Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005737 cytoplasm	IBA GO_REF:0000033	PENDING	Summary: TODO: Review this GOA annotation
GO:0006915 apoptotic process	IBA GO_REF:0000033	PENDING	Summary: TODO: Review this GOA annotation
GO:0004197 cysteine-type endopeptidase activity	IBA GO_REF:0000033	PENDING	Summary: TODO: Review this GOA annotation
GO:0006508 proteolysis	IBA GO_REF:0000033	PENDING	Summary: TODO: Review this GOA annotation
GO:0031264 death-inducing signaling complex	IBA GO_REF:0000033	PENDING	Summary: TODO: Review this GOA annotation
GO:0097194 execution phase of apoptosis	IBA GO_REF:0000033	PENDING	Summary: TODO: Review this GOA annotation
GO:0008047 enzyme activator activity	IBA GO_REF:0000033	PENDING	Summary: TODO: Review this GOA annotation
GO:0043525 positive regulation of neuron apoptotic process	IBA GO_REF:0000033	PENDING	Summary: TODO: Review this GOA annotation
GO:0030182 neuron differentiation	IBA GO_REF:0000033	PENDING	Summary: TODO: Review this GOA annotation
GO:0030216 keratinocyte differentiation	IBA GO_REF:0000033	PENDING	Summary: TODO: Review this GOA annotation
GO:0030218 erythrocyte differentiation	IBA GO_REF:0000033	PENDING	Summary: TODO: Review this GOA annotation
GO:0004197 cysteine-type endopeptidase activity	IEA GO_REF:0000120	PENDING	Summary: TODO: Review this GOA annotation
GO:0005737 cytoplasm	IEA GO_REF:0000120	PENDING	Summary: TODO: Review this GOA annotation
GO:0006508 proteolysis	IEA GO_REF:0000120	PENDING	Summary: TODO: Review this GOA annotation
GO:0007413 axonal fasciculation	IEA GO_REF:0000117	PENDING	Summary: TODO: Review this GOA annotation
GO:0008234 cysteine-type peptidase activity	IEA GO_REF:0000120	PENDING	Summary: TODO: Review this GOA annotation
GO:0010212 response to ionizing radiation	IEA GO_REF:0000117	PENDING	Summary: TODO: Review this GOA annotation
GO:0048513 animal organ development	IEA GO_REF:0000117	PENDING	Summary: TODO: Review this GOA annotation
GO:0001818 negative regulation of cytokine production	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0004175 endopeptidase activity	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0004190 aspartic-type endopeptidase activity	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0004861 cyclin-dependent protein serine/threonine kinase inhibitor activity	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0005634 nucleus	IEA GO_REF:0000120	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0006915 apoptotic process	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0008233 peptidase activity	IEA GO_REF:0000120	PENDING	Summary: TODO: Review this GOA annotation
GO:0008627 intrinsic apoptotic signaling pathway in response to osmotic stress	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0014069 postsynaptic density	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0016485 protein processing	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0030163 protein catabolic process	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0030218 erythrocyte differentiation	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0031647 regulation of protein stability	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0032880 regulation of protein localization	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0043065 positive regulation of apoptotic process	IEA GO_REF:0000120	PENDING	Summary: TODO: Review this GOA annotation
GO:0051604 protein maturation	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0070269 pyroptotic inflammatory response	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0072734 cellular response to staurosporine	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0097193 intrinsic apoptotic signaling pathway	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0097194 execution phase of apoptosis	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0098693 regulation of synaptic vesicle cycle	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0098883 synapse pruning	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0098978 glutamatergic synapse	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0140639 positive regulation of pyroptotic inflammatory response	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:1902004 positive regulation of amyloid-beta formation	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0098883 synapse pruning	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0098883 synapse pruning	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Transferred from mouse Casp3, where synapse pruning has direct experimental support. This mammalian neuronal remodeling role is plausible in rat but is context-specific and not part of Casp3 core apoptotic function.
GO:0045471 response to ethanol	IEP PMID:30926569 Effect of saffron (stigma of Crocus sativus L.) aqueous extr...	PENDING	Summary: TODO: Review this GOA annotation
GO:0045471 response to ethanol	IEP PMID:23102656 Effect of repetitive daily ethanol intoxication on adult rat...	PENDING	Summary: TODO: Review this GOA annotation
GO:0036269 swimming behavior	IEP PMID:33574912 Insulin-like growth factor-1 improves postoperative cognitiv...	MARK AS OVER ANNOTATED	Summary: The cited study uses the Morris Water Maze (a swimming-based test) to assess learning and memory in a postoperative-cognitive-dysfunction model, and measures caspase-3 by Western blot purely as a hippocampal apoptosis marker. Swimming is the assay modality, not a function of caspase-3, which is an apoptotic executioner protease. Reason: Spurious IEP over-annotation derived from the swimming-based Morris Water Maze memory assay; the paper assays cognition/apoptosis, not swimming behaviour, and caspase-3 has no proximal role in locomotion or swimming. Supporting Evidence: PMID:33574912 To assess learning and memory abilities, MWM tests were performed as described previously
GO:0043523 regulation of neuron apoptotic process	IEP PMID:33574912 Insulin-like growth factor-1 improves postoperative cognitiv...	PENDING	Summary: TODO: Review this GOA annotation
GO:1990418 response to insulin-like growth factor stimulus	IEP PMID:33574912 Insulin-like growth factor-1 improves postoperative cognitiv...	PENDING	Summary: TODO: Review this GOA annotation
GO:0043065 positive regulation of apoptotic process	ISO GO_REF:0000121	MODIFY	Summary: Transferred from mature human CASP3 chain annotations, but the GO term is broader than the conserved effector step. The more precise conserved transfer is execution phase of apoptosis. Proposed replacements: execution phase of apoptosis
GO:1902512 positive regulation of apoptotic DNA fragmentation	ISO GO_REF:0000121	ACCEPT	Summary: Transferred from mature human CASP3 chain annotations. Promotion of apoptotic DNA fragmentation is a canonical downstream consequence of effector caspase-3 activation and is conserved across mammals.
GO:0005737 cytoplasm	IDA PMID:21630211 Immunohistochemical study of the apoptosis process in epider...	PENDING	Summary: TODO: Review this GOA annotation
GO:0072347 response to anesthetic	IEP PMID:27498600 Neuroprotective effects of caffeic acid phenethyl ester agai...	PENDING	Summary: TODO: Review this GOA annotation
GO:0014069 postsynaptic density	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Transferred from mouse Casp3, where postsynaptic-density localization has direct synaptic evidence. This neuronal localization is plausible in rat but is a specialized non-core context rather than the principal Casp3 function.
GO:0098693 regulation of synaptic vesicle cycle	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Transferred from mouse Casp3 with direct synaptic evidence. Regulation of synaptic vesicle cycle reflects a specialized neuronal remodeling role, not the core conserved apoptotic assignment for rat Casp3.
GO:0098978 glutamatergic synapse	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Transferred from mouse Casp3 with direct synaptic evidence at glutamatergic synapses. Likely a real mammalian neuronal context, but not a core rat Casp3 function.
GO:0016485 protein processing	ISO GO_REF:0000121	MODIFY	Summary: Transferred from human CASP3, where the source evidence reflects protease-mediated substrate cleavage. Protein processing is too generic; proteolysis is the clearer conserved process term. Proposed replacements: proteolysis
GO:0001818 negative regulation of cytokine production	ISO GO_REF:0000121	REMOVE	Summary: Transferred from human CASP3, but the source support is an indirect cross-taxonomic evidence chain rather than a clean human ortholog experiment. This is too far from rat Casp3 core function and is likely an over-transfer.
GO:0001666 response to hypoxia	IEP PMID:24089674 Neuroprotective effects of microRNA-210 on hypoxic-ischemic ...	PENDING	Summary: TODO: Review this GOA annotation
GO:0006915 apoptotic process	ISO GO_REF:0000121	ACCEPT	Summary: Transferred from human CASP3, which has strong experimental support for apoptotic process. This is a core, conserved effector-caspase assignment for rat Casp3.
GO:0070269 pyroptotic inflammatory response	ISO GO_REF:0000121	MARK AS OVER ANNOTATED	Summary: Transferred from human CASP3 with direct source evidence, but pyroptotic inflammatory response is a specialized context-dependent cross-talk role rather than a broadly conserved core rat Casp3 function.
GO:0005829 cytosol	ISO GO_REF:0000121	ACCEPT	Summary: Transferred from human CASP3 with direct localization evidence. Cytosolic localization is consistent with conserved effector-caspase biology in rat.
GO:0051604 protein maturation	ISO GO_REF:0000121	MODIFY	Summary: Transferred from human CASP3, but protein maturation is too generic for an effector caspase that primarily acts through substrate proteolysis. Use proteolysis instead. Proposed replacements: proteolysis
GO:0140639 positive regulation of pyroptotic inflammatory response	ISO GO_REF:0000121	MARK AS OVER ANNOTATED	Summary: Transferred from human CASP3 with direct source evidence, but positive regulation of pyroptotic inflammatory response is a specialized context and too specific for a general rat orthology transfer.
GO:0005737 cytoplasm	ISO GO_REF:0000121	ACCEPT	Summary: Transferred from human CASP3 with direct localization evidence. Cytoplasmic localization is a conserved and appropriate core assignment for rat Casp3.
GO:0097193 intrinsic apoptotic signaling pathway	ISO GO_REF:0000121	MODIFY	Summary: Transferred from human CASP3, but the intrinsic-pathway label is too pathway-specific for a downstream effector caspase that operates in multiple apoptotic routes. The more precise conserved transfer is execution phase of apoptosis. Proposed replacements: execution phase of apoptosis
GO:0005634 nucleus	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Transferred from human CASP3 with direct source evidence for nuclear activity/localization in apoptotic settings. This is a valid context-dependent localization but not a core rat Casp3 assignment.
GO:0030163 protein catabolic process	ISO GO_REF:0000121	MODIFY	Summary: Transferred from human CASP3, but protein catabolic process overgeneralizes the substrate-cleavage role. Proteolysis is the clearer conserved process term. Proposed replacements: proteolysis
GO:0097194 execution phase of apoptosis	ISO GO_REF:0000121	ACCEPT	Summary: Transferred from mouse Casp3, where execution phase of apoptosis is directly supported. This is a core, conserved effector-caspase role in rat.
GO:0010996 response to auditory stimulus	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Transferred from chinchilla Casp3, where the source ortholog has direct experimental evidence for auditory-response biology. The term may reflect a genuine mammalian sensory context, but it is non-core for rat Casp3.
GO:0004197 cysteine-type endopeptidase activity	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0004175 endopeptidase activity	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0004175 endopeptidase activity	ISO GO_REF:0000121	MODIFY	Summary: Transferred from mouse Casp3 with direct catalytic evidence, but endopeptidase activity is too broad. The conserved specific activity is cysteine-type endopeptidase activity. Proposed replacements: cysteine-type endopeptidase activity
GO:0006508 proteolysis	ISO GO_REF:0000121	ACCEPT	Summary: Transferred from human CASP3 with direct source evidence. Proteolysis is a core conserved biological process for rat Casp3.
GO:0006508 proteolysis	IDA PMID:17553422 Depletion of GGA3 stabilizes BACE and enhances beta-secretas...	PENDING	Summary: TODO: Review this GOA annotation
GO:0031647 regulation of protein stability	ISO GO_REF:0000121	REMOVE	Summary: Transferred from human CASP3, but regulation of protein stability summarizes downstream substrate-specific consequences rather than a conserved core rat Casp3 function.
GO:0031647 regulation of protein stability	IDA PMID:17553422 Depletion of GGA3 stabilizes BACE and enhances beta-secretas...	PENDING	Summary: TODO: Review this GOA annotation
GO:1902004 positive regulation of amyloid-beta formation	ISO GO_REF:0000121	REMOVE	Summary: Transferred from human CASP3 in an amyloid-beta/APP disease context. This is too disease-specific and not an appropriate conserved orthology transfer to rat Casp3.
GO:1902004 positive regulation of amyloid-beta formation	IDA PMID:17553422 Depletion of GGA3 stabilizes BACE and enhances beta-secretas...	PENDING	Summary: TODO: Review this GOA annotation
GO:0051146 striated muscle cell differentiation	IEP PMID:28899909 Depletion of the mRNA translation initiation inhibitor, prog...	PENDING	Summary: TODO: Review this GOA annotation
GO:0071887 leukocyte apoptotic process	IEP PMID:26861981 Time course of apoptosis induced by photodynamic therapy wit...	PENDING	Summary: TODO: Review this GOA annotation
GO:0001554 luteolysis	IEP PMID:25332219 Endoplasmic reticulum stress-mediated apoptotic pathway is i...	PENDING	Summary: TODO: Review this GOA annotation
GO:0007413 axonal fasciculation	IMP PMID:25898930 Death Receptor 6 and Caspase-6 Regulate Prion Peptide-Induce...	PENDING	Summary: TODO: Review this GOA annotation
GO:0043025 neuronal cell body	IDA PMID:25898930 Death Receptor 6 and Caspase-6 Regulate Prion Peptide-Induce...	PENDING	Summary: TODO: Review this GOA annotation
GO:0061713 anterior neural tube closure	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Transferred from mouse Casp3 with direct developmental phenotype evidence. This may be a real mammalian developmental context, but it is pleiotropic and non-core for rat Casp3.
GO:0004197 cysteine-type endopeptidase activity	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0004197 cysteine-type endopeptidase activity	ISO GO_REF:0000121	ACCEPT	Summary: Transferred from human CASP3 with extensive direct catalytic evidence. This is the defining conserved molecular function of rat Casp3.
GO:0005737 cytoplasm	ISO GO_REF:0000121	REMOVE	Summary: Transferred from dog CASP3, but the dog source record already mixes IBA/IDA/IEA/ISO evidence and rat already has stronger human and mouse source annotations for cytoplasmic localization. Remove this redundant second-hop transfer.
GO:0008627 intrinsic apoptotic signaling pathway in response to osmotic stress	ISO GO_REF:0000121	MARK AS OVER ANNOTATED	Summary: Transferred from mouse Casp3 with direct source evidence, but the osmotic-stress variant is too stimulus-specific to treat as a general conserved rat orthology transfer.
GO:0008627 intrinsic apoptotic signaling pathway in response to osmotic stress	ISO GO_REF:0000121	REMOVE	Summary: Transferred from dog CASP3. Although the dog source has mixed evidence, this is still a stimulus-specific second-hop transfer and weaker than the direct mouse source. Remove.
GO:0043065 positive regulation of apoptotic process	ISO GO_REF:0000121	MODIFY	Summary: Transferred from mouse Casp3, but positive regulation of apoptotic process is broader than the conserved downstream effector role. Execution phase of apoptosis is the more precise conserved term. Proposed replacements: execution phase of apoptosis
GO:0043065 positive regulation of apoptotic process	ISO GO_REF:0000121	REMOVE	Summary: Transferred from dog CASP3, whose source record already mixes direct and inferred evidence and duplicates stronger human/mouse sources. Remove as a redundant second-hop transfer.
GO:0072734 cellular response to staurosporine	ISO GO_REF:0000121	REMOVE	Summary: Transferred from human CASP3, but cellular response to staurosporine is a pharmacologic stimulus-specific context and not an appropriate conserved core orthology transfer.
GO:0005634 nucleus	ISO GO_REF:0000121	REMOVE	Summary: Transferred from pig CASP3, but the pig source record is mixed and redundant with better-supported human/mouse nuclear localization rows. Remove this second-hop transfer.
GO:0005737 cytoplasm	ISO GO_REF:0000121	REMOVE	Summary: Transferred from pig CASP3, but the pig source record is mixed and redundant with stronger human/mouse cytoplasmic localization transfers. Remove this second-hop row.
GO:0005737 cytoplasm	ISO GO_REF:0000121	ACCEPT	Summary: Transferred from mouse Casp3 with direct localization evidence. Cytoplasmic localization is conserved and appropriate for rat Casp3.
GO:0048011 neurotrophin TRK receptor signaling pathway	ISO GO_REF:0000121	REMOVE	Summary: Transferred from human CASP3, but the source paper treats caspase-3 largely as a downstream apoptosis readout in neurotrophin signaling rather than a dedicated TRK-pathway component. This is an over-transfer.
GO:0006915 apoptotic process	ISO GO_REF:0000121	REMOVE	Summary: Transferred from mouse Casp3 with direct apoptosis evidence, but rat already retains a stronger involved_in apoptotic-process ISO row from human. Remove this weaker duplicate transfer.
GO:0005634 nucleus	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Transferred from mouse Casp3 with direct localization evidence. Nuclear localization occurs in apoptotic contexts but is not a core default state for rat Casp3.
GO:0002020 protease binding	IPI PMID:17518537 FasL, Fas, and death-inducing signaling complex (DISC) prote...	PENDING	Summary: TODO: Review this GOA annotation
GO:0005123 death receptor binding	IPI PMID:17518537 FasL, Fas, and death-inducing signaling complex (DISC) prote...	PENDING	Summary: TODO: Review this GOA annotation
GO:0031264 death-inducing signaling complex	IDA PMID:17518537 FasL, Fas, and death-inducing signaling complex (DISC) prote...	PENDING	Summary: TODO: Review this GOA annotation
GO:0044877 protein-containing complex binding	IPI PMID:17518537 FasL, Fas, and death-inducing signaling complex (DISC) prote...	PENDING	Summary: TODO: Review this GOA annotation
GO:0004190 aspartic-type endopeptidase activity	ISO GO_REF:0000121	REMOVE	Summary: Transferred from mouse Casp3, but CASP3 is a cysteine protease, not an aspartic protease. This conflicts with conserved catalytic mechanism and should be removed.
GO:0030218 erythrocyte differentiation	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Transferred from human CASP3 with direct source evidence for erythroid differentiation. This is plausible mammalian pleiotropy, but it is non-core for rat Casp3.
GO:0097194 execution phase of apoptosis	ISO GO_REF:0000121	ACCEPT	Summary: Transferred from human CASP3 with direct source evidence. Execution phase of apoptosis is a core conserved effector-caspase assignment for rat Casp3.
GO:0097194 execution phase of apoptosis	ISO GO_REF:0000121	REMOVE	Summary: Transferred from mouse Casp3 with direct source evidence, but rat already retains stronger involved_in execution-phase rows. Remove this weaker duplicate qualifier transfer.
GO:0034349 glial cell apoptotic process	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Transferred from mouse Casp3 with experimental glial-apoptosis evidence. Likely a real mammalian neural context, but it is non-core for rat Casp3.
GO:0051402 neuron apoptotic process	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Transferred from mouse Casp3 with direct neuronal-apoptosis evidence. This is a plausible mammalian context-specific role, but not a core rat Casp3 assignment.
GO:0005634 nucleus	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Transferred from human CASP3 with direct source evidence for nuclear localization in apoptotic settings. Keep as a non-core context-dependent localization.
GO:0004197 cysteine-type endopeptidase activity	ISO GO_REF:0000121	ACCEPT	Summary: Transferred from mouse Casp3 with extensive direct catalytic evidence. This is a core conserved molecular function for rat Casp3.
GO:0009611 response to wounding	ISO GO_REF:0000121	REMOVE	Summary: Transferred from mouse Casp3 in a wound-response context. This is too context-specific and indirect to retain as a conserved rat orthology transfer.
GO:0016485 protein processing	ISO GO_REF:0000121	MODIFY	Summary: Transferred from mouse Casp3 with source evidence for substrate cleavage, but protein processing is too generic. Proteolysis is the more appropriate conserved process term. Proposed replacements: proteolysis
GO:0005515 protein binding	IPI PMID:18485100 Nuclear translocation of X-linked inhibitor of apoptosis (XI...	PENDING	Summary: TODO: Review this GOA annotation
GO:0008234 cysteine-type peptidase activity	IDA PMID:16336964 In vivo delivery of a XIAP (BIR3-RING) fusion protein contai...	PENDING	Summary: TODO: Review this GOA annotation
GO:0008234 cysteine-type peptidase activity	IDA PMID:17182030 Inhibition of HtrA2/Omi ameliorates heart dysfunction follow...	PENDING	Summary: TODO: Review this GOA annotation
GO:0043065 positive regulation of apoptotic process	IMP PMID:17869439 Role of inhibitor of apoptosis protein in gentamicin-induced...	PENDING	Summary: TODO: Review this GOA annotation
GO:0008234 cysteine-type peptidase activity	IDA PMID:18316105 Implication of caspases and subcellular compartments in tert...	PENDING	Summary: TODO: Review this GOA annotation
GO:0030163 protein catabolic process	IDA PMID:18316105 Implication of caspases and subcellular compartments in tert...	PENDING	Summary: TODO: Review this GOA annotation
GO:0034349 glial cell apoptotic process	IEP PMID:18931364 Bax and Bid act in synergy to bring about T11TS-mediated gli...	PENDING	Summary: TODO: Review this GOA annotation
GO:0035094 response to nicotine	IEP PMID:18477628 Nicotine suppresses tunicamycin-induced, but not thapsigargi...	PENDING	Summary: TODO: Review this GOA annotation
GO:0009749 response to glucose	IDA PMID:19356108 Heme oxygenase-derived carbon monoxide restores vascular fun...	PENDING	Summary: TODO: Review this GOA annotation
GO:0032025 response to cobalt ion	IEP PMID:18598848 Estradiol protects PC12 cells against CoCl2-induced apoptosi...	PENDING	Summary: TODO: Review this GOA annotation
GO:0032355 response to estradiol	IEP PMID:18598848 Estradiol protects PC12 cells against CoCl2-induced apoptosi...	PENDING	Summary: TODO: Review this GOA annotation
GO:0008234 cysteine-type peptidase activity	ISO GO_REF:0000121	MODIFY	Summary: Transferred from mouse Casp3 with direct catalytic evidence, but cysteine-type peptidase activity is broader than the best conserved term. Use cysteine-type endopeptidase activity. Proposed replacements: cysteine-type endopeptidase activity
GO:0008234 cysteine-type peptidase activity	IDA PMID:17218406 Luteinizing hormone-induced caspase activation in rat preovu...	PENDING	Summary: TODO: Review this GOA annotation
GO:0008233 peptidase activity	ISO GO_REF:0000121	MODIFY	Summary: Transferred from human CASP3 with direct catalytic support, but peptidase activity is too generic. Use cysteine-type endopeptidase activity. Proposed replacements: cysteine-type endopeptidase activity
GO:0005829 cytosol	ISO GO_REF:0000121	ACCEPT	Summary: Transferred from human CASP3 with direct localization evidence. Cytosolic localization is conserved and appropriate for rat Casp3.
GO:0001666 response to hypoxia	IEP PMID:18466900 Chronic hypobaric hypoxia induced apoptosis in CA1 region of...	PENDING	Summary: TODO: Review this GOA annotation
GO:0007611 learning or memory	IMP PMID:18239768 Central injection of caspase inhibitors facilitates the form...	PENDING	Summary: TODO: Review this GOA annotation
GO:0009410 response to xenobiotic stimulus	IEP PMID:18274634 The protecting effects and mechanisms of Baicalin and Octreo...	PENDING	Summary: TODO: Review this GOA annotation
GO:0010038 response to metal ion	IEP PMID:18483861 Pravastatin attenuates carboplatin-induced cardiotoxicity vi...	PENDING	Summary: TODO: Review this GOA annotation
GO:0010165 response to X-ray	IEP PMID:18239382 Low-dose local kidney irradiation inhibits progression of ex...	PENDING	Summary: TODO: Review this GOA annotation
GO:0021766 hippocampus development	IEP PMID:18459132 Different expression of caspase-3 in rat hippocampal subregi...	PENDING	Summary: TODO: Review this GOA annotation
GO:0032496 response to lipopolysaccharide	IEP PMID:18289516 Caspase activation in fetal rat brain following experimental...	PENDING	Summary: TODO: Review this GOA annotation
GO:0042542 response to hydrogen peroxide	IDA PMID:18479463 Leptin protects H9c2 rat cardiomyocytes from H2O2-induced ap...	PENDING	Summary: TODO: Review this GOA annotation
GO:0043200 response to amino acid	IEP PMID:18423997 Glutamate-induced losses of oligodendrocytes and neurons and...	PENDING	Summary: TODO: Review this GOA annotation
GO:0043525 positive regulation of neuron apoptotic process	IMP PMID:18404518 P2X(7) nucleotide receptors mediate caspase-8/9/3-dependent ...	PENDING	Summary: TODO: Review this GOA annotation
GO:0051384 response to glucocorticoid	IEP PMID:18288275 Protecting effects of dexamethasone on thymus of rats with s...	PENDING	Summary: TODO: Review this GOA annotation
GO:0006974 DNA damage response	ISO GO_REF:0000121	REMOVE	Summary: Transferred from mouse Casp3 in DNA-damage response experiments, but this reflects an upstream stimulus context rather than a core conserved Casp3 function in rat.
GO:0030163 protein catabolic process	IDA PMID:15004018 Minocycline up-regulates Bcl-2 and protects against cell dea...	PENDING	Summary: TODO: Review this GOA annotation
GO:0007605 sensory perception of sound	ISO GO_REF:0000121	REMOVE	Summary: Transferred from mouse Casp3 as a sensory/hearing phenotype. This is too phenotype-specific for a general conserved rat Casp3 transfer and is weaker than the chinchilla auditory-response row.
GO:0007507 heart development	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Transferred from mouse Casp3 with developmental phenotype evidence. Heart-development effects are plausible pleiotropy but non-core for rat Casp3.
GO:0009411 response to UV	ISO GO_REF:0000121	REMOVE	Summary: Transferred from mouse Casp3 in a UV-response context. This stimulus-specific response is too indirect and over-transferred for rat Casp3.
GO:0008233 peptidase activity	ISO GO_REF:0000121	MODIFY	Summary: Transferred from mouse Casp3 with direct catalytic evidence, but peptidase activity is too generic. Use cysteine-type endopeptidase activity. Proposed replacements: cysteine-type endopeptidase activity
GO:0030182 neuron differentiation	IEP PMID:15248196 Active caspase-3 expression during postnatal development of ...	PENDING	Summary: TODO: Review this GOA annotation
GO:0016005 phospholipase A2 activator activity	IMP PMID:12492473 Signaling events mediating activation of brain ethanolamine ...	PENDING	Summary: TODO: Review this GOA annotation
GO:0035556 intracellular signal transduction	IMP PMID:12492473 Signaling events mediating activation of brain ethanolamine ...	PENDING	Summary: TODO: Review this GOA annotation
GO:0030216 keratinocyte differentiation	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Transferred from mouse Casp3 with keratinocyte-differentiation phenotype evidence. This is plausible mammalian pleiotropy but non-core for rat Casp3.
GO:0045165 cell fate commitment	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Transferred from mouse Casp3 with developmental phenotype evidence. Cell-fate commitment is non-core pleiotropy rather than a defining rat Casp3 function.
GO:0001782 B cell homeostasis	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Transferred from mouse Casp3 knockout immunophenotypes. The biology may be real in lymphocyte contexts, but it is not a core rat Casp3 function.
GO:0004861 cyclin-dependent protein serine/threonine kinase inhibitor activity	ISO GO_REF:0000121	REMOVE	Summary: Transferred from mouse Casp3, but the source evidence is phenotype-based and does not demonstrate a direct cyclin-dependent kinase inhibitor molecular function for CASP3. This is an over-annotation.
GO:0030889 negative regulation of B cell proliferation	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Transferred from mouse Casp3 knockout immunophenotypes. Keep only as non-core pleiotropy.
GO:0043029 T cell homeostasis	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Transferred from mouse Casp3 knockout immunophenotypes. Keep as non-core because it reflects context-specific immune phenotypes rather than Casp3 core function.
GO:0045736 negative regulation of cyclin-dependent protein serine/threonine kinase activity	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Transferred from mouse Casp3 knockout immunophenotypes. The regulatory phenotype may be real, but it is not a core rat Casp3 function.
GO:0045786 negative regulation of cell cycle	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Transferred from mouse Casp3 knockout immunophenotypes. Keep only as non-core pleiotropy.
GO:0046007 negative regulation of activated T cell proliferation	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Transferred from mouse Casp3 knockout immunophenotypes. This is a context-specific immune phenotype, not a core rat Casp3 function.

Core Functions

Conserved effector caspase that cleaves protein substrates during the execution phase of apoptosis.

Molecular Function:

cysteine-type endopeptidase activity

Directly Involved In:

apoptotic process execution phase of apoptosis proteolysis positive regulation of apoptotic DNA fragmentation

Cellular Locations:

cytoplasm cytosol

References

GO_REF:0000024

TODO: Fetch title

GO_REF:0000033

TODO: Fetch title

GO_REF:0000107

TODO: Fetch title

GO_REF:0000117

TODO: Fetch title

GO_REF:0000120

TODO: Fetch title

GO_REF:0000121

TODO: Fetch title

PMID:12492473

Signaling events mediating activation of brain ethanolamine plasmalogen hydrolysis by ceramide.

PMID:15004018

Minocycline up-regulates Bcl-2 and protects against cell death in mitochondria.

PMID:15248196

Active caspase-3 expression during postnatal development of rat cerebellum is not systematically or consistently associated with apoptosis.

PMID:16336964

In vivo delivery of a XIAP (BIR3-RING) fusion protein containing the protein transduction domain protects against neuronal death induced by seizures.

PMID:17182030

Inhibition of HtrA2/Omi ameliorates heart dysfunction following ischemia/reperfusion injury in rat heart in vivo.

PMID:17218406

Luteinizing hormone-induced caspase activation in rat preovulatory follicles is coupled to mitochondrial steroidogenesis.

PMID:17518537

FasL, Fas, and death-inducing signaling complex (DISC) proteins are recruited to membrane rafts after spinal cord injury.

PMID:17553422

Depletion of GGA3 stabilizes BACE and enhances beta-secretase activity.

PMID:17869439

Role of inhibitor of apoptosis protein in gentamicin-induced cochlear hair cell damage.

PMID:18239382

Low-dose local kidney irradiation inhibits progression of experimental crescentic nephritis by promoting apoptosis.

PMID:18239768

Central injection of caspase inhibitors facilitates the formation of freezing behavior in rats.

PMID:18274634

The protecting effects and mechanisms of Baicalin and Octreotide on heart injury in rats with SAP.

PMID:18288275

Protecting effects of dexamethasone on thymus of rats with severe acute pancreatitis.

PMID:18289516

Caspase activation in fetal rat brain following experimental intrauterine inflammation.

PMID:18316105

Implication of caspases and subcellular compartments in tert-butylhydroperoxide induced apoptosis.

PMID:18404518

P2X(7) nucleotide receptors mediate caspase-8/9/3-dependent apoptosis in rat primary cortical neurons.

PMID:18423997

Glutamate-induced losses of oligodendrocytes and neurons and activation of caspase-3 in the rat spinal cord.

PMID:18459132

Different expression of caspase-3 in rat hippocampal subregions during postnatal development.

PMID:18466900

Chronic hypobaric hypoxia induced apoptosis in CA1 region of hippocampus: a possible role of NMDAR mediated p75NTR upregulation.

PMID:18477628

Nicotine suppresses tunicamycin-induced, but not thapsigargin-induced, expression of GRP78 during ER stress-mediated apoptosis in PC12 cells.

PMID:18479463

Leptin protects H9c2 rat cardiomyocytes from H2O2-induced apoptosis.

PMID:18483861

Pravastatin attenuates carboplatin-induced cardiotoxicity via inhibition of oxidative stress associated apoptosis.

PMID:18485100

Nuclear translocation of X-linked inhibitor of apoptosis (XIAP) determines cell fate after hypoxia ischemia in neonatal brain.

PMID:18598848

Estradiol protects PC12 cells against CoCl2-induced apoptosis.

PMID:18931364

Bax and Bid act in synergy to bring about T11TS-mediated glioma apoptosis via the release of mitochondrial cytochrome c and subsequent caspase activation.

PMID:19356108

Heme oxygenase-derived carbon monoxide restores vascular function in type 1 diabetes.

PMID:21630211

Immunohistochemical study of the apoptosis process in epidermal epithelial cells of rats under a physiological condition.

PMID:23102656

Effect of repetitive daily ethanol intoxication on adult rat brain: significant changes in phospholipase A2 enzyme levels in association with increased PARP-1 indicate neuroinflammatory pathway activation.

PMID:24089674

Neuroprotective effects of microRNA-210 on hypoxic-ischemic encephalopathy.

PMID:25332219

Endoplasmic reticulum stress-mediated apoptotic pathway is involved in corpus luteum regression in rats.

PMID:25898930

Death Receptor 6 and Caspase-6 Regulate Prion Peptide-Induced Axonal Degeneration in Rat Spinal Neurons.

PMID:26861981

Time course of apoptosis induced by photodynamic therapy with PsD007 in LT12 acute myeloid leukemia cells.

PMID:27498600

Neuroprotective effects of caffeic acid phenethyl ester against sevoflurane‑induced neuronal degeneration in the hippocampus of neonatal rats involve MAPK and PI3K/Akt signaling pathways.

PMID:28899909

Depletion of the mRNA translation initiation inhibitor, programmed cell death protein 4 (PDCD4), impairs L6 myotube formation.

PMID:30926569

Effect of saffron (stigma of Crocus sativus L.) aqueous extract on ethanol toxicity in rats: A biochemical, histopathological and molecular study.

PMID:33574912

Insulin-like growth factor-1 improves postoperative cognitive dysfunction following splenectomy in aged rats.

Deep Research

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 35 citations 2026-03-21T17:50:07.756818

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: Rat Casp3 (Caspase-3) — Functional Annotation (UniProt P55213)

Executive summary

Rat Casp3 encodes caspase-3, the canonical executioner (effector) caspase in apoptosis, functioning as a cysteine protease that cleaves substrates after Asp residues and preferentially recognizes DExD/DEVD-type motifs. Its activation requires proteolytic processing into p17 and p12 subunits (cleavage at Asp28-Ser29 and Asp175-Ser176) and assembly into an active complex. Beyond apoptosis, recent 2024 work highlights caspase-3 as a node of crosstalk between apoptosis and pyroptosis via gasdermin cleavage and as a target of bacterial immune evasion strategies. (cohen1997caspasestheexecutioners pages 6-7, nicholson1999caspasestructureproteolytic pages 1-2, wright2024abacterialtoxin pages 1-3, ge2024phosphorylationofcaspases pages 5-5)

0) Mandatory identity verification (gene/protein disambiguation)

Target identity is consistent and unambiguous with the user-provided UniProt context (P55213; rat Casp3; caspase-3/CPP32/apopain/Yama). Seminal biochemical reviews explicitly equate caspase-3 with CPP32/Yama/apopain and describe its hallmark processing into p17/p12 and DEVD-based substrate/inhibitor usage. (cohen1997caspasestheexecutioners pages 5-6, cohen1997caspasestheexecutioners pages 6-7)

Synonyms used in literature: CPP32, apopain, Yama; caspase-3 is an effector caspase in the caspase family with conserved active-site motif QACXG/QACRG. (cohen1997caspasestheexecutioners pages 5-6, cohen1997caspasestheexecutioners pages 6-7)

1) Key concepts and definitions (current understanding)

1.1 Caspase-3 biochemical function and catalytic mechanism

Caspases are cysteine proteases with an absolute requirement for Asp at P1 of the scissile bond; caspase-3 is classified among effector caspases and is a principal apoptosis executioner. (nicholson1999caspasestructureproteolytic pages 1-2, zhra2024acomprehensiveexploration pages 1-2)

Caspase-3 is described as a cysteine protease (CPP32) that cleaves key apoptotic substrates such as PARP; the PARP cleavage site DEVD/G motivated the widely used synthetic substrate Ac-DEVD-AMC and corresponding inhibitors used to report caspase-3 activity. (cohen1997caspasestheexecutioners pages 5-6, chen1998inductionofcaspase3like pages 12-14)

1.2 Substrate specificity (reaction and substrate preference)

At a functional-annotation level, caspase-3 catalyzes peptide bond hydrolysis C-terminal to Asp residues within preferred recognition motifs. Caspase-3 (group II caspase) is more stringent at S4, typically requiring P4 Asp, with a preferred motif described as DExD, consistent with the canonical DEVD motif widely used in assays. (nicholson1999caspasestructureproteolytic pages 1-2, cohen1997caspasestheexecutioners pages 5-6)

A recent protein-biosensor study reinforces that caspase-3 minimally recognizes a short motif and that DEVD↓-like motifs are canonical; it also emphasizes that protein context/exosites can shape apparent motif tolerance relative to peptide libraries. (blais2026usingabioluminescence pages 1-2, blais2026usingabioluminescence pages 12-13)

1.3 Zymogen processing and activation into p17/p12

Caspase-3 is synthesized as an inactive precursor and activated by proteolytic processing into p17 (large) and p12 (small) subunits. A seminal review specifies cleavage at Asp28-Ser29 and Asp175-Ser176 to generate the active enzyme composed of p17 and p12. (cohen1997caspasestheexecutioners pages 6-7)

Mechanistic synthesis further describes that initiator caspase cleavage at Asp175 separates large and small subunits, followed by autocatalytic cleavage at Asp28 to remove the prodomain; activation increases activity on the order of ~100-fold. (malavez2012mechanismsofcaspase3 pages 36-41)

A 2024 Legionella study explicitly refers to self-processing at the prodomain linker ESMD28-S29 as part of maturation to the p17 subunit and indicates mature p17 forms an active complex with p12. (ge2024phosphorylationofcaspases pages 5-6)

1.4 Pathway placement: intrinsic and extrinsic apoptosis cascades

Apoptosis can proceed through:
- Extrinsic pathway (death receptor/DISC): initiator caspase-8 (±10) activates effector caspases including caspase-3. (blais2026usingabioluminescence pages 2-3, nicholson1999caspasestructureproteolytic pages 1-2)
- Intrinsic pathway (mitochondrial): cytochrome c and APAF-1 form the apoptosome to activate caspase-9, which activates caspase-3. (blais2026usingabioluminescence pages 2-3, nicholson1999caspasestructureproteolytic pages 1-2)

2) Recent developments and latest research (prioritizing 2023–2024)

2.1 Apoptosis–pyroptosis crosstalk via gasdermin cleavage (2024)

A 2024 Cell Reports study shows that bacterial Shiga toxin (Stx) suppresses noncanonical inflammasome signaling by activating caspase-3, which then cleaves and inactivates the active pore-forming NT-GSDMD fragment generated by caspase-11, thereby limiting pyroptosis and IL-1β maturation. (Wright et al., published Apr 23, 2024; https://doi.org/10.1016/j.celrep.2024.114004) (wright2024abacterialtoxin pages 1-3)

This work operationally reframes caspase-3 from being solely an apoptosis executor to also being a regulator of inflammatory lytic cell death through cleavage of gasdermin effectors in infection contexts. (wright2024abacterialtoxin pages 1-3)

2.2 Pathogen immune evasion via caspase phosphorylation (Legionella LegK3; 2024)

A 2024 Nature Communications paper identifies the Legionella effector kinase LegK3 as a direct modifier of apoptosis signaling. LegK3 phosphorylates caspase-3 at Ser29 and reduces its cleavage/activation by initiator caspases while leaving intrinsic proteolytic activity intact. (Ge et al., accepted Sep 20, 2024; https://doi.org/10.1038/s41467-024-52817-1) (ge2024phosphorylationofcaspases pages 1-2, ge2024phosphorylationofcaspases pages 5-5)

Mechanistically, Ser29 lies in the prodomain linker (ESMD28-S29) associated with maturation to the p17 subunit; LegK3-mediated phosphorylation makes procaspase-3 less suitable as a substrate for caspase-8/-9. (ge2024phosphorylationofcaspases pages 5-6, ge2024phosphorylationofcaspases pages 5-5)

Cropped figure panels from this paper document the Ser29 phosphosite identification by mass spectrometry and functional inhibition of activation cleavage. (ge2024phosphorylationofcaspases media 7149fc8b, ge2024phosphorylationofcaspases media bca9b615)

2.3 Methodological advances in defining caspase-3 specificity (2024–2026)

A 2024 methods review summarizes a decade of innovation in caspase detection, highlighting advances enabling temporal/spatial measurement (live-cell imaging; FRET; FLICAs; activatable probes), microfluidic platforms, and MS-based degradomics and substrate mapping. (Zhra et al., May 2024; https://doi.org/10.3390/ijms25105460) (zhra2024acomprehensiveexploration pages 1-2)

A recent recombinant-protein BRET2 caspase-3 biosensor system supports quantitative kinetic measurements (kcat/KM) of cleavage-site variants in a protein context, emphasizing that protein-context specificity can be narrower than peptide library estimates. (Blais & Denault, Mar 2026; https://doi.org/10.1042/BSR20254030) (blais2026usingabioluminescence pages 1-2)

3) Localization and where the gene product acts

The retrieved sources emphasize caspase-3 activation as a cytosolic protease cascade endpoint (initiator caspases activate executioners), but do not provide a rat-specific subcellular localization map (e.g., cytosol vs nucleus dynamics) in the excerpted text. What is supported is the processing-based transition from inactive precursor to active p17/p12 complex that cleaves cytosolic and nuclear substrates (e.g., PARP). (cohen1997caspasestheexecutioners pages 6-7, chen1998inductionofcaspase3like pages 12-14)

4) Current applications and real-world implementations (emphasis on 2023–2024)

4.1 Quantitative analytical assays (electrochemical biosensing; 2024)

A 2024 Molecules paper demonstrates an electrochemical “signal-on” caspase-3 assay using a DEVD-containing peptide (Ac-GDEVDGGGPPPPC) on a gold electrode and methylene blue-loaded MOFs for amplification. It reports a linear range of 0.1–25 pg/mL and LOD of 0.04 pg/mL, and quantifies active caspase-3 in apoptosis-induced HeLa cells. (Huang et al., Aug 2024; https://doi.org/10.3390/molecules29153700) (huang2024signalondetectionof pages 1-2)

4.2 Imaging and live-cell readouts (2024 review synthesis)

The 2024 IJMS review catalogs widely implemented modalities for caspase-3 activity, including:
- Fluorescent-labeled inhibitors (FLIs/FLICAs) and activity-based probes for live-cell labeling
- FRET sensors and genetically encoded reporters
- Activatable multifunctional probes for in vivo imaging
- Microfluidic + electrochemical platforms for live-cell caspase readouts
- MS-based formats (SAMDI-MS, LC-MS/MS, MALDI-TOF) for substrate/cleavage-product quantification and inhibitor screening
It also notes that noninvasive optical imaging of apoptosis using caspase-targeted probes has been demonstrated in preclinical and clinical settings. (Zhra et al., May 2024; https://doi.org/10.3390/ijms25105460) (zhra2024acomprehensiveexploration pages 12-13)

The same review reports quantitative performance examples across platforms, including an organic electrochemical transistor format with detection limit down to 0.1 pM and an SPR-based approach with 1 pg/mL LOD (in cited implementations). (zhra2024acomprehensiveexploration pages 9-11)

4.3 Ratiometric fluorescent probes (2024)

A 2024 Frontiers in Chemistry paper reports a DEVD-based, self-immolative ratiometric probe (Ac-DEVD-PABC-Naph) for caspase-3, stating that Km, kcat, and LOD were obtained and that the probe is selective for caspase-3 over other endogenous species; however, numeric values are not present in the excerpted pages. (Wynne & Elmes, Jul 2024; https://doi.org/10.3389/fchem.2024.1418378) (wynne2024utilisinga18naphthalimide pages 1-2)

5) Rat-specific functional evidence and data (in vivo)

A rat transient global ischemia model provides direct rat-specific evidence: caspase-3 mRNA/protein induction in hippocampus and caudate-putamen after ischemia, increased p17 immunoreactivity over 4–72 h, increased DEVDase activity, and neuroprotection by intracerebroventricular infusion of the caspase-3 inhibitor Z-DEVD-FMK (reduced caspase-3-like activity, DNA fragmentation, and delayed CA1 neuronal loss). (Chen et al., Jul 1998; https://doi.org/10.1523/JNEUROSCI.18-13-04914.1998) (chen1998inductionofcaspase3like pages 12-14)

6) Expert opinions and authoritative analysis

Authoritative reviews (1997–1999, and updated 2024 methods synthesis) converge on the conceptual model that apoptotic signaling cascades converge on caspase-3 activation as a dominant effector step that drives widespread but selective proteolysis of apoptosis substrates (e.g., PARP), with high specificity for Asp-containing motifs. (cohen1997caspasestheexecutioners pages 5-6, nicholson1999caspasestructureproteolytic pages 1-2, zhra2024acomprehensiveexploration pages 1-2)

Recent expert synthesis emphasizes that detection technology has evolved from endpoint immunoblots to tools enabling spatiotemporal monitoring and high-throughput drug screening, including live-cell imaging and MS-based substrate mapping. (zhra2024acomprehensiveexploration pages 1-2, zhra2024acomprehensiveexploration pages 12-13)

Evidence map (condensed)

Topic	Key points (concise)	Evidence (what experiment/approach)	Recent/seminal source (author, year)	URL/DOI
Identity / synonyms	Rat Casp3 (UniProt P55213) encodes caspase-3, an executioner cysteine-aspartate protease; major synonyms include CPP32, apopain, Yama; belongs to the caspase family with conserved QACXG/QACRG active-site motif and apoptotic substrate cleavage after Asp. (cohen1997caspasestheexecutioners pages 5-6)	Seminal biochemical review integrating cloning, sequence alignment, substrate and structural studies.	Cohen, 1997; Nicholson, 1999	https://doi.org/10.1042/bj3260001 ; https://doi.org/10.1038/sj.cdd.4400598
Activation processing sites	Procaspase-3 is activated by cleavage at Asp175-Ser176 and prodomain cleavage at Asp28-Ser29 (older literature also noted Asp9 as possible in vitro site); mature enzyme contains p17 and p12 subunits. (malavez2012mechanismsofcaspase3 pages 36-41, cohen1997caspasestheexecutioners pages 6-7, ge2024phosphorylationofcaspases pages 5-6)	Immunoblot/processing analyses; mechanistic synthesis of activation steps; phosphosite-focused bacterial kinase study referencing maturation linker.	Cohen, 1997; Malavez, 2012; Ge et al., 2024	https://doi.org/10.1042/bj3260001 ; https://doi.org/10.1038/s41467-024-52817-1
Substrate specificity	Caspase-3 has near-absolute requirement for P1 Asp and classically prefers DExD/DEVD motifs; P4 Asp is strongly favored, though protein context broadens tolerance. PARP cleavage and DEVD-AMC/DEVD-based assays are canonical readouts. (cohen1997caspasestheexecutioners pages 5-6, nicholson1999caspasestructureproteolytic pages 1-2, blais2026usingabioluminescence pages 12-13, huang2024signalondetectionof pages 1-2)	Peptide substrate/inhibitor studies, structural analyses, degradomics/protein-biosensor assays, electrochemical DEVD-peptide sensor design.	Cohen, 1997; Nicholson, 1999; Blais & Denault, 2026; Huang et al., 2024	https://doi.org/10.1042/bj3260001 ; https://doi.org/10.1038/sj.cdd.4400598 ; https://doi.org/10.1042/BSR20254030 ; https://doi.org/10.3390/molecules29153700
Pathways upstream of activation	In the extrinsic pathway, death receptors activate caspase-8 (and -10), which cleaves/activates caspase-3; in the intrinsic pathway, cytochrome c + APAF-1 apoptosome activates caspase-9, which activates caspase-3. (blais2026usingabioluminescence pages 2-3, zhra2024acomprehensiveexploration pages 2-4, nicholson1999caspasestructureproteolytic pages 1-2)	Pathway reconstitution, biochemical and review synthesis of DISC/apoptosome signaling.	Nicholson, 1999; Zhra et al., 2024; Blais & Denault, 2026	https://doi.org/10.1038/sj.cdd.4400598 ; https://doi.org/10.3390/ijms25105460 ; https://doi.org/10.1042/BSR20254030
Localization / active complex	Caspase-3 is synthesized as an inactive zymogen; after processing, p17 and p12 assemble into the active enzyme, described structurally as a heterotetramer / (p17:p12)2 complex. (cohen1997caspasestheexecutioners pages 5-6, ge2024phosphorylationofcaspases pages 5-6)	Structural/biochemical analyses and maturation models.	Cohen, 1997; Ge et al., 2024	https://doi.org/10.1042/bj3260001 ; https://doi.org/10.1038/s41467-024-52817-1
Rat in vivo evidence	In rat global cerebral ischemia, hippocampus/caudate-putamen showed increased caspase-3 mRNA, precursor processing, p17 accumulation, and DEVDase activity; intracerebroventricular Z-DEVD-FMK reduced caspase-3-like activity, DNA fragmentation, and delayed CA1 neuronal loss. (chen1998inductionofcaspase3like pages 12-14)	Rat brain cDNA cloning, in situ hybridization, Western blot, DEVD-AMC activity assay, inhibitor infusion, histology/TUNEL.	Chen et al., 1998	https://doi.org/10.1523/JNEUROSCI.18-13-04914.1998
Non-apoptotic / crosstalk roles	Beyond classical apoptosis, caspase-3 can cleave gasdermins and participate in apoptosis–pyroptosis crosstalk; reviews note caspase-3 intersection with autophagy/stress programs, and pathogen studies show caspase-3 activity can occur without overt apoptosis. (zhra2024acomprehensiveexploration pages 2-4, wright2024abacterialtoxin pages 1-3, ge2024phosphorylationofcaspases pages 1-2, ge2024phosphorylationofcaspases pages 7-8)	Review synthesis plus primary cell-death crosstalk studies in macrophages and infection models.	Zhra et al., 2024; Wright et al., 2024; Ge et al., 2024	https://doi.org/10.3390/ijms25105460 ; https://doi.org/10.1016/j.celrep.2024.114004 ; https://doi.org/10.1038/s41467-024-52817-1
Pathogen modulation	Legionella effector LegK3 phosphorylates caspase-3 at Ser29, reducing cleavage by initiator caspases while sparing intrinsic proteolytic activity; EHEC/Shiga toxin activates caspase-3, which cleaves and inactivates NT-GSDMD, limiting macrophage pyroptosis. (ge2024phosphorylationofcaspases pages 5-6, ge2024phosphorylationofcaspases pages 1-2, ge2024phosphorylationofcaspases pages 5-5, wright2024abacterialtoxin pages 1-3, wright2024abacterialtoxin pages 10-12)	Mass spectrometry phosphosite mapping, phosphomimetic mutants, cleavage assays, infection models, in vitro GSDMD/caspase reactions with catalytic mutant controls.	Ge et al., 2024; Wright et al., 2024	https://doi.org/10.1038/s41467-024-52817-1 ; https://doi.org/10.1016/j.celrep.2024.114004
Assay / probe applications	A 2024 electrochemical MOF biosensor using Ac-GDEVDGGGPPPPC achieved 0.1–25 pg/mL linear range and 0.04 pg/mL LOD for caspase-3; a 2026 BRET2 protein biosensor quantified kcat/KM across nearly all P4 substitutions (all except Arg/Lys), showing narrower protein-context specificity differences than peptide libraries. (huang2024signalondetectionof pages 1-2, blais2026usingabioluminescence pages 1-2, blais2026usingabioluminescence pages 12-13)	Electrochemical amplified signal-on assay in HeLa apoptosis samples; recombinant protein BRET2 kinetics in vitro and apoptotic cells.	Huang et al., 2024; Blais & Denault, 2026	https://doi.org/10.3390/molecules29153700 ; https://doi.org/10.1042/BSR20254030

Table: This table condenses core functional-annotation facts for rat Casp3/caspase-3 in the UniProt P55213 context, linking canonical apoptotic biology with recent 2024–2026 findings on crosstalk, pathogen modulation, and assay development. It is useful as a rapid evidence map for function, pathway placement, and experimental support.

Visual evidence (example figure panel)

Ge et al. (Nature Communications 2024) figure panels show identification of the Ser29 phosphorylation site on caspase-3 and inhibition of activation cleavage, supporting pathogen-directed regulation of caspase-3 activation. (ge2024phosphorylationofcaspases media 7149fc8b, ge2024phosphorylationofcaspases media bca9b615)

Conclusions

Casp3 in rat encodes caspase-3, an executioner caspase central to apoptosis via proteolysis after Asp in DExD/DEVD motifs and requiring activation cleavage into p17/p12. Rat in vivo work supports its functional contribution to neuronal injury after ischemia and protection by DEVD-based inhibitors. In 2024, caspase-3 biology broadened further via strong evidence for bacterial manipulation (LegK3 phosphorylation) and immune crosstalk (Shiga toxin–driven caspase-3 cleavage of NT-GSDMD), reinforcing caspase-3 as a nexus in regulated cell-death network control and a key measurable biomarker/target in assays and imaging. (ge2024phosphorylationofcaspases pages 5-5, wright2024abacterialtoxin pages 1-3, chen1998inductionofcaspase3like pages 12-14)

Notes on scope/limitations

EC number (3.4.22.56) and explicit UniProt sequence/domain annotations were provided by the user but did not appear explicitly in the retrieved full-text excerpts; therefore, EC- and domain-level statements beyond the conserved caspase motif were not expanded without direct database text evidence. (cohen1997caspasestheexecutioners pages 6-7, zhra2024acomprehensiveexploration pages 1-2)
Subcellular localization dynamics (cytosol↔nucleus trafficking during apoptosis) were not explicitly described in the excerpted texts for rat Casp3; claims were restricted to processing/activation and substrate cleavage evidence present in the sources. (chen1998inductionofcaspase3like pages 12-14, cohen1997caspasestheexecutioners pages 6-7)

References

(cohen1997caspasestheexecutioners pages 6-7): Gerald M. COHEN. Caspases: the executioners of apoptosis. The Biochemical journal, 326 ( Pt 1):1-16, Aug 1997. URL: https://doi.org/10.1042/bj3260001, doi:10.1042/bj3260001. This article has 6789 citations.
(nicholson1999caspasestructureproteolytic pages 1-2): DW Nicholson. Caspase structure, proteolytic substrates, and function during apoptotic cell death. Cell Death and Differentiation, 6:1028-1042, Nov 1999. URL: https://doi.org/10.1038/sj.cdd.4400598, doi:10.1038/sj.cdd.4400598. This article has 2225 citations and is from a domain leading peer-reviewed journal.
(wright2024abacterialtoxin pages 1-3): Skylar S. Wright, Chengliang Wang, Atri Ta, Morena S. Havira, Jianbin Ruan, Vijay A. Rathinam, and Sivapriya Kailasan Vanaja. A bacterial toxin co-opts caspase-3 to disable active gasdermin d and limit macrophage pyroptosis. Cell Reports, 43:114004, Apr 2024. URL: https://doi.org/10.1016/j.celrep.2024.114004, doi:10.1016/j.celrep.2024.114004. This article has 23 citations and is from a highest quality peer-reviewed journal.
(ge2024phosphorylationofcaspases pages 5-5): Jinli Ge, Ying Wang, Xueyu Li, Qian Lu, Hangqian Yu, Hongtao Liu, Kelong Ma, Xuming Deng, Zhao-Qing Luo, Xiaoyun Liu, and Jiazhang Qiu. Phosphorylation of caspases by a bacterial kinase inhibits host programmed cell death. Nature Communications, Sep 2024. URL: https://doi.org/10.1038/s41467-024-52817-1, doi:10.1038/s41467-024-52817-1. This article has 13 citations and is from a highest quality peer-reviewed journal.
(cohen1997caspasestheexecutioners pages 5-6): Gerald M. COHEN. Caspases: the executioners of apoptosis. The Biochemical journal, 326 ( Pt 1):1-16, Aug 1997. URL: https://doi.org/10.1042/bj3260001, doi:10.1042/bj3260001. This article has 6789 citations.
(zhra2024acomprehensiveexploration pages 1-2): 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 27 citations.
(chen1998inductionofcaspase3like pages 12-14): Jun Chen, Tetsuya Nagayama, Kunlin Jin, R. Anne Stetler, Raymond L. Zhu, Steven H. Graham, and Roger P. Simon. Induction of caspase-3-like protease may mediate delayed neuronal death in the hippocampus after transient cerebral ischemia. The Journal of Neuroscience, 18:4914-4928, Jul 1998. URL: https://doi.org/10.1523/jneurosci.18-13-04914.1998, doi:10.1523/jneurosci.18-13-04914.1998. This article has 969 citations.
(blais2026usingabioluminescence pages 1-2): Véronique Blais and Jean-Bernard Denault. Using a bioluminescence resonance energy transfer (bret2) 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.
(blais2026usingabioluminescence pages 12-13): Véronique Blais and Jean-Bernard Denault. Using a bioluminescence resonance energy transfer (bret2) 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.
(malavez2012mechanismsofcaspase3 pages 36-41): Y Malavez. Mechanisms of caspase-3 regulation in the execution of cell death. Unknown journal, 2012.
(ge2024phosphorylationofcaspases pages 5-6): Jinli Ge, Ying Wang, Xueyu Li, Qian Lu, Hangqian Yu, Hongtao Liu, Kelong Ma, Xuming Deng, Zhao-Qing Luo, Xiaoyun Liu, and Jiazhang Qiu. Phosphorylation of caspases by a bacterial kinase inhibits host programmed cell death. Nature Communications, Sep 2024. URL: https://doi.org/10.1038/s41467-024-52817-1, doi:10.1038/s41467-024-52817-1. This article has 13 citations and is from a highest quality peer-reviewed journal.
(blais2026usingabioluminescence pages 2-3): Véronique Blais and Jean-Bernard Denault. Using a bioluminescence resonance energy transfer (bret2) 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.
(ge2024phosphorylationofcaspases pages 1-2): Jinli Ge, Ying Wang, Xueyu Li, Qian Lu, Hangqian Yu, Hongtao Liu, Kelong Ma, Xuming Deng, Zhao-Qing Luo, Xiaoyun Liu, and Jiazhang Qiu. Phosphorylation of caspases by a bacterial kinase inhibits host programmed cell death. Nature Communications, Sep 2024. URL: https://doi.org/10.1038/s41467-024-52817-1, doi:10.1038/s41467-024-52817-1. This article has 13 citations and is from a highest quality peer-reviewed journal.
(ge2024phosphorylationofcaspases media 7149fc8b): Jinli Ge, Ying Wang, Xueyu Li, Qian Lu, Hangqian Yu, Hongtao Liu, Kelong Ma, Xuming Deng, Zhao-Qing Luo, Xiaoyun Liu, and Jiazhang Qiu. Phosphorylation of caspases by a bacterial kinase inhibits host programmed cell death. Nature Communications, Sep 2024. URL: https://doi.org/10.1038/s41467-024-52817-1, doi:10.1038/s41467-024-52817-1. This article has 13 citations and is from a highest quality peer-reviewed journal.
(ge2024phosphorylationofcaspases media bca9b615): Jinli Ge, Ying Wang, Xueyu Li, Qian Lu, Hangqian Yu, Hongtao Liu, Kelong Ma, Xuming Deng, Zhao-Qing Luo, Xiaoyun Liu, and Jiazhang Qiu. Phosphorylation of caspases by a bacterial kinase inhibits host programmed cell death. Nature Communications, Sep 2024. URL: https://doi.org/10.1038/s41467-024-52817-1, doi:10.1038/s41467-024-52817-1. This article has 13 citations and is from a highest quality peer-reviewed journal.
(huang2024signalondetectionof pages 1-2): 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.
(zhra2024acomprehensiveexploration pages 12-13): 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 27 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 27 citations.
(wynne2024utilisinga18naphthalimide pages 1-2): Conor Wynne and Robert B. P. Elmes. Utilising a 1,8-naphthalimide probe for the ratiometric fluorescent visualisation of caspase-3. Frontiers in Chemistry, Jul 2024. URL: https://doi.org/10.3389/fchem.2024.1418378, doi:10.3389/fchem.2024.1418378. This article has 11 citations.
(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 27 citations.
(ge2024phosphorylationofcaspases pages 7-8): Jinli Ge, Ying Wang, Xueyu Li, Qian Lu, Hangqian Yu, Hongtao Liu, Kelong Ma, Xuming Deng, Zhao-Qing Luo, Xiaoyun Liu, and Jiazhang Qiu. Phosphorylation of caspases by a bacterial kinase inhibits host programmed cell death. Nature Communications, Sep 2024. URL: https://doi.org/10.1038/s41467-024-52817-1, doi:10.1038/s41467-024-52817-1. This article has 13 citations and is from a highest quality peer-reviewed journal.
(wright2024abacterialtoxin pages 10-12): Skylar S. Wright, Chengliang Wang, Atri Ta, Morena S. Havira, Jianbin Ruan, Vijay A. Rathinam, and Sivapriya Kailasan Vanaja. A bacterial toxin co-opts caspase-3 to disable active gasdermin d and limit macrophage pyroptosis. Cell Reports, 43:114004, Apr 2024. URL: https://doi.org/10.1016/j.celrep.2024.114004, doi:10.1016/j.celrep.2024.114004. This article has 23 citations and is from a highest quality peer-reviewed journal.

Citations

cohen1997caspasestheexecutioners pages 6-7
ge2024phosphorylationofcaspases pages 5-6
wright2024abacterialtoxin pages 1-3
zhra2024acomprehensiveexploration pages 1-2
blais2026usingabioluminescence pages 1-2
huang2024signalondetectionof pages 1-2
zhra2024acomprehensiveexploration pages 12-13
zhra2024acomprehensiveexploration pages 9-11
cohen1997caspasestheexecutioners pages 5-6
nicholson1999caspasestructureproteolytic pages 1-2
ge2024phosphorylationofcaspases pages 5-5
blais2026usingabioluminescence pages 12-13
blais2026usingabioluminescence pages 2-3
ge2024phosphorylationofcaspases pages 1-2
zhra2024acomprehensiveexploration pages 2-4
ge2024phosphorylationofcaspases pages 7-8
wright2024abacterialtoxin pages 10-12
https://doi.org/10.1016/j.celrep.2024.114004
https://doi.org/10.1038/s41467-024-52817-1
https://doi.org/10.3390/ijms25105460
https://doi.org/10.1042/BSR20254030
https://doi.org/10.3390/molecules29153700
https://doi.org/10.3389/fchem.2024.1418378
https://doi.org/10.1523/JNEUROSCI.18-13-04914.1998
https://doi.org/10.1042/bj3260001
https://doi.org/10.1038/sj.cdd.4400598
https://doi.org/10.1042/bj3260001,
https://doi.org/10.1038/sj.cdd.4400598,
https://doi.org/10.1016/j.celrep.2024.114004,
https://doi.org/10.1038/s41467-024-52817-1,
https://doi.org/10.3390/ijms25105460,
https://doi.org/10.1523/jneurosci.18-13-04914.1998,
https://doi.org/10.1042/bsr20254030,
https://doi.org/10.3390/molecules29153700,
https://doi.org/10.3389/fchem.2024.1418378,

📚 Additional Documentation

Bioreason Rl Predictions

(Casp3-bioreason-rl-predictions.md)

BioReason Chat Export

Exported on March 22, 2026 at 12:53 AM

Organism: Rattus norvegicus

Sequence:

MDNNETSVDSKSINNFETKTIHGSKSMDSGIYLDSSYKMDYPEMGLCIIINNKNFHKSTGMSARNGTDVDAANLRETFMALKYEVRNKNDLTREEIMELMDSVSKEDHSKRSSFVCVILSHGDEGVIFGTNGPVDLKKLTSFFRGDYCRSLTGKPKLFIIQACRGTELDCGIETDSGTDDDMACQKIPVEADFLYAYSTAPGYYSWRNSRDGSWFIQSLCAMLKLYAHKLEFMHILTRVNRKVATEFESFSLDATFHAKKQIPCIVSMLTKELYFYH

Thinking Trace

I begin by dissecting the InterPro architecture. The polypeptide core is defined by multiple C14-family caspase signatures: IPR002398 (Peptidase C14 family, residues 33–275) and IPR015917 (Peptidase C14A, caspase catalytic domain, residues 36–277) establish a classical caspase scaffold. Within this scaffold, the architecture resolves into the hallmark two-domain layout: an N-terminal p20 catalytic module and a C-terminal p10 non-catalytic module. This is explicitly captured by IPR001309 (Peptidase C14, p20 domain, residues 43–167) followed by IPR002138 (Peptidase C14, caspase non-catalytic subunit p10, residues 183–277). The global fold is reinforced by IPR029030 (Caspase-like domain superfamily, residues 36–276) and IPR011600 (Peptidase C14, caspase domain, residues 45–274), which together describe the conserved caspase β-sheet/α-helix core that supports dimerization and activation. Critically, the catalytic residues are specified: IPR016129 annotates the histidine active-site region at residues 108–122, and IPR033139 annotates the cysteine active-site region at residues 154–165. This His–Cys dyad is diagnostic of cysteine-dependent endopeptidases and causes acyl-enzyme formation and peptide bond hydrolysis after aspartate residues.

From this architecture, the molecular function follows directly. The juxtaposition of the p20 and p10 domains, together with the His/Cys dyad and C14A specificity, defines an endopeptidase that cleaves substrates after aspartate, characteristic of caspases. Thus the primary function is cysteine-type endopeptidase activity (GO:0004197). The presence of both the catalytic and non-catalytic subunits implies activation by proteolytic maturation and dimerization—mechanistically consistent with executioner/caspase behavior.

This enzymatic role positions the protein within programmed cell death pathways. Caspase family chemistry drives irreversible cleavage of key cellular targets, thereby executing apoptosis and shaping cell-fate decisions. Therefore, the biological process centers on apoptosis (GO:0006915), with broader implications for cell-fate regulation consistent with the caspase mechanism.

The cellular component can be inferred from the soluble caspase fold and lack of transmembrane features in the annotated spans. The caspase core lacks signal peptides or membrane anchors, favoring a soluble intracellular localization. Caspase-mediated apoptosis proceeds primarily in the cytosol where substrates and activation platforms accumulate; thus a cytosolic residency is most parsimonious, with transient redistribution to other compartments possible during complex formation.

Mechanistically, the p20–p10 architecture supports activation via cleavage-dependent assembly into an active dimer. The His/Cys dyad executes nucleophilic attack and tetrapeptide release at aspartate sites, enabling downstream apoptotic cascades. Likely interaction partners include zymogen activators and adaptors that present substrates and regulate timing. I hypothesize associations with apoptotic adaptors and scaffolds that chaperone caspase activation, as well as endogenous inhibitors that temper protease activity. These assemblies would localize in the cytosol and orchestrate precise substrate processing during apoptosis.

Functional Summary

A soluble cysteine protease that assembles as a p20–p10 caspase and becomes catalytically active after proteolytic maturation to cleave substrates after aspartate residues. Through this caspase-driven proteolysis, it executes and regulates apoptotic pathways in the cytosol. Activation arises from dimerization of the two-domain architecture and a histidine–cysteine catalytic dyad that drives peptide bond hydrolysis, enabling orderly progression of programmed cell death.

UniProt Summary

Probable cysteine protease.

InterPro Domains

Peptidase C14 family (IPR002398, family) — residues 33-275
Peptidase C14A, caspase catalytic domain (IPR015917, domain) — residues 36-277
Caspase-like domain superfamily (IPR029030, homologous_superfamily) — residues 36-276
Peptidase C14, p20 domain (IPR001309, domain) — residues 43-167
Peptidase C14, caspase domain (IPR011600, domain) — residues 45-274
Peptidase family C14A, His active site (IPR016129, active_site) — residues 108-122
Peptidase family C14A, cysteine active site (IPR033139, active_site) — residues 154-165
Peptidase C14, caspase non-catalytic subunit p10 (IPR002138, domain) — residues 183-277

GO Terms

Molecular Function: molecular_function (GO:0003674), molecular function regulator activity (GO:0098772), binding (GO:0005488), catalytic activity (GO:0003824), enzyme regulator activity (GO:0030234), molecular function activator activity (GO:0140677), hydrolase activity (GO:0016787), protein-containing complex binding (GO:0044877), catalytic activity, acting on a protein (GO:0140096), protein binding (GO:0005515), peptidase activity (GO:0008233), signaling receptor binding (GO:0005102), enzyme binding (GO:0019899), enzyme activator activity (GO:0008047), cytokine receptor binding (GO:0005126), lipase activator activity (GO:0060229), cysteine-type peptidase activity (GO:0008234), protease binding (GO:0002020), phospholipase activator activity (GO:0016004), tumor necrosis factor receptor superfamily binding (GO:0032813), death receptor binding (GO:0005123)

Biological Process: biological_process (GO:0008150), positive regulation of biological process (GO:0048518), regulation of biological process (GO:0050789), signaling (GO:0023052), reproduction (GO:0000003), multicellular organismal process (GO:0032501), biological regulation (GO:0065007), rhythmic process (GO:0048511), response to stimulus (GO:0050896), developmental process (GO:0032502), cellular process (GO:0009987), metabolic process (GO:0008152), biological process involved in interspecies interaction between organisms (GO:0044419), reproductive process (GO:0022414), response to external stimulus (GO:0009605), anatomical structure development (GO:0048856), response to chemical (GO:0042221), nitrogen compound metabolic process (GO:0006807), cellular component organization or biogenesis (GO:0071840), multicellular organism reproduction (GO:0032504), developmental process involved in reproduction (GO:0003006), regulation of biological quality (GO:0065008), response to biotic stimulus (GO:0009607), response to endogenous stimulus (GO:0009719), cell death (GO:0008219), regulation of cellular process (GO:0050794), cell recognition (GO:0008037), cellular response to stimulus (GO:0051716), response to other organism (GO:0051707), signal transduction (GO:0007165), cellular developmental process (GO:0048869), response to abiotic stimulus (GO:0009628), multicellular organism development (GO:0007275), regulation of metabolic process (GO:0019222), organic substance metabolic process (GO:0071704), catabolic process (GO:0009056), system process (GO:0003008), ovulation cycle process (GO:0022602), ovulation cycle (GO:0042698), positive regulation of metabolic process (GO:0009893), response to stress (GO:0006950), multicellular organismal reproductive process (GO:0048609), cell communication (GO:0007154), primary metabolic process (GO:0044238), behavior (GO:0007610), positive regulation of cellular process (GO:0048522), response to acid chemical (GO:0001101), response to hypoxia (GO:0001666), positive regulation of cell death (GO:0010942), neuron recognition (GO:0008038), programmed cell death (GO:0012501), response to external biotic stimulus (GO:0043207), cell development (GO:0048468), response to xenobiotic stimulus (GO:0009410), cell differentiation (GO:0030154), response to radiation (GO:0009314), system development (GO:0048731), response to oxygen levels (GO:0070482), animal organ development (GO:0048513), regulation of macromolecule metabolic process (GO:0060255), reproductive structure development (GO:0048608), development of primary sexual characteristics (GO:0045137), response to hormone (GO:0009725), response to inorganic substance (GO:0010035), learning or memory (GO:0007611), forebrain development (GO:0030900), regulation of nitrogen compound metabolic process (GO:0051171), pallium development (GO:0021543), cellular component organization (GO:0016043), sex differentiation (GO:0007548), organic substance catabolic process (GO:1901575), response to nicotine (GO:0035094), positive regulation of nitrogen compound metabolic process (GO:0051173), female sex differentiation (GO:0046660), hippocampus development (GO:0021766), organonitrogen compound metabolic process (GO:1901564), intracellular signal transduction (GO:0035556), response to wounding (GO:0009611), positive regulation of macromolecule metabolic process (GO:0010604), response to oxidative stress (GO:0006979), telencephalon development (GO:0021537), protein metabolic process (GO:0019538), response to oxygen-containing compound (GO:1901700), regulation of protein stability (GO:0031647), macromolecule metabolic process (GO:0043170), response to organic substance (GO:0010033), muscle structure development (GO:0061061), regulation of cell death (GO:0010941), response to nitrogen compound (GO:1901698), head development (GO:0060322), cellular response to chemical stimulus (GO:0070887), response to bacterium (GO:0009617), response to antibiotic (GO:0046677), nervous system process (GO:0050877), regulation of primary metabolic process (GO:0080090), cell projection organization (GO:0030030), response to estradiol (GO:0032355), regulation of protein metabolic process (GO:0051246), regulation of programmed cell death (GO:0043067), protein catabolic process (GO:0030163), response to steroid hormone (GO:0048545), gonad development (GO:0008406), response to molecule of bacterial origin (GO:0002237), neuron development (GO:0048666), brain development (GO:0007420), macromolecule catabolic process (GO:0009057), nervous system development (GO:0007399), limbic system development (GO:0021761), muscle cell differentiation (GO:0042692), response to decreased oxygen levels (GO:0036293), central nervous system development (GO:0007417), response to ionizing radiation (GO:0010212), response to metal ion (GO:0010038), positive regulation of neuron death (GO:1901216), response to carbohydrate (GO:0009743), reproductive system development (GO:0061458), cognition (GO:0050890), response to lipopolysaccharide (GO:0032496), response to amino acid (GO:0043200), axonal fasciculation (GO:0007413), organonitrogen compound catabolic process (GO:1901565), proteolysis (GO:0006508), positive regulation of amide metabolic process (GO:0034250), cellular response to organic substance (GO:0071310), positive regulation of programmed cell death (GO:0043068), regulation of neuron death (GO:1901214), neurogenesis (GO:0022008), wound healing (GO:0042060), regulation of amide metabolic process (GO:0034248), response to organonitrogen compound (GO:0010243), development of primary female sexual characteristics (GO:0046545), response to lipid (GO:0033993), apoptotic process (GO:0006915), positive regulation of protein metabolic process (GO:0051247), response to organic cyclic compound (GO:0014070), response to hydrogen peroxide (GO:0042542), response to reactive oxygen species (GO:0000302), neuron differentiation (GO:0030182), regulation of apoptotic process (GO:0042981), female gonad development (GO:0008585), response to cobalt ion (GO:0032025), response to corticosteroid (GO:0031960), regulation of neuron apoptotic process (GO:0043523), regulation of amyloid precursor protein catabolic process (GO:1902991), positive regulation of amyloid-beta formation (GO:1902004), positive regulation of amyloid precursor protein catabolic process (GO:1902993), generation of neurons (GO:0048699), positive regulation of neuron apoptotic process (GO:0043525), positive regulation of apoptotic process (GO:0043065), regulation of amyloid-beta formation (GO:1902003), plasma membrane bounded cell projection organization (GO:0120036), response to monosaccharide (GO:0034284), cellular response to organic cyclic compound (GO:0071407), striated muscle cell differentiation (GO:0051146), neuron projection development (GO:0031175), leukocyte apoptotic process (GO:0071887), response to X-ray (GO:0010165), response to glucocorticoid (GO:0051384), axon development (GO:0061564), neuron projection fasciculation (GO:0106030), response to hexose (GO:0009746), response to glucose (GO:0009749)

Cellular Component: cellular_component (GO:0005575), protein-containing complex (GO:0032991), cellular anatomical entity (GO:0110165), intracellular anatomical structure (GO:0005622), membrane (GO:0016020), cell body (GO:0044297), cytosol (GO:0005829), somatodendritic compartment (GO:0036477), cytoplasm (GO:0005737), cell periphery (GO:0071944), membrane protein complex (GO:0098796), plasma membrane protein complex (GO:0098797), neuronal cell body (GO:0043025), membrane microdomain (GO:0098857), plasma membrane (GO:0005886), membrane raft (GO:0045121)

Generated by BioReason

Bioreason Rl Review

(Casp3-bioreason-rl-review.md)

BioReason-Pro RL Review: Casp3 (rat)

Source: Casp3-bioreason-rl-predictions.md

Correctness: 5/5
Completeness: 3/5

Functional Summary Review

The functional summary states:

A soluble cysteine protease that assembles as a p20-p10 caspase and becomes catalytically active after proteolytic maturation to cleave substrates after aspartate residues. Through this caspase-driven proteolysis, it executes and regulates apoptotic pathways in the cytosol.

This is entirely correct. The curated review confirms cysteine-type endopeptidase activity (GO:0004197), apoptotic process (GO:0006915), execution phase of apoptosis (GO:0097194), cytoplasm (GO:0005737), and proteolysis (GO:0006508) -- all matching the BioReason narrative.

The description of the His-Cys catalytic dyad, p20-p10 architecture, and activation by proteolytic maturation is accurate and well-supported by the domain analysis.

However, the summary is limited to the apoptosis axis alone. The curated review includes several non-obvious annotations: neuron differentiation (GO:0030182), keratinocyte differentiation (GO:0030216), erythrocyte differentiation (GO:0030218), positive regulation of neuron apoptotic process (GO:0043525), enzyme activator activity (GO:0008047), and association with the death-inducing signaling complex (GO:0031264). These developmental and differentiation roles are well-established for Casp3 and represent important biology beyond simple apoptosis execution. BioReason captures only the core protease/apoptosis function without addressing the broader biological context.

Comparison with interpro2go:

There are no GO_REF:0000002 (interpro2go) annotations in the Casp3 ai-review.yaml. BioReason's summary is therefore not recapitulating interpro2go but rather deriving function from the C14 caspase domain family signatures. The derivation is sound and consistent with what interpro2go-type mappings would predict (cysteine peptidase activity, proteolysis). No errors from domain-based inference are present.

Notes on thinking trace

The trace is well-structured, walking through the C14 family signatures, p20/p10 domain layout, and His/Cys active site residues in a logical progression. The reasoning is conservative and accurate, though the hypothesized interactions ("apoptotic adaptors and scaffolds") remain generic rather than naming specific partners like APAF-1 or the apoptosome.

📄 View Raw YAML

id: P55213
gene_symbol: Casp3
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:10116
  label: Rattus norvegicus
description: Casp3 encodes rat caspase-3, the conserved effector cysteine protease
  that executes apoptosis after initiator-caspase activation. The ISO trace shows
  that the best-supported conserved transfers are cysteine-type endopeptidase activity,
  proteolysis, cytoplasmic/cytosolic localization, apoptotic process, execution phase
  of apoptosis, and apoptotic DNA fragmentation. Many additional ISO rows are second-hop
  transitive transfers or over-specific context terms from human, mouse, dog, pig,
  and chinchilla ortholog records, especially for stimulus-specific responses, pyroptosis,
  and pleiotropic developmental or immune phenotypes; those are kept as non-core,
  modified to more precise core terms, or removed.
existing_annotations:
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: is_active_in
  supporting_entities:
  - FB:FBgn0010501
  - FB:FBgn0019972
  - FB:FBgn0020381
  - FB:FBgn0028381
  - FB:FBgn0033051
  - MGI:MGI:107700
  - MGI:MGI:107739
  - MGI:MGI:1261423
  - MGI:MGI:1277950
  - MGI:MGI:1312922
  - MGI:MGI:1336166
  - MGI:MGI:97295
  - PANTHER:PTN000047947
  - RGD:2275
  - RGD:61867
  - RGD:620945
  - UniProtKB:O15519
  - UniProtKB:P31944
  - UniProtKB:P42574
  - UniProtKB:P49662
  - UniProtKB:P51878
  - UniProtKB:P55210
  - UniProtKB:P55211
  - UniProtKB:P55212
  - UniProtKB:Q14790
  - UniProtKB:Q6UXS9
  - UniProtKB:Q8MKI5
  - UniProtKB:Q92851
  - UniProtKB:Q95ND5
  - WB:WBGene00000417
  - ZFIN:ZDB-GENE-000616-3
  - ZFIN:ZDB-GENE-020812-1
- term:
    id: GO:0006915
    label: apoptotic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - FB:FBgn0010501
  - FB:FBgn0019972
  - FB:FBgn0020381
  - FB:FBgn0028381
  - FB:FBgn0033051
  - FB:FBgn0033659
  - MGI:MGI:107739
  - MGI:MGI:109383
  - MGI:MGI:1261423
  - MGI:MGI:1277950
  - MGI:MGI:1312922
  - MGI:MGI:97295
  - PANTHER:PTN000047947
  - RGD:2275
  - RGD:61867
  - RGD:620944
  - RGD:621758
  - UniProtKB:A0A1D5PPP7
  - UniProtKB:O15519
  - UniProtKB:P42574
  - UniProtKB:P42575
  - UniProtKB:P49662
  - UniProtKB:P55210
  - UniProtKB:P55211
  - UniProtKB:P55212
  - UniProtKB:Q14790
  - UniProtKB:Q8MKI5
  - WB:WBGene00000417
  - ZFIN:ZDB-GENE-011210-1
  - ZFIN:ZDB-GENE-030825-3
- term:
    id: GO:0004197
    label: cysteine-type endopeptidase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: enables
  supporting_entities:
  - FB:FBgn0010501
  - FB:FBgn0019972
  - FB:FBgn0020381
  - FB:FBgn0028381
  - FB:FBgn0033659
  - MGI:MGI:107700
  - MGI:MGI:107739
  - MGI:MGI:109383
  - MGI:MGI:1261423
  - MGI:MGI:1277950
  - MGI:MGI:1312922
  - MGI:MGI:97295
  - PANTHER:PTN000047947
  - RGD:620945
  - UniProtKB:A0A1D5PPP7
  - UniProtKB:F1NV61
  - UniProtKB:P42574
  - UniProtKB:P42575
  - UniProtKB:P49662
  - UniProtKB:P51878
  - UniProtKB:P55210
  - UniProtKB:P55211
  - UniProtKB:P55212
  - UniProtKB:Q14790
  - UniProtKB:Q92851
  - WB:WBGene00000417
  - ZFIN:ZDB-GENE-000616-3
  - ZFIN:ZDB-GENE-020812-1
- term:
    id: GO:0006508
    label: proteolysis
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - MGI:MGI:107739
  - PANTHER:PTN008499732
  - RGD:2275
  - UniProtKB:P42574
- term:
    id: GO:0031264
    label: death-inducing signaling complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: part_of
  supporting_entities:
  - PANTHER:PTN002573018
  - RGD:2275
- term:
    id: GO:0097194
    label: execution phase of apoptosis
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - MGI:MGI:107739
  - PANTHER:PTN008499732
  - UniProtKB:P42574
- term:
    id: GO:0008047
    label: enzyme activator activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: enables
  supporting_entities:
  - PANTHER:PTN008499732
  - RGD:2275
- term:
    id: GO:0043525
    label: positive regulation of neuron apoptotic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - MGI:MGI:1277950
  - PANTHER:PTN000047947
  - RGD:2275
  - RGD:620945
  - RGD:69274
  - RGD:70967
  - WB:WBGene00000417
- term:
    id: GO:0030182
    label: neuron differentiation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - PANTHER:PTN002573018
  - RGD:2275
- term:
    id: GO:0030216
    label: keratinocyte differentiation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - MGI:MGI:107739
  - PANTHER:PTN002573018
- term:
    id: GO:0030218
    label: erythrocyte differentiation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - PANTHER:PTN002573018
  - UniProtKB:P42574
- term:
    id: GO:0004197
    label: cysteine-type endopeptidase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: enables
  supporting_entities:
  - UniProtKB:P42574
  - ensembl:ENSP00000311032
  - UniProtKB:P70677
  - ensembl:ENSMUSP00000147767
  - InterPro:IPR001309
  - InterPro:IPR002138
  - InterPro:IPR002398
  - InterPro:IPR011600
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: located_in
  supporting_entities:
  - ARBA:ARBA00026971
  - UniProtKB:P42574
  - ensembl:ENSP00000311032
  - UniProtKB:P70677
  - ensembl:ENSMUSP00000147767
  - UniProtKB-SubCell:SL-0086
- term:
    id: GO:0006508
    label: proteolysis
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
  - ensembl:ENSP00000311032
  - InterPro:IPR001309
  - InterPro:IPR002138
  - InterPro:IPR002398
  - InterPro:IPR011600
- term:
    id: GO:0007413
    label: axonal fasciculation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - ARBA:ARBA00084186
- term:
    id: GO:0008234
    label: cysteine-type peptidase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: enables
  supporting_entities:
  - UniProtKB:P70677
  - ensembl:ENSMUSP00000147767
  - InterPro:IPR015917
- term:
    id: GO:0010212
    label: response to ionizing radiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - ARBA:ARBA00090590
- term:
    id: GO:0048513
    label: animal organ development
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - ARBA:ARBA00029247
- term:
    id: GO:0001818
    label: negative regulation of cytokine production
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
  - ensembl:ENSP00000311032
- term:
    id: GO:0004175
    label: endopeptidase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: enables
  supporting_entities:
  - UniProtKB:P70677
  - ensembl:ENSMUSP00000147767
- term:
    id: GO:0004190
    label: aspartic-type endopeptidase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: enables
  supporting_entities:
  - UniProtKB:P70677
  - ensembl:ENSMUSP00000147767
- term:
    id: GO:0004861
    label: cyclin-dependent protein serine/threonine kinase inhibitor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: enables
  supporting_entities:
  - UniProtKB:P70677
  - ensembl:ENSMUSP00000147767
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: located_in
  supporting_entities:
  - UniProtKB:P42574
  - ensembl:ENSP00000311032
  - UniProtKB:P70677
  - ensembl:ENSMUSP00000147767
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: located_in
  supporting_entities:
  - UniProtKB:P42574
  - ensembl:ENSP00000311032
- term:
    id: GO:0006915
    label: apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
  - ensembl:ENSP00000311032
- term:
    id: GO:0008233
    label: peptidase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: enables
  supporting_entities:
  - ARBA:ARBA00027408
  - UniProtKB:P42574
  - ensembl:ENSP00000311032
  - UniProtKB:P70677
  - ensembl:ENSMUSP00000147767
- term:
    id: GO:0008627
    label: intrinsic apoptotic signaling pathway in response to osmotic stress
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P70677
  - ensembl:ENSMUSP00000147767
- term:
    id: GO:0014069
    label: postsynaptic density
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: is_active_in
  supporting_entities:
  - UniProtKB:P70677
  - ensembl:ENSMUSP00000147767
- term:
    id: GO:0016485
    label: protein processing
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
  - ensembl:ENSP00000311032
- term:
    id: GO:0030163
    label: protein catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
  - ensembl:ENSP00000311032
- term:
    id: GO:0030218
    label: erythrocyte differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
  - ensembl:ENSP00000311032
- term:
    id: GO:0031647
    label: regulation of protein stability
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
  - ensembl:ENSP00000311032
- term:
    id: GO:0032880
    label: regulation of protein localization
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
  - ensembl:ENSP00000311032
- term:
    id: GO:0043065
    label: positive regulation of apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - ARBA:ARBA00027745
  - UniProtKB:P70677
  - ensembl:ENSMUSP00000147767
- term:
    id: GO:0051604
    label: protein maturation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
  - ensembl:ENSP00000311032
- term:
    id: GO:0070269
    label: pyroptotic inflammatory response
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
  - ensembl:ENSP00000311032
- term:
    id: GO:0072734
    label: cellular response to staurosporine
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
  - ensembl:ENSP00000311032
- term:
    id: GO:0097193
    label: intrinsic apoptotic signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
  - ensembl:ENSP00000311032
- term:
    id: GO:0097194
    label: execution phase of apoptosis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
  - ensembl:ENSP00000311032
- term:
    id: GO:0098693
    label: regulation of synaptic vesicle cycle
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P70677
  - ensembl:ENSMUSP00000147767
- term:
    id: GO:0098883
    label: synapse pruning
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P70677
  - ensembl:ENSMUSP00000147767
- term:
    id: GO:0098978
    label: glutamatergic synapse
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: is_active_in
  supporting_entities:
  - UniProtKB:P70677
  - ensembl:ENSMUSP00000147767
- term:
    id: GO:0140639
    label: positive regulation of pyroptotic inflammatory response
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
  - ensembl:ENSP00000311032
- term:
    id: GO:1902004
    label: positive regulation of amyloid-beta formation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
  - ensembl:ENSP00000311032
- term:
    id: GO:0098883
    label: synapse pruning
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P70677
- term:
    id: GO:0098883
    label: synapse pruning
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: KEEP_AS_NON_CORE
    summary: Transferred from mouse Casp3, where synapse pruning has direct experimental
      support. This mammalian neuronal remodeling role is plausible in rat but is
      context-specific and not part of Casp3 core apoptotic function.
  qualifier: involved_in
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0045471
    label: response to ethanol
  evidence_type: IEP
  original_reference_id: PMID:30926569
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0045471
    label: response to ethanol
  evidence_type: IEP
  original_reference_id: PMID:23102656
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0036269
    label: swimming behavior
  evidence_type: IEP
  original_reference_id: PMID:33574912
  review:
    summary: The cited study uses the Morris Water Maze (a swimming-based test) to assess
      learning and memory in a postoperative-cognitive-dysfunction model, and measures
      caspase-3 by Western blot purely as a hippocampal apoptosis marker. Swimming is the
      assay modality, not a function of caspase-3, which is an apoptotic executioner protease.
    action: MARK_AS_OVER_ANNOTATED
    reason: Spurious IEP over-annotation derived from the swimming-based Morris Water Maze memory
      assay; the paper assays cognition/apoptosis, not swimming behaviour, and caspase-3 has no
      proximal role in locomotion or swimming.
    supported_by:
    - reference_id: PMID:33574912
      supporting_text: To assess learning and memory abilities, MWM tests were performed as described
        previously
  qualifier: involved_in
- term:
    id: GO:0043523
    label: regulation of neuron apoptotic process
  evidence_type: IEP
  original_reference_id: PMID:33574912
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:1990418
    label: response to insulin-like growth factor stimulus
  evidence_type: IEP
  original_reference_id: PMID:33574912
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0043065
    label: positive regulation of apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: MODIFY
    summary: Transferred from mature human CASP3 chain annotations, but the GO term
      is broader than the conserved effector step. The more precise conserved transfer
      is execution phase of apoptosis.
    proposed_replacement_terms: &id002
    - id: GO:0097194
      label: execution phase of apoptosis
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
  - UniProtKB:P42574-PRO_0000004571
  - UniProtKB:P42574-PRO_0000004572
- term:
    id: GO:1902512
    label: positive regulation of apoptotic DNA fragmentation
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: ACCEPT
    summary: Transferred from mature human CASP3 chain annotations. Promotion of apoptotic
      DNA fragmentation is a canonical downstream consequence of effector caspase-3
      activation and is conserved across mammals.
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
  - UniProtKB:P42574-PRO_0000004571
  - UniProtKB:P42574-PRO_0000004572
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:21630211
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: located_in
- term:
    id: GO:0072347
    label: response to anesthetic
  evidence_type: IEP
  original_reference_id: PMID:27498600
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0014069
    label: postsynaptic density
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: KEEP_AS_NON_CORE
    summary: Transferred from mouse Casp3, where postsynaptic-density localization
      has direct synaptic evidence. This neuronal localization is plausible in rat
      but is a specialized non-core context rather than the principal Casp3 function.
  qualifier: is_active_in
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0098693
    label: regulation of synaptic vesicle cycle
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: KEEP_AS_NON_CORE
    summary: Transferred from mouse Casp3 with direct synaptic evidence. Regulation
      of synaptic vesicle cycle reflects a specialized neuronal remodeling role, not
      the core conserved apoptotic assignment for rat Casp3.
  qualifier: involved_in
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0098978
    label: glutamatergic synapse
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: KEEP_AS_NON_CORE
    summary: Transferred from mouse Casp3 with direct synaptic evidence at glutamatergic
      synapses. Likely a real mammalian neuronal context, but not a core rat Casp3
      function.
  qualifier: is_active_in
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0016485
    label: protein processing
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: MODIFY
    summary: Transferred from human CASP3, where the source evidence reflects protease-mediated
      substrate cleavage. Protein processing is too generic; proteolysis is the clearer
      conserved process term.
    proposed_replacement_terms: &id001
    - id: GO:0006508
      label: proteolysis
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
- term:
    id: GO:0001818
    label: negative regulation of cytokine production
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: REMOVE
    summary: Transferred from human CASP3, but the source support is an indirect cross-taxonomic
      evidence chain rather than a clean human ortholog experiment. This is too far
      from rat Casp3 core function and is likely an over-transfer.
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
- term:
    id: GO:0001666
    label: response to hypoxia
  evidence_type: IEP
  original_reference_id: PMID:24089674
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0006915
    label: apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: ACCEPT
    summary: Transferred from human CASP3, which has strong experimental support for
      apoptotic process. This is a core, conserved effector-caspase assignment for
      rat Casp3.
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
- term:
    id: GO:0070269
    label: pyroptotic inflammatory response
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: MARK_AS_OVER_ANNOTATED
    summary: Transferred from human CASP3 with direct source evidence, but pyroptotic
      inflammatory response is a specialized context-dependent cross-talk role rather
      than a broadly conserved core rat Casp3 function.
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: ACCEPT
    summary: Transferred from human CASP3 with direct localization evidence. Cytosolic
      localization is consistent with conserved effector-caspase biology in rat.
  qualifier: is_active_in
  supporting_entities:
  - UniProtKB:P42574
- term:
    id: GO:0051604
    label: protein maturation
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: MODIFY
    summary: Transferred from human CASP3, but protein maturation is too generic for
      an effector caspase that primarily acts through substrate proteolysis. Use proteolysis
      instead.
    proposed_replacement_terms: *id001
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
- term:
    id: GO:0140639
    label: positive regulation of pyroptotic inflammatory response
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: MARK_AS_OVER_ANNOTATED
    summary: Transferred from human CASP3 with direct source evidence, but positive
      regulation of pyroptotic inflammatory response is a specialized context and
      too specific for a general rat orthology transfer.
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: ACCEPT
    summary: Transferred from human CASP3 with direct localization evidence. Cytoplasmic
      localization is a conserved and appropriate core assignment for rat Casp3.
  qualifier: is_active_in
  supporting_entities:
  - UniProtKB:P42574
- term:
    id: GO:0097193
    label: intrinsic apoptotic signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: MODIFY
    summary: Transferred from human CASP3, but the intrinsic-pathway label is too
      pathway-specific for a downstream effector caspase that operates in multiple
      apoptotic routes. The more precise conserved transfer is execution phase of
      apoptosis.
    proposed_replacement_terms: *id002
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: KEEP_AS_NON_CORE
    summary: Transferred from human CASP3 with direct source evidence for nuclear
      activity/localization in apoptotic settings. This is a valid context-dependent
      localization but not a core rat Casp3 assignment.
  qualifier: is_active_in
  supporting_entities:
  - UniProtKB:P42574
- term:
    id: GO:0030163
    label: protein catabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: MODIFY
    summary: Transferred from human CASP3, but protein catabolic process overgeneralizes
      the substrate-cleavage role. Proteolysis is the clearer conserved process term.
    proposed_replacement_terms: *id001
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
- term:
    id: GO:0097194
    label: execution phase of apoptosis
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: ACCEPT
    summary: Transferred from mouse Casp3, where execution phase of apoptosis is directly
      supported. This is a core, conserved effector-caspase role in rat.
  qualifier: involved_in
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0010996
    label: response to auditory stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: KEEP_AS_NON_CORE
    summary: Transferred from chinchilla Casp3, where the source ortholog has direct
      experimental evidence for auditory-response biology. The term may reflect a
      genuine mammalian sensory context, but it is non-core for rat Casp3.
  qualifier: involved_in
  supporting_entities:
  - RGD:9026791
- term:
    id: GO:0004197
    label: cysteine-type endopeptidase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: enables
  supporting_entities:
  - UniProtKB:P42574
- term:
    id: GO:0004175
    label: endopeptidase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: enables
  supporting_entities:
  - UniProtKB:P70677
- term:
    id: GO:0004175
    label: endopeptidase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: MODIFY
    summary: Transferred from mouse Casp3 with direct catalytic evidence, but endopeptidase
      activity is too broad. The conserved specific activity is cysteine-type endopeptidase
      activity.
    proposed_replacement_terms: &id003
    - id: GO:0004197
      label: cysteine-type endopeptidase activity
  qualifier: enables
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0006508
    label: proteolysis
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: ACCEPT
    summary: Transferred from human CASP3 with direct source evidence. Proteolysis
      is a core conserved biological process for rat Casp3.
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
- term:
    id: GO:0006508
    label: proteolysis
  evidence_type: IDA
  original_reference_id: PMID:17553422
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0031647
    label: regulation of protein stability
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: REMOVE
    summary: Transferred from human CASP3, but regulation of protein stability summarizes
      downstream substrate-specific consequences rather than a conserved core rat
      Casp3 function.
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
- term:
    id: GO:0031647
    label: regulation of protein stability
  evidence_type: IDA
  original_reference_id: PMID:17553422
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:1902004
    label: positive regulation of amyloid-beta formation
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: REMOVE
    summary: Transferred from human CASP3 in an amyloid-beta/APP disease context.
      This is too disease-specific and not an appropriate conserved orthology transfer
      to rat Casp3.
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
- term:
    id: GO:1902004
    label: positive regulation of amyloid-beta formation
  evidence_type: IDA
  original_reference_id: PMID:17553422
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0051146
    label: striated muscle cell differentiation
  evidence_type: IEP
  original_reference_id: PMID:28899909
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0071887
    label: leukocyte apoptotic process
  evidence_type: IEP
  original_reference_id: PMID:26861981
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0001554
    label: luteolysis
  evidence_type: IEP
  original_reference_id: PMID:25332219
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0007413
    label: axonal fasciculation
  evidence_type: IMP
  original_reference_id: PMID:25898930
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: IDA
  original_reference_id: PMID:25898930
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: located_in
- term:
    id: GO:0061713
    label: anterior neural tube closure
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: KEEP_AS_NON_CORE
    summary: Transferred from mouse Casp3 with direct developmental phenotype evidence.
      This may be a real mammalian developmental context, but it is pleiotropic and
      non-core for rat Casp3.
  qualifier: acts_upstream_of_or_within
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0004197
    label: cysteine-type endopeptidase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: enables
  supporting_entities:
  - UniProtKB:P42574
- term:
    id: GO:0004197
    label: cysteine-type endopeptidase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: ACCEPT
    summary: Transferred from human CASP3 with extensive direct catalytic evidence.
      This is the defining conserved molecular function of rat Casp3.
  qualifier: enables
  supporting_entities:
  - UniProtKB:P42574
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: REMOVE
    summary: Transferred from dog CASP3, but the dog source record already mixes IBA/IDA/IEA/ISO
      evidence and rat already has stronger human and mouse source annotations for
      cytoplasmic localization. Remove this redundant second-hop transfer.
  qualifier: located_in
  supporting_entities:
  - RGD:12072547
- term:
    id: GO:0008627
    label: intrinsic apoptotic signaling pathway in response to osmotic stress
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: MARK_AS_OVER_ANNOTATED
    summary: Transferred from mouse Casp3 with direct source evidence, but the osmotic-stress
      variant is too stimulus-specific to treat as a general conserved rat orthology
      transfer.
  qualifier: involved_in
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0008627
    label: intrinsic apoptotic signaling pathway in response to osmotic stress
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: REMOVE
    summary: Transferred from dog CASP3. Although the dog source has mixed evidence,
      this is still a stimulus-specific second-hop transfer and weaker than the direct
      mouse source. Remove.
  qualifier: involved_in
  supporting_entities:
  - RGD:12072547
- term:
    id: GO:0043065
    label: positive regulation of apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: MODIFY
    summary: Transferred from mouse Casp3, but positive regulation of apoptotic process
      is broader than the conserved downstream effector role. Execution phase of apoptosis
      is the more precise conserved term.
    proposed_replacement_terms: *id002
  qualifier: involved_in
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0043065
    label: positive regulation of apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: REMOVE
    summary: Transferred from dog CASP3, whose source record already mixes direct
      and inferred evidence and duplicates stronger human/mouse sources. Remove as
      a redundant second-hop transfer.
  qualifier: involved_in
  supporting_entities:
  - RGD:12072547
- term:
    id: GO:0072734
    label: cellular response to staurosporine
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: REMOVE
    summary: Transferred from human CASP3, but cellular response to staurosporine
      is a pharmacologic stimulus-specific context and not an appropriate conserved
      core orthology transfer.
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: REMOVE
    summary: Transferred from pig CASP3, but the pig source record is mixed and redundant
      with better-supported human/mouse nuclear localization rows. Remove this second-hop
      transfer.
  qualifier: located_in
  supporting_entities:
  - RGD:14134172
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: REMOVE
    summary: Transferred from pig CASP3, but the pig source record is mixed and redundant
      with stronger human/mouse cytoplasmic localization transfers. Remove this second-hop
      row.
  qualifier: located_in
  supporting_entities:
  - RGD:14134172
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: ACCEPT
    summary: Transferred from mouse Casp3 with direct localization evidence. Cytoplasmic
      localization is conserved and appropriate for rat Casp3.
  qualifier: located_in
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0048011
    label: neurotrophin TRK receptor signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: REMOVE
    summary: Transferred from human CASP3, but the source paper treats caspase-3 largely
      as a downstream apoptosis readout in neurotrophin signaling rather than a dedicated
      TRK-pathway component. This is an over-transfer.
  qualifier: acts_upstream_of_or_within
  supporting_entities:
  - UniProtKB:P42574
- term:
    id: GO:0006915
    label: apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: REMOVE
    summary: Transferred from mouse Casp3 with direct apoptosis evidence, but rat
      already retains a stronger involved_in apoptotic-process ISO row from human.
      Remove this weaker duplicate transfer.
  qualifier: acts_upstream_of_or_within
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: KEEP_AS_NON_CORE
    summary: Transferred from mouse Casp3 with direct localization evidence. Nuclear
      localization occurs in apoptotic contexts but is not a core default state for
      rat Casp3.
  qualifier: located_in
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0002020
    label: protease binding
  evidence_type: IPI
  original_reference_id: PMID:17518537
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: enables
  supporting_entities:
  - RGD:620945
- term:
    id: GO:0005123
    label: death receptor binding
  evidence_type: IPI
  original_reference_id: PMID:17518537
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: enables
  supporting_entities:
  - RGD:619831
- term:
    id: GO:0031264
    label: death-inducing signaling complex
  evidence_type: IDA
  original_reference_id: PMID:17518537
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: part_of
- term:
    id: GO:0044877
    label: protein-containing complex binding
  evidence_type: IPI
  original_reference_id: PMID:17518537
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: enables
  supporting_entities:
  - RGD:619831
  - RGD:620945
- term:
    id: GO:0004190
    label: aspartic-type endopeptidase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: REMOVE
    summary: Transferred from mouse Casp3, but CASP3 is a cysteine protease, not an
      aspartic protease. This conflicts with conserved catalytic mechanism and should
      be removed.
  qualifier: enables
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0030218
    label: erythrocyte differentiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: KEEP_AS_NON_CORE
    summary: Transferred from human CASP3 with direct source evidence for erythroid
      differentiation. This is plausible mammalian pleiotropy, but it is non-core
      for rat Casp3.
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
- term:
    id: GO:0097194
    label: execution phase of apoptosis
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: ACCEPT
    summary: Transferred from human CASP3 with direct source evidence. Execution phase
      of apoptosis is a core conserved effector-caspase assignment for rat Casp3.
  qualifier: involved_in
  supporting_entities:
  - UniProtKB:P42574
- term:
    id: GO:0097194
    label: execution phase of apoptosis
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: REMOVE
    summary: Transferred from mouse Casp3 with direct source evidence, but rat already
      retains stronger involved_in execution-phase rows. Remove this weaker duplicate
      qualifier transfer.
  qualifier: acts_upstream_of_or_within
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0034349
    label: glial cell apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: KEEP_AS_NON_CORE
    summary: Transferred from mouse Casp3 with experimental glial-apoptosis evidence.
      Likely a real mammalian neural context, but it is non-core for rat Casp3.
  qualifier: acts_upstream_of_or_within
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0051402
    label: neuron apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: KEEP_AS_NON_CORE
    summary: Transferred from mouse Casp3 with direct neuronal-apoptosis evidence.
      This is a plausible mammalian context-specific role, but not a core rat Casp3
      assignment.
  qualifier: acts_upstream_of_or_within
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: KEEP_AS_NON_CORE
    summary: Transferred from human CASP3 with direct source evidence for nuclear
      localization in apoptotic settings. Keep as a non-core context-dependent localization.
  qualifier: located_in
  supporting_entities:
  - UniProtKB:P42574
- term:
    id: GO:0004197
    label: cysteine-type endopeptidase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: ACCEPT
    summary: Transferred from mouse Casp3 with extensive direct catalytic evidence.
      This is a core conserved molecular function for rat Casp3.
  qualifier: enables
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0009611
    label: response to wounding
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: REMOVE
    summary: Transferred from mouse Casp3 in a wound-response context. This is too
      context-specific and indirect to retain as a conserved rat orthology transfer.
  qualifier: acts_upstream_of_or_within
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0016485
    label: protein processing
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: MODIFY
    summary: Transferred from mouse Casp3 with source evidence for substrate cleavage,
      but protein processing is too generic. Proteolysis is the more appropriate conserved
      process term.
    proposed_replacement_terms: *id001
  qualifier: acts_upstream_of_or_within
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18485100
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: enables
  supporting_entities:
  - RGD:620692
- term:
    id: GO:0008234
    label: cysteine-type peptidase activity
  evidence_type: IDA
  original_reference_id: PMID:16336964
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: enables
- term:
    id: GO:0008234
    label: cysteine-type peptidase activity
  evidence_type: IDA
  original_reference_id: PMID:17182030
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: enables
- term:
    id: GO:0043065
    label: positive regulation of apoptotic process
  evidence_type: IMP
  original_reference_id: PMID:17869439
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0008234
    label: cysteine-type peptidase activity
  evidence_type: IDA
  original_reference_id: PMID:18316105
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: enables
- term:
    id: GO:0030163
    label: protein catabolic process
  evidence_type: IDA
  original_reference_id: PMID:18316105
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0034349
    label: glial cell apoptotic process
  evidence_type: IEP
  original_reference_id: PMID:18931364
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0035094
    label: response to nicotine
  evidence_type: IEP
  original_reference_id: PMID:18477628
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0009749
    label: response to glucose
  evidence_type: IDA
  original_reference_id: PMID:19356108
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0032025
    label: response to cobalt ion
  evidence_type: IEP
  original_reference_id: PMID:18598848
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0032355
    label: response to estradiol
  evidence_type: IEP
  original_reference_id: PMID:18598848
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0008234
    label: cysteine-type peptidase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: MODIFY
    summary: Transferred from mouse Casp3 with direct catalytic evidence, but cysteine-type
      peptidase activity is broader than the best conserved term. Use cysteine-type
      endopeptidase activity.
    proposed_replacement_terms: *id003
  qualifier: enables
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0008234
    label: cysteine-type peptidase activity
  evidence_type: IDA
  original_reference_id: PMID:17218406
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: enables
- term:
    id: GO:0008233
    label: peptidase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: MODIFY
    summary: Transferred from human CASP3 with direct catalytic support, but peptidase
      activity is too generic. Use cysteine-type endopeptidase activity.
    proposed_replacement_terms: *id003
  qualifier: enables
  supporting_entities:
  - UniProtKB:P42574
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: ACCEPT
    summary: Transferred from human CASP3 with direct localization evidence. Cytosolic
      localization is conserved and appropriate for rat Casp3.
  qualifier: located_in
  supporting_entities:
  - UniProtKB:P42574
- term:
    id: GO:0001666
    label: response to hypoxia
  evidence_type: IEP
  original_reference_id: PMID:18466900
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0007611
    label: learning or memory
  evidence_type: IMP
  original_reference_id: PMID:18239768
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0009410
    label: response to xenobiotic stimulus
  evidence_type: IEP
  original_reference_id: PMID:18274634
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0010038
    label: response to metal ion
  evidence_type: IEP
  original_reference_id: PMID:18483861
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0010165
    label: response to X-ray
  evidence_type: IEP
  original_reference_id: PMID:18239382
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0021766
    label: hippocampus development
  evidence_type: IEP
  original_reference_id: PMID:18459132
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0032496
    label: response to lipopolysaccharide
  evidence_type: IEP
  original_reference_id: PMID:18289516
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0042542
    label: response to hydrogen peroxide
  evidence_type: IDA
  original_reference_id: PMID:18479463
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0043200
    label: response to amino acid
  evidence_type: IEP
  original_reference_id: PMID:18423997
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0043525
    label: positive regulation of neuron apoptotic process
  evidence_type: IMP
  original_reference_id: PMID:18404518
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0051384
    label: response to glucocorticoid
  evidence_type: IEP
  original_reference_id: PMID:18288275
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0006974
    label: DNA damage response
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: REMOVE
    summary: Transferred from mouse Casp3 in DNA-damage response experiments, but
      this reflects an upstream stimulus context rather than a core conserved Casp3
      function in rat.
  qualifier: acts_upstream_of_or_within
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0030163
    label: protein catabolic process
  evidence_type: IDA
  original_reference_id: PMID:15004018
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0007605
    label: sensory perception of sound
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: REMOVE
    summary: Transferred from mouse Casp3 as a sensory/hearing phenotype. This is
      too phenotype-specific for a general conserved rat Casp3 transfer and is weaker
      than the chinchilla auditory-response row.
  qualifier: acts_upstream_of_or_within
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0007507
    label: heart development
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: KEEP_AS_NON_CORE
    summary: Transferred from mouse Casp3 with developmental phenotype evidence. Heart-development
      effects are plausible pleiotropy but non-core for rat Casp3.
  qualifier: acts_upstream_of_or_within
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0009411
    label: response to UV
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: REMOVE
    summary: Transferred from mouse Casp3 in a UV-response context. This stimulus-specific
      response is too indirect and over-transferred for rat Casp3.
  qualifier: acts_upstream_of_or_within
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0008233
    label: peptidase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: MODIFY
    summary: Transferred from mouse Casp3 with direct catalytic evidence, but peptidase
      activity is too generic. Use cysteine-type endopeptidase activity.
    proposed_replacement_terms: *id003
  qualifier: enables
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0030182
    label: neuron differentiation
  evidence_type: IEP
  original_reference_id: PMID:15248196
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0016005
    label: phospholipase A2 activator activity
  evidence_type: IMP
  original_reference_id: PMID:12492473
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: enables
- term:
    id: GO:0035556
    label: intracellular signal transduction
  evidence_type: IMP
  original_reference_id: PMID:12492473
  review:
    summary: 'TODO: Review this GOA annotation'
    action: PENDING
  qualifier: involved_in
- term:
    id: GO:0030216
    label: keratinocyte differentiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: KEEP_AS_NON_CORE
    summary: Transferred from mouse Casp3 with keratinocyte-differentiation phenotype
      evidence. This is plausible mammalian pleiotropy but non-core for rat Casp3.
  qualifier: acts_upstream_of_or_within
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0045165
    label: cell fate commitment
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: KEEP_AS_NON_CORE
    summary: Transferred from mouse Casp3 with developmental phenotype evidence. Cell-fate
      commitment is non-core pleiotropy rather than a defining rat Casp3 function.
  qualifier: acts_upstream_of_or_within
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0001782
    label: B cell homeostasis
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: KEEP_AS_NON_CORE
    summary: Transferred from mouse Casp3 knockout immunophenotypes. The biology may
      be real in lymphocyte contexts, but it is not a core rat Casp3 function.
  qualifier: acts_upstream_of_or_within
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0004861
    label: cyclin-dependent protein serine/threonine kinase inhibitor activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: REMOVE
    summary: Transferred from mouse Casp3, but the source evidence is phenotype-based
      and does not demonstrate a direct cyclin-dependent kinase inhibitor molecular
      function for CASP3. This is an over-annotation.
  qualifier: enables
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0030889
    label: negative regulation of B cell proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: KEEP_AS_NON_CORE
    summary: Transferred from mouse Casp3 knockout immunophenotypes. Keep only as
      non-core pleiotropy.
  qualifier: acts_upstream_of_or_within
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0043029
    label: T cell homeostasis
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: KEEP_AS_NON_CORE
    summary: Transferred from mouse Casp3 knockout immunophenotypes. Keep as non-core
      because it reflects context-specific immune phenotypes rather than Casp3 core
      function.
  qualifier: acts_upstream_of_or_within
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0045736
    label: negative regulation of cyclin-dependent protein serine/threonine kinase
      activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: KEEP_AS_NON_CORE
    summary: Transferred from mouse Casp3 knockout immunophenotypes. The regulatory
      phenotype may be real, but it is not a core rat Casp3 function.
  qualifier: acts_upstream_of_or_within
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0045786
    label: negative regulation of cell cycle
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: KEEP_AS_NON_CORE
    summary: Transferred from mouse Casp3 knockout immunophenotypes. Keep only as
      non-core pleiotropy.
  qualifier: acts_upstream_of_or_within
  supporting_entities:
  - MGI:MGI:107739
- term:
    id: GO:0046007
    label: negative regulation of activated T cell proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    action: KEEP_AS_NON_CORE
    summary: Transferred from mouse Casp3 knockout immunophenotypes. This is a context-specific
      immune phenotype, not a core rat Casp3 function.
  qualifier: acts_upstream_of_or_within
  supporting_entities:
  - MGI:MGI:107739
core_functions:
- description: Conserved effector caspase that cleaves protein substrates during the
    execution phase of apoptosis.
  molecular_function:
    id: GO:0004197
    label: cysteine-type endopeptidase activity
  directly_involved_in:
  - id: GO:0006915
    label: apoptotic process
  - id: GO:0097194
    label: execution phase of apoptosis
  - id: GO:0006508
    label: proteolysis
  - id: GO:1902512
    label: positive regulation of apoptotic DNA fragmentation
  locations:
  - id: GO:0005737
    label: cytoplasm
  - id: GO:0005829
    label: cytosol
references:
- id: GO_REF:0000024
  title: 'TODO: Fetch title'
  findings: []
- id: GO_REF:0000033
  title: 'TODO: Fetch title'
  findings: []
- id: GO_REF:0000107
  title: 'TODO: Fetch title'
  findings: []
- id: GO_REF:0000117
  title: 'TODO: Fetch title'
  findings: []
- id: GO_REF:0000120
  title: 'TODO: Fetch title'
  findings: []
- id: GO_REF:0000121
  title: 'TODO: Fetch title'
  findings: []
- id: PMID:12492473
  title: Signaling events mediating activation of brain ethanolamine plasmalogen hydrolysis
    by ceramide.
  findings: []
- id: PMID:15004018
  title: Minocycline up-regulates Bcl-2 and protects against cell death in mitochondria.
  findings: []
- id: PMID:15248196
  title: Active caspase-3 expression during postnatal development of rat cerebellum
    is not systematically or consistently associated with apoptosis.
  findings: []
- id: PMID:16336964
  title: In vivo delivery of a XIAP (BIR3-RING) fusion protein containing the protein
    transduction domain protects against neuronal death induced by seizures.
  findings: []
- id: PMID:17182030
  title: Inhibition of HtrA2/Omi ameliorates heart dysfunction following ischemia/reperfusion
    injury in rat heart in vivo.
  findings: []
- id: PMID:17218406
  title: Luteinizing hormone-induced caspase activation in rat preovulatory follicles
    is coupled to mitochondrial steroidogenesis.
  findings: []
- id: PMID:17518537
  title: FasL, Fas, and death-inducing signaling complex (DISC) proteins are recruited
    to membrane rafts after spinal cord injury.
  findings: []
- id: PMID:17553422
  title: Depletion of GGA3 stabilizes BACE and enhances beta-secretase activity.
  findings: []
- id: PMID:17869439
  title: Role of inhibitor of apoptosis protein in gentamicin-induced cochlear hair
    cell damage.
  findings: []
- id: PMID:18239382
  title: Low-dose local kidney irradiation inhibits progression of experimental crescentic
    nephritis by promoting apoptosis.
  findings: []
- id: PMID:18239768
  title: Central injection of caspase inhibitors facilitates the formation of freezing
    behavior in rats.
  findings: []
- id: PMID:18274634
  title: The protecting effects and mechanisms of Baicalin and Octreotide on heart
    injury in rats with SAP.
  findings: []
- id: PMID:18288275
  title: Protecting effects of dexamethasone on thymus of rats with severe acute pancreatitis.
  findings: []
- id: PMID:18289516
  title: Caspase activation in fetal rat brain following experimental intrauterine
    inflammation.
  findings: []
- id: PMID:18316105
  title: Implication of caspases and subcellular compartments in tert-butylhydroperoxide
    induced apoptosis.
  findings: []
- id: PMID:18404518
  title: P2X(7) nucleotide receptors mediate caspase-8/9/3-dependent apoptosis in
    rat primary cortical neurons.
  findings: []
- id: PMID:18423997
  title: Glutamate-induced losses of oligodendrocytes and neurons and activation of
    caspase-3 in the rat spinal cord.
  findings: []
- id: PMID:18459132
  title: Different expression of caspase-3 in rat hippocampal subregions during postnatal
    development.
  findings: []
- id: PMID:18466900
  title: 'Chronic hypobaric hypoxia induced apoptosis in CA1 region of hippocampus:
    a possible role of NMDAR mediated p75NTR upregulation.'
  findings: []
- id: PMID:18477628
  title: Nicotine suppresses tunicamycin-induced, but not thapsigargin-induced, expression
    of GRP78 during ER stress-mediated apoptosis in PC12 cells.
  findings: []
- id: PMID:18479463
  title: Leptin protects H9c2 rat cardiomyocytes from H2O2-induced apoptosis.
  findings: []
- id: PMID:18483861
  title: Pravastatin attenuates carboplatin-induced cardiotoxicity via inhibition
    of oxidative stress associated apoptosis.
  findings: []
- id: PMID:18485100
  title: Nuclear translocation of X-linked inhibitor of apoptosis (XIAP) determines
    cell fate after hypoxia ischemia in neonatal brain.
  findings: []
- id: PMID:18598848
  title: Estradiol protects PC12 cells against CoCl2-induced apoptosis.
  findings: []
- id: PMID:18931364
  title: Bax and Bid act in synergy to bring about T11TS-mediated glioma apoptosis
    via the release of mitochondrial cytochrome c and subsequent caspase activation.
  findings: []
- id: PMID:19356108
  title: Heme oxygenase-derived carbon monoxide restores vascular function in type
    1 diabetes.
  findings: []
- id: PMID:21630211
  title: Immunohistochemical study of the apoptosis process in epidermal epithelial
    cells of rats under a physiological condition.
  findings: []
- id: PMID:23102656
  title: 'Effect of repetitive daily ethanol intoxication on adult rat brain: significant
    changes in phospholipase A2 enzyme levels in association with increased PARP-1
    indicate neuroinflammatory pathway activation.'
  findings: []
- id: PMID:24089674
  title: Neuroprotective effects of microRNA-210 on hypoxic-ischemic encephalopathy.
  findings: []
- id: PMID:25332219
  title: Endoplasmic reticulum stress-mediated apoptotic pathway is involved in corpus
    luteum regression in rats.
  findings: []
- id: PMID:25898930
  title: Death Receptor 6 and Caspase-6 Regulate Prion Peptide-Induced Axonal Degeneration
    in Rat Spinal Neurons.
  findings: []
- id: PMID:26861981
  title: Time course of apoptosis induced by photodynamic therapy with PsD007 in LT12
    acute myeloid leukemia cells.
  findings: []
- id: PMID:27498600
  title: Neuroprotective effects of caffeic acid phenethyl ester against sevoflurane‑induced
    neuronal degeneration in the hippocampus of neonatal rats involve MAPK and PI3K/Akt
    signaling pathways.
  findings: []
- id: PMID:28899909
  title: Depletion of the mRNA translation initiation inhibitor, programmed cell death
    protein 4 (PDCD4), impairs L6 myotube formation.
  findings: []
- id: PMID:30926569
  title: 'Effect of saffron (stigma of Crocus sativus L.) aqueous extract on ethanol
    toxicity in rats: A biochemical, histopathological and molecular study.'
  findings: []
- id: PMID:33574912
  title: Insulin-like growth factor-1 improves postoperative cognitive dysfunction
    following splenectomy in aged rats.
  findings: []

Casp3

Gene Description

Existing Annotations Review

Core Functions

Conserved effector caspase that cleaves protein substrates during the execution phase of apoptosis.

References

Deep Research

Falcon

Research Report: Rat Casp3 (Caspase-3) — Functional Annotation (UniProt P55213)

Executive summary

0) Mandatory identity verification (gene/protein disambiguation)

1) Key concepts and definitions (current understanding)

1.1 Caspase-3 biochemical function and catalytic mechanism

1.2 Substrate specificity (reaction and substrate preference)

1.3 Zymogen processing and activation into p17/p12

1.4 Pathway placement: intrinsic and extrinsic apoptosis cascades

2) Recent developments and latest research (prioritizing 2023–2024)

2.1 Apoptosis–pyroptosis crosstalk via gasdermin cleavage (2024)

2.2 Pathogen immune evasion via caspase phosphorylation (Legionella LegK3; 2024)

2.3 Methodological advances in defining caspase-3 specificity (2024–2026)

3) Localization and where the gene product acts

4) Current applications and real-world implementations (emphasis on 2023–2024)

4.1 Quantitative analytical assays (electrochemical biosensing; 2024)

4.2 Imaging and live-cell readouts (2024 review synthesis)

4.3 Ratiometric fluorescent probes (2024)

5) Rat-specific functional evidence and data (in vivo)

6) Expert opinions and authoritative analysis

Evidence map (condensed)

Visual evidence (example figure panel)

Conclusions

Notes on scope/limitations

Citations

📚 Additional Documentation

Bioreason Rl Predictions

BioReason Chat Export

Thinking Trace

Functional Summary

UniProt Summary

InterPro Domains

GO Terms

Bioreason Rl Review

BioReason-Pro RL Review: Casp3 (rat)

Functional Summary Review

Notes on thinking trace

📄 View Raw YAML