: Caspase-3 cleaves tau, linking amyloid and neurofibrillary tangles (proteolysis). Reason: Proteolysis is correct and consistent with the cysteine-type endopeptidase function; this substrate cleavage is a concrete instance. Kept consistent with the other proteolysis annotations. Supporting Evidence: PMID:12888622 Caspase cleavage of tau: linking amyloid and neurofibrillary tangles in Alzheimer's disease. |
| GO:0005515 protein binding | IPI PMID:9736630 Tau cleavage and dephosphorylation in cerebellar granule neu... | MARK AS OVER ANNOTATED | Summary: This IPI captures a physical interaction (Tau cleavage interaction in apoptotic neurons.) but the generic protein binding term is uninformative about caspase-3's molecular function. Reason: Bare protein binding (GO:0005515) does not describe a distinct caspase-3 molecular activity; the functionally meaningful interactions (substrate cleavage, inhibitor binding) are better represented by the endopeptidase activity and protease binding terms. Retained but flagged as uninformative. Supporting Evidence: PMID:9736630 Tau cleavage and dephosphorylation in cerebellar granule neurons undergoing apoptosis. |
| GO:0004197 cysteine-type endopeptidase activity | TAS PMID:10942389 HIV-1 gp120- and gp160-induced apoptosis in cultured endothe... | ACCEPT | Summary: Direct evidence of caspase-3 cysteine-type endopeptidase activity. HIV-1 gp120/gp160-induced endothelial apoptosis mediated by caspases including caspase-3. Reason: This is the core molecular function of caspase-3, repeatedly demonstrated experimentally on diverse substrates. Retained as a core function. Supporting Evidence: PMID:10942389 HIV-1 gp120- and gp160-induced apoptosis in cultured endothelial cells is mediated by caspases. |
| GO:0006915 apoptotic process | TAS PMID:7983002 CPP32, a novel human apoptotic protein with homology to Caen... | ACCEPT | Summary: CPP32 (caspase-3) is an apoptotic protein homologous to CED-3/ICE (original cloning, TAS). Reason: Foundational evidence for caspase-3's role in the apoptotic process; core. Supporting Evidence: PMID:7983002 CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme. |
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Download this section (compressed HTML)Q: To what extent are caspase-3 non-apoptotic roles (erythroid/keratinocyte differentiation, synapse pruning, platelet formation) driven by spatially or temporally restricted sublethal caspase-3 activity, and can substrate repertoires be defined that distinguish lethal from non-lethal activation?
Suggested experts: Salvesen GS, Martin SJ
Q: Which GO_REF:0000107 ortholog-transferred stimulus/response and tissue terms on CASP3 represent genuine direct roles versus over-propagation across the caspase family, and should questionable molecular-function transfers (aspartic-type endopeptidase, CDK inhibitor, phospholipase A2 activator) be removed upstream?
Suggested experts: Thornberry NA
Experiment: Perform N-terminomics (e.g., TAILS/subtiligase) on cells undergoing caspase-3-dependent differentiation versus apoptosis, with caspase-3 knockout and caspase-resistant substrate mutants as controls, to map the differentiation-specific cleavage repertoire.
Hypothesis: Caspase-3 substrate cleavage during sublethal/non-apoptotic activation produces a distinct proteome from that during full apoptosis, explaining its differentiation roles.
Type: degradomics / N-terminomics
Experiment: Titrate GSDME expression and caspase-3 activation kinetics in isogenic cell lines (including non-cleavable GSDME D270A) and quantify apoptosis versus pyroptosis outcomes and IL-1 beta release.
Hypothesis: The balance between caspase-3-driven apoptosis and GSDME-driven pyroptosis is set by GSDME abundance and caspase-3 activity kinetics.
Type: cell death pathway dissection
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