Casp3

Summary: cytoplasm is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: apoptotic process is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: cysteine-type endopeptidase activity is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: proteolysis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: DISC membership traces to an experimental annotation on the rat ortholog, so it is retained as a context-specific, non-core localization.

Reason: The sole IBD seed at PANTHER node PTN002573018 is RGD:2275, the rat caspase-3 record (P55213, corroborated through its UniProt cross-reference), which carries its own IDA to this term from PMID:17518537. That cached publication states that after spinal cord injury Fas associates with FADD, caspase-8, cFLIP-long and caspase-3 to form a DISC, so the source is an experimental annotation on the direct ortholog rather than a paralog or family overreach, and there is no mouse evidence of loss. Removing it would overrule a curated experimental annotation on the orthologous gene on textbook grounds alone. Retained as non-core: the association is injury- and context-specific and is not part of the core effector-protease function.

Summary: execution phase of apoptosis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: enzyme activator activity likely overstates a direct role for Casp3 relative to the curated effector-caspase evidence.

Reason: The evidence supports Casp3 as a protease whose substrate cleavage can have downstream effects; this term is too broad or indirect for a direct/core annotation.

Summary: positive regulation of neuron apoptotic process reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: neuron differentiation reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: keratinocyte differentiation reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: erythrocyte differentiation reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: aspartic-type endopeptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.

Reason: Casp3 is a cysteine-type effector caspase with cleavage specificity after Asp residues, not an aspartic protease; the specific cysteine-type endopeptidase term is more accurate.

Proposed replacements: cysteine-type endopeptidase activity

Summary: cysteine-type endopeptidase activity is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: cytoplasm is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: proteolysis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: Cysteine-type peptidase activity is correct but under-specific for Casp3.

Reason: Use GO:0004197 cysteine-type endopeptidase activity, which better captures executioner caspase-3 proteolytic activity.

Proposed replacements: cysteine-type endopeptidase activity

Summary: Response to UV is not supported as a positive Casp3 annotation in the reviewed evidence.

Reason: The directly cited UV/DNA-damage neural precursor study (PMID:11092819) reports dependence on p53 and caspase 9 but not caspase 3, which is visible in the cached abstract and is sufficient ground for this electronic row. Scoped to this row only: the IGI row on this term rests on a different paper (PMID:16469926) that is cached abstract-only and is therefore UNDECIDED rather than removed, so nothing here should be read as a verdict on it.

Summary: Neuron apoptotic process is a valid developmental or neuronal context for Casp3, but not its core molecular function.

Reason: Casp3 core function is cysteine-type endopeptidase executioner caspase activity; neuron apoptosis is a context-specific process output.

Summary: protein binding is not a supported direct annotation for Casp3 in this review.

Reason: The term conflicts with, or is too far removed from, the direct effector-caspase role. Generic protein-binding/signaling terms and incorrect molecular functions should not be retained for Casp3.

Summary: protein binding is not a supported direct annotation for Casp3 in this review.

Reason: The term conflicts with, or is too far removed from, the direct effector-caspase role. Generic protein-binding/signaling terms and incorrect molecular functions should not be retained for Casp3.

Summary: protein binding is not a supported direct annotation for Casp3 in this review.

Reason: The term conflicts with, or is too far removed from, the direct effector-caspase role. Generic protein-binding/signaling terms and incorrect molecular functions should not be retained for Casp3.

Summary: luteolysis is likely an over-annotation for Casp3 without term-specific evidence in the review materials.

Reason: Casp3 core biology is executioner cysteine endopeptidase activity in apoptosis; this broad stimulus/physiology term lacks direct term-specific support and should not be retained as a confident non-core assertion.

Summary: response to hypoxia is likely an over-annotation for Casp3 without term-specific evidence in the review materials.

Reason: Casp3 core biology is executioner cysteine endopeptidase activity in apoptosis; this broad stimulus/physiology term lacks direct term-specific support and should not be retained as a confident non-core assertion.

Summary: negative regulation of cytokine production reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: protease binding is not a supported direct annotation for Casp3 in this review.

Reason: The term conflicts with, or is too far removed from, the direct effector-caspase role. Generic protein-binding/signaling terms and incorrect molecular functions should not be retained for Casp3.

Summary: death receptor binding is not a supported direct annotation for Casp3 in this review.

Reason: The term conflicts with, or is too far removed from, the direct effector-caspase role. Generic protein-binding/signaling terms and incorrect molecular functions should not be retained for Casp3.

Summary: nucleus reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: cytosol is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: apoptotic process is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: axonal fasciculation reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: learning or memory reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: peptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.

Reason: Casp3 is a cysteine-type effector caspase with cleavage specificity after Asp residues, not an aspartic protease; the specific cysteine-type endopeptidase term is more accurate.

Proposed replacements: cysteine-type endopeptidase activity

Summary: response to xenobiotic stimulus is likely an over-annotation for Casp3 without term-specific evidence in the review materials.

Reason: Casp3 core biology is executioner cysteine endopeptidase activity in apoptosis; this broad stimulus/physiology term lacks direct term-specific support and should not be retained as a confident non-core assertion.

Summary: response to glucose is likely an over-annotation for Casp3 without term-specific evidence in the review materials.

Reason: Casp3 core biology is executioner cysteine endopeptidase activity in apoptosis; this broad stimulus/physiology term lacks direct term-specific support and should not be retained as a confident non-core assertion.

Summary: response to metal ion is likely an over-annotation for Casp3 without term-specific evidence in the review materials.

Reason: Casp3 core biology is executioner cysteine endopeptidase activity in apoptosis; this broad stimulus/physiology term lacks direct term-specific support and should not be retained as a confident non-core assertion.

Summary: response to X-ray is likely an over-annotation for Casp3 without term-specific evidence in the review materials.

Reason: Casp3 core biology is executioner cysteine endopeptidase activity in apoptosis; this broad stimulus/physiology term lacks direct term-specific support and should not be retained as a confident non-core assertion.

Summary: phospholipase A2 activator activity is not a molecular function Casp3 enables; the cited evidence places it upstream of phospholipase A2 activation in a pathway, which is not the same as being that enzyme's activator.

Reason: GO:0016005 is phospholipase A2 activator activity, an enables molecular-function term, and Casp3 is a cysteine-type endopeptidase. Two grounds, and only the second touches the paper. Molecular identity: a protease is not an enzyme activator - the argument that keeps GO:0004861 at REMOVE, about Casp3 itself, needing no full text. And what the transfer rests on: PMID:12492473 is cached abstract-only, and that abstract establishes inhibitor epistasis, "experiments with Ac-DEVD-CMK (caspase-3 specific inhibitor) have led us to conclude that caspase-3 is downstream of ceramide in activating the brain plasmalogen-selective phospholipase A2" - placing Casp3 upstream of PLA2 activation in a ceramide pathway. Indirect pathway participation typed as a direct enables MF is the fault, and it is why the term is withdrawn rather than kept as non-core. An earlier revision of this reason said the paper records Casp3 proteolytically cleaving iPLA2; it records neither - the cached text contains no cleavage assay, and names the enzyme a plasmalogen-selective phospholipase A2. Retracted here because asserting what an abstract-only paper contains is the error this review converted 48 rows to UNDECIDED over. This row reaches Casp3 by an electronic ortholog mapping from UniProtKB:P55213, the same rat record behind the GO:0031264 rows retained as non-core; there the donor evidence is a part_of cellular_component IDA - a location Casp3 occupies - whereas this is an enables molecular_function claim it does not support.

Summary: protein processing reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: hippocampus development reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: protein catabolic process likely overstates a direct role for Casp3 relative to the curated effector-caspase evidence.

Reason: The evidence supports Casp3 as a protease whose substrate cleavage can have downstream effects; this term is too broad or indirect for a direct/core annotation.

Summary: neuron differentiation reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: erythrocyte differentiation reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: Retained as non-core on the same grounds as the IBA GO_REF:0000033 row on this term, which this review kept because the transfer's donor carries its own experimental annotation. Caspase-3's DISC association is contextual rather than absent.

Reason: Downgraded from REMOVE for consistency with the IBA row on this same term. All three GO:0031264 rows trace to one donor: this row's WITH/FROM is UniProtKB:P55213|ensembl:ENSRNOP00000014096, and rat Casp3 carries part_of GO:0031264 with ECO:0000314 IDA from PMID:17518537 (P55213 = Caspase-3, Rattus norvegicus, in PTHR10454-entries.csv). So the ground for keeping the IBA row - that removing would overrule a curated ortholog annotation - applies verbatim here. The previous shared reason offered a disjunction, "conflicts with, or is too far removed from, the direct effector-caspase role"; the disjunct that fits is the second, and being too far removed from the core role is what KEEP_AS_NON_CORE encodes rather than an argument for removal. Casp3 is an effector caspase acting downstream of DISC assembly, so the term is a genuine but peripheral location for it, reached here by an electronic ortholog mapping.

Summary: regulation of protein stability is not a supported direct annotation for Casp3 in this review.

Reason: The term conflicts with, or is too far removed from, the direct effector-caspase role. Generic protein-binding/signaling terms and incorrect molecular functions should not be retained for Casp3.

Summary: response to cobalt ion is likely an over-annotation for Casp3 without term-specific evidence in the review materials.

Reason: Casp3 core biology is executioner cysteine endopeptidase activity in apoptosis; this broad stimulus-response term lacks direct term-specific support and should not be retained as a confident non-core assertion.

Summary: response to estradiol is likely an over-annotation for Casp3 without term-specific evidence in the review materials.

Reason: Casp3 core biology is executioner cysteine endopeptidase activity in apoptosis; this broad stimulus-response term lacks direct term-specific support and should not be retained as a confident non-core assertion.

Summary: response to lipopolysaccharide is likely an over-annotation for Casp3 without term-specific evidence in the review materials.

Reason: Casp3 core biology is executioner cysteine endopeptidase activity in apoptosis; this broad stimulus-response term lacks direct term-specific support and should not be retained as a confident non-core assertion.

Summary: regulation of protein localization reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: glial cell apoptotic process reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: response to nicotine is likely an over-annotation for Casp3 without term-specific evidence in the review materials.

Reason: Casp3 core biology is executioner cysteine endopeptidase activity in apoptosis; this broad stimulus/physiology term lacks direct term-specific support and should not be retained as a confident non-core assertion.

Summary: intracellular signal transduction is not a supported direct annotation for Casp3 in this review.

Reason: The term conflicts with, or is too far removed from, the direct effector-caspase role. Generic protein-binding/signaling terms and incorrect molecular functions should not be retained for Casp3.

Summary: swimming behavior reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: response to hydrogen peroxide is likely an over-annotation for Casp3 without term-specific evidence in the review materials.

Reason: Casp3 core biology is executioner cysteine endopeptidase activity in apoptosis; this broad stimulus-response term lacks direct term-specific support and should not be retained as a confident non-core assertion.

Summary: neuronal cell body reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: positive regulation of apoptotic process reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: response to amino acid is likely an over-annotation for Casp3 without term-specific evidence in the review materials.

Reason: Casp3 core biology is executioner cysteine endopeptidase activity in apoptosis; this broad stimulus-response term lacks direct term-specific support and should not be retained as a confident non-core assertion.

Summary: regulation of neuron apoptotic process reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: positive regulation of neuron apoptotic process reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: protein-containing complex binding is not a supported direct annotation for Casp3 in this review.

Reason: The term conflicts with, or is too far removed from, the direct effector-caspase role. Generic protein-binding/signaling terms and incorrect molecular functions should not be retained for Casp3.

Summary: response to ethanol is likely an over-annotation for Casp3 without term-specific evidence in the review materials.

Reason: Casp3 core biology is executioner cysteine endopeptidase activity in apoptosis; this broad stimulus-response term lacks direct term-specific support and should not be retained as a confident non-core assertion.

Summary: striated muscle cell differentiation reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: response to glucocorticoid is likely an over-annotation for Casp3 without term-specific evidence in the review materials.

Reason: Casp3 core biology is executioner cysteine endopeptidase activity in apoptosis; this broad stimulus-response term lacks direct term-specific support and should not be retained as a confident non-core assertion.

Summary: protein maturation reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: pyroptotic inflammatory response reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: leukocyte apoptotic process reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: response to anesthetic is likely an over-annotation for Casp3 without term-specific evidence in the review materials.

Reason: Casp3 core biology is executioner cysteine endopeptidase activity in apoptosis; this broad stimulus/physiology term lacks direct term-specific support and should not be retained as a confident non-core assertion.

Summary: cellular response to staurosporine is likely an over-annotation for Casp3 without term-specific evidence in the review materials.

Reason: Casp3 core biology is executioner cysteine endopeptidase activity in apoptosis; this broad stimulus-response term lacks direct term-specific support and should not be retained as a confident non-core assertion.

Summary: intrinsic apoptotic signaling pathway reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: execution phase of apoptosis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: positive regulation of pyroptotic inflammatory response reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: positive regulation of amyloid-beta formation likely overstates a direct role for Casp3 relative to the curated effector-caspase evidence.

Reason: The evidence supports Casp3 as a protease whose substrate cleavage can have downstream effects; this term is too broad or indirect for a direct/core annotation.

Summary: response to insulin-like growth factor stimulus is likely an over-annotation for Casp3 without term-specific evidence in the review materials.

Reason: Casp3 core biology is executioner cysteine endopeptidase activity in apoptosis; this broad stimulus/physiology term lacks direct term-specific support and should not be retained as a confident non-core assertion.

Summary: Retained as non-core on the same grounds as the IBA GO_REF:0000033 row on this term, which this review kept because the transfer's donor carries its own experimental annotation. Caspase-3's DISC association is contextual rather than absent.

Reason: Downgraded from REMOVE for consistency with the IBA row on this same term. All three GO:0031264 rows trace to one donor: this row's WITH/FROM is RGD:2275, the rat caspase-3 record itself, and rat Casp3 carries part_of GO:0031264 with ECO:0000314 IDA from PMID:17518537 (P55213 = Caspase-3, Rattus norvegicus, in PTHR10454-entries.csv). So the ground for keeping the IBA row - that removing would overrule a curated ortholog annotation - applies verbatim here. The previous shared reason offered a disjunction, "conflicts with, or is too far removed from, the direct effector-caspase role"; the disjunct that fits is the second, and being too far removed from the core role is what KEEP_AS_NON_CORE encodes rather than an argument for removal. Casp3 is an effector caspase acting downstream of DISC assembly, so the term is a genuine but peripheral location for it, reached here by pairwise ortholog transfer.

Summary: caspase complex is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: positive regulation of apoptotic process reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: positive regulation of apoptotic DNA fragmentation is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: synapse pruning reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: cytosol is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: negative regulation of cytokine production reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: protease binding is not a supported direct annotation for Casp3 in this review.

Reason: The term conflicts with, or is too far removed from, the direct effector-caspase role. Generic protein-binding/signaling terms and incorrect molecular functions should not be retained for Casp3.

Summary: cysteine-type endopeptidase activity is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: death receptor binding is not a supported direct annotation for Casp3 in this review.

Reason: The term conflicts with, or is too far removed from, the direct effector-caspase role. Generic protein-binding/signaling terms and incorrect molecular functions should not be retained for Casp3.

Summary: nucleus reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: cytoplasm is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: cytoplasm is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: proteolysis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: proteolysis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: apoptotic process is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: axonal fasciculation reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: learning or memory reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: peptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.

Reason: Casp3 is a cysteine-type effector caspase with cleavage specificity after Asp residues, not an aspartic protease; the specific cysteine-type endopeptidase term is more accurate.

Proposed replacements: cysteine-type endopeptidase activity

Summary: Cysteine-type peptidase activity is correct but under-specific for Casp3.

Reason: Use GO:0004197 cysteine-type endopeptidase activity, which better captures executioner caspase-3 proteolytic activity.

Proposed replacements: cysteine-type endopeptidase activity

Summary: response to glucose is likely an over-annotation for Casp3 without term-specific evidence in the review materials.

Reason: Casp3 core biology is executioner cysteine endopeptidase activity in apoptosis; this broad stimulus/physiology term lacks direct term-specific support and should not be retained as a confident non-core assertion.

Summary: phospholipase A2 activator activity is not a molecular function Casp3 enables; the cited evidence places it upstream of phospholipase A2 activation in a pathway, which is not the same as being that enzyme's activator.

Reason: GO:0016005 is phospholipase A2 activator activity, an enables molecular-function term, and Casp3 is a cysteine-type endopeptidase. Two grounds, and only the second touches the paper. Molecular identity: a protease is not an enzyme activator - the argument that keeps GO:0004861 at REMOVE, about Casp3 itself, needing no full text. And what the transfer rests on: PMID:12492473 is cached abstract-only, and that abstract establishes inhibitor epistasis, "experiments with Ac-DEVD-CMK (caspase-3 specific inhibitor) have led us to conclude that caspase-3 is downstream of ceramide in activating the brain plasmalogen-selective phospholipase A2" - placing Casp3 upstream of PLA2 activation in a ceramide pathway. Indirect pathway participation typed as a direct enables MF is the fault, and it is why the term is withdrawn rather than kept as non-core. An earlier revision of this reason said the paper records Casp3 proteolytically cleaving iPLA2; it records neither - the cached text contains no cleavage assay, and names the enzyme a plasmalogen-selective phospholipase A2. Retracted here because asserting what an abstract-only paper contains is the error this review converted 48 rows to UNDECIDED over. This row reaches Casp3 by pairwise ortholog transfer from RGD:2275, the same rat record behind the GO:0031264 rows retained as non-core; there the donor evidence is a part_of cellular_component IDA - a location Casp3 occupies - whereas this is an enables molecular_function claim it does not support.

Summary: protein processing reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: protein catabolic process likely overstates a direct role for Casp3 relative to the curated effector-caspase evidence.

Reason: The evidence supports Casp3 as a protease whose substrate cleavage can have downstream effects; this term is too broad or indirect for a direct/core annotation.

Summary: protein catabolic process likely overstates a direct role for Casp3 relative to the curated effector-caspase evidence.

Reason: The evidence supports Casp3 as a protease whose substrate cleavage can have downstream effects; this term is too broad or indirect for a direct/core annotation.

Summary: erythrocyte differentiation reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: regulation of protein stability is not a supported direct annotation for Casp3 in this review.

Reason: The term conflicts with, or is too far removed from, the direct effector-caspase role. Generic protein-binding/signaling terms and incorrect molecular functions should not be retained for Casp3.

Summary: regulation of protein stability is not a supported direct annotation for Casp3 in this review.

Reason: The term conflicts with, or is too far removed from, the direct effector-caspase role. Generic protein-binding/signaling terms and incorrect molecular functions should not be retained for Casp3.

Summary: intracellular signal transduction is not a supported direct annotation for Casp3 in this review.

Reason: The term conflicts with, or is too far removed from, the direct effector-caspase role. Generic protein-binding/signaling terms and incorrect molecular functions should not be retained for Casp3.

Summary: interleukin-18-mediated signaling pathway is not a supported direct annotation for Casp3 in this review.

Reason: The term conflicts with, or is too far removed from, the direct effector-caspase role. Generic protein-binding/signaling terms and incorrect molecular functions should not be retained for Casp3.

Summary: response to hydrogen peroxide is likely an over-annotation for Casp3 without term-specific evidence in the review materials.

Reason: Casp3 core biology is executioner cysteine endopeptidase activity in apoptosis; this broad stimulus-response term lacks direct term-specific support and should not be retained as a confident non-core assertion.

Summary: neuronal cell body reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: positive regulation of apoptotic process reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: positive regulation of neuron apoptotic process reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: protein-containing complex binding is not a supported direct annotation for Casp3 in this review.

Reason: The term conflicts with, or is too far removed from, the direct effector-caspase role. Generic protein-binding/signaling terms and incorrect molecular functions should not be retained for Casp3.

Summary: protein maturation reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: protein poly-ADP-ribosylation is not a supported direct annotation for Casp3 in this review.

Reason: The term conflicts with, or is too far removed from, the direct effector-caspase role. Generic protein-binding/signaling terms and incorrect molecular functions should not be retained for Casp3.

Summary: pyroptotic inflammatory response reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: cellular response to staurosporine is likely an over-annotation for Casp3 without term-specific evidence in the review materials.

Reason: Casp3 core biology is executioner cysteine endopeptidase activity in apoptosis; this broad stimulus-response term lacks direct term-specific support and should not be retained as a confident non-core assertion.

Summary: intrinsic apoptotic signaling pathway reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: execution phase of apoptosis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: positive regulation of pyroptotic inflammatory response reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: positive regulation of amyloid-beta formation likely overstates a direct role for Casp3 relative to the curated effector-caspase evidence.

Reason: The evidence supports Casp3 as a protease whose substrate cleavage can have downstream effects; this term is too broad or indirect for a direct/core annotation.

Summary: positive regulation of amyloid-beta formation likely overstates a direct role for Casp3 relative to the curated effector-caspase evidence.

Reason: The evidence supports Casp3 as a protease whose substrate cleavage can have downstream effects; this term is too broad or indirect for a direct/core annotation.

Summary: postsynaptic density is supported as a specialized non-apoptotic neuronal context for Casp3, not as its core molecular function.

Reason: Primary neuronal studies support local synaptic/spine or vesicle-pool roles for caspase-3, but the core function remains executioner caspase protease activity.

Summary: postsynaptic density is supported as a specialized non-apoptotic neuronal context for Casp3, not as its core molecular function.

Reason: Primary neuronal studies support local synaptic/spine or vesicle-pool roles for caspase-3, but the core function remains executioner caspase protease activity.

Summary: regulation of synaptic vesicle cycle is supported as a specialized non-apoptotic neuronal context for Casp3, not as its core molecular function.

Reason: Primary neuronal studies support local synaptic/spine or vesicle-pool roles for caspase-3, but the core function remains executioner caspase protease activity.

Summary: regulation of synaptic vesicle cycle is supported as a specialized non-apoptotic neuronal context for Casp3, not as its core molecular function.

Reason: Primary neuronal studies support local synaptic/spine or vesicle-pool roles for caspase-3, but the core function remains executioner caspase protease activity.

Summary: glutamatergic synapse is supported as a specialized non-apoptotic neuronal context for Casp3, not as its core molecular function.

Reason: Primary neuronal studies support local synaptic/spine or vesicle-pool roles for caspase-3, but the core function remains executioner caspase protease activity.

Summary: glutamatergic synapse is supported as a specialized non-apoptotic neuronal context for Casp3, not as its core molecular function.

Reason: Primary neuronal studies support local synaptic/spine or vesicle-pool roles for caspase-3, but the core function remains executioner caspase protease activity.

Summary: cysteine-type endopeptidase activity is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: execution phase of apoptosis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: cysteine-type endopeptidase activity is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: Neuron apoptotic process is a valid developmental or neuronal context for Casp3, but not its core molecular function.

Reason: Casp3 core function is cysteine-type endopeptidase executioner caspase activity; neuron apoptosis is a context-specific process output.

Summary: endopeptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.

Reason: Casp3 is a cysteine-type effector caspase with cleavage specificity after Asp residues, not an aspartic protease; the specific cysteine-type endopeptidase term is more accurate.

Proposed replacements: cysteine-type endopeptidase activity

Summary: regulation of protein stability is not a supported direct annotation for Casp3 in this review.

Reason: The term conflicts with, or is too far removed from, the direct effector-caspase role. Generic protein-binding/signaling terms and incorrect molecular functions should not be retained for Casp3.

Summary: positive regulation of amyloid-beta formation likely overstates a direct role for Casp3 relative to the curated effector-caspase evidence.

Reason: The evidence supports Casp3 as a protease whose substrate cleavage can have downstream effects; this term is too broad or indirect for a direct/core annotation.

Summary: anterior neural tube closure reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: cysteine-type endopeptidase activity is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: cytoplasm is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: intrinsic apoptotic signaling pathway in response to osmotic stress reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: positive regulation of apoptotic process reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: cytoplasm is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: neurotrophin TRK receptor signaling pathway is not a supported direct annotation for Casp3 in this review.

Reason: The term conflicts with, or is too far removed from, the direct effector-caspase role. Generic protein-binding/signaling terms and incorrect molecular functions should not be retained for Casp3.

Summary: intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: Cannot be adjudicated here: PMID:12970760 is cached abstract-only. Prior observation, not a verdict: PMID:12970760 does not support Casp3 as required for apoptosis in this B-cell context; Casp3-deficient B cells showed normal apoptosis but abnormal cycling/homeostasis.

Reason: PMID:12970760 is cached abstract-only, so the curator's experimental evidence cannot be inspected here; per CLAUDE.md an experimental annotation is not overruled on that basis. Recorded observation, not a verdict: This row was flagged because the publication supports a B-cell cycling/homeostasis phenotype rather than apoptotic-process support for Casp3.

Summary: apoptotic process is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: apoptotic process is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: execution phase of apoptosis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: nucleus reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: cysteine-type endopeptidase activity is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: cytoplasm is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: aspartic-type endopeptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.

Reason: Casp3 is a cysteine-type effector caspase with cleavage specificity after Asp residues, not an aspartic protease; the specific cysteine-type endopeptidase term is more accurate.

Proposed replacements: cysteine-type endopeptidase activity

Summary: execution phase of apoptosis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: cysteine-type endopeptidase activity is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: cysteine-type endopeptidase activity is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: execution phase of apoptosis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: cysteine-type endopeptidase activity is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: glial cell apoptotic process reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: Neuron apoptotic process is a valid developmental or neuronal context for Casp3, but not its core molecular function.

Reason: Casp3 core function is cysteine-type endopeptidase executioner caspase activity; neuron apoptosis is a context-specific process output.

Summary: execution phase of apoptosis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: cysteine-type endopeptidase activity is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: Neuron apoptotic process is a valid developmental or neuronal context for Casp3, but not its core molecular function.

Reason: Casp3 core function is cysteine-type endopeptidase executioner caspase activity; neuron apoptosis is a context-specific process output.

Summary: Neuron apoptotic process is a valid developmental or neuronal context for Casp3, but not its core molecular function.

Reason: Casp3 core function is cysteine-type endopeptidase executioner caspase activity; neuron apoptosis is a context-specific process output.

Summary: execution phase of apoptosis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: Neuron apoptotic process is a valid developmental or neuronal context for Casp3, but not its core molecular function.

Reason: Casp3 core function is cysteine-type endopeptidase executioner caspase activity; neuron apoptosis is a context-specific process output.

Summary: cytosol is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: cytosol is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: cysteine-type endopeptidase activity is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: response to wounding reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: aspartic-type endopeptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.

Reason: Casp3 is a cysteine-type effector caspase with cleavage specificity after Asp residues, not an aspartic protease; the specific cysteine-type endopeptidase term is more accurate.

Proposed replacements: cysteine-type endopeptidase activity

Summary: protein processing reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: apoptotic process is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: apoptotic process is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: Cannot be adjudicated here: PMID:17544522 is cached abstract-only. Prior observation, not a verdict: Cysteine-type endopeptidase activity is correct for Casp3, but PMID:17544522 uses caspase-3/7 activation as an apoptosis readout in Ints1/KIAA1440 mutant embryos rather than assaying Casp3 enzyme activity.

Reason: PMID:17544522 is cached abstract-only, so the curator's experimental evidence cannot be inspected here; per CLAUDE.md an experimental annotation is not overruled on that basis. Recorded observation, not a verdict: This row was flagged because the cited publication is not a Casp3-specific peptidase assay; Casp3 catalytic activity is retained through other supported annotations.

Summary: peptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.

Reason: Casp3 is a cysteine-type effector caspase with cleavage specificity after Asp residues, not an aspartic protease; the specific cysteine-type endopeptidase term is more accurate.

Proposed replacements: cysteine-type endopeptidase activity

Summary: peptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.

Reason: Casp3 is a cysteine-type effector caspase with cleavage specificity after Asp residues, not an aspartic protease; the specific cysteine-type endopeptidase term is more accurate.

Proposed replacements: cysteine-type endopeptidase activity

Summary: peptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.

Reason: Casp3 is a cysteine-type effector caspase with cleavage specificity after Asp residues, not an aspartic protease; the specific cysteine-type endopeptidase term is more accurate.

Proposed replacements: cysteine-type endopeptidase activity

Summary: peptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.

Reason: Casp3 is a cysteine-type effector caspase with cleavage specificity after Asp residues, not an aspartic protease; the specific cysteine-type endopeptidase term is more accurate.

Proposed replacements: cysteine-type endopeptidase activity

Summary: peptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.

Reason: Casp3 is a cysteine-type effector caspase with cleavage specificity after Asp residues, not an aspartic protease; the specific cysteine-type endopeptidase term is more accurate.

Proposed replacements: cysteine-type endopeptidase activity

Summary: peptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.

Reason: Casp3 is a cysteine-type effector caspase with cleavage specificity after Asp residues, not an aspartic protease; the specific cysteine-type endopeptidase term is more accurate.

Proposed replacements: cysteine-type endopeptidase activity

Summary: Cannot be adjudicated here: PMID:11092819 is cached abstract-only. Prior observation, not a verdict: PMID:11092819 does not support a positive Casp3 role in DNA damage response.

Reason: PMID:11092819 is cached abstract-only, so the curator's experimental evidence cannot be inspected here; per CLAUDE.md an experimental annotation is not overruled on that basis. Recorded observation, not a verdict: The cited neural precursor DNA-damage study reports dependence on p53 and caspase 9 but not caspase 3, so this Casp3 DNA-damage response row was questioned.

Summary: Cannot be adjudicated here: PMID:11092819 is cached abstract-only. Prior observation, not a verdict: Response to UV is not supported as a positive Casp3 annotation in the reviewed evidence.

Reason: PMID:11092819 is cached abstract-only, so the curator's experimental evidence cannot be inspected here; per CLAUDE.md an experimental annotation is not overruled on that basis. Recorded observation, not a verdict: The directly cited UV/DNA-damage neural precursor study reports dependence on p53 and caspase 9 but not caspase 3; IEA/IGI UV-response carryover was questioned.

Summary: negative regulation of apoptotic process is not a supported direct annotation for Casp3 in this review.

Reason: The term conflicts with, or is too far removed from, the direct effector-caspase role. Generic protein-binding/signaling terms and incorrect molecular functions should not be retained for Casp3.

Summary: Neuron apoptotic process is a valid developmental or neuronal context for Casp3, but not its core molecular function.

Reason: Casp3 core function is cysteine-type endopeptidase executioner caspase activity; neuron apoptosis is a context-specific process output.

Summary: sensory perception of sound reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: heart development reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: Cannot be adjudicated here: PMID:16469926 is cached abstract-only. Prior observation, not a verdict: Response to UV is not supported as a positive Casp3 annotation in the reviewed evidence.

Reason: PMID:16469926 is cached abstract-only, so the curator's experimental evidence cannot be inspected here; per CLAUDE.md an experimental annotation is not overruled on that basis. Recorded observation, not a verdict: The directly cited UV/DNA-damage neural precursor study reports dependence on p53 and caspase 9 but not caspase 3; IEA/IGI UV-response carryover was questioned.

Summary: peptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.

Reason: Casp3 is a cysteine-type effector caspase with cleavage specificity after Asp residues, not an aspartic protease; the specific cysteine-type endopeptidase term is more accurate.

Proposed replacements: cysteine-type endopeptidase activity

Summary: proteolysis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.

Reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.

Summary: keratinocyte differentiation reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: cell fate commitment reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: B cell homeostasis reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: cyclin-dependent protein serine/threonine kinase inhibitor activity is not a supported direct annotation for Casp3 in this review.

Reason: GO:0004861 is cyclin-dependent protein serine/threonine kinase inhibitor activity, an enables molecular-function term. Casp3 is a cysteine-type endopeptidase: cleaving a CDK inhibitor is not the same as being one, so the term assigns the substrate's activity to the protease. That is a molecular-identity argument about Casp3 itself, needing no access to the cited full text, which is why this row stays REMOVE while the abstract-only class elsewhere in this file is UNDECIDED.

Summary: peptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.

Reason: Casp3 is a cysteine-type effector caspase with cleavage specificity after Asp residues, not an aspartic protease; the specific cysteine-type endopeptidase term is more accurate.

Proposed replacements: cysteine-type endopeptidase activity

Summary: negative regulation of B cell proliferation reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: T cell homeostasis reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: negative regulation of cyclin-dependent protein serine/threonine kinase activity reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: negative regulation of cell cycle reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: negative regulation of activated T cell proliferation reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.

Reason: Casp3 can be required in many developmental, neuronal, inflammatory, and stress contexts, but these annotations are downstream of or peripheral to its core protease activity in apoptotic execution.

Summary: peptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.

Reason: Casp3 is a cysteine-type effector caspase with cleavage specificity after Asp residues, not an aspartic protease; the specific cysteine-type endopeptidase term is more accurate.

Proposed replacements: cysteine-type endopeptidase activity

Summary: Cannot be adjudicated here: PMID:12477715 is cached abstract-only. Prior observation, not a verdict: PMID:12477715 studies caspase-2 nuclear localization/importin binding and does not support mouse Casp3 cytoplasmic localization.

Reason: PMID:12477715 is cached abstract-only, so the curator's experimental evidence cannot be inspected here; per CLAUDE.md an experimental annotation is not overruled on that basis. Recorded observation, not a verdict: This row was flagged because the cited paper concerns caspase-2 localization rather than Casp3 localization; Casp3 cytoplasmic/cytosolic localization is retained through other supported annotations.