Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0006915 apoptotic process	IBA GO_REF:0000033	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0004197 cysteine-type endopeptidase activity	IBA GO_REF:0000033	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0006508 proteolysis	IBA GO_REF:0000033	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0031264 death-inducing signaling complex	IBA GO_REF:0000033	REMOVE	Summary: death-inducing signaling complex 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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
GO:0097194 execution phase of apoptosis	IBA GO_REF:0000033	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0008047 enzyme activator activity	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports Casp3 as an executioner protease; broad substrate/pathway outputs can overstate direct Casp3 function.
GO:0043525 positive regulation of neuron apoptotic process	IBA GO_REF:0000033	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0030182 neuron differentiation	IBA GO_REF:0000033	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0030216 keratinocyte differentiation	IBA GO_REF:0000033	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0030218 erythrocyte differentiation	IBA GO_REF:0000033	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0004190 aspartic-type endopeptidase activity	IEA GO_REF:0000117	MODIFY	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 Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
GO:0004197 cysteine-type endopeptidase activity	IEA GO_REF:0000120	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0005737 cytoplasm	IEA GO_REF:0000120	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0006508 proteolysis	IEA GO_REF:0000120	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0008234 cysteine-type peptidase activity	IEA GO_REF:0000120	MODIFY	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 Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis. file:mouse/Casp3/Casp3-uniprot.txt Involved in the activation cascade of caspases responsible for apoptosis execution.
GO:0009411 response to UV	IEA GO_REF:0000117	REMOVE	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 reports dependence on p53 and caspase 9 but not caspase 3; IEA/IGI UV-response carryover should therefore not be retained. Supporting Evidence: PMID:11092819 critically dependent on p53 and caspase 9, but neither Bax nor caspase 3 expression.
GO:0051402 neuron apoptotic process	IEA GO_REF:0000117	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis. file:mouse/Casp3/Casp3-uniprot.txt Involved in the activation cascade of caspases responsible for apoptosis execution.
GO:0005515 protein binding	IPI PMID:17124493 Huntingtin inhibits caspase-3 activation.	REMOVE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
GO:0005515 protein binding	IPI PMID:18585351 Ronin is essential for embryogenesis and the pluripotency of...	REMOVE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
GO:0005515 protein binding	IPI PMID:19759058 Proteome-wide substrate analysis indicates substrate exclusi...	REMOVE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
GO:0001554 luteolysis	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
GO:0001666 response to hypoxia	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
GO:0001818 negative regulation of cytokine production	IEA GO_REF:0000107	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0002020 protease binding	IEA GO_REF:0000107	REMOVE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
GO:0005123 death receptor binding	IEA GO_REF:0000107	REMOVE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
GO:0005634 nucleus	IEA GO_REF:0000107	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0005829 cytosol	IEA GO_REF:0000107	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0006915 apoptotic process	IEA GO_REF:0000107	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0007413 axonal fasciculation	IEA GO_REF:0000107	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0007611 learning or memory	IEA GO_REF:0000107	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0008233 peptidase activity	IEA GO_REF:0000107	MODIFY	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 Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
GO:0009410 response to xenobiotic stimulus	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
GO:0009749 response to glucose	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
GO:0010038 response to metal ion	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
GO:0010165 response to X-ray	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
GO:0016005 phospholipase A2 activator activity	IEA GO_REF:0000107	REMOVE	Summary: phospholipase A2 activator activity 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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
GO:0016485 protein processing	IEA GO_REF:0000107	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0021766 hippocampus development	IEA GO_REF:0000107	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0030163 protein catabolic process	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports Casp3 as an executioner protease; broad substrate/pathway outputs can overstate direct Casp3 function.
GO:0030182 neuron differentiation	IEA GO_REF:0000107	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0030218 erythrocyte differentiation	IEA GO_REF:0000107	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0031264 death-inducing signaling complex	IEA GO_REF:0000107	REMOVE	Summary: death-inducing signaling complex 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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
GO:0031647 regulation of protein stability	IEA GO_REF:0000120	REMOVE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
GO:0032025 response to cobalt ion	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
GO:0032355 response to estradiol	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
GO:0032496 response to lipopolysaccharide	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
GO:0032880 regulation of protein localization	IEA GO_REF:0000107	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0034349 glial cell apoptotic process	IEA GO_REF:0000107	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0035094 response to nicotine	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
GO:0035556 intracellular signal transduction	IEA GO_REF:0000107	REMOVE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
GO:0036269 swimming behavior	IEA GO_REF:0000107	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0042542 response to hydrogen peroxide	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
GO:0043025 neuronal cell body	IEA GO_REF:0000107	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0043065 positive regulation of apoptotic process	IEA GO_REF:0000107	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0043200 response to amino acid	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
GO:0043523 regulation of neuron apoptotic process	IEA GO_REF:0000107	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0043525 positive regulation of neuron apoptotic process	IEA GO_REF:0000107	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0044877 protein-containing complex binding	IEA GO_REF:0000107	REMOVE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
GO:0045471 response to ethanol	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
GO:0051146 striated muscle cell differentiation	IEA GO_REF:0000107	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0051384 response to glucocorticoid	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
GO:0051604 protein maturation	IEA GO_REF:0000120	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0070269 pyroptotic inflammatory response	IEA GO_REF:0000107	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0071887 leukocyte apoptotic process	IEA GO_REF:0000107	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0072347 response to anesthetic	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
GO:0072734 cellular response to staurosporine	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
GO:0097193 intrinsic apoptotic signaling pathway	IEA GO_REF:0000107	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0097194 execution phase of apoptosis	IEA GO_REF:0000120	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0140639 positive regulation of pyroptotic inflammatory response	IEA GO_REF:0000107	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:1902004 positive regulation of amyloid-beta formation	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports Casp3 as an executioner protease; broad substrate/pathway outputs can overstate direct Casp3 function.
GO:1990418 response to insulin-like growth factor stimulus	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
GO:0031264 death-inducing signaling complex	ISO GO_REF:0000096	REMOVE	Summary: death-inducing signaling complex 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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
GO:0008303 caspase complex	ISO GO_REF:0000119	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0043065 positive regulation of apoptotic process	ISO GO_REF:0000119	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:1902512 positive regulation of apoptotic DNA fragmentation	ISO GO_REF:0000119	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0098883 synapse pruning	IMP PMID:24478350 Local pruning of dendrites and spines by caspase-3-dependent...	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0005829 cytosol	ISO GO_REF:0000119	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0001818 negative regulation of cytokine production	ISO GO_REF:0000119	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0002020 protease binding	ISO GO_REF:0000096	REMOVE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
GO:0004197 cysteine-type endopeptidase activity	ISO GO_REF:0000119	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0005123 death receptor binding	ISO GO_REF:0000096	REMOVE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
GO:0005634 nucleus	ISO GO_REF:0000119	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0005737 cytoplasm	ISO GO_REF:0000119	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0005737 cytoplasm	ISO GO_REF:0000096	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0006508 proteolysis	ISO GO_REF:0000096	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0006508 proteolysis	ISO GO_REF:0000119	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0006915 apoptotic process	ISO GO_REF:0000119	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0007413 axonal fasciculation	ISO GO_REF:0000096	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0007611 learning or memory	ISO GO_REF:0000096	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0008233 peptidase activity	ISO GO_REF:0000119	MODIFY	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 Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
GO:0008234 cysteine-type peptidase activity	ISO GO_REF:0000096	MODIFY	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 Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis. file:mouse/Casp3/Casp3-uniprot.txt Involved in the activation cascade of caspases responsible for apoptosis execution.
GO:0009749 response to glucose	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
GO:0016005 phospholipase A2 activator activity	ISO GO_REF:0000096	REMOVE	Summary: phospholipase A2 activator activity 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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
GO:0016485 protein processing	ISO GO_REF:0000119	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0030163 protein catabolic process	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports Casp3 as an executioner protease; broad substrate/pathway outputs can overstate direct Casp3 function.
GO:0030163 protein catabolic process	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports Casp3 as an executioner protease; broad substrate/pathway outputs can overstate direct Casp3 function.
GO:0030218 erythrocyte differentiation	ISO GO_REF:0000119	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0031647 regulation of protein stability	ISO GO_REF:0000096	REMOVE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
GO:0031647 regulation of protein stability	ISO GO_REF:0000119	REMOVE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
GO:0035556 intracellular signal transduction	ISO GO_REF:0000096	REMOVE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
GO:0035655 interleukin-18-mediated signaling pathway	ISO GO_REF:0000119	REMOVE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
GO:0042542 response to hydrogen peroxide	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
GO:0043025 neuronal cell body	ISO GO_REF:0000096	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0043065 positive regulation of apoptotic process	ISO GO_REF:0000096	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0043525 positive regulation of neuron apoptotic process	ISO GO_REF:0000096	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0044877 protein-containing complex binding	ISO GO_REF:0000096	REMOVE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
GO:0051604 protein maturation	ISO GO_REF:0000119	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0070212 protein poly-ADP-ribosylation	ISO GO_REF:0000119	REMOVE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
GO:0070269 pyroptotic inflammatory response	ISO GO_REF:0000119	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0072734 cellular response to staurosporine	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
GO:0097193 intrinsic apoptotic signaling pathway	ISO GO_REF:0000119	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0097194 execution phase of apoptosis	ISO GO_REF:0000119	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0140639 positive regulation of pyroptotic inflammatory response	ISO GO_REF:0000119	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:1902004 positive regulation of amyloid-beta formation	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports Casp3 as an executioner protease; broad substrate/pathway outputs can overstate direct Casp3 function.
GO:1902004 positive regulation of amyloid-beta formation	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports Casp3 as an executioner protease; broad substrate/pathway outputs can overstate direct Casp3 function.
GO:0014069 postsynaptic density	IEP PMID:21151119 Caspase-3 triggers early synaptic dysfunction in a mouse mod...	KEEP AS NON CORE	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. Supporting Evidence: PMID:21151119 non-apoptotic baseline caspase-3 activity in hippocampal dendritic spines PMID:21151119 removal of the GluR1 subunit of AMPA-type receptor from postsynaptic sites
GO:0014069 postsynaptic density	IDA PMID:21151119 Caspase-3 triggers early synaptic dysfunction in a mouse mod...	KEEP AS NON CORE	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. Supporting Evidence: PMID:21151119 non-apoptotic baseline caspase-3 activity in hippocampal dendritic spines PMID:21151119 removal of the GluR1 subunit of AMPA-type receptor from postsynaptic sites
GO:0098693 regulation of synaptic vesicle cycle	IMP PMID:33303681 The BAD-BAX-Caspase-3 Cascade Modulates Synaptic Vesicle Poo...	KEEP AS NON CORE	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. Supporting Evidence: PMID:33303681 the BAD-BAX-caspase-3 pathway regulates autophagy, which in turn limits the size of synaptic vesicle pools PMID:33303681 nonapoptotic function of the BAD-BAX-caspase-3 pathway in presynaptic terminals
GO:0098693 regulation of synaptic vesicle cycle	IDA PMID:33303681 The BAD-BAX-Caspase-3 Cascade Modulates Synaptic Vesicle Poo...	KEEP AS NON CORE	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. Supporting Evidence: PMID:33303681 the BAD-BAX-caspase-3 pathway regulates autophagy, which in turn limits the size of synaptic vesicle pools PMID:33303681 nonapoptotic function of the BAD-BAX-caspase-3 pathway in presynaptic terminals
GO:0098978 glutamatergic synapse	IEP PMID:21151119 Caspase-3 triggers early synaptic dysfunction in a mouse mod...	KEEP AS NON CORE	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. Supporting Evidence: PMID:21151119 glutamatergic synaptic transmission and plasticity PMID:21151119 caspase-3-dependent mechanism that drives synaptic failure
GO:0098978 glutamatergic synapse	IDA PMID:21151119 Caspase-3 triggers early synaptic dysfunction in a mouse mod...	KEEP AS NON CORE	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. Supporting Evidence: PMID:21151119 glutamatergic synaptic transmission and plasticity PMID:21151119 caspase-3-dependent mechanism that drives synaptic failure
GO:0004197 cysteine-type endopeptidase activity	IDA PMID:37327784 Gasdermin D licenses MHCII induction to maintain food tolera...	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0097194 execution phase of apoptosis	IMP PMID:8934524 Decreased apoptosis in the brain and premature lethality in ...	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0004197 cysteine-type endopeptidase activity	IDA PMID:25231987 Exposure of phosphatidylserine by Xk-related protein family ...	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0051402 neuron apoptotic process	IDA PMID:15231831 BAD is a pro-survival factor prior to activation of its pro-...	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis. file:mouse/Casp3/Casp3-uniprot.txt Involved in the activation cascade of caspases responsible for apoptosis execution.
GO:0004175 endopeptidase activity	IDA PMID:12124386 The role of Asp-462 in regulating Akt activity.	MODIFY	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 Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
GO:0031647 regulation of protein stability	ISS GO_REF:0000024	REMOVE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
GO:1902004 positive regulation of amyloid-beta formation	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports Casp3 as an executioner protease; broad substrate/pathway outputs can overstate direct Casp3 function.
GO:0061713 anterior neural tube closure	IMP PMID:21515572 Focusing forward genetics: a tripartite ENU screen for neuro...	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0004197 cysteine-type endopeptidase activity	ISS GO_REF:0000024	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0005737 cytoplasm	IDA PMID:21716255 Cyclooxygenase-2-dependent phosphorylation of the pro-apopto...	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0008627 intrinsic apoptotic signaling pathway in response to osmotic stress	IDA PMID:21716255 Cyclooxygenase-2-dependent phosphorylation of the pro-apopto...	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0043065 positive regulation of apoptotic process	IDA PMID:21716255 Cyclooxygenase-2-dependent phosphorylation of the pro-apopto...	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0005737 cytoplasm	IDA PMID:25139234 Mammalian target of rapamycin is essential for cardiomyocyte...	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0048011 neurotrophin TRK receptor signaling pathway	ISO PMID:23954828 Dok5 is involved in the signaling pathway of neurotrophin-3 ...	REMOVE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	NAS PMID:12097332 An endoplasmic reticulum stress-specific caspase cascade in ...	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0006915 apoptotic process	IMP PMID:12970760 Caspase-3 regulates cell cycle in B cells: a consequence of ...	REMOVE	Summary: 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: Remove this evidence row because the publication supports a B-cell cycling/homeostasis phenotype rather than apoptotic-process support for Casp3. Supporting Evidence: PMID:12970760 Casp3-/- mice have increased numbers of splenic B cells that show normal apoptosis but enhanced proliferation in vivo and hyperproliferation after mitogenic stimulation in vitro.
GO:0006915 apoptotic process	IMP PMID:16469926 Caspases 3 and 7: key mediators of mitochondrial events of a...	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0006915 apoptotic process	IMP PMID:9512515 Essential contribution of caspase 3/CPP32 to apoptosis and i...	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0097194 execution phase of apoptosis	IDA PMID:12954857 Ischemic preconditioning by caspase cleavage of poly(ADP-rib...	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0005634 nucleus	IDA PMID:22358842 Maintenance of muscle stem-cell quiescence by microRNA-489.	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0004197 cysteine-type endopeptidase activity	IDA PMID:24378336 BDNF and NT4 play interchangeable roles in gustatory develop...	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0005737 cytoplasm	IDA PMID:23861879 Loss of Usp9x disrupts cortical architecture, hippocampal de...	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0004190 aspartic-type endopeptidase activity	IDA PMID:23727203 Nek5, a novel substrate for caspase-3, promotes skeletal mus...	MODIFY	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 Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
GO:0097194 execution phase of apoptosis	IGI PMID:16469926 Caspases 3 and 7: key mediators of mitochondrial events of a...	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0004197 cysteine-type endopeptidase activity	IDA PMID:16183742 Apoptosis caused by p53-induced protein with death domain (P...	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0004197 cysteine-type endopeptidase activity	IDA PMID:15456877 Vhlh gene deletion induces Hif-1-mediated cell death in thym...	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0097194 execution phase of apoptosis	IDA PMID:15456877 Vhlh gene deletion induces Hif-1-mediated cell death in thym...	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0004197 cysteine-type endopeptidase activity	IDA PMID:14657025 Transcriptional activation of known and novel apoptotic path...	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0034349 glial cell apoptotic process	IMP PMID:11549719 Caspase 3 deficiency rescues peripheral nervous system defec...	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0051402 neuron apoptotic process	IMP PMID:11549719 Caspase 3 deficiency rescues peripheral nervous system defec...	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis. file:mouse/Casp3/Casp3-uniprot.txt Involved in the activation cascade of caspases responsible for apoptosis execution.
GO:0097194 execution phase of apoptosis	IMP PMID:11549719 Caspase 3 deficiency rescues peripheral nervous system defec...	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0004197 cysteine-type endopeptidase activity	IDA PMID:12124386 The role of Asp-462 in regulating Akt activity.	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0051402 neuron apoptotic process	IMP PMID:10618441 Epistatic and independent functions of caspase-3 and Bcl-X(L...	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis. file:mouse/Casp3/Casp3-uniprot.txt Involved in the activation cascade of caspases responsible for apoptosis execution.
GO:0051402 neuron apoptotic process	IGI PMID:10618441 Epistatic and independent functions of caspase-3 and Bcl-X(L...	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis. file:mouse/Casp3/Casp3-uniprot.txt Involved in the activation cascade of caspases responsible for apoptosis execution.
GO:0097194 execution phase of apoptosis	IDA PMID:12124386 The role of Asp-462 in regulating Akt activity.	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0051402 neuron apoptotic process	IMP PMID:10479688 Bax-dependent caspase-3 activation is a key determinant in p...	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis. file:mouse/Casp3/Casp3-uniprot.txt Involved in the activation cascade of caspases responsible for apoptosis execution.
GO:0005829 cytosol	TAS Reactome:R-MMU-418855	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0005829 cytosol	TAS Reactome:R-NUL-2534247	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0004197 cysteine-type endopeptidase activity	IDA PMID:19759058 Proteome-wide substrate analysis indicates substrate exclusi...	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0009611 response to wounding	IDA PMID:14507967 Enhanced oligodendrocyte survival after spinal cord injury i...	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0004190 aspartic-type endopeptidase activity	IDA PMID:15231831 BAD is a pro-survival factor prior to activation of its pro-...	MODIFY	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 Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
GO:0016485 protein processing	IDA PMID:15231831 BAD is a pro-survival factor prior to activation of its pro-...	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0006915 apoptotic process	IDA PMID:17901126 Estrogen suppresses uterine epithelial apoptosis by inducing...	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0006915 apoptotic process	IDA PMID:12847083 Bax and Bak can localize to the endoplasmic reticulum to ini...	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0008234 cysteine-type peptidase activity	IDA PMID:17544522 Targeted disruption of the murine large nuclear KIAA1440/Int...	REMOVE	Summary: 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: Remove this evidence row because the cited publication is not a Casp3-specific peptidase assay; Casp3 catalytic activity is retained through other supported annotations. Supporting Evidence: PMID:17544522 Both TUNEL and FAM-caspase-3/7 assays performed on these embryos consistently showed that E3.5 KIAA1440-/- embryos had activated caspase-3/7, which then induced an apoptotic response predominantly within the inner cell mass of the blastocyst.
GO:0008233 peptidase activity	ISO GO_REF:0000008	MODIFY	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 Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
GO:0008233 peptidase activity	IDA PMID:12427836 p73 is required for survival and maintenance of CNS neurons.	MODIFY	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 Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
GO:0008233 peptidase activity	RCA PMID:12819136 Comparative analysis of apoptosis and inflammation genes of ...	MODIFY	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 Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
GO:0008233 peptidase activity	IDA PMID:13679151 Roles of MGMT and MLH1 proteins in alkylation-induced apopto...	MODIFY	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 Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
GO:0008233 peptidase activity	IDA PMID:14561754 Molecular components of a cell death pathway activated by en...	MODIFY	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 Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
GO:0008233 peptidase activity	IMP PMID:16469926 Caspases 3 and 7: key mediators of mitochondrial events of a...	MODIFY	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 Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
GO:0006974 DNA damage response	IDA PMID:11092819 DNA damage-induced neural precursor cell apoptosis requires ...	REMOVE	Summary: PMID:11092819 does not support a positive Casp3 role in DNA damage response. Reason: 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 should not be retained. Supporting Evidence: PMID:11092819 critically dependent on p53 and caspase 9, but neither Bax nor caspase 3 expression.
GO:0009411 response to UV	IDA PMID:11092819 DNA damage-induced neural precursor cell apoptosis requires ...	REMOVE	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 reports dependence on p53 and caspase 9 but not caspase 3; IEA/IGI UV-response carryover should therefore not be retained. Supporting Evidence: PMID:11092819 critically dependent on p53 and caspase 9, but neither Bax nor caspase 3 expression.
GO:0043066 negative regulation of apoptotic process	ISO GO_REF:0000008	REMOVE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
GO:0051402 neuron apoptotic process	IDA PMID:12427836 p73 is required for survival and maintenance of CNS neurons.	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-falcon.md CASP3 is the principal executioner caspase that dismantles cells during apoptosis. file:mouse/Casp3/Casp3-uniprot.txt Involved in the activation cascade of caspases responsible for apoptosis execution.
GO:0007605 sensory perception of sound	IMP PMID:11374883 Deafness due to degeneration of cochlear neurons in caspase-...	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0007507 heart development	IGI PMID:16469926 Caspases 3 and 7: key mediators of mitochondrial events of a...	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0009411 response to UV	IGI PMID:16469926 Caspases 3 and 7: key mediators of mitochondrial events of a...	REMOVE	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 reports dependence on p53 and caspase 9 but not caspase 3; IEA/IGI UV-response carryover should therefore not be retained. Supporting Evidence: PMID:11092819 critically dependent on p53 and caspase 9, but neither Bax nor caspase 3 expression.
GO:0008233 peptidase activity	IMP PMID:11549719 Caspase 3 deficiency rescues peripheral nervous system defec...	MODIFY	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 Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
GO:0006508 proteolysis	RCA PMID:12819136 Comparative analysis of apoptosis and inflammation genes of ...	ACCEPT	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
GO:0030216 keratinocyte differentiation	IMP PMID:15068794 High commitment of embryonic keratinocytes to terminal diffe...	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0045165 cell fate commitment	IMP PMID:15068794 High commitment of embryonic keratinocytes to terminal diffe...	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0001782 B cell homeostasis	IMP PMID:12970760 Caspase-3 regulates cell cycle in B cells: a consequence of ...	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0004861 cyclin-dependent protein serine/threonine kinase inhibitor activity	IMP PMID:12970760 Caspase-3 regulates cell cycle in B cells: a consequence of ...	REMOVE	Summary: cyclin-dependent protein serine/threonine kinase inhibitor activity 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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
GO:0008233 peptidase activity	IMP PMID:12970760 Caspase-3 regulates cell cycle in B cells: a consequence of ...	MODIFY	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 Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
GO:0030889 negative regulation of B cell proliferation	IMP PMID:12970760 Caspase-3 regulates cell cycle in B cells: a consequence of ...	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0043029 T cell homeostasis	IMP PMID:12970760 Caspase-3 regulates cell cycle in B cells: a consequence of ...	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0045736 negative regulation of cyclin-dependent protein serine/threonine kinase activity	IMP PMID:12970760 Caspase-3 regulates cell cycle in B cells: a consequence of ...	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0045786 negative regulation of cell cycle	IMP PMID:12970760 Caspase-3 regulates cell cycle in B cells: a consequence of ...	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0046007 negative regulation of activated T cell proliferation	IMP PMID:12970760 Caspase-3 regulates cell cycle in B cells: a consequence of ...	KEEP AS NON CORE	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. Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
GO:0008233 peptidase activity	IDA PMID:12954857 Ischemic preconditioning by caspase cleavage of poly(ADP-rib...	MODIFY	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 Supporting Evidence: file:mouse/Casp3/Casp3-deep-research-codex.md Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible. file:mouse/Casp3/Casp3-uniprot.txt Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. file:mouse/Casp3/Casp3-deep-research-falcon.md Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
GO:0005737 cytoplasm	IDA PMID:12477715 Role of prodomain in importin-mediated nuclear localization ...	REMOVE	Summary: PMID:12477715 studies caspase-2 nuclear localization/importin binding and does not support mouse Casp3 cytoplasmic localization. Reason: Remove this evidence row because the cited paper concerns caspase-2 localization rather than Casp3 localization; Casp3 cytoplasmic/cytosolic localization is retained through other supported annotations. Supporting Evidence: PMID:12477715 In this study we sought to map specific functional regions in the caspase-2 prodomain that regulate its nuclear transport and also its activation.

Core Functions

Casp3 is the canonical apoptotic effector cysteine protease. After activation by initiator caspases, it cleaves many substrates to execute apoptosis and promote apoptotic DNA fragmentation.

Molecular Function:

cysteine-type endopeptidase activity

Directly Involved In:

execution phase of apoptosis positive regulation of apoptotic DNA fragmentation proteolysis

Cellular Locations:

cytoplasm cytosol

Supporting Evidence:

file:mouse/Casp3/Casp3-uniprot.txt
Following cleavage and activation by initiator caspases ... mediates execution of apoptosis by catalyzing cleavage of many proteins.
file:mouse/Casp3/Casp3-deep-research-codex.md
Casp3 is a major effector caspase activated by initiator caspases and cleaves many substrates during the execution phase of apoptosis.
file:mouse/Casp3/Casp3-deep-research-falcon.md
Caspase-3 is a cysteine-aspartate executioner protease that hydrolyzes protein substrates after Asp residues during apoptotic execution.

The active Casp3 enzyme functions as a caspase complex formed from p17 and p12 subunits; this mature complex carries out the proteolytic execution program.

Molecular Function:

cysteine-type endopeptidase activity

Directly Involved In:

execution phase of apoptosis

Cellular Locations:

cytoplasm

In Complex:

caspase complex

Supporting Evidence:

file:mouse/Casp3/Casp3-uniprot.txt
Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 17 kDa (p17) and a 12 kDa (p12) subunit.
file:mouse/Casp3/Casp3-deep-research-falcon.md
Caspase-3 is a cysteine-aspartate executioner protease that hydrolyzes protein substrates after Asp residues during apoptotic execution.

References

GO_REF:0000008

Gene Ontology annotation by the MGI curatorial staff, curated orthology

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000096

Automated transfer of experimentally-verified manual GO annotation data to mouse-rat orthologs

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000119

Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:10479688

Bax-dependent caspase-3 activation is a key determinant in p53-induced apoptosis in neurons.

PMID:10618441

Epistatic and independent functions of caspase-3 and Bcl-X(L) in developmental programmed cell death.

PMID:11092819

DNA damage-induced neural precursor cell apoptosis requires p53 and caspase 9 but neither Bax nor caspase 3.

PMID:11374883

Deafness due to degeneration of cochlear neurons in caspase-3-deficient mice.

PMID:11549719

Caspase 3 deficiency rescues peripheral nervous system defect in retinoblastoma nullizygous mice.

PMID:12097332

An endoplasmic reticulum stress-specific caspase cascade in apoptosis. Cytochrome c-independent activation of caspase-9 by caspase-12.

PMID:12124386

The role of Asp-462 in regulating Akt activity.

PMID:12427836

p73 is required for survival and maintenance of CNS neurons.

PMID:12477715

Role of prodomain in importin-mediated nuclear localization and activation of caspase-2.

PMID:12819136

Comparative analysis of apoptosis and inflammation genes of mice and humans.

PMID:12847083

Bax and Bak can localize to the endoplasmic reticulum to initiate apoptosis.

PMID:12954857

Ischemic preconditioning by caspase cleavage of poly(ADP-ribose) polymerase-1.

PMID:12970760

Caspase-3 regulates cell cycle in B cells: a consequence of substrate specificity.

PMID:13679151

Roles of MGMT and MLH1 proteins in alkylation-induced apoptosis and mutagenesis.

PMID:14507967

Enhanced oligodendrocyte survival after spinal cord injury in Bax-deficient mice and mice with delayed Wallerian degeneration.

PMID:14561754

Molecular components of a cell death pathway activated by endoplasmic reticulum stress.

PMID:14657025

Transcriptional activation of known and novel apoptotic pathways by Nur77 orphan steroid receptor.

PMID:15068794

High commitment of embryonic keratinocytes to terminal differentiation through a Notch1-caspase 3 regulatory mechanism.

PMID:15231831

BAD is a pro-survival factor prior to activation of its pro-apoptotic function.

PMID:15456877

Vhlh gene deletion induces Hif-1-mediated cell death in thymocytes.

PMID:16183742

Apoptosis caused by p53-induced protein with death domain (PIDD) depends on the death adapter protein RAIDD.

PMID:16469926

Caspases 3 and 7: key mediators of mitochondrial events of apoptosis.

PMID:17124493

Huntingtin inhibits caspase-3 activation.

PMID:17544522

Targeted disruption of the murine large nuclear KIAA1440/Ints1 protein causes growth arrest in early blastocyst stage embryos and eventual apoptotic cell death.

PMID:17901126

Estrogen suppresses uterine epithelial apoptosis by inducing birc1 expression.

PMID:18585351

Ronin is essential for embryogenesis and the pluripotency of mouse embryonic stem cells.

PMID:19759058

Proteome-wide substrate analysis indicates substrate exclusion as a mechanism to generate caspase-7 versus caspase-3 specificity.

PMID:21151119

Caspase-3 triggers early synaptic dysfunction in a mouse model of Alzheimer's disease.

PMID:21515572

Focusing forward genetics: a tripartite ENU screen for neurodevelopmental mutations in the mouse.

PMID:21716255

Cyclooxygenase-2-dependent phosphorylation of the pro-apoptotic protein Bad inhibits tonicity-induced apoptosis in renal medullary cells.

PMID:22358842

Maintenance of muscle stem-cell quiescence by microRNA-489.

PMID:23727203

Nek5, a novel substrate for caspase-3, promotes skeletal muscle differentiation by up-regulating caspase activity.

PMID:23861879

Loss of Usp9x disrupts cortical architecture, hippocampal development and TGFβ-mediated axonogenesis.

PMID:23954828

Dok5 is involved in the signaling pathway of neurotrophin-3 against TrkC-induced apoptosis.

PMID:24378336

BDNF and NT4 play interchangeable roles in gustatory development.

PMID:24478350

Local pruning of dendrites and spines by caspase-3-dependent and proteasome-limited mechanisms.

PMID:25139234

Mammalian target of rapamycin is essential for cardiomyocyte survival and heart development in mice.

PMID:25231987

Exposure of phosphatidylserine by Xk-related protein family members during apoptosis.

PMID:33303681

The BAD-BAX-Caspase-3 Cascade Modulates Synaptic Vesicle Pools via Autophagy.

PMID:37327784

Gasdermin D licenses MHCII induction to maintain food tolerance in small intestine.

PMID:8934524

Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice.

PMID:9512515

Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes.

Reactome:R-MMU-418855

Caspase cleavage of Unc5h1

Reactome:R-NUL-2534247

E-cadherin strand dimer degradation by Casp3

file:mouse/Casp3/Casp3-uniprot.txt

UniProt record for mouse Casp3

Casp3 is the major effector caspase in the execution phase of apoptosis.

"Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis...mediates execution of apoptosis by catalyzing cleavage of many proteins"
The active Casp3 enzyme is a heterotetramer with p17 and p12 subunits.

"Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 17 kDa (p17) and a 12 kDa (p12) subunit."

file:mouse/Casp3/Casp3-deep-research-codex.md

Manual deep research synthesis for mouse Casp3

The strongest curated picture is that Casp3 is a canonical apoptotic effector protease, while many orthology-transferred inflammatory and stimulus-specific terms are non-core or overextended.

file:mouse/Casp3/Casp3-deep-research-falcon.md

Falcon deep research report on mouse Casp3

Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease in apoptotic proteolysis, with context-specific pyroptotic and non-apoptotic outputs.

"Caspase-3 is a cysteine-aspartate protease functioning as a principal executioner protease in apoptotic cell death."

Suggested Experiments

Experiment: Use catalytically inactive Casp3 rescue alleles in apoptotic and non-apoptotic mouse cells to separate direct protease-dependent functions from downstream phenotypes.

Experiment: Perform substrate-trapping proteomics for active Casp3 in apoptotic cells, neurons, and inflammatory epithelial cells to identify context-specific direct substrates.

Deep Research

Codex

(Casp3-deep-research-codex.md)

Deep Research Report: Casp3 (Mus musculus) Codex

Deep Research Report: Casp3 (Mus musculus)

Executive Summary

Casp3 is a major effector caspase activated by initiator caspases and cleaves many substrates during the execution phase of apoptosis. Mouse and mammalian evidence consistently support Casp3 as a cysteine-aspartate protease that becomes active after proteolytic processing, forms an active heterotetramer, and drives hallmark apoptotic events including substrate cleavage and apoptotic DNA fragmentation [file:mouse/Casp3/Casp3-uniprot.txt; PMID:9512515; PMID:16469926].

Much of Casp3 biology in mouse centers on developmental and stress-induced apoptosis, especially in neurons and other differentiating tissues. Casp3-deficient neurons show delayed apoptosis and reduced TUNEL staining after p53 induction, and developmental studies place Casp3 downstream of Bcl-xL in postmitotic neuronal death while also affecting neuronal progenitor apoptosis [PMID:10479688; PMID:10618441]. Additional mouse work supports a role in apoptosis triggered by ER stress and other cell-death stimuli, but many stimulus-specific or disease-specific downstream phenotypes are context dependent rather than core gene functions PMID:12847083.

Mouse experiments also support a non-lethal neuronal remodeling role. Caspase-3 activity can act locally in dendrites to regulate spine density and dendrite morphology without causing cell death, and Casp3 knockout mice show increased spine density in vivo PMID:24478350. This supports specialized neuronal remodeling annotations, but these should generally be treated as non-core relative to the canonical apoptotic effector role.

Molecular Function

Casp3 is a major effector caspase activated by initiator caspases and cleaves many substrates during the execution phase of apoptosis. The UniProt record describes Casp3 as a thiol protease activated by CASP8, CASP9, and/or CASP10 that cleaves many apoptotic substrates including PARP1 and other caspases [file:mouse/Casp3/Casp3-uniprot.txt].

The active enzyme is a heterotetramer composed of p17 and p12 subunits and is primarily cytoplasmic or cytosolic before context-dependent redistribution during apoptosis [file:mouse/Casp3/Casp3-uniprot.txt]. Genetic and biochemical studies in mice support the core catalytic assignment to cysteine-type endopeptidase or peptidase activity rather than broad generic binding terms [PMID:9512515; PMID:16469926].

Biological Process Roles

Execution phase of apoptosis is the strongest core process assignment for Casp3. Caspase-3-deficient mouse cells and tissues show reduced or delayed apoptosis, impaired nuclear apoptotic changes, and resistance to several apoptotic stimuli, consistent with an obligate downstream effector role [PMID:9512515; PMID:10479688; PMID:16469926].

Positive regulation of apoptotic DNA fragmentation is also well supported as a mechanistic extension of the effector role because Casp3 activity is tightly linked to the nuclear changes and DNA degradation that follow apoptotic commitment PMID:9512515. Broader terms such as generic positive regulation of apoptotic process are usually correct but less precise than execution phase of apoptosis.

Some orthology-derived annotations are likely overextended. Mouse Casp3 may participate in specific inflammatory, neuronal, or disease contexts, but broad transfers to cytokine regulation, interleukin-18 signaling, amyloid-beta formation, pyroptotic inflammatory response, response to glucose, or cellular response to staurosporine do not summarize the core conserved activity of the gene and often represent downstream context rather than direct evolved function [file:mouse/Casp3/Casp3-uniprot.txt; PMID:24478350].

The neurotrophin TRK receptor signaling pathway transfer tied to PMID:23954828 appears especially weak for Casp3 itself: that paper is centered on Dok5 and TrkC survival signaling, with caspase-3 measured as a downstream apoptosis readout rather than as a dedicated Trk pathway component.

Cellular Localization and Complexes

Casp3 is primarily a cytoplasmic or cytosolic effector protease, which is consistent with both UniProt and multiple mouse annotations [file:mouse/Casp3/Casp3-uniprot.txt]. The active enzyme is a heterotetramer, so the cellular component term caspase complex is consistent with the mature protease state [file:mouse/Casp3/Casp3-uniprot.txt].

Nuclear localization can occur in apoptotic contexts and is plausible as a non-core, context-dependent localization tied to substrate cleavage and nuclear apoptotic changes PMID:9512515. In contrast, terms such as death-inducing signaling complex or direct death receptor binding are not well supported as core Casp3 localizations or molecular functions for the mouse protein itself.

Annotation Risk Assessment

The safest ISO transfers are the ones that match the established effector-caspase identity of Casp3: cysteine-type endopeptidase activity, peptidase activity, cytoplasm/cytosol, proteolysis, apoptotic process, execution phase of apoptosis, and positive regulation of apoptotic DNA fragmentation. Context-specific neuronal or differentiation annotations may be kept as non-core when they align with mouse phenotypes, but they should not define the gene.

The least defensible ISO transfers are the overly generic or mechanistically indirect ones. Protease binding, protein-containing complex binding, death receptor binding, intracellular signal transduction, protein poly-ADP-ribosylation, and several stimulus-specific response terms do not capture Casp3's direct activity. Likewise, inflammatory and amyloid-related transfers appear to summarize specialized downstream settings rather than the core role of the gene.

Key Sources

UniProt mouse Casp3 record: catalytic mechanism, active heterotetramer, cytoplasmic localization, and broad substrate cleavage claims [file:mouse/Casp3/Casp3-uniprot.txt]
Mouse developmental and neuronal apoptosis studies [PMID:10479688; PMID:10618441; PMID:9512515]
Mouse effector-caspase genetics showing critical role in mitochondrial events of apoptosis PMID:16469926
Mouse ER-stress apoptosis context PMID:12847083
Mouse synapse pruning and spine-density regulation PMID:24478350

Falcon

(Casp3-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 32 citations 2026-05-03T13:57:23.133739

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research Report: Mouse Casp3 (Caspase-3) — Functional Annotation (UniProt P70677)

0) Target verification (critical disambiguation)

The research below is focused on mouse Casp3, encoding caspase-3, an executioner (effector) caspase produced as a zymogen/precursor that is proteolytically processed into the large and small catalytic subunits during activation. This identity is consistent with the UniProt description provided (caspase-3 precursor; EC 3.4.22.56; peptidase C14 family) and with the way Casp3 is genetically manipulated and biochemically assayed in mouse-focused studies reviewed here. (zhra2024acomprehensiveexploration pages 2-4, newton2024caspasecleavageof pages 2-5)

Note on accession verification: the current full-text corpus did not explicitly restate the mapping “UniProt P70677 = mouse Casp3” inside the retrieved paper texts; however, all cited evidence is specific to caspase-3 biology and/or explicitly uses Casp3 knockout mouse genetics, matching the intended target. (zhu2024caspase3promotesoncogeneinduced pages 2-3, newton2024caspasecleavageof pages 2-5)

1) Key concepts and definitions (current understanding)

1.1 Caspase-3 definition and biochemical class

Caspase-3 is a cysteine-aspartate protease (“caspase”) functioning as a principal executioner protease in apoptotic cell death. Caspases are synthesized as precursors and are activated by proteolytic processing to generate a catalytically competent enzyme consisting of a large (p20) and small (p10) subunit. (zhra2024acomprehensiveexploration pages 2-4)

1.2 Apoptotic pathways upstream of Casp3

Caspase-3 activation sits downstream of two canonical initiation routes:
- Intrinsic (mitochondrial) apoptosis: cytochrome c and APAF1 form the apoptosome to activate caspase-9, which then processes and activates effector caspases including caspase-3. (zhra2024acomprehensiveexploration pages 2-4, araya2021deorphanizingcaspase3and pages 19-21)
- Extrinsic (death receptor) apoptosis: death-receptor signaling activates caspase-8, which can activate downstream effector caspases and/or amplify death signaling through mitochondrial engagement. (zhra2024acomprehensiveexploration pages 2-4)

1.3 Catalytic reaction and substrate specificity

Reaction: caspase-3 hydrolyzes peptide bonds in protein substrates after an aspartate (Asp) residue at P1.

Motif preference: deep N-terminomics substrate profiling showed that caspase-3 cleavage sites overwhelmingly contain P1 Asp and support a common consensus DEVD↓(G/S/A) (P4–P1↓P1′) motif. (araya2021deorphanizingcaspase3and pages 4-6)

Quantitative enzymology: the same profiling work reports caspase-3 catalytic efficiency of kcat/Km = 7.6 × 10^5 M−1 s−1 (measured in that study’s enzymatic context), illustrating why caspase-3 is considered highly proteolytically proficient among caspases. (araya2021deorphanizingcaspase3and pages 4-6)

2) Functional roles and pathway placement for annotation

2.1 Primary function: execution of apoptotic proteolysis

Caspase-3’s primary functional annotation is to execute apoptosis by cleaving a wide spectrum of substrates, dismantling cellular architecture and regulatory systems.

A large unbiased substrate dataset identified 906 putative protein substrates and 1126 cleavage sites for caspase-3 in native lysates, underscoring its broad substrate repertoire. (araya2021deorphanizingcaspase3and pages 4-6)

2.2 Subcellular context and where Casp3 acts

In the same profiling work, substrates were most enriched in cytoplasm (49%) and nucleus (48%), consistent with caspase-3 driving both cytoplasmic structural dismantling and nuclear execution events (e.g., chromatin/repair-associated substrate cleavage in apoptosis). (araya2021deorphanizingcaspase3and pages 4-6)

This supports the functional-annotation expectation that active caspase-3 operates mainly in the cytosol and nucleus once activated, though its consequences can propagate across organelles. (araya2021deorphanizingcaspase3and pages 4-6)

3) Recent developments (prioritizing 2023–2024)

3.1 2023: Caspase-3 as an executioner of pyroptosis via GSDME in an aged-mouse sarcopenia context

A 2023 Cell Death Discovery study connected inflammatory TNF-α signaling to muscle loss by implicating a TNF Complex IIb → caspase-8 → caspase-3 → GSDME axis that results in GSDME-mediated pyroptosis in skeletal muscle cells, contributing to sarcopenia phenotypes in naturally aged mice. (wu2023tnfαcontributesto pages 1-3, wu2023tnfαcontributesto pages 4-6)

Key evidence and data:
- In vivo, aged mice exhibited elevated TNF-α with biochemical evidence of cleaved caspase-8, cleaved caspase-3, and GSDME cleavage in gastrocnemius, with muscle functional/structural decline consistent with sarcopenia. (wu2023tnfαcontributesto pages 1-3, wu2023tnfαcontributesto pages 4-6)
- In vitro, TNF-α caused dose- and time-dependent GSDME cleavage in myotubes, with key experiments using TNF-α 100 ng/mL and observing effects by 48–72 h; caspase-8 inhibitor Z-IETD-FMK (50 μM) and caspase-3 inhibitor Z-DEVD-FMK (50 μM) reduced pyroptosis readouts (e.g., PI positivity/LDH release) and reversed TNF-α-associated reduction in MHC1. (wu2023tnfαcontributesto pages 3-4, wu2023tnfαcontributesto pages 4-6)

Functional-annotation implication: caspase-3 can act as a pivotal protease that switches death modalities by cleaving gasdermins (here GSDME), linking apoptosis signaling to lytic inflammatory death outcomes in tissue pathology. (wu2023tnfαcontributesto pages 4-6)

3.2 2024: Caspase-3 promotes malignant transformation and tumor progression in mouse models (non-apoptotic/pro-tumor function)

A 2024 Cell Death & Disease study reported that caspase-3 can support oncogene-induced malignant transformation and breast cancer progression (MMTV-PyMT model), through an EndoG-dependent Src–STAT3 phosphorylation mechanism. (zhu2024caspase3promotesoncogeneinduced pages 2-3, zhu2024caspase3promotesoncogeneinduced pages 1-2)

Key quantitative findings:
- During oncogene-driven transformation, approximately 80% of emerging colonies were caspase-3 reporter-positive (persistent caspase-3 activity); subpopulations with higher caspase-3 activity formed colonies more frequently, while extreme activity correlated with apoptosis. (zhu2024caspase3promotesoncogeneinduced pages 2-3)
- In MMTV-PyMT mice, Casp3 knockout profoundly delayed tumor appearance: median age of first palpable tumor was 100 days in Casp3KO;PyMT vs 47.7 days in WT. (zhu2024caspase3promotesoncogeneinduced pages 2-3, zhu2024caspase3promotesoncogeneinduced media 24728636)

Functional-annotation implication: beyond its canonical pro-death role, caspase-3 can participate in sublethal/non-apoptotic signaling that promotes oncogenic phenotypes, emphasizing context-dependent outcomes of caspase-3 activation. (zhu2024caspase3promotesoncogeneinduced pages 2-3)

3.3 2024: Caspase-3-dependent cleavage of RIPK3 at Asp333 is real but dispensable for embryogenesis

A 2024 Cell Death and Differentiation paper dissected RIPK3 cleavage and found:
- Mouse RIPK3 is cleaved after Asp333; mutation to Ala (Ripk3D333A) blocks the 38 kDa cleavage fragment. (newton2024caspasecleavageof pages 2-5)
- Endogenous RIPK3 cleavage in apoptosis was caspase-3 dependent: Casp3−/− macrophages lacked RIPK3 cleavage under apoptotic stimuli. (newton2024caspasecleavageof pages 2-5)
- Nevertheless, Ripk3D333A/D333A knock-in mice were viable, healthy (followed for at least a year), and born at expected Mendelian frequencies, indicating RIPK3 cleavage at Asp333 is dispensable for mouse development. (newton2024caspasecleavageof pages 2-5, newton2024caspasecleavageof pages 1-2)

Functional-annotation implication: this provides a validated in vivo caspase-3 substrate cleavage site (RIPK3 Asp333) while illustrating that not all caspase-3-mediated cleavages are essential for organismal viability.

3.4 2024: Mechanistic insight into caspase-3/7 discrimination for GSDME cleavage (pyroptosis crosstalk)

A 2024 eLife study clarified why caspase-3 and caspase-7—despite sharing DxxD motif recognition—differ in GSDME cleavage:
- Human caspase-3 cleaves human GSDME at DMPD to release the pore-forming N-terminus and trigger pyroptosis; mutating Asp residues blocks cleavage. (xu2024themolecularmechanism pages 2-3)
- A residue in the caspase-7 p10 subunit (S234) was identified as a determinant preventing human caspase-7 from cleaving human GSDME. (xu2024themolecularmechanism pages 2-3)

This supports a refined view that caspase substrate selectivity is shaped not only by the tetrapeptide motif but also by structural determinants within caspase subunits.

4) Current applications and real-world implementations

4.1 Caspase-3 as an apoptosis/regulated cell death biomarker and mechanistic readout

A 2024 methods-focused review summarizes that caspase activity (including caspase-3) is routinely monitored using:
- Antibody-based detection of cleaved caspases/substrates,
- FLICA/FLI activity-based probes for live-cell labeling,
- Genetically encoded FRET sensors and other real-time reporters,
- Activatable probes for in vivo imaging,
- Mass spectrometry workflows for substrate/cleavage-product discovery and quantification. (zhra2024acomprehensiveexploration pages 1-2, zhra2024acomprehensiveexploration pages 5-7)

These tools are widely implemented in cancer biology, toxicology, and drug discovery to quantify apoptosis engagement and to stratify death pathways. (zhra2024acomprehensiveexploration pages 1-2)

4.2 Performance statistics from recent assay implementations (selected examples)

The 2024 review reports high sensitivity in modern biosensing formats, including:
- Organic electrochemical transistor biosensor: LOD 0.1 pM,
- SPR imaging assay: LOD 1 pg/mL. (zhra2024acomprehensiveexploration pages 9-11)

These statistics illustrate continued engineering progress enabling low-abundance caspase-3 detection for analytical and screening use-cases.

5) Expert opinions/authoritative synthesis (what the field emphasizes)

Authoritative reviews emphasize that caspase-3 is a central node in apoptosis and that modern detection methods (single-cell imaging, activatable probes, MS-based degradomics) are increasingly important for disentangling spatiotemporal and sublethal caspase signaling from terminal apoptosis. (zhra2024acomprehensiveexploration pages 1-2, zhra2024acomprehensiveexploration pages 5-7)

Primary-mechanistic 2023–2024 studies reinforce this: caspase-3 can drive distinct outcomes (apoptosis, pyroptosis, or pro-oncogenic signaling) depending on cellular context, upstream complex assembly (e.g., TNF Complex IIb), and substrate availability (e.g., GSDME). (wu2023tnfαcontributesto pages 4-6, zhu2024caspase3promotesoncogeneinduced pages 2-3)

6) Key statistics and data points (recent literature)

906 substrates / 1126 cleavage sites mapped for caspase-3 in deep substrate profiling; DEVD↓(G/S/A) motif and P1 Asp constraint supported. (araya2021deorphanizingcaspase3and pages 4-6)
Caspase-3 enzymatic efficiency reported as kcat/Km = 7.6 × 10^5 M−1 s−1 in that profiling study. (araya2021deorphanizingcaspase3and pages 4-6)
Sarcopenia study: aged mouse cohorts (~20, 60, 88 weeks) with TNF-α elevation and cleaved caspase-8/-3 + GSDME cleavage; TNF-α myotube experiments used 100 ng/mL, with effects by 48–72 h, and inhibitors Z-IETD-FMK 50 μM and Z-DEVD-FMK 50 μM. (wu2023tnfαcontributesto pages 3-4, wu2023tnfαcontributesto pages 10-12)
Tumorigenesis: MMTV-PyMT median age of first palpable tumor 100 d (Casp3KO;PyMT) vs 47.7 d (WT), with cohort sizes n=20 KO vs n=18 WT. (zhu2024caspase3promotesoncogeneinduced pages 2-3, zhu2024caspase3promotesoncogeneinduced media 24728636)

Summary table

Topic	Key claim	Evidence details/quantitative stats	Key citation IDs	Publication info (journal, year, URL)
Target identity and core role	Mouse Casp3 encodes caspase-3, a canonical executioner/effector caspase in apoptosis, matching the UniProt P70677 description and peptidase C14 family assignment.	Reviews and substrate-profiling papers describe caspase-3 as a downstream executioner activated by initiator caspases in intrinsic/extrinsic apoptosis; caspases are synthesized as precursors and processed into large/small catalytic subunits.	(araya2021deorphanizingcaspase3and pages 19-21, zhra2024acomprehensiveexploration pages 2-4)	ACS Chemical Biology, 2021, https://doi.org/10.1021/acschembio.1c00456; International Journal of Molecular Sciences, 2024, https://doi.org/10.3390/ijms25105460
Activation pathway	Caspase-3 is activated downstream of apoptosome/caspase-9 in the intrinsic pathway and downstream of death-receptor/caspase-8 signaling in the extrinsic pathway.	Intrinsic pathway: cytochrome c + APAF1 activate caspase-9, which processes effector caspases including caspase-3; extrinsic pathway: death-receptor signaling activates caspase-8, which can directly activate downstream caspases or engage mitochondrial amplification.	(araya2021deorphanizingcaspase3and pages 19-21, zhra2024acomprehensiveexploration pages 2-4, blais2026usingabioluminescence pages 2-3)	ACS Chemical Biology, 2021, https://doi.org/10.1021/acschembio.1c00456; International Journal of Molecular Sciences, 2024, https://doi.org/10.3390/ijms25105460; Bioscience Reports, 2026, https://doi.org/10.1042/bsr20254030
Catalytic specificity	Caspase-3 is a cysteine-aspartate protease with a strict requirement for Asp at P1 and preference for DEVD-like motifs.	Deep substrate profiling identified 1126 cleavage sites across 906 proteins with P1 Asp and a DEVD↓(G/S/A) motif; catalytic efficiency reported as kcat/Km = 7.6 × 10^5 M−1 s−1 in that study.	(araya2021deorphanizingcaspase3and pages 4-6, blais2026usingabioluminescence pages 2-3)	ACS Chemical Biology, 2021, https://doi.org/10.1021/acschembio.1c00456; Bioscience Reports, 2026, https://doi.org/10.1042/bsr20254030
Representative substrate landscape	Caspase-3 cleaves a broad substrate repertoire concentrated in cytoplasmic and nuclear proteins that drive apoptotic dismantling.	Substrate profiling found substrates enriched in cytoplasm (49%) and nucleus (48%); 577 sites (51%) were newly reported relative to DegraBase.	(araya2021deorphanizingcaspase3and pages 4-6, araya2021deorphanizingcaspase3and pages 13-14)	ACS Chemical Biology, 2021, https://doi.org/10.1021/acschembio.1c00456
Representative cleavage events	Caspase-3 cleaves multiple substrates at aspartate residues, including apoptotic hallmark substrates and newer mechanistic substrates.	Literature referenced in the evidence set includes PARP1 as a hallmark target; the profiling study notes cleavage at distinct Asp sites in overlapping substrates.	(araya2021deorphanizingcaspase3and pages 13-14, blais2026usingabioluminescence pages 2-3)	ACS Chemical Biology, 2021, https://doi.org/10.1021/acschembio.1c00456; Bioscience Reports, 2026, https://doi.org/10.1042/bsr20254030
2024 non-apoptotic role: oncogenic transformation	Caspase-3 can promote malignant transformation in a non-apoptotic context via EndoG-dependent Src-STAT3 phosphorylation.	In transformed fibroblasts, about 80% of emerging colonies were caspase-3 reporter-positive; Casp3 loss reduced soft-agar growth and delayed tumorigenesis. In MMTV-PyMT mice, median age of first palpable tumor was 100 days in Casp3KO;PyMT vs 47.7 days in WT; cohorts n=20 KO vs n=18 WT.	(zhu2024caspase3promotesoncogeneinduced pages 2-3, zhu2024caspase3promotesoncogeneinduced pages 1-2)	Cell Death & Disease, 2024, https://doi.org/10.1038/s41419-024-06884-3
2023 apoptosis-pyroptosis crosstalk	In aged mouse skeletal muscle, TNF-α can drive sarcopenia through TNF Complex IIb → caspase-8 → caspase-3 → GSDME-mediated pyroptosis.	Naturally aged mice (~20, 60, 88 weeks) showed elevated local/serum TNF-α, cleaved caspase-8, cleaved caspase-3, and GSDME but not GSDMD cleavage. In C2C12 myotubes, TNF-α induced dose/time-dependent GSDME cleavage; key conditions included 100 ng/mL TNF-α, with effects detectable by 48 h and maximal around 72 h. Inhibitors included Z-IETD-FMK 50 μM, Z-DEVD-FMK 50 μM, GSK'872 1 μM; mouse groups n=9–14, cell experiments typically n=4–5.	(wu2023tnfαcontributesto pages 1-3, wu2023tnfαcontributesto pages 3-4, wu2023tnfαcontributesto pages 4-6, wu2023tnfαcontributesto pages 10-12)	Cell Death Discovery, 2023, https://doi.org/10.1038/s41420-023-01365-6
2024 substrate/pathway insight	RIPK3 is a bona fide mouse caspase-3 substrate cleaved after Asp333, but this cleavage is not essential for development.	Ripk3D333A/D333A knock-in mice lacked the 38 kDa cleavage fragment yet were viable, born at expected Mendelian ratios, and healthy; in BMDMs, RIPK3 cleavage required caspase activity and was absent in Casp3−/− cells under apoptotic conditions.	(newton2024caspasecleavageof pages 2-5, newton2024caspasecleavageof pages 5-5, newton2024caspasecleavageof pages 1-2, newton2024caspasecleavageof pages 5-7)	Cell Death and Differentiation, 2024, https://doi.org/10.1038/s41418-023-01255-5
Structural/mechanistic insight into pyroptosis linkage	Caspase-3 directly activates GSDME-mediated pyroptosis by cleaving GSDME at a DxxD motif; caspase-3/7 substrate discrimination depends on specific structural determinants.	Human CASP3 cleaves human GSDME at DMPD to release the pore-forming N-terminus; mutation of Asp residues blocks cleavage. A key determinant of why human CASP7 fails to cleave human GSDME is S234 in the CASP7 p10 subunit.	(xu2024themolecularmechanism pages 2-3)	eLife, 2024, https://doi.org/10.7554/elife.89974
Applications: live-cell and in vivo detection	Caspase-3 is widely used as a practical apoptosis readout in cell biology, toxicology, drug screening, and translational biomarker work.	2024 review catalogs antibody assays, FLICA/FLIs, FRET reporters, single-cell imaging, activatable probes, and MS-based substrate mapping as current implementations for detecting caspase activity and downstream cleavage products.	(zhra2024acomprehensiveexploration pages 9-11, zhra2024acomprehensiveexploration pages 1-2, zhra2024acomprehensiveexploration pages 5-7, zhra2024acomprehensiveexploration pages 7-9)	International Journal of Molecular Sciences, 2024, https://doi.org/10.3390/ijms25105460
Applications: assay/reporting performance examples	Recent biosensors for caspase-3 achieve very high analytical sensitivity, supporting apoptosis quantification and drug-response monitoring.	Review-reported examples include an organic electrochemical transistor biosensor with LOD 0.1 pM and an SPR imaging assay with LOD 1 pg/mL. Separate 2024 primary-method papers reported a fluorescent rGO probe with linear range 0.4–7 U/mL and LOD 0.33 U/mL, and an electrochemical MOF-based assay with linear range 0.1–25 pg/mL and LOD 0.04 pg/mL.	(zhra2024acomprehensiveexploration pages 9-11, huang2024signalondetectionof pages 10-12)	International Journal of Molecular Sciences, 2024, https://doi.org/10.3390/ijms25105460; The Analyst, 2024, https://doi.org/10.1039/d4an01059k; Molecules, 2024, https://doi.org/10.3390/molecules29153700

Table: This table condenses key functional-annotation facts for mouse Casp3/caspase-3, including its enzymology, activation pathways, representative substrates, recent 2023-2024 mechanistic findings, and practical assay applications. It is useful as a quick evidence-backed reference for annotation and interpretation.

References (URLs and publication dates)

Wu J et al. TNF-α contributes to sarcopenia through caspase-8/caspase-3/GSDME-mediated pyroptosis. Cell Death Discovery (Feb 2023). https://doi.org/10.1038/s41420-023-01365-6 (wu2023tnfαcontributesto pages 1-3)
Newton K et al. Caspase cleavage of RIPK3 after Asp333 is dispensable for mouse embryogenesis. Cell Death and Differentiation (Jan 2024). https://doi.org/10.1038/s41418-023-01255-5 (newton2024caspasecleavageof pages 2-5)
Zhu C et al. Caspase-3 promotes oncogene-induced malignant transformation via EndoG-dependent Src-STAT3 phosphorylation. Cell Death & Disease (Jul 2024). https://doi.org/10.1038/s41419-024-06884-3 (zhu2024caspase3promotesoncogeneinduced pages 2-3)
Xu H et al. The molecular mechanism and evolutionary divergence of caspase 3/7-regulated gasdermin E activation. eLife (Mar 2024). https://doi.org/10.7554/eLife.89974 (xu2024themolecularmechanism pages 2-3)
Zhra M et al. A Comprehensive Exploration of Caspase Detection Methods: From Classical Approaches to Cutting-Edge Innovations. Int J Mol Sci (May 2024). https://doi.org/10.3390/ijms25105460 (zhra2024acomprehensiveexploration pages 9-11)
Araya LE et al. Deorphanizing Caspase-3 and Caspase-9 Substrates In and Out of Apoptosis with Deep Substrate Profiling. ACS Chem Biol (Sep 2021). https://doi.org/10.1021/acschembio.1c00456 (araya2021deorphanizingcaspase3and pages 4-6)

References

(zhra2024acomprehensiveexploration pages 2-4): Mahmoud Zhra, Rani J. Qasem, Fai Aldossari, Rimah Saleem, and Ahmad Aljada. A comprehensive exploration of caspase detection methods: from classical approaches to cutting-edge innovations. International Journal of Molecular Sciences, 25:5460, May 2024. URL: https://doi.org/10.3390/ijms25105460, doi:10.3390/ijms25105460. This article has 28 citations.
(newton2024caspasecleavageof pages 2-5): Kim Newton, Katherine E. Wickliffe, Allie Maltzman, Debra L. Dugger, Joshua D. Webster, Hongyan Guo, and Vishva M. Dixit. Caspase cleavage of ripk3 after asp333 is dispensable for mouse embryogenesis. Cell Death and Differentiation, 31:254-262, Jan 2024. URL: https://doi.org/10.1038/s41418-023-01255-5, doi:10.1038/s41418-023-01255-5. This article has 15 citations and is from a domain leading peer-reviewed journal.
(zhu2024caspase3promotesoncogeneinduced pages 2-3): Chenchen Zhu, Fushun Fan, Chuan-Yuan Li, Yan Xiong, and Xinjian Liu. Caspase-3 promotes oncogene-induced malignant transformation via endog-dependent src-stat3 phosphorylation. Cell Death & Disease, Jul 2024. URL: https://doi.org/10.1038/s41419-024-06884-3, doi:10.1038/s41419-024-06884-3. This article has 35 citations and is from a peer-reviewed journal.
(araya2021deorphanizingcaspase3and pages 19-21): Luam E. Araya, Ishankumar V. Soni, Jeanne A. Hardy, and Olivier Julien. Deorphanizing caspase-3 and caspase-9 substrates in and out of apoptosis with deep substrate profiling. ACS chemical biology, 16:2280-2296, Sep 2021. URL: https://doi.org/10.1021/acschembio.1c00456, doi:10.1021/acschembio.1c00456. This article has 152 citations and is from a domain leading peer-reviewed journal.
(araya2021deorphanizingcaspase3and pages 4-6): Luam E. Araya, Ishankumar V. Soni, Jeanne A. Hardy, and Olivier Julien. Deorphanizing caspase-3 and caspase-9 substrates in and out of apoptosis with deep substrate profiling. ACS chemical biology, 16:2280-2296, Sep 2021. URL: https://doi.org/10.1021/acschembio.1c00456, doi:10.1021/acschembio.1c00456. This article has 152 citations and is from a domain leading peer-reviewed journal.
(wu2023tnfαcontributesto pages 1-3): Jingying Wu, Siming Lin, Weixiao Chen, Guili Lian, Weibin Wu, Ai Chen, Mohammad Ismail Hajary Sagor, Li Luo, Huajun Wang, and Liang-di Xie. Tnf-α contributes to sarcopenia through caspase-8/caspase-3/gsdme-mediated pyroptosis. Cell Death Discovery, Feb 2023. URL: https://doi.org/10.1038/s41420-023-01365-6, doi:10.1038/s41420-023-01365-6. This article has 109 citations and is from a peer-reviewed journal.
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(zhu2024caspase3promotesoncogeneinduced pages 1-2): Chenchen Zhu, Fushun Fan, Chuan-Yuan Li, Yan Xiong, and Xinjian Liu. Caspase-3 promotes oncogene-induced malignant transformation via endog-dependent src-stat3 phosphorylation. Cell Death & Disease, Jul 2024. URL: https://doi.org/10.1038/s41419-024-06884-3, doi:10.1038/s41419-024-06884-3. This article has 35 citations and is from a peer-reviewed journal.
(zhu2024caspase3promotesoncogeneinduced media 24728636): Chenchen Zhu, Fushun Fan, Chuan-Yuan Li, Yan Xiong, and Xinjian Liu. Caspase-3 promotes oncogene-induced malignant transformation via endog-dependent src-stat3 phosphorylation. Cell Death & Disease, Jul 2024. URL: https://doi.org/10.1038/s41419-024-06884-3, doi:10.1038/s41419-024-06884-3. This article has 35 citations and is from a peer-reviewed journal.
(newton2024caspasecleavageof pages 1-2): Kim Newton, Katherine E. Wickliffe, Allie Maltzman, Debra L. Dugger, Joshua D. Webster, Hongyan Guo, and Vishva M. Dixit. Caspase cleavage of ripk3 after asp333 is dispensable for mouse embryogenesis. Cell Death and Differentiation, 31:254-262, Jan 2024. URL: https://doi.org/10.1038/s41418-023-01255-5, doi:10.1038/s41418-023-01255-5. This article has 15 citations and is from a domain leading peer-reviewed journal.
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(zhra2024acomprehensiveexploration pages 5-7): Mahmoud Zhra, Rani J. Qasem, Fai Aldossari, Rimah Saleem, and Ahmad Aljada. A comprehensive exploration of caspase detection methods: from classical approaches to cutting-edge innovations. International Journal of Molecular Sciences, 25:5460, May 2024. URL: https://doi.org/10.3390/ijms25105460, doi:10.3390/ijms25105460. This article has 28 citations.
(zhra2024acomprehensiveexploration pages 9-11): Mahmoud Zhra, Rani J. Qasem, Fai Aldossari, Rimah Saleem, and Ahmad Aljada. A comprehensive exploration of caspase detection methods: from classical approaches to cutting-edge innovations. International Journal of Molecular Sciences, 25:5460, May 2024. URL: https://doi.org/10.3390/ijms25105460, doi:10.3390/ijms25105460. This article has 28 citations.
(wu2023tnfαcontributesto pages 10-12): Jingying Wu, Siming Lin, Weixiao Chen, Guili Lian, Weibin Wu, Ai Chen, Mohammad Ismail Hajary Sagor, Li Luo, Huajun Wang, and Liang-di Xie. Tnf-α contributes to sarcopenia through caspase-8/caspase-3/gsdme-mediated pyroptosis. Cell Death Discovery, Feb 2023. URL: https://doi.org/10.1038/s41420-023-01365-6, doi:10.1038/s41420-023-01365-6. This article has 109 citations and is from a peer-reviewed journal.
(blais2026usingabioluminescence pages 2-3): Véronique Blais and Jean-Bernard Denault. Using a bioluminescence resonance energy transfer caspase biosensor to study caspase-3 cleavage site specificity. Bioscience Reports, Mar 2026. URL: https://doi.org/10.1042/bsr20254030, doi:10.1042/bsr20254030. This article has 0 citations and is from a peer-reviewed journal.
(araya2021deorphanizingcaspase3and pages 13-14): Luam E. Araya, Ishankumar V. Soni, Jeanne A. Hardy, and Olivier Julien. Deorphanizing caspase-3 and caspase-9 substrates in and out of apoptosis with deep substrate profiling. ACS chemical biology, 16:2280-2296, Sep 2021. URL: https://doi.org/10.1021/acschembio.1c00456, doi:10.1021/acschembio.1c00456. This article has 152 citations and is from a domain leading peer-reviewed journal.
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(zhra2024acomprehensiveexploration pages 7-9): Mahmoud Zhra, Rani J. Qasem, Fai Aldossari, Rimah Saleem, and Ahmad Aljada. A comprehensive exploration of caspase detection methods: from classical approaches to cutting-edge innovations. International Journal of Molecular Sciences, 25:5460, May 2024. URL: https://doi.org/10.3390/ijms25105460, doi:10.3390/ijms25105460. This article has 28 citations.
(huang2024signalondetectionof pages 10-12): Yaliang Huang, Jiaqiang Wang, Yirui Xu, Jiwen Zhang, and Ning Xia. Signal-on detection of caspase-3 with methylene blue-loaded metal-organic frameworks as signal reporters. Molecules, 29:3700, Aug 2024. URL: https://doi.org/10.3390/molecules29153700, doi:10.3390/molecules29153700. This article has 7 citations.

Citations

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Manual

(Casp3-deep-research-manual.md)

Executive Summary Manual

Executive Summary

Caspase-3 (Casp3) in Mus musculus is a cysteine protease that serves as a pivotal executioner of apoptosis, orchestrating the controlled demolition of cells through targeted protein cleavage (pmc.ncbi.nlm.nih.gov). Synthesized as an inactive proenzyme, Casp3 is activated by initiator caspases (e.g. caspase-8 or caspase-9) via proteolytic processing into large (≈17 kDa) and small (≈12 kDa) subunits that assemble into the active heterotetrameric enzyme (pmc.ncbi.nlm.nih.gov). Once active, Casp3 cleaves a broad spectrum of substrates – it is noted as a “promiscuous” enzyme with hundreds of targets – driving classical apoptotic events such as DNA fragmentation, chromatin condensation, membrane blebbing, and phosphatidylserine exposure (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In the context of development, Casp3-mediated apoptosis is indispensable for proper tissue morphogenesis; mice lacking Casp3 show impaired programmed cell death and developmental abnormalities (especially in the nervous system) due to failure to eliminate excess cells (pmc.ncbi.nlm.nih.gov). Beyond apoptosis, emerging evidence links Casp3 to diverse biological roles including regulation of differentiation, tissue remodeling, and immune signaling (pmc.ncbi.nlm.nih.gov). For example, Casp3 can trigger a form of pro-inflammatory cell death (pyroptosis) by activating gasdermin-E pores in certain contexts (pubmed.ncbi.nlm.nih.gov), and it cleaves key antiviral signaling proteins to dampen immune activation during apoptosis (pubmed.ncbi.nlm.nih.gov). Casp3 predominantly resides in the cytosol of healthy cells (pmc.ncbi.nlm.nih.gov), with a subset localized to mitochondria and potentially nucleus, and upon activation it translocates to nuclear and other compartments to cleave substrates wherever they reside (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This report details Casp3’s molecular function, activation mechanism, subcellular localization, and the major biological processes it influences in mice. We distinguish Casp3’s well-established core functions from context-specific or pleiotropic roles, guiding Gene Ontology (GO) annotations to reflect the most robustly supported activities while cautioning against over-extension of annotations beyond the evidence. Key recent literature (2019–2024) is highlighted to ensure up-to-date understanding of Casp3’s functions and regulatory interactions.

Molecular Function

Protease Activity and Substrate Specificity: Caspase-3 is a thiol-dependent endopeptidase that recognizes and cleaves peptide bonds C-terminal to aspartate residues in substrate proteins (pmc.ncbi.nlm.nih.gov). It belongs to the cysteine-aspartic protease family (“caspases”) and is often referred to as a cysteine-type peptidase with aspartate specificity (EC 3.4.22.56). Casp3 typically targets substrates containing a conserved tetrapeptide motif ending in Asp; a classic example is the DEVD↓ motif (Asp-Glu-Val-Asp↓) which is efficiently cleaved and forms the basis of many Casp3 synthetic substrates and inhibitors (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In fact, Casp3 exhibits broad specificity, capable of cleaving a wide array of caspase recognition sequences – it has been shown to cleave substrates preferred by other caspases (e.g. sequences for caspase-6, -7, -8, etc.), albeit with varying efficiencies (pmc.ncbi.nlm.nih.gov). This broad substrate profile underlies its central role in dismantling diverse cellular components during apoptosis. Key physiological substrates of Casp3 include structural and repair proteins such as poly(ADP-ribose) polymerase-1 (PARP1, a DNA repair enzyme cleaved early in apoptosis), nuclear lamins (cleavage leads to nuclear envelope breakdown), the inhibitor of caspase-activated DNase (ICAD; cleavage releases CAD endonuclease to fragment DNA), cytoskeletal proteins (e.g. gelsolin, fodrin, etc., contributing to cytoskeletal collapse), and numerous signaling proteins (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Through these cleavages, Casp3 executes the apoptotic program.

Activation Mechanism: Caspase-3 is produced as an inactive pro-caspase (32 kDa zymogen) that must be proteolytically processed to become active (pmc.ncbi.nlm.nih.gov). Activation typically occurs via the initiator caspases of the apoptotic pathways: in the extrinsic (death receptor) pathway, caspase-8 (or -10 in humans) cleaves procaspase-3; in the intrinsic (mitochondrial) pathway, caspase-9 (within the Apaf-1 apoptosome complex) cleaves procaspase-3 (pmc.ncbi.nlm.nih.gov). The procaspase-3 molecule is cleaved at two aspartate sites, removing the N-terminal prodomain and separating the large and small subunits. These subunits then dimerize, and two such heterodimers associate to form the active caspase-3 enzyme (p17/p12)_2 (pmc.ncbi.nlm.nih.gov). The requirement for aspartate-specific cleavage ensures that Casp3 activation is tightly controlled by upstream caspases. Notably, once active, Casp3 can further amplify the cascade by cleaving and activating other effector caspases (e.g. caspase-7 and caspase-6) and even cleaving initiator caspases themselves in feedback loops (pmc.ncbi.nlm.nih.gov). This amplifying capacity cements Casp3’s role as a point-of-no-return in apoptosis. Casp3’s activity is calcium-independent (unlike some non-caspase proteases) and is primarily regulated by proteolytic activation and inhibition by dedicated proteins rather than by cofactors.

Regulation and Inhibition: In healthy cells, procaspase-3 is kept in check by the lack of upstream activating signals and by endogenous inhibitors. One major class of regulators are the Inhibitor of Apoptosis Proteins (IAPs). XIAP (X-linked IAP) binds directly to active caspase-3 and -7 via its BIR2 domain and an N-terminal linker, occluding the caspase active site and thereby blocking substrate access (pmc.ncbi.nlm.nih.gov). This potent inhibition is relieved when mitochondrial pro-apoptotic factors like Smac/DIABLO are released; Smac binds XIAP and neutralizes it, freeing Casp3 to act. Another giant IAP, BIRC6 (also known as Bruce), has been shown to bind caspase-3 and facilitate its ubiquitination and degradation, providing an additional layer of control (evidenced by increased caspase activity and apoptosis in cells or mice lacking BIRC6) (pmc.ncbi.nlm.nih.gov). Post-translational modifications of Casp3 (e.g. phosphorylation by protein kinase Akt or others) have also been reported to modulate its activity or susceptibility to activation in some contexts (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov)，though the dominant mode of control remains proteolytic processing and inhibitor binding. Summarily, Casp3’s molecular function is executioner protease activity – it irreversibly cleaves a wide range of cellular proteins once activated, an activity that is kept latent until the appropriate apoptotic signals are received.

Biological Process Roles

Execution of Apoptosis: Caspase-3’s most prominent role is in mediating the execution phase of apoptosis. Both major apoptotic pathways converge on Casp3 activation (pmc.ncbi.nlm.nih.gov), making it essential for the orderly dismantling of cells. In the extrinsic pathway, ligand binding to death receptors (e.g. Fas, TNF receptor) activates caspase-8, which directly cleaves procaspase-3 (and -7), thereby initiating the execution phase (pmc.ncbi.nlm.nih.gov). In the intrinsic pathway, cellular stress or developmental cues lead to mitochondrial outer membrane permeabilization and release of cytochrome c, which together with Apaf-1 and caspase-9 forms the apoptosome; caspase-9 then proteolyzes procaspase-3 (pmc.ncbi.nlm.nih.gov). Active Casp3 proceeds to cleave critical intracellular targets to carry out apoptosis. For example, Casp3 cleaves PARP1, halting DNA repair and trapping the cell in a death trajectory (pmc.ncbi.nlm.nih.gov). It cleaves ICAD, liberating CAD to fragment chromosomal DNA into nucleosomal units (the biochemical hallmark of apoptosis). It also cleaves nuclear lamin proteins, causing nuclear structure collapse, and cytoskeletal and adhesion proteins (like ROCK1, gelsolin, and desmoglein-2), leading to membrane blebbing and cell detachment (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Through cleavage of proteins like Xkr8 (a lipid scramblase) and other Xk-related family members, Casp3 triggers the externalization of phosphatidylserine on the cell surface – an “eat-me” signal that facilitates phagocytic uptake of the dying cell (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). All these events are coordinated to ensure the apoptotic cell is neatly disassembled and removed without leakage of harmful contents. Experimentally, Casp3 is often indispensable for these processes: genetic ablation of Casp3 in mice results in cells that undergo initiation of apoptosis but fail to complete the demolition stage effectively (e.g. they show reduced DNA fragmentation and persisting cellular structures) (pmc.ncbi.nlm.nih.gov). In vivo, Casp3-driven apoptosis is crucial for processes like digit separation, elimination of autoreactive immune cells, and neuron pruning during development. Indeed, developmental programmed cell death relies on Casp3: mice lacking Casp3 in certain genetic backgrounds exhibit ,e.g., aberrant brain development with hyperplasia and disorganized neuronal layering due to impaired apoptosis in neural progenitors (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This underscores that Casp3’s core biological process is apoptotic execution, necessary for normal development and tissue homeostasis.

Immune and Inflammatory Regulation: Although apoptosis is often considered immunologically “silent,” Caspase-3 has significant impacts on immune signaling. A striking example is its role in modulating type-I interferon (IFN) responses during cell death. Casp3 (and caspase-7) can cleave central proteins of the antiviral innate immune pathway – specifically the DNA sensor cGAS, the MAVS adaptor on mitochondria, and the transcription factor IRF3 – thereby inactivating these pathways and preventing an excessive IFN response as cells undergo apoptosis (pubmed.ncbi.nlm.nih.gov). Ning et al. (2019) demonstrated that in human cells activated caspase-3 cleaves cGAS, MAVS, and IRF3, and in Casp3-deficient murine cells there is a failure to shut off IFN production (pubmed.ncbi.nlm.nih.gov). As a result, Casp3^-/- mice showed elevated baseline IFN levels and were more resistant to viral infections, indicating that apoptotic caspases normally suppress antiviral cytokine production (pubmed.ncbi.nlm.nih.gov). This suggests Casp3 helps maintain immune homeostasis by ensuring that apoptotic cell clearance does not trigger autoimmune or inflammatory reactions. Another facet of Casp3’s immune role is its ability to process cytokines: Casp3 can cleave pro-IL-1β and pro-IL-18 (the pro-inflammatory cytokines classically matured by caspase-1). Casp3’s cut on IL-18 has been shown to be inactivating under some conditions (trimming it in a way that prevents signalling), which may further dampen inflammation (www.nature.com). Intriguingly, a recent study found that a shorter form of IL-18 generated by Casp3 cleavage can actually mobilize NK cells to fight tumors (www.nature.com), reflecting a nuanced regulatory role. Moreover, Casp3 is intimately involved in the apoptosis of immune cells themselves – for instance, during negative selection in the thymus (eliminating self-reactive T cells) or during contraction of immune responses, Casp3 executes the death of these lymphocytes. Phenotypically, Casp3 knockout mice show dysregulation in certain immune cell populations (for example, altered T and B cell homeostasis has been reported) due to cells surviving when they should be deleted (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Thus, Casp3 contributes to immune system processes both by culling cells and by biochemical crosstalk with inflammatory signaling.

Pyroptosis and Pro-inflammatory Cell Death: Apart from apoptosis, Caspase-3 can also drive pyroptosis, a lytic form of programmed cell death, under specific circumstances. Pyroptosis is typically mediated by inflammatory caspases (caspase-1/11 in mice) through cleavage of Gasdermin D, but Casp3 provides an alternative pathway via Gasdermin E (GSDME). In cells that express GSDME, Casp3 cleavage of GSDME’s inhibitory domain produces a pore-forming N-terminal fragment that perforates the plasma membrane, causing cell swelling and lysis (pmc.ncbi.nlm.nih.gov). This Casp3/GSDME axis effectively switches a would-be apoptotic event into a pyroptotic one, often accompanied by release of pro-inflammatory contents (e.g. HMGB1, IL-1 family cytokines) (pmc.ncbi.nlm.nih.gov). Wang et al. (2017) first showed that certain chemotherapy drugs kill cancer cells through Casp3-mediated GSDME activation, leading to pyroptosis rather than apoptosis (pmc.ncbi.nlm.nih.gov). Subsequent studies in 2020–2023 have revealed Casp3/GSDME-induced pyroptosis plays important roles in various contexts: it has been implicated in anti-tumor immunity (dying tumor cells releasing signals to attract immune cells) and in pathological conditions like sepsis and tissue injury where heightened inflammation occurs (pubmed.ncbi.nlm.nih.gov). For example, Jiao et al. (2023) highlight that Casp3/GSDME-mediated pyroptosis is a significant pathway in sepsis, proposing it as a therapeutic target in hyperinflammatory diseases (pubmed.ncbi.nlm.nih.gov). It’s important to note that GSDME is not ubiquitously expressed; thus, this pyroptotic outcome for Casp3 is context-dependent (e.g. high in some tumors, certain tissues). In Mus musculus, the Gsdme gene is functional (also known as DFNA5 in humans), and Casp3-driven pyroptosis has been observed in mouse models of chemotherapy and inflammatory injury (pmc.ncbi.nlm.nih.gov). Therefore, while Casp3’s default role leads to apoptotic cell death, in GSDME-positive environments it can participate in pyroptotic, pro-inflammatory death, bridging apoptosis and inflammation.

Neuronal Roles – Development and Synaptic Remodeling: Caspase-3 plays a critical role in neuronal development by removing excess neurons and sculpting neural circuits. During embryogenesis and early postnatal development, waves of Casp3-mediated apoptosis eliminate neurons that fail to integrate properly into circuits. As mentioned, Casp3-null mice in certain strains suffer brain overgrowth, ectopic neurons, and perinatal lethality due to insufficient developmental apoptosis in the CNS (pmc.ncbi.nlm.nih.gov). Beyond this developmental pruning, there is growing evidence that Casp3 has sub-lethal functions in mature neurons, particularly in synaptic plasticity and remodeling. Low levels of Casp3 activity have been detected in neurons undergoing adaptive changes without overt cell death. For instance, localized Casp3 activation is required for activity-dependent synapse elimination in the visual system: in a 2025 study, Yu et al. demonstrated that knocking out Casp3 in mice prevented microglia from engulfing weak synapses during circuit refinement, indicating Casp3 activity in neurons acts as a tag for synapse removal (elifesciences.org) (elifesciences.org). In hippocampal neurons, mild Casp3 activation has been linked to forms of long-term depression (LTD) and dendritic pruning – Jo et al. (2011) showed that suppression of LTP (long-term potentiation) and induction of LTD can require Casp3 activity, likely via cleavage of specific synaptic proteins (elifesciences.org). Additionally, aberrant Casp3 activation is implicated in neurodegenerative disease models: e.g., D’Amelio et al. (2011) reported early synaptic dysfunction in an Alzheimer’s model correlated with Casp3 activation in neurons (elifesciences.org). Mechanistically, Casp3 can cleave substrates like Akt kinase in dendrites, which leads to AMPA receptor internalization and synapse weakening (observed in LTD paradigms) (pmc.ncbi.nlm.nih.gov). Thus, synaptic remodeling and plasticity are influenced by Casp3 as a signaling protease, independent of killing the neuron. These non-apoptotic neural roles are usually tightly restricted in space and time, to avoid triggering full apoptosis. However, they underline Casp3’s versatility: it not only eliminates neurons wholesale during development, but also fine-tunes synaptic connections in the adult brain.

Cell Differentiation and Tissue Remodeling: Apart from its death-dealing functions, Casp3 has been implicated in the regulation of differentiation in multiple systems. In several contexts, a transient activation of Casp3 occurs without causing cell death but instead promotes a change in cell state. One well-characterized example is in muscle regeneration: Dick et al. (2015) found that activation of Casp3 in muscle satellite cells (muscle stem cells) is required to trigger their differentiation into muscle fibers (pubmed.ncbi.nlm.nih.gov). Casp3 directly cleaves the transcription factor Pax7, which is a master regulator of satellite cell self-renewal; cleavage of Pax7 by Casp3 inactivates it, thereby pushing the cells out of the stem-like state and allowing myogenic differentiation to proceed (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). In Pax7 cleavage-site mutant mice or when Casp3 is chemically inhibited, satellite cells fail to differentiate properly and muscle regeneration is impaired, demonstrating a non-apoptotic role for Casp3 in tissue repair (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). Similar phenomena have been observed in other lineages: during erythroid differentiation, Casp3 cleaves certain RNA-binding proteins to facilitate maturation of red blood cells (pmc.ncbi.nlm.nih.gov); during lens fiber cell differentiation, caspases (including Casp3) are activated to remove the nucleus and organelles of lens cells in a non-lethal manner (the cells survive as anucleate lens fibers). Casp3 has also been associated with regulating the cell cycle in progenitor cells – for instance, cleaving cell-cycle inhibitors or regulators to bias cells towards cycle exit and differentiation (pmc.ncbi.nlm.nih.gov). These sub-apoptotic roles typically involve careful control of Casp3 activity (partial activation or spatial confinement). They highlight that Casp3’s biological process involvement isn’t strictly limited to executing cell death: it can also act as a switch in cell-fate decisions and morphogenesis. Nonetheless, such roles are context-specific and often intersect with apoptotic pathways (sometimes termed “pre-apoptotic” signaling).

In summary, Casp3 is centrally involved in programmed cell death (apoptosis), with broad downstream effects on development and homeostasis. It also partakes in inflammatory regulation (via pyroptosis and cytokine/interferon modulation), in neuronal circuit refinement and function, and in certain differentiation programs. Each of these roles is supported by experimental evidence, particularly from gene knockout studies and biochemical analyses in mice. However, the strength of evidence and physiological relevance can vary, as discussed below.

Cellular Localization and Complexes

Subcellular Localization: Caspase-3 is predominantly a cytosolic protein. In healthy cells, the procaspase-3 is found diffusely in the cytosol and also, notably, within the mitochondrial intermembrane space (pmc.ncbi.nlm.nih.gov). Mancini et al. (1998) showed that a fraction of procaspase-3 resides inside mitochondria, which may facilitate efficient coupling of mitochondrial apoptotic signals to Casp3 activation (pmc.ncbi.nlm.nih.gov). There is also evidence for a low level of nuclear localization of procaspase-3 in some cell types: for example, studies in lymphoid cells detected constitutive presence of procaspase-3 in the nucleus (often colocalized with its substrate ICAD) (pmc.ncbi.nlm.nih.gov). This suggests Casp3 is poised in multiple compartments. Upon apoptotic stimulation, active (cleaved) Casp3 has been observed initially in the cytoplasm and then rapidly accumulating in the nucleus (pmc.ncbi.nlm.nih.gov). This translocation allows Casp3 to access nuclear substrates like ICAD, PARP1, and lamins to execute nuclear dismantling. In apoptotic cells, cleaved Casp3 is commonly detected in both cytosol and nucleus, consistent with its role in globally cleaving targets throughout the cell. Casp3 does not have a membrane-targeting domain and lacks signal peptides, so it is generally excluded from organelles like the endoplasmic reticulum or secretory pathway. However, because some procaspase-3 is in the mitochondrial intermembrane space, once mitochondria rupture (during apoptosis) that Casp3 is released into the cytosol, potentially providing a burst of local activity (pmc.ncbi.nlm.nih.gov). Casp3 is not typically secreted (unlike inflammatory caspases, which can be released in inflammasomes), so its action is cell-intrinsic. For GO annotation, the well-supported localizations for mouse Casp3 are cytosol, cytoplasm (including centrosomal and perinuclear regions as reported in some cells), and nucleus (particularly during apoptosis). Additionally, by virtue of being in the mitochondrial intermembrane space, Casp3 could be annotated to mitochondria, though this subfraction’s functional significance is to augment intrinsic pathway signaling (pmc.ncbi.nlm.nih.gov). No stable presence of Casp3 on the plasma membrane or extracellular space has been noted, in line with it functioning inside cells.

Protein Complexes and Interactions: In its active form, Casp3 exists as a homodimer of heterodimers (p17/p12)_2, but this form is not known to be part of large stable holoenzymes – rather, it diffuses and cleaves substrates. That said, Casp3 does engage in several important molecular interactions and transient complexes:

Apoptosome: Caspase-3 is downstream of the Apaf-1/cytochrome c/caspase-9 apoptosome complex. While Casp3 is not a component of the apoptosome, it rapidly associates upon activation. Caspase-9 within the apoptosome cleaves procaspase-3 that is recruited to the vicinity. Thus, one can consider Casp3 as functionally linked to the apoptosome, and it might be co-immunoprecipitated as part of the post-activation complex. The apoptosome and Casp3 together propagate the intrinsic apoptosis signal (pmc.ncbi.nlm.nih.gov).
Death-Inducing Signaling Complex (DISC): In extrinsic apoptosis, Casp3 is again not a direct component of the DISC (which contains Fas/TNFR, FADD, procaspase-8, etc.), but active caspase-8 from the DISC cleaves procaspase-3 in proximity. Casp3 can briefly interact with components like caspase-8 during this handoff. In some cases, caspase-8 might first activate caspase-3 which then feedback cleaves additional caspase-8 molecules, forming a transient amplification complex.
IAP Complexes: A crucial regulatory complex involving Casp3 is with Inhibitor of Apoptosis Proteins. XIAP (BIRC4) binds caspase-3 in a binary complex – the BIR2 domain of XIAP plus its linker region binds across the Casp3 dimer interface, inserting into the active site cleft of Casp3 (pmc.ncbi.nlm.nih.gov). This steric inhibition prevents Casp3 from cleaving substrates. Structural and biochemical studies (e.g. Scott et al., 2005) detail how XIAP’s linker occupies the substrate-binding groove of Casp3 (pmc.ncbi.nlm.nih.gov). In cells, Casp3–XIAP complexes are common immediately after Casp3 activation, until Smac/DIABLO is released from mitochondria to displace XIAP. BIRC6 (Bruce) is another anti-apoptotic protein that interacts with Casp3. BIRC6 is a 528 kDa ubiquitin-conjugating enzyme/IAP hybrid; it has been shown to bind procaspase-3 and possibly active Casp3, sequestering it and tagging it for ubiquitination (pmc.ncbi.nlm.nih.gov). For instance, Birc6 mutant mouse embryos exhibited elevated caspase-3 activity and excessive cell death, indicating that the BIRC6–caspase-3 interaction normally restrains caspase-3 (pmc.ncbi.nlm.nih.gov). Thus Casp3 can be part of a complex with IAPs in resting cells (procaspase-3–BIRC6) or in recently activated cells (caspase-3–XIAP).
Caspase Cascades: Casp3 also transiently interacts with other caspases during activation. For example, caspase-3 can form a complex with caspase-9 when caspase-9 cleaves it, or Casp3 can dimerize with caspase-7 under certain conditions (heterodimer formation, although primarily it functions as homodimer). In a broader sense, Casp3 is part of the executioner caspase complex (caspase-3, -6, -7) that often co-localize and share substrates in apoptotic cells, but there isn’t a stable ternary complex – rather, they act in parallel and can compensate for each other to some degree (pmc.ncbi.nlm.nih.gov).
Substrate Complexes: As an enzyme, Casp3 binds briefly to its substrates during cleavage. Some cleavage events occur in specific subcellular locales, e.g., Casp3 cleaving gelsolin at the plasma membrane to promote blebbing, or Casp3 cleaving Akt1 at synapses during LTD (pmc.ncbi.nlm.nih.gov). These could be considered micro-complexes of Casp3 with a target protein at a location, sometimes scaffolded by other molecules. For instance, Casp3’s cleavage of Xkr8 at the membrane might involve a momentary complex on the inner leaflet of the plasma membrane (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). However, such interactions are transient and typically not captured as stable complexes suitable for GO “protein complex” annotation.

In summary, Casp3 is largely a soluble cytosolic/nuclear enzyme that can shuttle between cytoplasm and nucleus upon activation. It does not reside in membranes or organelle structures (aside from the intramitochondrial pool of procaspase). It operates within higher-order signaling assemblies like the apoptosome only transiently. The most well-defined stable binding partnerships of Casp3 are with its inhibitors (IAPs), which form inhibitory complexes to regulate Casp3’s activity. These interactions and localizations are strongly supported by biochemical fractionation, confocal microscopy, and structural studies (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov), providing confidence in annotating Casp3 to compartments like cytosol, mitochondrion, nucleus and to protein binding functions like IAP binding.

Annotation Risk Assessment

Core Functions vs. Context-Specific Roles: Caspase-3’s core functions – as an executioner of apoptosis – are firmly established and should form the backbone of its GO annotations. These include Molecular Function terms like cysteine-type endopeptidase activity and Biological Process terms such as execution phase of apoptosis (and child terms like intrinsic apoptotic signaling pathway and extrinsic apoptotic signaling pathway, where Casp3 acts downstream) (pmc.ncbi.nlm.nih.gov). Also well-supported is Casp3’s role in developmental programmed cell death, given clear phenotypes in mouse knockouts showing failure of proper developmental apoptosis (pmc.ncbi.nlm.nih.gov). Annotations to Cellular Component for cytosol and nucleus are low-risk, as multiple studies confirm Casp3 localization in those compartments (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). These core annotations reflect ubiquitous, conserved functions of Casp3 and are unlikely to change with new data.

However, Casp3’s pleiotropy means it has been implicated in many processes beyond canonical apoptosis, and curators should carefully evaluate which of these warrant direct annotation. Some reported roles might be secondary consequences of apoptosis rather than independent functions. For example, Casp3 knockout mice show altered T-cell and B-cell homeostasis (presumably because apoptosis is required for removing excess immune cells) (pmc.ncbi.nlm.nih.gov). While it could be annotated to “regulation of lymphocyte homeostasis”, this is essentially via its apoptotic role. Curators should ensure that such process annotations are backed by direct evidence that Casp3 is mechanistically involved, and not merely that Casp3^-/- mice have more cells (an indirect phenotype). In this case, “apoptotic process involved in T cell homeostasis” might be more precise than broadly stating “T cell homeostasis.”

Similarly, Casp3 influences cell cycle and proliferation by killing cells or cleaving cell-cycle regulators during apoptosis. Annotations like “negative regulation of cell proliferation” could apply (since Casp3-mediated apoptosis curtails cell numbers), but this might overlap with the apoptosis terms. Unless there is evidence of Casp3 directly modulating the cell cycle in a non-lethal context, such annotations should be used with caution. Svandova et al. (2024) note that caspases (including Casp3) can target pathways beyond apoptosis, such as cell proliferation and differentiation (pmc.ncbi.nlm.nih.gov), but these functions are context-dependent and often subtle.

Context-Specific Roles: New research has expanded Casp3’s functional repertoire, but not all of these findings are universally applicable. For instance, Casp3’s role in synaptic plasticity and elimination is supported by robust studies in the visual system and hippocampus (elifesciences.org) (elifesciences.org). It may be appropriate to annotate Casp3 to processes like synapse pruning or long-term synaptic depression in the nervous system. Yet, these are highly cell-type specific. If GO has terms such as “axon pruning” or “synapse elimination in developmental growth cone remodeling,” Casp3 could be linked with an evidence code from the eLife 2025 study (IMP from mutant phenotype) (elifesciences.org). The risk is that such annotations might be over-generalized. In a GO context, one might add “caspase-3 involved in synapse elimination (IMP)” with a taxon constraint to mouse, and perhaps a comment about context (e.g. activity-dependent pruning in visual thalamus). This ensures that the annotation reflects a specific biological scenario rather than a universal function of Casp3.

Another example is Casp3 in muscle differentiation: the PNAS 2015 study provides strong evidence that Casp3 activity is required for muscle stem cell differentiation (via Pax7 cleavage) (pubmed.ncbi.nlm.nih.gov). This justifies an annotation to “positive regulation of muscle cell differentiation” or “skeletal muscle regeneration.” Yet, curators should note this is a non-apoptotic role where Casp3 is briefly active without causing cell death. It’s a bona fide function (with mechanistic basis) in muscle biology, so it can be included, but with the understanding that it’s context-specific (satellite cells post-injury). One could annotate Casp3 with “proteolysis involved in cell differentiation” or similar, referencing that study. The risk of omitting such roles is missing important biology, but the risk of including them is potentially implying Casp3 always does this – which it doesn’t (in most other cell types, Casp3 activation = death, not differentiation). Thus, annotations should be as specific as possible (e.g., regulation of myoblast differentiation with evidence from that experiment).

Pyroptosis and Cytokine Processing: Casp3’s role in pyroptosis via GSDME is now well-supported by multiple studies (pmc.ncbi.nlm.nih.gov). It would be reasonable to annotate Casp3 to “pyroptosis” or “gasdermin-mediated programmed cell death” with appropriate evidence, perhaps with a qualifier that it’s observed in cells expressing GSDME. The risk here is minimal, as the literature consensus since 2017 acknowledges caspase-3/GSDME pyroptosis in both human and mouse cells (pmc.ncbi.nlm.nih.gov). However, curators should avoid conflating this with caspase-1 mediated pyroptosis – it might be useful to specify “caspase-3-dependent pyroptosis” in a free-text comment. For cytokine maturation, Casp3 cleavage of IL-1β and IL-18 is documented, but this is not the primary pathway for these cytokines. GO has specific terms for “interleukin-1 beta maturation”. Casp3 could be annotated as a protease that participates in an alternative IL-18 processing pathway (www.nature.com), but that might be considered a bit peripheral. The UniProt entry notes IL-18 inactivation by Casp3 (“by similarity”), indicating it’s not strongly experimentally shown in mouse yet. It may be safer to hold off annotating Casp3 to IL-18 processing until more direct evidence in mice is published (the 2025 Nature Immunology study in tumors suggests a functional outcome, but one might wait for confirmation). Over-extension in this area could mislead if Casp3 is thought to be a routine IL-18 activator (which it is not in normal inflammasome responses).

Pleiotropy and Cautions: Because Casp3 is such a central protease, perturbations can produce wide-ranging phenotypes that tempt broad GO annotations. One should consider whether Casp3 is directly executing a process or if the process is a downstream effect of apoptosis. For example, an annotation like “axon guidance” would be inappropriate even if Casp3 knockout mice have neuron wiring defects – the direct role is in axon pruning via apoptosis, not guidance cues. Another example: Casp3-deficient mice reportedly have a modest resistance to certain infections and reduced severity of experimental autoimmune encephalomyelitis (EAE) due to higher IFN levels (pubmed.ncbi.nlm.nih.gov). While one could annotate “negative regulation of type I interferon production” to Casp3, it’s important to note this is a consequence of Casp3’s cleavage of cGAS/IRF3 (pubmed.ncbi.nlm.nih.gov). Given the strong mechanistic basis, this particular annotation is actually justified (with IMP from the Mol Cell 2019 study). But care must be taken: such immunomodulatory annotations should be clearly supported by specific experiments (e.g. Casp3^-/- vs WT comparisons showing differential cytokine responses) to avoid speculative links.

In GO revision, it’s advisable to separate core annotations from context-specific ones. Core annotations (apoptosis, executioner caspase activity, cytosol/nucleus localization) carry essentially no controversy. Contextual annotations (synaptic plasticity, muscle regeneration, innate immune regulation, pyroptosis) should be tagged with the evidence type and perhaps a note indicating the context (which GO allows via annotation extensions or notes). This will help users of GO understand that, for instance, Casp3 is not generally causing pyroptosis in all cells, but does so in the presence of GSDME (an annotation extension could even specify acts_in_presence_of Gsdme if such formalism existed).

Finally, curators should monitor ongoing research. Casp3’s newly discovered roles – especially non-apoptotic ones – are an active area. For instance, evidence for Casp3 in learning and memory processes is growing (elifesciences.org), but we’d await consensus before adding a term like “memory consolidation” to Casp3. The annotation strategy should prioritize well-reproduced functions and use high-quality, recent references for any new roles. By balancing inclusivity of new findings with caution against one-off results, the GO annotations for Casp3 will remain accurate and informative.

Key Literature

Svandová et al., Apoptosis, 2024 (June 2, 2024): “Exploring caspase functions in mouse models.” – Comprehensive review of caspase knockout phenotypes and functions. Summarizes Casp3 as a ubiquitous executioner caspase with broad substrates, essential for developmental apoptosis (strain-specific Casp3^-/- phenotypes in brain) and also highlights non-apoptotic roles in differentiation, proliferation, and immunomodulation (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). (DOI: 10.1007/s10495-024-01976-z)
Ning et al., Molecular Cell, 2019 (Apr 4, 2019): “Apoptotic caspases suppress type I interferon production via cleavage of cGAS, MAVS, and IRF3.” – Identified caspase-3 (in human cells) and caspase-7 (in mice) as key negative regulators of cytosolic DNA/RNA sensing pathways. Showed that activated Casp3 cleaves antiviral signaling proteins, dampening IFN-β output during apoptosis (pubmed.ncbi.nlm.nih.gov). Casp3^-/- mice exhibited heightened IFN and virus resistance, linking Casp3 to immune homeostasis (pubmed.ncbi.nlm.nih.gov). (DOI: 10.1016/j.molcel.2019.02.013)
Bhat et al., Int. J. Biol. Macromolecules, 2023 (Jul 1, 2023): “The pyroptotic role of caspase-3/GSDME signaling pathway among various cancers: A review.” – Recent review detailing how caspase-3 cleavage of Gasdermin E can induce pyroptotic cell death. Discusses evidence across cancer types that Casp3/GSDME activation leads to inflammatory cell lysis, with implications for cancer therapy and immune response (pubmed.ncbi.nlm.nih.gov). Highlights the concept of Casp3 as a switch between apoptosis and pyroptosis depending on cellular context. (DOI: 10.1016/j.ijbiomac.2023.124832)
Wang et al., Nature, 2017 (July 6, 2017): “Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin.” – Seminal study that first demonstrated caspase-3 can drive pyroptosis. Showed that certain chemotherapeutic agents activate Casp3, which cleaves Gasdermin E to form membrane pores, causing pyroptosis in cancer cells (pmc.ncbi.nlm.nih.gov). Provided a mechanistic link between apoptotic pathways and inflammatory death, explaining chemotherapy-induced tumor cell immunogenicity. (DOI: 10.1038/nature22393)
Yu & Gutu et al., eLife, 2025 (Oct 18, 2024 preprint; Jun 10, 2025 final): “Activity-dependent synapse elimination requires caspase-3 activation.” – Cutting-edge research in neuroscience showing that Casp3 is necessary for developmental synaptic pruning. In Casp3 KO mice, microglia failed to eliminate weaker synapses in the visual thalamus, resulting in improper circuit refinement (elifesciences.org). Demonstrated localized Casp3 activation at synapses following activity blockade and linked it to engulfment signals (likely via phosphatidylserine exposure on synapses). (eLife 13: e101779, 2025.)
Dick et al., PNAS, 2015 (Sep 22, 2015): “Caspase 3 cleavage of Pax7 inhibits self-renewal of satellite cells.” – Provided direct evidence of Casp3 in a differentiation context. Showed that Casp3 is transiently activated in muscle satellite cells after injury, cleaving the Pax7 transcription factor (pubmed.ncbi.nlm.nih.gov). This cleavage drives satellite cells out of quiescence into differentiation, and blocking Casp3 activity impeded muscle regeneration (pubmed.ncbi.nlm.nih.gov). Highlights a non-apoptotic role for Casp3 in tissue regeneration. (PMID: 26372956, PMCID: PMC4586837)
Suzuki et al., J. Biol. Chem., 2014 (Oct 31, 2014): “Exposure of phosphatidylserine by Xk-related protein family members during apoptosis.” – Investigated how apoptotic cells expose “eat-me” signals. Found that Caspase-3/7 directly cleave Xkr8, Xkr4, Xkr9 membrane proteins at conserved caspase sites, activating these scramblases (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This established the mechanism by which Casp3 causes phosphatidylserine exposure on dying cell surfaces to promote phagocytosis. (JBC 289(44):30257–67)
Scott et al., EMBO J., 2005 (Jan 13, 2005): “XIAP inhibits caspase-3 and -7 using two binding sites.” – Structural and biochemical analysis of the Casp3–XIAP interaction. Revealed that XIAP’s BIR2 domain and adjacent linker bind caspase-3, blocking its catalytic pocket (pmc.ncbi.nlm.nih.gov). Mutational studies showed this interaction is crucial for XIAP’s inhibition of apoptosis. This is a key reference for understanding caspase regulation by IAP complexes. (PMCID: PMC548652)

Each of these sources provides valuable insights: from broad reviews of caspase function to specific experimental findings on Casp3’s roles in apoptosis, immunity, neural development, and beyond. They underpin the annotations and statements made in this report, ensuring that the information is both current and grounded in experimental evidence.

📄 View Raw YAML

id: P70677
gene_symbol: Casp3
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:10090
  label: Mus musculus
description: >-
  Mouse Casp3 encodes caspase-3, a cysteine-aspartate effector protease that is activated by initiator
  caspases and executes apoptosis by cleaving many cellular substrates, including PARP1 and other proteins
  that drive apoptotic morphology and DNA fragmentation. Its core biology is cytoplasmic/cytosolic proteolysis
  during the execution phase of apoptosis, with additional context-specific roles in neuronal remodeling,
  inflammation, and development.
existing_annotations:
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: cytoplasm is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0006915
    label: apoptotic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: apoptotic process is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0004197
    label: cysteine-type endopeptidase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: cysteine-type endopeptidase activity is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0006508
    label: proteolysis
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: proteolysis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0031264
    label: death-inducing signaling complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: death-inducing signaling complex is not a supported direct annotation for Casp3 in this review.
    action: REMOVE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
- term:
    id: GO:0097194
    label: execution phase of apoptosis
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: execution phase of apoptosis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0008047
    label: enzyme activator activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: enzyme activator activity likely overstates a direct role for Casp3 relative to the curated effector-caspase evidence.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports Casp3 as an executioner protease; broad substrate/pathway outputs can overstate direct Casp3 function.
- term:
    id: GO:0043525
    label: positive regulation of neuron apoptotic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0030182
    label: neuron differentiation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0030216
    label: keratinocyte differentiation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0030218
    label: erythrocyte differentiation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0004190
    label: aspartic-type endopeptidase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: aspartic-type endopeptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.
    action: MODIFY
    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_replacement_terms: &id001
    - id: GO:0004197
      label: cysteine-type endopeptidase activity
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
- term:
    id: GO:0004197
    label: cysteine-type endopeptidase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: cysteine-type endopeptidase activity is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: cytoplasm is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0006508
    label: proteolysis
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: proteolysis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0008234
    label: cysteine-type peptidase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Cysteine-type peptidase activity is correct but under-specific for Casp3.
    action: MODIFY
    reason: Use GO:0004197 cysteine-type endopeptidase activity, which better captures executioner caspase-3 proteolytic activity.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Involved in the activation cascade of caspases responsible for apoptosis execution.
    proposed_replacement_terms:
    - id: GO:0004197
      label: cysteine-type endopeptidase activity
- term:
    id: GO:0009411
    label: response to UV
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Response to UV is not supported as a positive Casp3 annotation in the reviewed evidence.
    action: REMOVE
    reason: 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 should therefore not be retained.
    supported_by:
    - reference_id: PMID:11092819
      supporting_text: critically dependent on p53 and caspase 9, but neither Bax nor caspase 3 expression.
- term:
    id: GO:0051402
    label: neuron apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Neuron apoptotic process is a valid developmental or neuronal context for Casp3, but not its core molecular function.
    action: KEEP_AS_NON_CORE
    reason: Casp3 core function is cysteine-type endopeptidase executioner caspase activity; neuron apoptosis is a context-specific process output.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Involved in the activation cascade of caspases responsible for apoptosis execution.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17124493
  review:
    summary: protein binding is not a supported direct annotation for Casp3 in this review.
    action: REMOVE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18585351
  review:
    summary: protein binding is not a supported direct annotation for Casp3 in this review.
    action: REMOVE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19759058
  review:
    summary: protein binding is not a supported direct annotation for Casp3 in this review.
    action: REMOVE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
- term:
    id: GO:0001554
    label: luteolysis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: luteolysis is likely an over-annotation for Casp3 without term-specific evidence in the review materials.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
- term:
    id: GO:0001666
    label: response to hypoxia
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to hypoxia is likely an over-annotation for Casp3 without term-specific evidence in the review materials.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
- term:
    id: GO:0001818
    label: negative regulation of cytokine production
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0002020
    label: protease binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: protease binding is not a supported direct annotation for Casp3 in this review.
    action: REMOVE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
- term:
    id: GO:0005123
    label: death receptor binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: death receptor binding is not a supported direct annotation for Casp3 in this review.
    action: REMOVE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: nucleus reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cytosol is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0006915
    label: apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: apoptotic process is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0007413
    label: axonal fasciculation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0007611
    label: learning or memory
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0008233
    label: peptidase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: peptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.
    action: MODIFY
    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_replacement_terms: *id001
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
- term:
    id: GO:0009410
    label: response to xenobiotic stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to xenobiotic stimulus is likely an over-annotation for Casp3 without term-specific evidence in the review materials.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
- term:
    id: GO:0009749
    label: response to glucose
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to glucose is likely an over-annotation for Casp3 without term-specific evidence in the review materials.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
- term:
    id: GO:0010038
    label: response to metal ion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to metal ion is likely an over-annotation for Casp3 without term-specific evidence in the review materials.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
- term:
    id: GO:0010165
    label: response to X-ray
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to X-ray is likely an over-annotation for Casp3 without term-specific evidence in the review materials.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
- term:
    id: GO:0016005
    label: phospholipase A2 activator activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: phospholipase A2 activator activity is not a supported direct annotation for Casp3 in this review.
    action: REMOVE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
- term:
    id: GO:0016485
    label: protein processing
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0021766
    label: hippocampus development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0030163
    label: protein catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: protein catabolic process likely overstates a direct role for Casp3 relative to the curated effector-caspase evidence.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports Casp3 as an executioner protease; broad substrate/pathway outputs can overstate direct Casp3 function.
- term:
    id: GO:0030182
    label: neuron differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0030218
    label: erythrocyte differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0031264
    label: death-inducing signaling complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: death-inducing signaling complex is not a supported direct annotation for Casp3 in this review.
    action: REMOVE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
- term:
    id: GO:0031647
    label: regulation of protein stability
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: regulation of protein stability is not a supported direct annotation for Casp3 in this review.
    action: REMOVE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
- term:
    id: GO:0032025
    label: response to cobalt ion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to cobalt ion is likely an over-annotation for Casp3 without term-specific evidence in the review materials.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
- term:
    id: GO:0032355
    label: response to estradiol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to estradiol is likely an over-annotation for Casp3 without term-specific evidence in the review materials.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
- term:
    id: GO:0032496
    label: response to lipopolysaccharide
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to lipopolysaccharide is likely an over-annotation for Casp3 without term-specific evidence in the review materials.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
- term:
    id: GO:0032880
    label: regulation of protein localization
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0034349
    label: glial cell apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0035094
    label: response to nicotine
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to nicotine is likely an over-annotation for Casp3 without term-specific evidence in the review materials.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
- term:
    id: GO:0035556
    label: intracellular signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: intracellular signal transduction is not a supported direct annotation for Casp3 in this review.
    action: REMOVE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
- term:
    id: GO:0036269
    label: swimming behavior
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0042542
    label: response to hydrogen peroxide
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to hydrogen peroxide is likely an over-annotation for Casp3 without term-specific evidence in the review materials.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0043065
    label: positive regulation of apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0043200
    label: response to amino acid
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to amino acid is likely an over-annotation for Casp3 without term-specific evidence in the review materials.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
- term:
    id: GO:0043523
    label: regulation of neuron apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0043525
    label: positive regulation of neuron apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0044877
    label: protein-containing complex binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: protein-containing complex binding is not a supported direct annotation for Casp3 in this review.
    action: REMOVE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
- term:
    id: GO:0045471
    label: response to ethanol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to ethanol is likely an over-annotation for Casp3 without term-specific evidence in the review materials.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
- term:
    id: GO:0051146
    label: striated muscle cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0051384
    label: response to glucocorticoid
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to glucocorticoid is likely an over-annotation for Casp3 without term-specific evidence in the review materials.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
- term:
    id: GO:0051604
    label: protein maturation
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0070269
    label: pyroptotic inflammatory response
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0071887
    label: leukocyte apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0072347
    label: response to anesthetic
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to anesthetic is likely an over-annotation for Casp3 without term-specific evidence in the review materials.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
- term:
    id: GO:0072734
    label: cellular response to staurosporine
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cellular response to staurosporine is likely an over-annotation for Casp3 without term-specific evidence in the review materials.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
- term:
    id: GO:0097193
    label: intrinsic apoptotic signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0097194
    label: execution phase of apoptosis
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: execution phase of apoptosis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0140639
    label: positive regulation of pyroptotic inflammatory response
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:1902004
    label: positive regulation of amyloid-beta formation
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: positive regulation of amyloid-beta formation likely overstates a direct role for Casp3 relative to the curated effector-caspase evidence.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports Casp3 as an executioner protease; broad substrate/pathway outputs can overstate direct Casp3 function.
- term:
    id: GO:1990418
    label: response to insulin-like growth factor stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to insulin-like growth factor stimulus is likely an over-annotation for Casp3 without term-specific evidence in the review materials.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
- term:
    id: GO:0031264
    label: death-inducing signaling complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: death-inducing signaling complex is not a supported direct annotation for Casp3 in this review.
    action: REMOVE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
- term:
    id: GO:0008303
    label: caspase complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: caspase complex is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0043065
    label: positive regulation of apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:1902512
    label: positive regulation of apoptotic DNA fragmentation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of apoptotic DNA fragmentation is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0098883
    label: synapse pruning
  evidence_type: IMP
  original_reference_id: PMID:24478350
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cytosol is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0001818
    label: negative regulation of cytokine production
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0002020
    label: protease binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: protease binding is not a supported direct annotation for Casp3 in this review.
    action: REMOVE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
- term:
    id: GO:0004197
    label: cysteine-type endopeptidase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cysteine-type endopeptidase activity is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0005123
    label: death receptor binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: death receptor binding is not a supported direct annotation for Casp3 in this review.
    action: REMOVE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: nucleus reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cytoplasm is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: cytoplasm is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0006508
    label: proteolysis
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: proteolysis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0006508
    label: proteolysis
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: proteolysis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0006915
    label: apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: apoptotic process is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0007413
    label: axonal fasciculation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0007611
    label: learning or memory
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0008233
    label: peptidase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: peptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.
    action: MODIFY
    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_replacement_terms: *id001
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
- term:
    id: GO:0008234
    label: cysteine-type peptidase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Cysteine-type peptidase activity is correct but under-specific for Casp3.
    action: MODIFY
    reason: Use GO:0004197 cysteine-type endopeptidase activity, which better captures executioner caspase-3 proteolytic activity.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Involved in the activation cascade of caspases responsible for apoptosis execution.
    proposed_replacement_terms:
    - id: GO:0004197
      label: cysteine-type endopeptidase activity
- term:
    id: GO:0009749
    label: response to glucose
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: response to glucose is likely an over-annotation for Casp3 without term-specific evidence in the review materials.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
- term:
    id: GO:0016005
    label: phospholipase A2 activator activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: phospholipase A2 activator activity is not a supported direct annotation for Casp3 in this review.
    action: REMOVE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
- term:
    id: GO:0016485
    label: protein processing
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0030163
    label: protein catabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: protein catabolic process likely overstates a direct role for Casp3 relative to the curated effector-caspase evidence.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports Casp3 as an executioner protease; broad substrate/pathway outputs can overstate direct Casp3 function.
- term:
    id: GO:0030163
    label: protein catabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: protein catabolic process likely overstates a direct role for Casp3 relative to the curated effector-caspase evidence.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports Casp3 as an executioner protease; broad substrate/pathway outputs can overstate direct Casp3 function.
- term:
    id: GO:0030218
    label: erythrocyte differentiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0031647
    label: regulation of protein stability
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: regulation of protein stability is not a supported direct annotation for Casp3 in this review.
    action: REMOVE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
- term:
    id: GO:0031647
    label: regulation of protein stability
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: regulation of protein stability is not a supported direct annotation for Casp3 in this review.
    action: REMOVE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
- term:
    id: GO:0035556
    label: intracellular signal transduction
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: intracellular signal transduction is not a supported direct annotation for Casp3 in this review.
    action: REMOVE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
- term:
    id: GO:0035655
    label: interleukin-18-mediated signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: interleukin-18-mediated signaling pathway is not a supported direct annotation for Casp3 in this review.
    action: REMOVE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
- term:
    id: GO:0042542
    label: response to hydrogen peroxide
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: response to hydrogen peroxide is likely an over-annotation for Casp3 without term-specific evidence in the review materials.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0043065
    label: positive regulation of apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0043525
    label: positive regulation of neuron apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0044877
    label: protein-containing complex binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: protein-containing complex binding is not a supported direct annotation for Casp3 in this review.
    action: REMOVE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
- term:
    id: GO:0051604
    label: protein maturation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0070212
    label: protein poly-ADP-ribosylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: protein poly-ADP-ribosylation is not a supported direct annotation for Casp3 in this review.
    action: REMOVE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
- term:
    id: GO:0070269
    label: pyroptotic inflammatory response
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0072734
    label: cellular response to staurosporine
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cellular response to staurosporine is likely an over-annotation for Casp3 without term-specific evidence in the review materials.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
- term:
    id: GO:0097193
    label: intrinsic apoptotic signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0097194
    label: execution phase of apoptosis
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: execution phase of apoptosis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0140639
    label: positive regulation of pyroptotic inflammatory response
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:1902004
    label: positive regulation of amyloid-beta formation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of amyloid-beta formation likely overstates a direct role for Casp3 relative to the curated effector-caspase evidence.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports Casp3 as an executioner protease; broad substrate/pathway outputs can overstate direct Casp3 function.
- term:
    id: GO:1902004
    label: positive regulation of amyloid-beta formation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of amyloid-beta formation likely overstates a direct role for Casp3 relative to the curated effector-caspase evidence.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports Casp3 as an executioner protease; broad substrate/pathway outputs can overstate direct Casp3 function.
- term:
    id: GO:0014069
    label: postsynaptic density
  evidence_type: IEP
  original_reference_id: PMID:21151119
  review:
    summary: postsynaptic density is supported as a specialized non-apoptotic neuronal context for Casp3, not as its core molecular function.
    action: KEEP_AS_NON_CORE
    reason: Primary neuronal studies support local synaptic/spine or vesicle-pool roles for caspase-3, but the core function remains executioner caspase protease activity.
    supported_by: &id002
    - reference_id: PMID:21151119
      supporting_text: non-apoptotic baseline caspase-3 activity in hippocampal dendritic spines
    - reference_id: PMID:21151119
      supporting_text: removal of the GluR1 subunit of AMPA-type receptor from postsynaptic sites
- term:
    id: GO:0014069
    label: postsynaptic density
  evidence_type: IDA
  original_reference_id: PMID:21151119
  review:
    summary: postsynaptic density is supported as a specialized non-apoptotic neuronal context for Casp3, not as its core molecular function.
    action: KEEP_AS_NON_CORE
    reason: Primary neuronal studies support local synaptic/spine or vesicle-pool roles for caspase-3, but the core function remains executioner caspase protease activity.
    supported_by: *id002
- term:
    id: GO:0098693
    label: regulation of synaptic vesicle cycle
  evidence_type: IMP
  original_reference_id: PMID:33303681
  review:
    summary: regulation of synaptic vesicle cycle is supported as a specialized non-apoptotic neuronal context for Casp3, not as its core molecular function.
    action: KEEP_AS_NON_CORE
    reason: Primary neuronal studies support local synaptic/spine or vesicle-pool roles for caspase-3, but the core function remains executioner caspase protease activity.
    supported_by: &id003
    - reference_id: PMID:33303681
      supporting_text: the BAD-BAX-caspase-3 pathway regulates autophagy, which in turn limits the size of synaptic vesicle pools
    - reference_id: PMID:33303681
      supporting_text: nonapoptotic function of the BAD-BAX-caspase-3 pathway in presynaptic terminals
- term:
    id: GO:0098693
    label: regulation of synaptic vesicle cycle
  evidence_type: IDA
  original_reference_id: PMID:33303681
  review:
    summary: regulation of synaptic vesicle cycle is supported as a specialized non-apoptotic neuronal context for Casp3, not as its core molecular function.
    action: KEEP_AS_NON_CORE
    reason: Primary neuronal studies support local synaptic/spine or vesicle-pool roles for caspase-3, but the core function remains executioner caspase protease activity.
    supported_by: *id003
- term:
    id: GO:0098978
    label: glutamatergic synapse
  evidence_type: IEP
  original_reference_id: PMID:21151119
  review:
    summary: glutamatergic synapse is supported as a specialized non-apoptotic neuronal context for Casp3, not as its core molecular function.
    action: KEEP_AS_NON_CORE
    reason: Primary neuronal studies support local synaptic/spine or vesicle-pool roles for caspase-3, but the core function remains executioner caspase protease activity.
    supported_by: &id004
    - reference_id: PMID:21151119
      supporting_text: glutamatergic synaptic transmission and plasticity
    - reference_id: PMID:21151119
      supporting_text: caspase-3-dependent mechanism that drives synaptic failure
- term:
    id: GO:0098978
    label: glutamatergic synapse
  evidence_type: IDA
  original_reference_id: PMID:21151119
  review:
    summary: glutamatergic synapse is supported as a specialized non-apoptotic neuronal context for Casp3, not as its core molecular function.
    action: KEEP_AS_NON_CORE
    reason: Primary neuronal studies support local synaptic/spine or vesicle-pool roles for caspase-3, but the core function remains executioner caspase protease activity.
    supported_by: *id004
- term:
    id: GO:0004197
    label: cysteine-type endopeptidase activity
  evidence_type: IDA
  original_reference_id: PMID:37327784
  review:
    summary: cysteine-type endopeptidase activity is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0097194
    label: execution phase of apoptosis
  evidence_type: IMP
  original_reference_id: PMID:8934524
  review:
    summary: execution phase of apoptosis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0004197
    label: cysteine-type endopeptidase activity
  evidence_type: IDA
  original_reference_id: PMID:25231987
  review:
    summary: cysteine-type endopeptidase activity is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0051402
    label: neuron apoptotic process
  evidence_type: IDA
  original_reference_id: PMID:15231831
  review:
    summary: Neuron apoptotic process is a valid developmental or neuronal context for Casp3, but not its core molecular function.
    action: KEEP_AS_NON_CORE
    reason: Casp3 core function is cysteine-type endopeptidase executioner caspase activity; neuron apoptosis is a context-specific process output.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Involved in the activation cascade of caspases responsible for apoptosis execution.
- term:
    id: GO:0004175
    label: endopeptidase activity
  evidence_type: IDA
  original_reference_id: PMID:12124386
  review:
    summary: endopeptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.
    action: MODIFY
    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_replacement_terms: *id001
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
- term:
    id: GO:0031647
    label: regulation of protein stability
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: regulation of protein stability is not a supported direct annotation for Casp3 in this review.
    action: REMOVE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
- term:
    id: GO:1902004
    label: positive regulation of amyloid-beta formation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: positive regulation of amyloid-beta formation likely overstates a direct role for Casp3 relative to the curated effector-caspase evidence.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports Casp3 as an executioner protease; broad substrate/pathway outputs can overstate direct Casp3 function.
- term:
    id: GO:0061713
    label: anterior neural tube closure
  evidence_type: IMP
  original_reference_id: PMID:21515572
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0004197
    label: cysteine-type endopeptidase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: cysteine-type endopeptidase activity is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:21716255
  review:
    summary: cytoplasm is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0008627
    label: intrinsic apoptotic signaling pathway in response to osmotic stress
  evidence_type: IDA
  original_reference_id: PMID:21716255
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0043065
    label: positive regulation of apoptotic process
  evidence_type: IDA
  original_reference_id: PMID:21716255
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:25139234
  review:
    summary: cytoplasm is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0048011
    label: neurotrophin TRK receptor signaling pathway
  evidence_type: ISO
  original_reference_id: PMID:23954828
  review:
    summary: neurotrophin TRK receptor signaling pathway is not a supported direct annotation for Casp3 in this review.
    action: REMOVE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
- term:
    id: GO:0070059
    label: intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
  evidence_type: NAS
  original_reference_id: PMID:12097332
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0006915
    label: apoptotic process
  evidence_type: IMP
  original_reference_id: PMID:12970760
  review:
    summary: 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.
    action: REMOVE
    reason: Remove this evidence row because the publication supports a B-cell cycling/homeostasis phenotype rather than apoptotic-process support for Casp3.
    supported_by:
    - reference_id: PMID:12970760
      supporting_text: Casp3-/- mice have increased numbers of splenic B cells that show normal apoptosis but enhanced proliferation in vivo and hyperproliferation after mitogenic stimulation in vitro.
- term:
    id: GO:0006915
    label: apoptotic process
  evidence_type: IMP
  original_reference_id: PMID:16469926
  review:
    summary: apoptotic process is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0006915
    label: apoptotic process
  evidence_type: IMP
  original_reference_id: PMID:9512515
  review:
    summary: apoptotic process is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0097194
    label: execution phase of apoptosis
  evidence_type: IDA
  original_reference_id: PMID:12954857
  review:
    summary: execution phase of apoptosis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:22358842
  review:
    summary: nucleus reflects a context-specific phenotype, cell type, stimulus response, localization, or specialized non-apoptotic role rather than the core Casp3 molecular function.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0004197
    label: cysteine-type endopeptidase activity
  evidence_type: IDA
  original_reference_id: PMID:24378336
  review:
    summary: cysteine-type endopeptidase activity is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:23861879
  review:
    summary: cytoplasm is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0004190
    label: aspartic-type endopeptidase activity
  evidence_type: IDA
  original_reference_id: PMID:23727203
  review:
    summary: aspartic-type endopeptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.
    action: MODIFY
    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_replacement_terms: *id001
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
- term:
    id: GO:0097194
    label: execution phase of apoptosis
  evidence_type: IGI
  original_reference_id: PMID:16469926
  review:
    summary: execution phase of apoptosis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0004197
    label: cysteine-type endopeptidase activity
  evidence_type: IDA
  original_reference_id: PMID:16183742
  review:
    summary: cysteine-type endopeptidase activity is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0004197
    label: cysteine-type endopeptidase activity
  evidence_type: IDA
  original_reference_id: PMID:15456877
  review:
    summary: cysteine-type endopeptidase activity is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0097194
    label: execution phase of apoptosis
  evidence_type: IDA
  original_reference_id: PMID:15456877
  review:
    summary: execution phase of apoptosis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0004197
    label: cysteine-type endopeptidase activity
  evidence_type: IDA
  original_reference_id: PMID:14657025
  review:
    summary: cysteine-type endopeptidase activity is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0034349
    label: glial cell apoptotic process
  evidence_type: IMP
  original_reference_id: PMID:11549719
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0051402
    label: neuron apoptotic process
  evidence_type: IMP
  original_reference_id: PMID:11549719
  review:
    summary: Neuron apoptotic process is a valid developmental or neuronal context for Casp3, but not its core molecular function.
    action: KEEP_AS_NON_CORE
    reason: Casp3 core function is cysteine-type endopeptidase executioner caspase activity; neuron apoptosis is a context-specific process output.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Involved in the activation cascade of caspases responsible for apoptosis execution.
- term:
    id: GO:0097194
    label: execution phase of apoptosis
  evidence_type: IMP
  original_reference_id: PMID:11549719
  review:
    summary: execution phase of apoptosis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0004197
    label: cysteine-type endopeptidase activity
  evidence_type: IDA
  original_reference_id: PMID:12124386
  review:
    summary: cysteine-type endopeptidase activity is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0051402
    label: neuron apoptotic process
  evidence_type: IMP
  original_reference_id: PMID:10618441
  review:
    summary: Neuron apoptotic process is a valid developmental or neuronal context for Casp3, but not its core molecular function.
    action: KEEP_AS_NON_CORE
    reason: Casp3 core function is cysteine-type endopeptidase executioner caspase activity; neuron apoptosis is a context-specific process output.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Involved in the activation cascade of caspases responsible for apoptosis execution.
- term:
    id: GO:0051402
    label: neuron apoptotic process
  evidence_type: IGI
  original_reference_id: PMID:10618441
  review:
    summary: Neuron apoptotic process is a valid developmental or neuronal context for Casp3, but not its core molecular function.
    action: KEEP_AS_NON_CORE
    reason: Casp3 core function is cysteine-type endopeptidase executioner caspase activity; neuron apoptosis is a context-specific process output.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Involved in the activation cascade of caspases responsible for apoptosis execution.
- term:
    id: GO:0097194
    label: execution phase of apoptosis
  evidence_type: IDA
  original_reference_id: PMID:12124386
  review:
    summary: execution phase of apoptosis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0051402
    label: neuron apoptotic process
  evidence_type: IMP
  original_reference_id: PMID:10479688
  review:
    summary: Neuron apoptotic process is a valid developmental or neuronal context for Casp3, but not its core molecular function.
    action: KEEP_AS_NON_CORE
    reason: Casp3 core function is cysteine-type endopeptidase executioner caspase activity; neuron apoptosis is a context-specific process output.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Involved in the activation cascade of caspases responsible for apoptosis execution.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-418855
  review:
    summary: cytosol is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-NUL-2534247
  review:
    summary: cytosol is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0004197
    label: cysteine-type endopeptidase activity
  evidence_type: IDA
  original_reference_id: PMID:19759058
  review:
    summary: cysteine-type endopeptidase activity is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0009611
    label: response to wounding
  evidence_type: IDA
  original_reference_id: PMID:14507967
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0004190
    label: aspartic-type endopeptidase activity
  evidence_type: IDA
  original_reference_id: PMID:15231831
  review:
    summary: aspartic-type endopeptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.
    action: MODIFY
    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_replacement_terms: *id001
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
- term:
    id: GO:0016485
    label: protein processing
  evidence_type: IDA
  original_reference_id: PMID:15231831
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0006915
    label: apoptotic process
  evidence_type: IDA
  original_reference_id: PMID:17901126
  review:
    summary: apoptotic process is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0006915
    label: apoptotic process
  evidence_type: IDA
  original_reference_id: PMID:12847083
  review:
    summary: apoptotic process is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0008234
    label: cysteine-type peptidase activity
  evidence_type: IDA
  original_reference_id: PMID:17544522
  review:
    summary: 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.
    action: REMOVE
    reason: Remove this evidence row because the cited publication is not a Casp3-specific peptidase assay; Casp3 catalytic activity is retained through other supported annotations.
    supported_by:
    - reference_id: PMID:17544522
      supporting_text: Both TUNEL and FAM-caspase-3/7 assays performed on these embryos consistently showed that E3.5 KIAA1440-/- embryos had activated caspase-3/7, which then induced an apoptotic response predominantly within the inner cell mass of the blastocyst.
- term:
    id: GO:0008233
    label: peptidase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000008
  review:
    summary: peptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.
    action: MODIFY
    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_replacement_terms: *id001
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
- term:
    id: GO:0008233
    label: peptidase activity
  evidence_type: IDA
  original_reference_id: PMID:12427836
  review:
    summary: peptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.
    action: MODIFY
    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_replacement_terms: *id001
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
- term:
    id: GO:0008233
    label: peptidase activity
  evidence_type: RCA
  original_reference_id: PMID:12819136
  review:
    summary: peptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.
    action: MODIFY
    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_replacement_terms: *id001
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
- term:
    id: GO:0008233
    label: peptidase activity
  evidence_type: IDA
  original_reference_id: PMID:13679151
  review:
    summary: peptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.
    action: MODIFY
    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_replacement_terms: *id001
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
- term:
    id: GO:0008233
    label: peptidase activity
  evidence_type: IDA
  original_reference_id: PMID:14561754
  review:
    summary: peptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.
    action: MODIFY
    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_replacement_terms: *id001
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
- term:
    id: GO:0008233
    label: peptidase activity
  evidence_type: IMP
  original_reference_id: PMID:16469926
  review:
    summary: peptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.
    action: MODIFY
    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_replacement_terms: *id001
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
- term:
    id: GO:0006974
    label: DNA damage response
  evidence_type: IDA
  original_reference_id: PMID:11092819
  review:
    summary: PMID:11092819 does not support a positive Casp3 role in DNA damage response.
    action: REMOVE
    reason: 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 should not be retained.
    supported_by:
    - reference_id: PMID:11092819
      supporting_text: critically dependent on p53 and caspase 9, but neither Bax nor caspase 3 expression.
- term:
    id: GO:0009411
    label: response to UV
  evidence_type: IDA
  original_reference_id: PMID:11092819
  review:
    summary: Response to UV is not supported as a positive Casp3 annotation in the reviewed evidence.
    action: REMOVE
    reason: 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 should therefore not be retained.
    supported_by:
    - reference_id: PMID:11092819
      supporting_text: critically dependent on p53 and caspase 9, but neither Bax nor caspase 3 expression.
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000008
  review:
    summary: negative regulation of apoptotic process is not a supported direct annotation for Casp3 in this review.
    action: REMOVE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
- term:
    id: GO:0051402
    label: neuron apoptotic process
  evidence_type: IDA
  original_reference_id: PMID:12427836
  review:
    summary: Neuron apoptotic process is a valid developmental or neuronal context for Casp3, but not its core molecular function.
    action: KEEP_AS_NON_CORE
    reason: Casp3 core function is cysteine-type endopeptidase executioner caspase activity; neuron apoptosis is a context-specific process output.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: CASP3 is the principal executioner caspase that dismantles cells during apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Involved in the activation cascade of caspases responsible for apoptosis execution.
- term:
    id: GO:0007605
    label: sensory perception of sound
  evidence_type: IMP
  original_reference_id: PMID:11374883
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0007507
    label: heart development
  evidence_type: IGI
  original_reference_id: PMID:16469926
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0009411
    label: response to UV
  evidence_type: IGI
  original_reference_id: PMID:16469926
  review:
    summary: Response to UV is not supported as a positive Casp3 annotation in the reviewed evidence.
    action: REMOVE
    reason: 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 should therefore not be retained.
    supported_by:
    - reference_id: PMID:11092819
      supporting_text: critically dependent on p53 and caspase 9, but neither Bax nor caspase 3 expression.
- term:
    id: GO:0008233
    label: peptidase activity
  evidence_type: IMP
  original_reference_id: PMID:11549719
  review:
    summary: peptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.
    action: MODIFY
    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_replacement_terms: *id001
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
- term:
    id: GO:0006508
    label: proteolysis
  evidence_type: RCA
  original_reference_id: PMID:12819136
  review:
    summary: proteolysis is consistent with Casp3 as an executioner caspase that cleaves protein substrates during apoptotic execution.
    action: ACCEPT
    reason: This term captures the core cysteine protease activity, apoptotic execution role, caspase complex context, or well-supported cytoplasmic/cytosolic localization of Casp3.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is the canonical effector cysteine protease activated by initiator caspases and cleaves many substrates during apoptotic execution.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease that cleaves substrates during apoptosis and functions mainly in cytosolic/nuclear apoptotic execution contexts.
- term:
    id: GO:0030216
    label: keratinocyte differentiation
  evidence_type: IMP
  original_reference_id: PMID:15068794
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0045165
    label: cell fate commitment
  evidence_type: IMP
  original_reference_id: PMID:15068794
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0001782
    label: B cell homeostasis
  evidence_type: IMP
  original_reference_id: PMID:12970760
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0004861
    label: cyclin-dependent protein serine/threonine kinase inhibitor activity
  evidence_type: IMP
  original_reference_id: PMID:12970760
  review:
    summary: cyclin-dependent protein serine/threonine kinase inhibitor activity is not a supported direct annotation for Casp3 in this review.
    action: REMOVE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: The strongest curated picture is that Casp3 is a canonical apoptotic effector protease; many signaling, binding, and stimulus terms are indirect or unsupported as direct Casp3 activities.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports specific caspase protease activity, not generic binding/signaling or molecular functions inconsistent with Casp3.
- term:
    id: GO:0008233
    label: peptidase activity
  evidence_type: IMP
  original_reference_id: PMID:12970760
  review:
    summary: peptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.
    action: MODIFY
    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_replacement_terms: *id001
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
- term:
    id: GO:0030889
    label: negative regulation of B cell proliferation
  evidence_type: IMP
  original_reference_id: PMID:12970760
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0043029
    label: T cell homeostasis
  evidence_type: IMP
  original_reference_id: PMID:12970760
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0045736
    label: negative regulation of cyclin-dependent protein serine/threonine kinase activity
  evidence_type: IMP
  original_reference_id: PMID:12970760
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0045786
    label: negative regulation of cell cycle
  evidence_type: IMP
  original_reference_id: PMID:12970760
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0046007
    label: negative regulation of activated T cell proliferation
  evidence_type: IMP
  original_reference_id: PMID:12970760
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a major effector caspase; developmental, neuronal, inflammatory, and stimulus-specific annotations are context-specific consequences or specialized functions rather than the core protease activity.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis describes pyroptosis, tumor, neuronal, inflammatory, and developmental contexts as specialized or downstream outcomes of Casp3 protease activity rather than the core function.
- term:
    id: GO:0008233
    label: peptidase activity
  evidence_type: IDA
  original_reference_id: PMID:12954857
  review:
    summary: peptidase activity is in the protease area but is either too broad or uses the wrong protease class for Casp3.
    action: MODIFY
    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_replacement_terms: *id001
    supported_by:
    - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
      supporting_text: Casp3 is a cysteine-type endopeptidase effector caspase; broad or incorrect peptidase terms should be replaced with the specific caspase activity where possible.
    - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
      supporting_text: Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
    - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
      supporting_text: Falcon synthesis supports Casp3 as a cysteine-aspartate protease with Asp-directed cleavage specificity, so broad or wrong-class peptidase terms should be replaced by cysteine-type endopeptidase activity.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:12477715
  review:
    summary: PMID:12477715 studies caspase-2 nuclear localization/importin binding and does not support mouse Casp3 cytoplasmic localization.
    action: REMOVE
    reason: Remove this evidence row because the cited paper concerns caspase-2 localization rather than Casp3 localization; Casp3 cytoplasmic/cytosolic localization is retained through other supported annotations.
    supported_by:
    - reference_id: PMID:12477715
      supporting_text: In this study we sought to map specific functional regions in the caspase-2 prodomain that regulate its nuclear transport and also its activation.
references:
- id: GO_REF:0000008
  title: Gene Ontology annotation by the MGI curatorial staff, curated orthology
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000096
  title: Automated transfer of experimentally-verified manual GO annotation data to mouse-rat orthologs
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000119
  title: Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10479688
  title: Bax-dependent caspase-3 activation is a key determinant in p53-induced apoptosis in neurons.
  findings: []
- id: PMID:10618441
  title: Epistatic and independent functions of caspase-3 and Bcl-X(L) in developmental programmed cell death.
  findings: []
- id: PMID:11092819
  title: DNA damage-induced neural precursor cell apoptosis requires p53 and caspase 9 but neither Bax nor caspase 3.
  findings: []
- id: PMID:11374883
  title: Deafness due to degeneration of cochlear neurons in caspase-3-deficient mice.
  findings: []
- id: PMID:11549719
  title: Caspase 3 deficiency rescues peripheral nervous system defect in retinoblastoma nullizygous mice.
  findings: []
- id: PMID:12097332
  title: An endoplasmic reticulum stress-specific caspase cascade in apoptosis. Cytochrome c-independent activation of caspase-9 by caspase-12.
  findings: []
- id: PMID:12124386
  title: The role of Asp-462 in regulating Akt activity.
  findings: []
- id: PMID:12427836
  title: p73 is required for survival and maintenance of CNS neurons.
  findings: []
- id: PMID:12477715
  title: Role of prodomain in importin-mediated nuclear localization and activation of caspase-2.
  findings: []
- id: PMID:12819136
  title: Comparative analysis of apoptosis and inflammation genes of mice and humans.
  findings: []
- id: PMID:12847083
  title: Bax and Bak can localize to the endoplasmic reticulum to initiate apoptosis.
  findings: []
- id: PMID:12954857
  title: Ischemic preconditioning by caspase cleavage of poly(ADP-ribose) polymerase-1.
  findings: []
- id: PMID:12970760
  title: 'Caspase-3 regulates cell cycle in B cells: a consequence of substrate specificity.'
  findings: []
- id: PMID:13679151
  title: Roles of MGMT and MLH1 proteins in alkylation-induced apoptosis and mutagenesis.
  findings: []
- id: PMID:14507967
  title: Enhanced oligodendrocyte survival after spinal cord injury in Bax-deficient mice and mice with delayed Wallerian degeneration.
  findings: []
- id: PMID:14561754
  title: Molecular components of a cell death pathway activated by endoplasmic reticulum stress.
  findings: []
- id: PMID:14657025
  title: Transcriptional activation of known and novel apoptotic pathways by Nur77 orphan steroid receptor.
  findings: []
- id: PMID:15068794
  title: High commitment of embryonic keratinocytes to terminal differentiation through a Notch1-caspase 3 regulatory mechanism.
  findings: []
- id: PMID:15231831
  title: BAD is a pro-survival factor prior to activation of its pro-apoptotic function.
  findings: []
- id: PMID:15456877
  title: Vhlh gene deletion induces Hif-1-mediated cell death in thymocytes.
  findings: []
- id: PMID:16183742
  title: Apoptosis caused by p53-induced protein with death domain (PIDD) depends on the death adapter protein RAIDD.
  findings: []
- id: PMID:16469926
  title: 'Caspases 3 and 7: key mediators of mitochondrial events of apoptosis.'
  findings: []
- id: PMID:17124493
  title: Huntingtin inhibits caspase-3 activation.
  findings: []
- id: PMID:17544522
  title: Targeted disruption of the murine large nuclear KIAA1440/Ints1 protein causes growth arrest in early blastocyst stage embryos and eventual apoptotic cell death.
  findings: []
- id: PMID:17901126
  title: Estrogen suppresses uterine epithelial apoptosis by inducing birc1 expression.
  findings: []
- id: PMID:18585351
  title: Ronin is essential for embryogenesis and the pluripotency of mouse embryonic stem cells.
  findings: []
- id: PMID:19759058
  title: Proteome-wide substrate analysis indicates substrate exclusion as a mechanism to generate caspase-7 versus caspase-3 specificity.
  findings: []
- id: PMID:21151119
  title: Caspase-3 triggers early synaptic dysfunction in a mouse model of Alzheimer's disease.
  findings: []
- id: PMID:21515572
  title: 'Focusing forward genetics: a tripartite ENU screen for neurodevelopmental mutations in the mouse.'
  findings: []
- id: PMID:21716255
  title: Cyclooxygenase-2-dependent phosphorylation of the pro-apoptotic protein Bad inhibits tonicity-induced apoptosis in renal medullary cells.
  findings: []
- id: PMID:22358842
  title: Maintenance of muscle stem-cell quiescence by microRNA-489.
  findings: []
- id: PMID:23727203
  title: Nek5, a novel substrate for caspase-3, promotes skeletal muscle differentiation by up-regulating caspase activity.
  findings: []
- id: PMID:23861879
  title: Loss of Usp9x disrupts cortical architecture, hippocampal development and TGFβ-mediated axonogenesis.
  findings: []
- id: PMID:23954828
  title: Dok5 is involved in the signaling pathway of neurotrophin-3 against TrkC-induced apoptosis.
  findings: []
- id: PMID:24378336
  title: BDNF and NT4 play interchangeable roles in gustatory development.
  findings: []
- id: PMID:24478350
  title: Local pruning of dendrites and spines by caspase-3-dependent and proteasome-limited mechanisms.
  findings: []
- id: PMID:25139234
  title: Mammalian target of rapamycin is essential for cardiomyocyte survival and heart development in mice.
  findings: []
- id: PMID:25231987
  title: Exposure of phosphatidylserine by Xk-related protein family members during apoptosis.
  findings: []
- id: PMID:33303681
  title: The BAD-BAX-Caspase-3 Cascade Modulates Synaptic Vesicle Pools via Autophagy.
  findings: []
- id: PMID:37327784
  title: Gasdermin D licenses MHCII induction to maintain food tolerance in small intestine.
  findings: []
- id: PMID:8934524
  title: Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice.
  findings: []
- id: PMID:9512515
  title: Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes.
  findings: []
- id: Reactome:R-MMU-418855
  title: Caspase cleavage of Unc5h1
  findings: []
- id: Reactome:R-NUL-2534247
  title: E-cadherin strand dimer degradation by Casp3
  findings: []
- id: file:mouse/Casp3/Casp3-uniprot.txt
  title: UniProt record for mouse Casp3
  findings:
  - statement: Casp3 is the major effector caspase in the execution phase of apoptosis.
    supporting_text: >-
      Thiol protease that acts as a major effector caspase involved in the
      execution phase of apoptosis...mediates execution of apoptosis by
      catalyzing cleavage of many proteins
  - statement: The active Casp3 enzyme is a heterotetramer with p17 and p12 subunits.
    supporting_text: >-
      Heterotetramer that consists of two anti-parallel arranged heterodimers,
      each one formed by a 17 kDa (p17) and a 12 kDa (p12) subunit.
- id: file:mouse/Casp3/Casp3-deep-research-codex.md
  title: Manual deep research synthesis for mouse Casp3
  findings:
  - statement: The strongest curated picture is that Casp3 is a canonical apoptotic effector protease, while many orthology-transferred inflammatory and stimulus-specific terms are non-core or overextended.
- id: file:mouse/Casp3/Casp3-deep-research-falcon.md
  title: Falcon deep research report on mouse Casp3
  findings:
  - statement: Falcon synthesis identifies mouse Casp3 as a cysteine-aspartate executioner protease in apoptotic proteolysis, with context-specific pyroptotic and non-apoptotic outputs.
    supporting_text: Caspase-3 is a cysteine-aspartate protease functioning as a principal executioner protease in apoptotic cell death.
core_functions:
- description: Casp3 is the canonical apoptotic effector cysteine protease. After activation by initiator caspases, it cleaves many substrates to execute apoptosis and promote apoptotic DNA fragmentation.
  molecular_function:
    id: GO:0004197
    label: cysteine-type endopeptidase activity
  directly_involved_in:
  - id: GO:0097194
    label: execution phase of apoptosis
  - id: GO:1902512
    label: positive regulation of apoptotic DNA fragmentation
  - id: GO:0006508
    label: proteolysis
  locations:
  - id: GO:0005737
    label: cytoplasm
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
    supporting_text: Following cleavage and activation by initiator caspases ... mediates execution of apoptosis by catalyzing cleavage of many proteins.
  - reference_id: file:mouse/Casp3/Casp3-deep-research-codex.md
    supporting_text: Casp3 is a major effector caspase activated by initiator caspases and cleaves many substrates during the execution phase of apoptosis.
  - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
    supporting_text: Caspase-3 is a cysteine-aspartate executioner protease that hydrolyzes protein substrates after Asp residues during apoptotic execution.
- description: The active Casp3 enzyme functions as a caspase complex formed from p17 and p12 subunits; this mature complex carries out the proteolytic execution program.
  molecular_function:
    id: GO:0004197
    label: cysteine-type endopeptidase activity
  directly_involved_in:
  - id: GO:0097194
    label: execution phase of apoptosis
  locations:
  - id: GO:0005737
    label: cytoplasm
  in_complex:
    id: GO:0008303
    label: caspase complex
  supported_by:
  - reference_id: file:mouse/Casp3/Casp3-uniprot.txt
    supporting_text: Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 17 kDa (p17) and a 12 kDa (p12) subunit.
  - reference_id: file:mouse/Casp3/Casp3-deep-research-falcon.md
    supporting_text: Caspase-3 is a cysteine-aspartate executioner protease that hydrolyzes protein substrates after Asp residues during apoptotic execution.
proposed_new_terms: []
suggested_questions:
- question: Which mouse Casp3 inflammatory and pyroptotic annotations reflect direct Casp3 substrate cleavage versus downstream consequences of apoptosis or gasdermin-E activation?
- question: Which non-lethal neuronal remodeling functions of Casp3 are sufficiently direct and conserved to retain as non-core GO annotations?
suggested_experiments:
- description: Use catalytically inactive Casp3 rescue alleles in apoptotic and non-apoptotic mouse cells to separate direct protease-dependent functions from downstream phenotypes.
- description: Perform substrate-trapping proteomics for active Casp3 in apoptotic cells, neurons, and inflammatory epithelial cells to identify context-specific direct substrates.

Casp3

Gene Description

Existing Annotations Review

Core Functions

Casp3 is the canonical apoptotic effector cysteine protease. After activation by initiator caspases, it cleaves many substrates to execute apoptosis and promote apoptotic DNA fragmentation.

The active Casp3 enzyme functions as a caspase complex formed from p17 and p12 subunits; this mature complex carries out the proteolytic execution program.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Codex

Deep Research Report: Casp3 (Mus musculus)

Executive Summary

Molecular Function

Biological Process Roles

Cellular Localization and Complexes

Annotation Risk Assessment

Key Sources

Falcon

Research Report: Mouse Casp3 (Caspase-3) — Functional Annotation (UniProt P70677)

0) Target verification (critical disambiguation)

1) Key concepts and definitions (current understanding)

1.1 Caspase-3 definition and biochemical class

1.2 Apoptotic pathways upstream of Casp3

1.3 Catalytic reaction and substrate specificity

2) Functional roles and pathway placement for annotation

2.1 Primary function: execution of apoptotic proteolysis

2.2 Subcellular context and where Casp3 acts

3) Recent developments (prioritizing 2023–2024)

3.1 2023: Caspase-3 as an executioner of pyroptosis via GSDME in an aged-mouse sarcopenia context

3.2 2024: Caspase-3 promotes malignant transformation and tumor progression in mouse models (non-apoptotic/pro-tumor function)

3.3 2024: Caspase-3-dependent cleavage of RIPK3 at Asp333 is real but dispensable for embryogenesis

3.4 2024: Mechanistic insight into caspase-3/7 discrimination for GSDME cleavage (pyroptosis crosstalk)

4) Current applications and real-world implementations

4.1 Caspase-3 as an apoptosis/regulated cell death biomarker and mechanistic readout

4.2 Performance statistics from recent assay implementations (selected examples)

5) Expert opinions/authoritative synthesis (what the field emphasizes)

6) Key statistics and data points (recent literature)

Summary table

References (URLs and publication dates)

Citations

Manual

Executive Summary

Molecular Function

Biological Process Roles

Cellular Localization and Complexes

Annotation Risk Assessment

Key Literature

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