Casp9 encodes mouse caspase-9, the CARD-containing initiator caspase of the intrinsic mitochondrial apoptosis pathway. Pro-caspase-9 is recruited to APAF1 apoptosomes after mitochondrial cytochrome c release, where proximity-induced activation allows caspase-9 to cleave and mature executioner procaspases and thereby amplify the execution phase of apoptosis. Mouse genetics place Casp9 in both developmental neuronal apoptosis and DNA-damage-induced neural precursor apoptosis, while more specialized stress and tissue phenotypes are contextual branches of this core initiator caspase activity.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001666 response to hypoxia | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: This transferred condition-response row is a downstream readout context rather than a direct Casp9 function. Reason: The annotation reaches mouse Casp9 by orthology or an automated family rule from a stimulus assay in another mammal. Hypoxia, ischemia, cobalt, ethanol, lipopolysaccharide, indole-3-methanol, anesthetic, and kidney-development contexts can converge on apoptosis, but they do not show Casp9 doing specific work in the named response. |
| GO:0001822 kidney development | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: This transferred condition-response row is a downstream readout context rather than a direct Casp9 function. Reason: The annotation reaches mouse Casp9 by orthology or an automated family rule from a stimulus assay in another mammal. Hypoxia, ischemia, cobalt, ethanol, lipopolysaccharide, indole-3-methanol, anesthetic, and kidney-development contexts can converge on apoptosis, but they do not show Casp9 doing specific work in the named response. |
| GO:0002931 response to ischemia | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: This transferred condition-response row is a downstream readout context rather than a direct Casp9 function. Reason: The annotation reaches mouse Casp9 by orthology or an automated family rule from a stimulus assay in another mammal. Hypoxia, ischemia, cobalt, ethanol, lipopolysaccharide, indole-3-methanol, anesthetic, and kidney-development contexts can converge on apoptosis, but they do not show Casp9 doing specific work in the named response. |
| GO:0004197 cysteine-type endopeptidase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Casp9 is the cysteine-aspartyl initiator protease activated around the apoptosome. Reason: Mouse Casp9 has the conserved caspase catalytic machinery and direct mouse evidence for LEHD cleavage or cross-species evidence that activated caspase-9 cleaves executioner procaspase-3, so this activity is correct for full-length Casp9. Supporting Evidence: PMID:12097332 The activated caspase-9 catalyzes cleavage of procaspase-3 |
| GO:0004197 cysteine-type endopeptidase activity | IDA PMID:16183742 Apoptosis caused by p53-induced protein with death domain (P... | ACCEPT | Summary: Casp9 is the cysteine-aspartyl initiator protease activated around the apoptosome. Reason: Mouse Casp9 has the conserved caspase catalytic machinery; PMID:16183742 is primarily a PIDD/RAIDD paper, but its TNF-positive control directly detected caspase-9 LEHD cleavage activity in wild-type mouse embryonic fibroblasts. Supporting Evidence: PMID:16183742 detected activation of caspase-2 (3.3-fold), caspase-3/-7 (8.9-fold), caspase-8 (1.8-fold), and caspase-9 (2.0-fold) |
| GO:0004197 cysteine-type endopeptidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Casp9 is the cysteine-aspartyl initiator protease activated around the apoptosome. Reason: Mouse Casp9 has the conserved caspase catalytic machinery and direct mouse evidence for LEHD cleavage or cross-species evidence that activated caspase-9 cleaves executioner procaspase-3, so this activity is correct for full-length Casp9. Supporting Evidence: PMID:12097332 The activated caspase-9 catalyzes cleavage of procaspase-3 |
| GO:0004197 cysteine-type endopeptidase activity | ISO GO_REF:0000119 | ACCEPT | Summary: Casp9 is the cysteine-aspartyl initiator protease activated around the apoptosome. Reason: Mouse Casp9 has the conserved caspase catalytic machinery and direct mouse evidence for LEHD cleavage or cross-species evidence that activated caspase-9 cleaves executioner procaspase-3, so this activity is correct for full-length Casp9. Supporting Evidence: PMID:12097332 The activated caspase-9 catalyzes cleavage of procaspase-3 |
| GO:0004197 cysteine-type endopeptidase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Casp9 is the cysteine-aspartyl initiator protease activated around the apoptosome. Reason: Mouse Casp9 has the conserved caspase catalytic machinery and direct mouse evidence for LEHD cleavage or cross-species evidence that activated caspase-9 cleaves executioner procaspase-3, so this activity is correct for full-length Casp9. Supporting Evidence: PMID:12097332 The activated caspase-9 catalyzes cleavage of procaspase-3 |
| GO:0005515 protein binding | IPI PMID:14561754 Molecular components of a cell death pathway activated by en... | UNDECIDED | Summary: The local ER-stress abstract does not expose the Casp9-specific interaction evidence behind this generic protein-binding row. Reason: The PMID:14561754 cache is abstract-only and foregrounds VCP and ALG-2 as ER-stress mediators without showing whether the tagged prey assay truly involved Casp9. Full text is needed before a specific replacement can be proposed. |
| GO:0005515 protein binding | IPI PMID:14561754 Molecular components of a cell death pathway activated by en... | UNDECIDED | Summary: The local ER-stress abstract does not expose the Casp9-specific interaction evidence behind this generic protein-binding row. Reason: The PMID:14561754 cache is abstract-only and foregrounds VCP and ALG-2 as ER-stress mediators without showing whether the tagged prey assay truly involved Casp9. Full text is needed before a specific replacement can be proposed. |
| GO:0005634 nucleus | IDA PMID:15271982 Nucling recruits Apaf-1/pro-caspase-9 complex for the induct... | KEEP AS NON CORE | Summary: Nucling can distribute an Apaf-1/pro-caspase-9 complex to the nuclear fraction during stress-induced apoptosis. Reason: This supports a stress-associated nuclear pool, but Casp9 is primarily a cytosolic apoptosome caspase, so nuclear localization is contextual rather than core. Supporting Evidence: PMID:15271982 After UV irradiation, Nucling was shown to reside in an Apaf-1/pro-caspase-9 complex |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Casp9 is recruited and activated from the cytoplasmic/cytosolic apoptosome pathway. Reason: Cytoplasmic and cytosolic localization agree with Casp9 recruitment into the Apaf-1 apoptosome that activates the protease upstream of executioner caspases. Supporting Evidence: PMID:15271982 After UV irradiation, Nucling was shown to reside in an Apaf-1/pro-caspase-9 complex |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | ACCEPT | Summary: Casp9 is recruited and activated from the cytoplasmic/cytosolic apoptosome pathway. Reason: Cytoplasmic and cytosolic localization agree with Casp9 recruitment into the Apaf-1 apoptosome that activates the protease upstream of executioner caspases. Supporting Evidence: PMID:15271982 After UV irradiation, Nucling was shown to reside in an Apaf-1/pro-caspase-9 complex |
| GO:0005737 cytoplasm | ISO GO_REF:0000096 | ACCEPT | Summary: Casp9 is recruited and activated from the cytoplasmic/cytosolic apoptosome pathway. Reason: Cytoplasmic and cytosolic localization agree with Casp9 recruitment into the Apaf-1 apoptosome that activates the protease upstream of executioner caspases. Supporting Evidence: PMID:15271982 After UV irradiation, Nucling was shown to reside in an Apaf-1/pro-caspase-9 complex |
| GO:0005739 mitochondrion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mitochondrial localization is secondary for a caspase whose activation occurs at the cytosolic apoptosome. Reason: The inherited human localization may reflect apoptotic redistribution or a minor pool. Mouse Casp9 core signaling is better represented by cytosol and apoptosome localization. |
| GO:0005739 mitochondrion | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Mitochondrial localization is secondary for a caspase whose activation occurs at the cytosolic apoptosome. Reason: The inherited human localization may reflect apoptotic redistribution or a minor pool. Mouse Casp9 core signaling is better represented by cytosol and apoptosome localization. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Casp9 is recruited and activated from the cytoplasmic/cytosolic apoptosome pathway. Reason: Cytoplasmic and cytosolic localization agree with Casp9 recruitment into the Apaf-1 apoptosome that activates the protease upstream of executioner caspases. Supporting Evidence: PMID:15271982 After UV irradiation, Nucling was shown to reside in an Apaf-1/pro-caspase-9 complex |
| GO:0005829 cytosol | IDA PMID:15271982 Nucling recruits Apaf-1/pro-caspase-9 complex for the induct... | ACCEPT | Summary: Casp9 is recruited and activated from the cytoplasmic/cytosolic apoptosome pathway. Reason: Cytoplasmic and cytosolic localization agree with Casp9 recruitment into the Apaf-1 apoptosome that activates the protease upstream of executioner caspases. Supporting Evidence: PMID:15271982 After UV irradiation, Nucling was shown to reside in an Apaf-1/pro-caspase-9 complex |
| GO:0005829 cytosol | IEA GO_REF:0000120 | ACCEPT | Summary: Casp9 is recruited and activated from the cytoplasmic/cytosolic apoptosome pathway. Reason: Cytoplasmic and cytosolic localization agree with Casp9 recruitment into the Apaf-1 apoptosome that activates the protease upstream of executioner caspases. Supporting Evidence: PMID:15271982 After UV irradiation, Nucling was shown to reside in an Apaf-1/pro-caspase-9 complex |
| GO:0005829 cytosol | ISO GO_REF:0000119 | ACCEPT | Summary: Casp9 is recruited and activated from the cytoplasmic/cytosolic apoptosome pathway. Reason: Cytoplasmic and cytosolic localization agree with Casp9 recruitment into the Apaf-1 apoptosome that activates the protease upstream of executioner caspases. Supporting Evidence: PMID:15271982 After UV irradiation, Nucling was shown to reside in an Apaf-1/pro-caspase-9 complex |
| GO:0005829 cytosol | ISO GO_REF:0000119 | ACCEPT | Summary: Casp9 is recruited and activated from the cytoplasmic/cytosolic apoptosome pathway. Reason: Cytoplasmic and cytosolic localization agree with Casp9 recruitment into the Apaf-1 apoptosome that activates the protease upstream of executioner caspases. Supporting Evidence: PMID:15271982 After UV irradiation, Nucling was shown to reside in an Apaf-1/pro-caspase-9 complex |
| GO:0005829 cytosol | TAS Reactome:R-MMU-6804642 | ACCEPT | Summary: Casp9 is recruited and activated from the cytoplasmic/cytosolic apoptosome pathway. Reason: Cytoplasmic and cytosolic localization agree with Casp9 recruitment into the Apaf-1 apoptosome that activates the protease upstream of executioner caspases. Supporting Evidence: PMID:15271982 After UV irradiation, Nucling was shown to reside in an Apaf-1/pro-caspase-9 complex |
| GO:0006508 proteolysis | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: proteolysis is a true but broad ancestor of the more informative Casp9 cysteine endopeptidase activity. Reason: Casp9 is a cysteine-aspartyl protease, but generic proteolysis and peptidase terms add only an ancestor of the reviewed cysteine-type endopeptidase activity and executioner-procaspase maturation function. |
| GO:0006508 proteolysis | RCA PMID:12819136 Comparative analysis of apoptosis and inflammation genes of ... | KEEP AS NON CORE | Summary: proteolysis is a true but broad ancestor of the more informative Casp9 cysteine endopeptidase activity. Reason: Casp9 is a cysteine-aspartyl protease, but generic proteolysis and peptidase terms add only an ancestor of the reviewed cysteine-type endopeptidase activity and executioner-procaspase maturation function. |
| GO:0006915 apoptotic process | IBA GO_REF:0000033 | MODIFY | Summary: Casp9 acts as the apoptosome-associated initiator caspase in intrinsic apoptosis; the top-level apoptotic-process term can be tightened. Reason: The broad apoptosis assertion is biologically correct, but Casp9 is specifically the intrinsic initiator downstream of APAF1/cytochrome c apoptosome assembly, so GO:0097193 is a better process term. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000047947 SUPPORTS SOURCE BUT NOT TARGET The PAINT node supports inherited caspase apoptosis biology, but mouse Casp9 is the intrinsic initiator and the top-level apoptotic-process term should be narrowed. Proposed replacements: intrinsic apoptotic signaling pathway Supporting Evidence: PMID:9708736 Casp9 acts downstream of cytochrome c |
| GO:0006915 apoptotic process | IDA PMID:12847083 Bax and Bak can localize to the endoplasmic reticulum to ini... | MODIFY | Summary: Casp9 acts as the apoptosome-associated initiator caspase in intrinsic apoptosis; the top-level apoptotic-process term can be tightened. Reason: The broad apoptosis assertion is biologically correct, but Casp9 is specifically the intrinsic initiator downstream of APAF1/cytochrome c apoptosome assembly, so GO:0097193 is a better process term. Proposed replacements: intrinsic apoptotic signaling pathway Supporting Evidence: PMID:12847083 ectopically expressed caspase 3 and caspase 9 resulted in apoptosis |
| GO:0006915 apoptotic process | IDA PMID:17901126 Estrogen suppresses uterine epithelial apoptosis by inducing... | UNDECIDED | Summary: The cached Birc1 uterine-survival abstract does not expose the Casp9-specific assay behind this row. Reason: The abstract centers on estrogen-induced Birc1 and active caspase binding. Because it does not show whether Casp9 was directly assayed, the broad apoptotic-process row should be deferred to full-text review rather than overruled from incomplete evidence. |
| GO:0006915 apoptotic process | IEA GO_REF:0000120 | MODIFY | Summary: Casp9 acts as the apoptosome-associated initiator caspase in intrinsic apoptosis; the top-level apoptotic-process term can be tightened. Reason: The broad apoptosis assertion is biologically correct, but Casp9 is specifically the intrinsic initiator downstream of APAF1/cytochrome c apoptosome assembly, so GO:0097193 is a better process term. Proposed replacements: intrinsic apoptotic signaling pathway Supporting Evidence: PMID:9708736 Casp9 acts downstream of cytochrome c |
| GO:0006915 apoptotic process | IMP PMID:16469926 Caspases 3 and 7: key mediators of mitochondrial events of a... | UNDECIDED | Summary: The cached caspase-3/caspase-7 abstract does not expose the Casp9-specific evidence behind this broad row. Reason: The abstract describes mitochondrial events in Casp3/Casp7-deficient fibroblasts, but does not show the Casp9 perturbation or assay that led MGI to annotate Casp9. Full-text review is needed before this broad apoptosis row is tightened or retained. |
| GO:0006915 apoptotic process | ISO GO_REF:0000119 | MODIFY | Summary: Casp9 acts as the apoptosome-associated initiator caspase in intrinsic apoptosis; the top-level apoptotic-process term can be tightened. Reason: The broad apoptosis assertion is biologically correct, but Casp9 is specifically the intrinsic initiator downstream of APAF1/cytochrome c apoptosome assembly, so GO:0097193 is a better process term. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P55211 SUPPORTS SOURCE BUT NOT TARGET The human CASP9 source supports apoptosome-associated intrinsic apoptosis, but the propagated top-level apoptotic-process term is less precise than intrinsic apoptotic signaling for mouse Casp9. Proposed replacements: intrinsic apoptotic signaling pathway Supporting Evidence: PMID:9708736 Casp9 acts downstream of cytochrome c |
| GO:0006974 DNA damage response | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | Summary: DNA damage and UV can use Casp9-dependent apoptosis in mouse neural precursors, but stimulus-response terms describe the upstream challenge rather than a Casp9 activity. Reason: The direct mouse DNA-damage phenotype is non-core for Casp9, and automated propagation of this upstream stimulus-response parent over-annotates Casp9 beyond its apoptosome-associated activation of downstream caspases. Supporting Evidence: PMID:11092819 DNA damage-induced neural precursor cell apoptosis, both in vitro and in vivo, was critically dependent on p53 and caspase 9 |
| GO:0006974 DNA damage response | IMP PMID:11092819 DNA damage-induced neural precursor cell apoptosis requires ... | KEEP AS NON CORE | Summary: DNA damage and UV can use Casp9-dependent apoptosis in mouse neural precursors, but stimulus-response terms describe the upstream challenge rather than a Casp9 activity. Reason: Mouse neural precursor apoptosis after DNA damage is Casp9-dependent, supporting a real phenotype in that cell type; keep this direct IMP row as non-core because Casp9's direct molecular work is apoptosome-associated activation of downstream caspases rather than DNA-damage sensing. Supporting Evidence: PMID:11092819 DNA damage-induced neural precursor cell apoptosis, both in vitro and in vivo, was critically dependent on p53 and caspase 9 |
| GO:0006974 DNA damage response | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: DNA damage and UV can use Casp9-dependent apoptosis in mouse neural precursors, but stimulus-response terms describe the upstream challenge rather than a Casp9 activity. Reason: The direct mouse DNA-damage phenotype is non-core for Casp9, and mouse-human orthology transfer of this upstream stimulus-response parent over-annotates Casp9 beyond its apoptosome-associated activation of downstream caspases. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P55211 SUPPORTS SOURCE BUT NOT TARGET DNA damage and UV are upstream stimulus contexts; the human source supports intrinsic Casp9 signaling but does not justify preserving this trigger-specific term as a propagated mouse core annotation. Supporting Evidence: PMID:11092819 DNA damage-induced neural precursor cell apoptosis, both in vitro and in vivo, was critically dependent on p53 and caspase 9 |
| GO:0006974 DNA damage response | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: DNA damage and UV can use Casp9-dependent apoptosis in mouse neural precursors, but stimulus-response terms describe the upstream challenge rather than a Casp9 activity. Reason: The direct mouse DNA-damage phenotype is non-core for Casp9, and similarity transfer from human of this upstream stimulus-response parent over-annotates Casp9 beyond its apoptosome-associated activation of downstream caspases. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P55211 SUPPORTS SOURCE BUT NOT TARGET DNA damage and UV are upstream stimulus contexts; the human source supports intrinsic Casp9 signaling but does not justify preserving this trigger-specific term as a propagated mouse core annotation. Supporting Evidence: PMID:11092819 DNA damage-induced neural precursor cell apoptosis, both in vitro and in vivo, was critically dependent on p53 and caspase 9 |
| GO:0008233 peptidase activity | IDA PMID:14561754 Molecular components of a cell death pathway activated by en... | KEEP AS NON CORE | Summary: peptidase activity is a true but broad ancestor of the more informative Casp9 cysteine endopeptidase activity. Reason: Casp9 is a cysteine-aspartyl protease, but generic proteolysis and peptidase terms add only an ancestor of the reviewed cysteine-type endopeptidase activity and executioner-procaspase maturation function. |
| GO:0008233 peptidase activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: peptidase activity is a true but broad ancestor of the more informative Casp9 cysteine endopeptidase activity. Reason: Casp9 is a cysteine-aspartyl protease, but generic proteolysis and peptidase terms add only an ancestor of the reviewed cysteine-type endopeptidase activity and executioner-procaspase maturation function. |
| GO:0008233 peptidase activity | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: peptidase activity is a true but broad ancestor of the more informative Casp9 cysteine endopeptidase activity. Reason: Casp9 is a cysteine-aspartyl protease, but generic proteolysis and peptidase terms add only an ancestor of the reviewed cysteine-type endopeptidase activity and executioner-procaspase maturation function. |
| GO:0008233 peptidase activity | RCA PMID:12819136 Comparative analysis of apoptosis and inflammation genes of ... | KEEP AS NON CORE | Summary: peptidase activity is a true but broad ancestor of the more informative Casp9 cysteine endopeptidase activity. Reason: Casp9 is a cysteine-aspartyl protease, but generic proteolysis and peptidase terms add only an ancestor of the reviewed cysteine-type endopeptidase activity and executioner-procaspase maturation function. |
| GO:0008234 cysteine-type peptidase activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: cysteine-type peptidase activity is a true but broad ancestor of the more informative Casp9 cysteine endopeptidase activity. Reason: Casp9 is a cysteine-aspartyl protease, but generic proteolysis and peptidase terms add only an ancestor of the reviewed cysteine-type endopeptidase activity and executioner-procaspase maturation function. |
| GO:0008234 cysteine-type peptidase activity | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: cysteine-type peptidase activity is a true but broad ancestor of the more informative Casp9 cysteine endopeptidase activity. Reason: Casp9 is a cysteine-aspartyl protease, but generic proteolysis and peptidase terms add only an ancestor of the reviewed cysteine-type endopeptidase activity and executioner-procaspase maturation function. |
| GO:0008303 caspase complex | IEA GO_REF:0000107 | ACCEPT | Summary: Casp9 is a proteolytic component of the apoptosome/caspase activation complex. Reason: Mouse Nucling recruits an Apaf-1/pro-caspase-9 complex under UV stress, and the conserved intrinsic pathway recruits full-length caspase-9 into the APAF1 apoptosome. Supporting Evidence: PMID:15271982 After UV irradiation, Nucling was shown to reside in an Apaf-1/pro-caspase-9 complex |
| GO:0008303 caspase complex | ISO GO_REF:0000119 | ACCEPT | Summary: Casp9 is a proteolytic component of the apoptosome/caspase activation complex. Reason: Mouse Nucling recruits an Apaf-1/pro-caspase-9 complex under UV stress, and the conserved intrinsic pathway recruits full-length caspase-9 into the APAF1 apoptosome. Supporting Evidence: PMID:15271982 After UV irradiation, Nucling was shown to reside in an Apaf-1/pro-caspase-9 complex |
| GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: DNA damage is a real Casp9-dependent apoptotic trigger in mouse neural precursors, but it is one branch into the broader intrinsic pathway. Reason: Casp9-deficient mouse neural precursors resist DNA damage-induced apoptosis, so this DNA-damage branch into the APAF1/Casp9 apoptosome pathway is biologically real; keep it as non-core because it is a stimulus-specific route into the core pathway. Supporting Evidence: PMID:11092819 DNA damage-induced neural precursor cell apoptosis, both in vitro and in vivo, was critically dependent on p53 and caspase 9 |
| GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: DNA damage is a real Casp9-dependent apoptotic trigger in mouse neural precursors, but it is one branch into the broader intrinsic pathway. Reason: Casp9-deficient mouse neural precursors resist DNA damage-induced apoptosis, so this DNA-damage branch into the APAF1/Casp9 apoptosome pathway is biologically real; keep it as non-core because it is a stimulus-specific route into the core pathway. Supporting Evidence: PMID:11092819 DNA damage-induced neural precursor cell apoptosis, both in vitro and in vivo, was critically dependent on p53 and caspase 9 |
| GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: DNA damage is a real Casp9-dependent apoptotic trigger in mouse neural precursors, but it is one branch into the broader intrinsic pathway. Reason: Casp9-deficient mouse neural precursors resist DNA damage-induced apoptosis, so this DNA-damage branch into the APAF1/Casp9 apoptosome pathway is biologically real; keep it as non-core because it is a stimulus-specific route into the core pathway. Supporting Evidence: PMID:11092819 DNA damage-induced neural precursor cell apoptosis, both in vitro and in vivo, was critically dependent on p53 and caspase 9 |
| GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: DNA damage is a real Casp9-dependent apoptotic trigger in mouse neural precursors, but it is one branch into the broader intrinsic pathway. Reason: Casp9-deficient mouse neural precursors resist DNA damage-induced apoptosis, so this DNA-damage branch into the APAF1/Casp9 apoptosome pathway is biologically real; keep it as non-core because it is a stimulus-specific route into the core pathway. Supporting Evidence: PMID:11092819 DNA damage-induced neural precursor cell apoptosis, both in vitro and in vivo, was critically dependent on p53 and caspase 9 |
| GO:0009411 response to UV | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: DNA damage and UV can use Casp9-dependent apoptosis in mouse neural precursors, but stimulus-response terms describe the upstream challenge rather than a Casp9 activity. Reason: The direct mouse UV phenotype is non-core for Casp9, and ARBA propagation of this upstream stimulus-response parent over-annotates Casp9 beyond its apoptosome-associated activation of downstream caspases. Supporting Evidence: PMID:11092819 DNA damage-induced neural precursor cell apoptosis, both in vitro and in vivo, was critically dependent on p53 and caspase 9 |
| GO:0009411 response to UV | IMP PMID:11092819 DNA damage-induced neural precursor cell apoptosis requires ... | KEEP AS NON CORE | Summary: DNA damage and UV can use Casp9-dependent apoptosis in mouse neural precursors, but stimulus-response terms describe the upstream challenge rather than a Casp9 activity. Reason: Mouse neural precursor apoptosis after UV irradiation is Casp9-dependent, supporting a real phenotype in that cell type; keep this direct IMP row as non-core because Casp9's direct molecular work is apoptosome-associated activation of downstream caspases rather than UV sensing. Supporting Evidence: PMID:11092819 DNA damage-induced neural precursor cell apoptosis, both in vitro and in vivo, was critically dependent on p53 and caspase 9 |
| GO:0016485 protein processing | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Casp9 promotes executioner-procaspase maturation downstream of intrinsic apoptotic signaling. Reason: Activated caspase-9 cleaves executioner procaspases. GO:0051604 captures that maturation step directly; GO:0016485 is a broader protein-processing parent and should be kept as non-core. Supporting Evidence: PMID:12097332 The activated caspase-9 catalyzes cleavage of procaspase-3 |
| GO:0016485 protein processing | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Casp9 promotes executioner-procaspase maturation downstream of intrinsic apoptotic signaling. Reason: Activated caspase-9 cleaves executioner procaspases. GO:0051604 captures that maturation step directly; GO:0016485 is a broader protein-processing parent and should be kept as non-core. Supporting Evidence: PMID:12097332 The activated caspase-9 catalyzes cleavage of procaspase-3 |
| GO:0019901 protein kinase binding | IEA GO_REF:0000107 | UNDECIDED | Summary: The inherited protein-kinase-binding row traces to the c-Abl/CASP9 model, which remains unsettled in the human source review. Reason: The source-side human protein-kinase-binding evidence for CASP9 is disputed, and the mouse row is transferred rather than directly assayed. Leave this undecided until the c-Abl phosphorylation mechanism is resolved. |
| GO:0019901 protein kinase binding | ISO GO_REF:0000119 | UNDECIDED | Summary: The inherited protein-kinase-binding row traces to the c-Abl/CASP9 model, which remains unsettled in the human source review. Reason: The source-side human protein-kinase-binding evidence for CASP9 is disputed, and the mouse row is transferred rather than directly assayed. Leave this undecided until the c-Abl phosphorylation mechanism is resolved. Propagation Review Root cause: UNRESOLVED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P55211 UNRESOLVED The transferred c-Abl protein-kinase-binding model is disputed in the human CASP9 source review, so the mouse ortholog assertion is unresolved rather than independently supported. |
| GO:0019901 protein kinase binding | ISS GO_REF:0000024 | UNDECIDED | Summary: The inherited protein-kinase-binding row traces to the c-Abl/CASP9 model, which remains unsettled in the human source review. Reason: The source-side human protein-kinase-binding evidence for CASP9 is disputed, and the mouse row is transferred rather than directly assayed. Leave this undecided until the c-Abl phosphorylation mechanism is resolved. Propagation Review Root cause: UNRESOLVED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P55211 UNRESOLVED The transferred c-Abl protein-kinase-binding model is disputed in the human CASP9 source review, so the mouse ortholog assertion is unresolved rather than independently supported. |
| GO:0032025 response to cobalt ion | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: This transferred condition-response row is a downstream readout context rather than a direct Casp9 function. Reason: The annotation reaches mouse Casp9 by orthology or an automated family rule from a stimulus assay in another mammal. Hypoxia, ischemia, cobalt, ethanol, lipopolysaccharide, indole-3-methanol, anesthetic, and kidney-development contexts can converge on apoptosis, but they do not show Casp9 doing specific work in the named response. |
| GO:0032355 response to estradiol | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: This transferred condition-response row is a downstream readout context rather than a direct Casp9 function. Reason: The annotation reaches mouse Casp9 by orthology or an automated family rule from a stimulus assay in another mammal. Hypoxia, ischemia, cobalt, ethanol, lipopolysaccharide, indole-3-methanol, anesthetic, and kidney-development contexts can converge on apoptosis, but they do not show Casp9 doing specific work in the named response. |
| GO:0032496 response to lipopolysaccharide | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: This transferred condition-response row is a downstream readout context rather than a direct Casp9 function. Reason: The annotation reaches mouse Casp9 by orthology or an automated family rule from a stimulus assay in another mammal. Hypoxia, ischemia, cobalt, ethanol, lipopolysaccharide, indole-3-methanol, anesthetic, and kidney-development contexts can converge on apoptosis, but they do not show Casp9 doing specific work in the named response. |
| GO:0032991 protein-containing complex | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Protein-containing complex is a broad ancestor of the Casp9 apoptosome and caspase-complex localizations. Reason: Casp9 indeed functions in protein complexes, but the meaningful complex for apoptosis curation is the apoptosome rather than a generic protein-containing complex parent. Supporting Evidence: PMID:15271982 After UV irradiation, Nucling was shown to reside in an Apaf-1/pro-caspase-9 complex |
| GO:0032991 protein-containing complex | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Protein-containing complex is a broad ancestor of the Casp9 apoptosome and caspase-complex localizations. Reason: Casp9 indeed functions in protein complexes, but the meaningful complex for apoptosis curation is the apoptosome rather than a generic protein-containing complex parent. Supporting Evidence: PMID:15271982 After UV irradiation, Nucling was shown to reside in an Apaf-1/pro-caspase-9 complex |
| GO:0034349 glial cell apoptotic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Casp9-dependent apoptosis contributes to neural and leukocyte developmental outcomes, but these cell-type rows are contextual. Reason: Mouse loss-of-function studies support a neuronal-apoptosis phenotype for Casp9, but cell-type-specific and leukocyte/glial apoptosis terms are downstream contexts rather than distinct Casp9 molecular functions. |
| GO:0034644 cellular response to UV | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: DNA damage and UV can use Casp9-dependent apoptosis in mouse neural precursors, but stimulus-response terms describe the upstream challenge rather than a Casp9 activity. Reason: Mouse neural precursor apoptosis after DNA damage is Casp9-dependent, supporting a real phenotype in that cell type. These rows are non-core or over-specific for Casp9, whose direct molecular work is apoptosome-associated activation of downstream caspases rather than sensing DNA damage or UV. Supporting Evidence: PMID:11092819 DNA damage-induced neural precursor cell apoptosis, both in vitro and in vivo, was critically dependent on p53 and caspase 9 |
| GO:0034644 cellular response to UV | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: DNA damage and UV can use Casp9-dependent apoptosis in mouse neural precursors, but stimulus-response terms describe the upstream challenge rather than a Casp9 activity. Reason: Mouse neural precursor apoptosis after DNA damage is Casp9-dependent, supporting a real phenotype in that cell type. These rows are non-core or over-specific for Casp9, whose direct molecular work is apoptosome-associated activation of downstream caspases rather than sensing DNA damage or UV. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P55211 SUPPORTS SOURCE BUT NOT TARGET DNA damage and UV are upstream stimulus contexts; the human source supports intrinsic Casp9 signaling but does not justify preserving this trigger-specific term as a propagated mouse core annotation. Supporting Evidence: PMID:11092819 DNA damage-induced neural precursor cell apoptosis, both in vitro and in vivo, was critically dependent on p53 and caspase 9 |
| GO:0034644 cellular response to UV | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: DNA damage and UV can use Casp9-dependent apoptosis in mouse neural precursors, but stimulus-response terms describe the upstream challenge rather than a Casp9 activity. Reason: Mouse neural precursor apoptosis after DNA damage is Casp9-dependent, supporting a real phenotype in that cell type. These rows are non-core or over-specific for Casp9, whose direct molecular work is apoptosome-associated activation of downstream caspases rather than sensing DNA damage or UV. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P55211 SUPPORTS SOURCE BUT NOT TARGET DNA damage and UV are upstream stimulus contexts; the human source supports intrinsic Casp9 signaling but does not justify preserving this trigger-specific term as a propagated mouse core annotation. Supporting Evidence: PMID:11092819 DNA damage-induced neural precursor cell apoptosis, both in vitro and in vivo, was critically dependent on p53 and caspase 9 |
| GO:0042770 signal transduction in response to DNA damage | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: DNA damage and UV can use Casp9-dependent apoptosis in mouse neural precursors, but stimulus-response terms describe the upstream challenge rather than a Casp9 activity. Reason: Mouse neural precursor apoptosis after DNA damage is Casp9-dependent, supporting a real phenotype in that cell type. These rows are non-core or over-specific for Casp9, whose direct molecular work is apoptosome-associated activation of downstream caspases rather than sensing DNA damage or UV. Supporting Evidence: PMID:11092819 DNA damage-induced neural precursor cell apoptosis, both in vitro and in vivo, was critically dependent on p53 and caspase 9 |
| GO:0042770 signal transduction in response to DNA damage | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: DNA damage and UV can use Casp9-dependent apoptosis in mouse neural precursors, but stimulus-response terms describe the upstream challenge rather than a Casp9 activity. Reason: Mouse neural precursor apoptosis after DNA damage is Casp9-dependent, supporting a real phenotype in that cell type. These rows are non-core or over-specific for Casp9, whose direct molecular work is apoptosome-associated activation of downstream caspases rather than sensing DNA damage or UV. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P55211 SUPPORTS SOURCE BUT NOT TARGET DNA damage and UV are upstream stimulus contexts; the human source supports intrinsic Casp9 signaling but does not justify preserving this trigger-specific term as a propagated mouse core annotation. Supporting Evidence: PMID:11092819 DNA damage-induced neural precursor cell apoptosis, both in vitro and in vivo, was critically dependent on p53 and caspase 9 |
| GO:0042770 signal transduction in response to DNA damage | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: DNA damage and UV can use Casp9-dependent apoptosis in mouse neural precursors, but stimulus-response terms describe the upstream challenge rather than a Casp9 activity. Reason: Mouse neural precursor apoptosis after DNA damage is Casp9-dependent, supporting a real phenotype in that cell type. These rows are non-core or over-specific for Casp9, whose direct molecular work is apoptosome-associated activation of downstream caspases rather than sensing DNA damage or UV. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P55211 SUPPORTS SOURCE BUT NOT TARGET DNA damage and UV are upstream stimulus contexts; the human source supports intrinsic Casp9 signaling but does not justify preserving this trigger-specific term as a propagated mouse core annotation. Supporting Evidence: PMID:11092819 DNA damage-induced neural precursor cell apoptosis, both in vitro and in vivo, was critically dependent on p53 and caspase 9 |
| GO:0042802 identical protein binding | ISO GO_REF:0000119 | ACCEPT | Summary: Identical protein binding is consistent with the homodimeric active caspase fold. Reason: Active caspase-9, like other execution and initiator caspases, forms a dimeric protease unit; the mouse ISO transfer from human is plausible and not over-specific. |
| GO:0042981 regulation of apoptotic process | IEA GO_REF:0000002 | MODIFY | Summary: Casp9 is not a generic apoptosis regulator; it is a positive initiator of apoptotic execution after apoptosome activation. Reason: A CARD-domain InterPro hit supports apoptosome recruitment, but the most informative process term for the full-length enzyme is positive regulation of the execution phase through effector-caspase maturation. Proposed replacements: positive regulation of execution phase of apoptosis Supporting Evidence: PMID:12097332 The activated caspase-9 catalyzes cleavage of procaspase-3 |
| GO:0043065 positive regulation of apoptotic process | IEA GO_REF:0000120 | MODIFY | Summary: The positive regulatory consequence of active Casp9 is activation of the execution phase of apoptosis. Reason: The broad positive-regulation parent is directionally correct but avoidably vague for Casp9, whose proximal pro-apoptotic role is the proteolytic maturation of executioner caspases. Proposed replacements: positive regulation of execution phase of apoptosis Supporting Evidence: PMID:12097332 The activated caspase-9 catalyzes cleavage of procaspase-3 |
| GO:0043065 positive regulation of apoptotic process | ISO GO_REF:0000096 | MODIFY | Summary: The positive regulatory consequence of active Casp9 is activation of the execution phase of apoptosis. Reason: The broad positive-regulation parent is directionally correct but avoidably vague for Casp9, whose proximal pro-apoptotic role is the proteolytic maturation of executioner caspases. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: RGD:61867 SUPPORTS SOURCE BUT NOT TARGET The source supports a pro-apoptotic Casp9 role, but the broad positive-regulation term should be tightened to execution-phase activation through effector-caspase maturation. Proposed replacements: positive regulation of execution phase of apoptosis Supporting Evidence: PMID:12097332 The activated caspase-9 catalyzes cleavage of procaspase-3 |
| GO:0043065 positive regulation of apoptotic process | ISO GO_REF:0000119 | MODIFY | Summary: The positive regulatory consequence of active Casp9 is activation of the execution phase of apoptosis. Reason: The broad positive-regulation parent is directionally correct but avoidably vague for Casp9, whose proximal pro-apoptotic role is the proteolytic maturation of executioner caspases. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P55211 SUPPORTS SOURCE BUT NOT TARGET The source supports a pro-apoptotic Casp9 role, but the broad positive-regulation term should be tightened to execution-phase activation through effector-caspase maturation. Proposed replacements: positive regulation of execution phase of apoptosis Supporting Evidence: PMID:12097332 The activated caspase-9 catalyzes cleavage of procaspase-3 |
| GO:0043293 apoptosome | IEA GO_REF:0000107 | ACCEPT | Summary: Casp9 is a proteolytic component of the apoptosome/caspase activation complex. Reason: Mouse Nucling recruits an Apaf-1/pro-caspase-9 complex under UV stress, and the conserved intrinsic pathway recruits full-length caspase-9 into the APAF1 apoptosome. Supporting Evidence: PMID:15271982 After UV irradiation, Nucling was shown to reside in an Apaf-1/pro-caspase-9 complex |
| GO:0043293 apoptosome | ISO GO_REF:0000119 | ACCEPT | Summary: Casp9 is a proteolytic component of the apoptosome/caspase activation complex. Reason: Mouse Nucling recruits an Apaf-1/pro-caspase-9 complex under UV stress, and the conserved intrinsic pathway recruits full-length caspase-9 into the APAF1 apoptosome. Supporting Evidence: PMID:15271982 After UV irradiation, Nucling was shown to reside in an Apaf-1/pro-caspase-9 complex |
| GO:0043525 positive regulation of neuron apoptotic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Casp9-dependent apoptosis contributes to neural and leukocyte developmental outcomes, but these cell-type rows are contextual. Reason: Mouse loss-of-function studies support a neuronal-apoptosis phenotype for Casp9, but cell-type-specific and leukocyte/glial apoptosis terms are downstream contexts rather than distinct Casp9 molecular functions. Supporting Evidence: PMID:11150333 The increased apoptosis of immature neurons observed in Bcl-X(L)-deficient embryos was completely prevented by concomitant Caspase-9 deficiency |
| GO:0043525 positive regulation of neuron apoptotic process | IGI PMID:11150333 Bcl-X(L)-caspase-9 interactions in the developing nervous sy... | KEEP AS NON CORE | Summary: Casp9-dependent apoptosis contributes to neural and leukocyte developmental outcomes, but these cell-type rows are contextual. Reason: Mouse loss-of-function studies support a neuronal-apoptosis phenotype for Casp9, but cell-type-specific and leukocyte/glial apoptosis terms are downstream contexts rather than distinct Casp9 molecular functions. Supporting Evidence: PMID:11150333 The increased apoptosis of immature neurons observed in Bcl-X(L)-deficient embryos was completely prevented by concomitant Caspase-9 deficiency |
| GO:0043525 positive regulation of neuron apoptotic process | IMP PMID:11092819 DNA damage-induced neural precursor cell apoptosis requires ... | KEEP AS NON CORE | Summary: Casp9-dependent apoptosis contributes to neural and leukocyte developmental outcomes, but these cell-type rows are contextual. Reason: Mouse loss-of-function studies support a neuronal-apoptosis phenotype for Casp9, but cell-type-specific and leukocyte/glial apoptosis terms are downstream contexts rather than distinct Casp9 molecular functions. Supporting Evidence: PMID:11150333 The increased apoptosis of immature neurons observed in Bcl-X(L)-deficient embryos was completely prevented by concomitant Caspase-9 deficiency |
| GO:0043525 positive regulation of neuron apoptotic process | IMP PMID:11150333 Bcl-X(L)-caspase-9 interactions in the developing nervous sy... | KEEP AS NON CORE | Summary: Casp9-dependent apoptosis contributes to neural and leukocyte developmental outcomes, but these cell-type rows are contextual. Reason: Mouse loss-of-function studies support a neuronal-apoptosis phenotype for Casp9, but cell-type-specific and leukocyte/glial apoptosis terms are downstream contexts rather than distinct Casp9 molecular functions. Supporting Evidence: PMID:11150333 The increased apoptosis of immature neurons observed in Bcl-X(L)-deficient embryos was completely prevented by concomitant Caspase-9 deficiency |
| GO:0045471 response to ethanol | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: This transferred condition-response row is a downstream readout context rather than a direct Casp9 function. Reason: The annotation reaches mouse Casp9 by orthology or an automated family rule from a stimulus assay in another mammal. Hypoxia, ischemia, cobalt, ethanol, lipopolysaccharide, indole-3-methanol, anesthetic, and kidney-development contexts can converge on apoptosis, but they do not show Casp9 doing specific work in the named response. |
| GO:0051604 protein maturation | IEA GO_REF:0000107 | ACCEPT | Summary: Casp9 promotes executioner-procaspase maturation downstream of intrinsic apoptotic signaling. Reason: Activated caspase-9 cleaves executioner procaspases. GO:0051604 captures that maturation step directly; GO:0016485 is a broader protein-processing parent and should be kept as non-core. Supporting Evidence: PMID:12097332 The activated caspase-9 catalyzes cleavage of procaspase-3 |
| GO:0051604 protein maturation | ISO GO_REF:0000119 | ACCEPT | Summary: Casp9 promotes executioner-procaspase maturation downstream of intrinsic apoptotic signaling. Reason: Activated caspase-9 cleaves executioner procaspases. GO:0051604 captures that maturation step directly; GO:0016485 is a broader protein-processing parent and should be kept as non-core. Supporting Evidence: PMID:12097332 The activated caspase-9 catalyzes cleavage of procaspase-3 |
| GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress | NAS PMID:12097332 An endoplasmic reticulum stress-specific caspase cascade in ... | KEEP AS NON CORE | Summary: Murine ER stress can activate a caspase-12 to caspase-9 cascade independently of cytochrome c. Reason: This is a specific stress branch in which Casp9 can act as a downstream caspase, but it is not the principal APAF1/cytochrome c core function represented by most Casp9 annotations. Supporting Evidence: PMID:12097332 caspase-12 can activate caspase-9 without involvement of cytochrome c |
| GO:0071549 cellular response to dexamethasone stimulus | IDA PMID:15944155 Regulation of the expression of caspase-9 by the transcripti... | MARK AS OVER ANNOTATED | Summary: Dexamethasone changes Casp9 expression in lymphoid and fibroblast cell contexts, but the GO row is a stimulus response rather than Casp9 catalysis or apoptosome participation. Reason: PMID:15944155 connects dexamethasone to AP-4-dependent Casp9 expression and activation, but Casp9 does not itself sense dexamethasone; its direct role remains initiator-caspase activity downstream of apoptosome control. Supporting Evidence: PMID:15944155 When the cells were treated with dexamethasone, a rapid down-regulation of AP-4 and Casp-9 was observed |
| GO:0071680 response to indole-3-methanol | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: This transferred condition-response row is a downstream readout context rather than a direct Casp9 function. Reason: The annotation reaches mouse Casp9 by orthology or an automated family rule from a stimulus assay in another mammal. Hypoxia, ischemia, cobalt, ethanol, lipopolysaccharide, indole-3-methanol, anesthetic, and kidney-development contexts can converge on apoptosis, but they do not show Casp9 doing specific work in the named response. |
| GO:0071680 response to indole-3-methanol | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: This transferred condition-response row is a downstream readout context rather than a direct Casp9 function. Reason: The annotation reaches mouse Casp9 by orthology or an automated family rule from a stimulus assay in another mammal. Hypoxia, ischemia, cobalt, ethanol, lipopolysaccharide, indole-3-methanol, anesthetic, and kidney-development contexts can converge on apoptosis, but they do not show Casp9 doing specific work in the named response. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: RGD:61867 SUPPORTS SOURCE BUT NOT TARGET The rat-source stimulus response is a chemical-treatment context and does not establish direct Casp9 work in the same response in mouse. |
| GO:0071887 leukocyte apoptotic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Casp9-dependent apoptosis contributes to neural and leukocyte developmental outcomes, but these cell-type rows are contextual. Reason: Mouse loss-of-function studies support a neuronal-apoptosis phenotype for Casp9, but cell-type-specific and leukocyte/glial apoptosis terms are downstream contexts rather than distinct Casp9 molecular functions. |
| GO:0072347 response to anesthetic | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: This transferred condition-response row is a downstream readout context rather than a direct Casp9 function. Reason: The annotation reaches mouse Casp9 by orthology or an automated family rule from a stimulus assay in another mammal. Hypoxia, ischemia, cobalt, ethanol, lipopolysaccharide, indole-3-methanol, anesthetic, and kidney-development contexts can converge on apoptosis, but they do not show Casp9 doing specific work in the named response. |
| GO:0097193 intrinsic apoptotic signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: Casp9 is the initiator caspase recruited to the APAF1 apoptosome in intrinsic apoptotic signaling. Reason: This term captures the endogenous cytosolic role of full-length Casp9 downstream of mitochondrial cytochrome c release. Supporting Evidence: PMID:9708736 Casp9 acts downstream of cytochrome c |
| GO:0097193 intrinsic apoptotic signaling pathway | ISO GO_REF:0000119 | ACCEPT | Summary: Casp9 is the initiator caspase recruited to the APAF1 apoptosome in intrinsic apoptotic signaling. Reason: This term captures the endogenous cytosolic role of full-length Casp9 downstream of mitochondrial cytochrome c release. Supporting Evidence: PMID:9708736 Casp9 acts downstream of cytochrome c |
| GO:0097193 intrinsic apoptotic signaling pathway | ISO GO_REF:0000119 | ACCEPT | Summary: Casp9 is the initiator caspase recruited to the APAF1 apoptosome in intrinsic apoptotic signaling. Reason: This term captures the endogenous cytosolic role of full-length Casp9 downstream of mitochondrial cytochrome c release. Supporting Evidence: PMID:9708736 Casp9 acts downstream of cytochrome c |
| GO:1900119 positive regulation of execution phase of apoptosis | IEA GO_REF:0000107 | ACCEPT | Summary: Casp9 positively regulates apoptotic execution by activating effector caspases. Reason: After activation in the intrinsic pathway, caspase-9 drives apoptotic execution by cleaving downstream procaspases such as procaspase-3. Supporting Evidence: PMID:12097332 The activated caspase-9 catalyzes cleavage of procaspase-3 |
| GO:1900119 positive regulation of execution phase of apoptosis | ISO GO_REF:0000119 | ACCEPT | Summary: Casp9 positively regulates apoptotic execution by activating effector caspases. Reason: After activation in the intrinsic pathway, caspase-9 drives apoptotic execution by cleaving downstream procaspases such as procaspase-3. Supporting Evidence: PMID:12097332 The activated caspase-9 catalyzes cleavage of procaspase-3 |
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Download this section (compressed HTML)Q: Which mouse stress-specific Casp9 annotations from older ER-stress and hormone-response literature represent direct Casp9 participation, and which are endpoint apoptosis readouts that should remain unpropagated?
Q: How much of the reported nuclear Casp9 pool in Nucling-dependent stress apoptosis represents a functional apoptosome-associated pool rather than relocalized inactive complex?
Experiment: Use endogenous Casp9 catalytic-dead and CARD-disrupting knock-in alleles in mouse cells to separate apoptosome recruitment, executioner-caspase maturation, and distal stress-response phenotypes.
Experiment: Repeat ER-stress and dexamethasone-induced apoptosis assays with modern Casp9 activity reporters and rescue by wild-type versus catalytic-dead Casp9 to determine which stimulus annotations reflect direct Casp9 execution.
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