Identifiers
HUGO:CASP9
caspase 9, apoptosis-related cysteine peptidase
HUGO:CASP9 HGNC:1511 ENTREZ:842 UNIPROT:P55211
"caspase 9 apoptosis-related cysteine protease"
HUGO:CASP9 HGNC:1511 ENTREZ:842 UNIPROT:P55211 GENECARDS:CASP9 REACTOME:57034 KEGG:842 ATLASONC:CASP9ID423ch1p36 WIKI:CASP9

Maps_Modules
HMC:RESISTING_CELL_DEATH
 Regulated Cell Death   / ANTIOXIDANT_RESPONSE 
 Regulated Cell Death   / APOPTOSIS 
 Regulated Cell Death   / STARVATION_AUTOPHAGY 
 Regulated Cell Death   / CASPASES 
 Regulated Cell Death   / DEATH_RECEPTOR_PATHWAYS 
 Regulated Cell Death   / DEPENDANCE_RECEPTORS 
 Regulated Cell Death   / MOMP_REGULATION 
 Regulated Cell Death   / RCD_GENES 
 Regulated Cell Death   / ER_STRESS 
HMC:EVADING_GROWTH_SUPPRESSORS
 Survival   / MAPK 
 Survival   / HEDGEHOG 
 Survival   / PI3K_AKT_MTOR 

References
PMID:9812896
PMID:19931333
PMID:26618107
PMID:12011067
DCC interacts with both caspase-3 and caspase-9 and drives the activation of caspase-3 through caspase-9
PMID:19465923
The Patched dependence receptor triggers apoptosis through a DRAL-caspase-9 complex.
PMID:22679284
Patched dependence receptor triggers apoptosis through ubiquitination of caspase-9.
Caspase9 is phosphorylated on Thr125 in a MEK1/2-dependent manner in vivo. Furthermore caspase9 is efficiently phosphorylated on Thr125 by ERK in vitro suggesting that it is targeted directly by ERK in vivo.
This is one of the ways ERK plays its anti-apoptotic role.
PMID:12792650
PMID:19788417
PMID:16977332

References
an_re34:( Angiogenesis  ) PMID:9812896

References
an_re34:( Angiogenesis  ) PMID:9812896

Maps_Modules
HMC:RESISTING_CELL_DEATH
 Regulated Cell Death   / ANTIOXIDANT_RESPONSE 
 Regulated Cell Death   / APOPTOSIS 
 Regulated Cell Death   / STARVATION_AUTOPHAGY 
 Regulated Cell Death   / CASPASES 
 Regulated Cell Death   / DEATH_RECEPTOR_PATHWAYS 
 Regulated Cell Death   / DEPENDANCE_RECEPTORS 
 Regulated Cell Death   / MOMP_REGULATION 
 Regulated Cell Death   / RCD_GENES 

References
rc_re5( Regulated Cell Death  ):
hierarchical:post-MOMP
PMID:9892620
PMID:10318956
PMID:12611882
rc_re103( Regulated Cell Death  ):
PMID:16857965
identification by Y2H
co-IP
in vitro, HAX1 prevents the processing of CASP9
in rat cardiac myocytes, HAX1 prevents the processing of CASP9 and attenuates apoptosis induced by hypoxia/reperfusion (ectopic expression, RNA interfernce)
interaction takes place within mitochondria (data not shown)
rc_re104( Regulated Cell Death  ):
PMID:14747474
in U937

Maps_Modules
HMC:RESISTING_CELL_DEATH
 Regulated Cell Death   / ANTIOXIDANT_RESPONSE 
 Regulated Cell Death   / APOPTOSIS 
 Regulated Cell Death   / STARVATION_AUTOPHAGY 
 Regulated Cell Death   / CASPASES 
 Regulated Cell Death   / DEATH_RECEPTOR_PATHWAYS 
 Regulated Cell Death   / DEPENDANCE_RECEPTORS 
 Regulated Cell Death   / MOMP_REGULATION 
 Regulated Cell Death   / RCD_GENES 

References
rc_re498( Regulated Cell Death  ):
PMID:12792650
Direct phosphorylation of CASP9 by ERK2 sufficient to block CASP9 processing
in vitro, recombinant hCASP9 phosphorylated on T125 by cytosolic extract or ERK2
in Hela cells, interaction GST-CASP9 / ERK
in Hela or HEK293, CASP9 T125 phosphorylation by OA, consititutively active MEK1, EGF or TPA
PMID:17466630
CASP9 T125 phosphorylation by CCNB1:CDC2
comment: phosphorylation during mitosis, when nuclear envelope is broken down
PMID:19081073
CASP9 T125 phosphorylation by DYRK1A
PMID:19016842
PMID:19586613
CASP9 T125 phosphorylation by DYRK1A and p38
rc_re499( Regulated Cell Death  ):
okadaic acid
PMID:16888006
in a murine T cell line stably transfected with the human IL2R, IL2 withdrawal induces PP1 alpha catalytic subunit PP1CA dephosphorylation and activation and CASP9 dephosphorylation

Maps_Modules
HMC:RESISTING_CELL_DEATH
 Regulated Cell Death   / ANTIOXIDANT_RESPONSE 
 Regulated Cell Death   / APOPTOSIS 
 Regulated Cell Death   / STARVATION_AUTOPHAGY 
 Regulated Cell Death   / CASPASES 
 Regulated Cell Death   / DEATH_RECEPTOR_PATHWAYS 
 Regulated Cell Death   / DEPENDANCE_RECEPTORS 
 Regulated Cell Death   / MOMP_REGULATION 
 Regulated Cell Death   / RCD_GENES 

References
rc_re495:( Regulated Cell Death  ) PMID:16287866

Maps_Modules
HMC:RESISTING_CELL_DEATH
 Regulated Cell Death   / ANTIOXIDANT_RESPONSE 
 Regulated Cell Death   / APOPTOSIS 
 Regulated Cell Death   / STARVATION_AUTOPHAGY 
 Regulated Cell Death   / CASPASES 
 Regulated Cell Death   / DEATH_RECEPTOR_PATHWAYS 
 Regulated Cell Death   / DEPENDANCE_RECEPTORS 
 Regulated Cell Death   / MOMP_REGULATION 
 Regulated Cell Death   / RCD_GENES 

References
rc_re493( Regulated Cell Death  ):
PMID:9812896
in 267 and MDCK (dog) cell lines
in vitro direct phosphorylation with human recombinant proteins

Maps_Modules
HMC:RESISTING_CELL_DEATH
 Regulated Cell Death   / ANTIOXIDANT_RESPONSE 
 Regulated Cell Death   / APOPTOSIS 
 Regulated Cell Death   / STARVATION_AUTOPHAGY 
 Regulated Cell Death   / CASPASES 
 Regulated Cell Death   / DEATH_RECEPTOR_PATHWAYS 
 Regulated Cell Death   / DEPENDANCE_RECEPTORS 
 Regulated Cell Death   / MOMP_REGULATION 
 Regulated Cell Death   / RCD_GENES 

References
rc_re494:( Regulated Cell Death  ) reactionType:is.a
rc_re493( Regulated Cell Death  ):
PMID:9812896
in 267 and MDCK (dog) cell lines
in vitro direct phosphorylation with human recombinant proteins

Maps_Modules
HMC:RESISTING_CELL_DEATH
 Regulated Cell Death   / ANTIOXIDANT_RESPONSE 
 Regulated Cell Death   / APOPTOSIS 
 Regulated Cell Death   / STARVATION_AUTOPHAGY 
 Regulated Cell Death   / CASPASES 
 Regulated Cell Death   / DEATH_RECEPTOR_PATHWAYS 
 Regulated Cell Death   / DEPENDANCE_RECEPTORS 
 Regulated Cell Death   / MOMP_REGULATION 
 Regulated Cell Death   / RCD_GENES 

References
rc_re496:( Regulated Cell Death  ) PMID:16287866
rc_re497:( Regulated Cell Death  ) reactionType:is.a

Maps_Modules
HMC:RESISTING_CELL_DEATH
 Regulated Cell Death   / ANTIOXIDANT_RESPONSE 
 Regulated Cell Death   / APOPTOSIS 
 Regulated Cell Death   / STARVATION_AUTOPHAGY 
 Regulated Cell Death   / CASPASES 
 Regulated Cell Death   / DEATH_RECEPTOR_PATHWAYS 
 Regulated Cell Death   / DEPENDANCE_RECEPTORS 
 Regulated Cell Death   / MOMP_REGULATION 
 Regulated Cell Death   / RCD_GENES 

References
rc_re499( Regulated Cell Death  ):
PMID:12792650
okadaic acid
PMID:16888006
in a murine T cell line stably transfected with the human IL2R, IL2 withdrawal induces PP1 alpha catalytic subunit PP1CA dephosphorylation and activation and CASP9 dephosphorylation
rc_re500:( Regulated Cell Death  ) reactionType:is.a
rc_re498( Regulated Cell Death  ):
Direct phosphorylation of CASP9 by ERK2 sufficient to block CASP9 processing
in vitro, recombinant hCASP9 phosphorylated on T125 by cytosolic extract or ERK2
in Hela cells, interaction GST-CASP9 / ERK
in Hela or HEK293, CASP9 T125 phosphorylation by OA, consititutively active MEK1, EGF or TPA
PMID:17466630
CASP9 T125 phosphorylation by CCNB1:CDC2
comment: phosphorylation during mitosis, when nuclear envelope is broken down
PMID:19081073
CASP9 T125 phosphorylation by DYRK1A
PMID:19016842
PMID:19586613
CASP9 T125 phosphorylation by DYRK1A and p38

Maps_Modules
HMC:RESISTING_CELL_DEATH
 Regulated Cell Death   / ANTIOXIDANT_RESPONSE 
 Regulated Cell Death   / APOPTOSIS 
 Regulated Cell Death   / STARVATION_AUTOPHAGY 
 Regulated Cell Death   / CASPASES 
 Regulated Cell Death   / DEATH_RECEPTOR_PATHWAYS 
 Regulated Cell Death   / DEPENDANCE_RECEPTORS 
 Regulated Cell Death   / MOMP_REGULATION 
 Regulated Cell Death   / RCD_GENES 

Maps_Modules
HMC:RESISTING_CELL_DEATH
 Regulated Cell Death   / ANTIOXIDANT_RESPONSE 
 Regulated Cell Death   / APOPTOSIS 
 Regulated Cell Death   / STARVATION_AUTOPHAGY 
 Regulated Cell Death   / CASPASES 
 Regulated Cell Death   / DEATH_RECEPTOR_PATHWAYS 
 Regulated Cell Death   / DEPENDANCE_RECEPTORS 
 Regulated Cell Death   / MOMP_REGULATION 
 Regulated Cell Death   / RCD_GENES 

Maps_Modules
HMC:RESISTING_CELL_DEATH
 Regulated Cell Death   / ANTIOXIDANT_RESPONSE 
 Regulated Cell Death   / APOPTOSIS 
 Regulated Cell Death   / STARVATION_AUTOPHAGY 
 Regulated Cell Death   / CASPASES 
 Regulated Cell Death   / DEATH_RECEPTOR_PATHWAYS 
 Regulated Cell Death   / DEPENDANCE_RECEPTORS 
 Regulated Cell Death   / MOMP_REGULATION 
 Regulated Cell Death   / RCD_GENES 

References
rc_re504:( Regulated Cell Death  ) reactionType:is.a
rc_re505( Regulated Cell Death  ):
PMID:12620238
cristal structure of the complex
rc_re506( Regulated Cell Death  ):
PMID:10671558
in vitro with recombinant proteins
cleavage of recombinant CASP9 by cellular extract, in a Ca2+ dose-dependent manner
in Hela cell extracts, preincubation with Ca2+ and CAPN2 prevents Cyt_c-mediated CASP3 cleavage
in SH-SY5Y human neuroblastoma cells Ca2+ ionophore (A23187) treatment
CAPN2-cleaved CASP9 is inactive
CASP78 are also cleaved by CAPN2, but the effect on their activity is unknown
rc_re659:( Regulated Cell Death  ) PMID:15300255
rc_re1027( Regulated Cell Death  ):
PMID:14701803
PMID:18497292

Maps_Modules
HMC:RESISTING_CELL_DEATH
 Regulated Cell Death   / ANTIOXIDANT_RESPONSE 
 Regulated Cell Death   / APOPTOSIS 
 Regulated Cell Death   / STARVATION_AUTOPHAGY 
 Regulated Cell Death   / CASPASES 
 Regulated Cell Death   / DEATH_RECEPTOR_PATHWAYS 
 Regulated Cell Death   / DEPENDANCE_RECEPTORS 
 Regulated Cell Death   / MOMP_REGULATION 
 Regulated Cell Death   / RCD_GENES 

References
rc_re659:( Regulated Cell Death  ) PMID:15300255

Maps_Modules
HMC:RESISTING_CELL_DEATH
 Regulated Cell Death   / ANTIOXIDANT_RESPONSE 
 Regulated Cell Death   / APOPTOSIS 
 Regulated Cell Death   / STARVATION_AUTOPHAGY 
 Regulated Cell Death   / CASPASES 
 Regulated Cell Death   / DEATH_RECEPTOR_PATHWAYS 
 Regulated Cell Death   / DEPENDANCE_RECEPTORS 
 Regulated Cell Death   / MOMP_REGULATION 
 Regulated Cell Death   / RCD_GENES 

References
rc_re1027( Regulated Cell Death  ):
PMID:14701803
PMID:18497292

Maps_Modules
HMC:RESISTING_CELL_DEATH
 Regulated Cell Death   / ANTIOXIDANT_RESPONSE 
 Regulated Cell Death   / APOPTOSIS 
 Regulated Cell Death   / STARVATION_AUTOPHAGY 
 Regulated Cell Death   / CASPASES 
 Regulated Cell Death   / DEATH_RECEPTOR_PATHWAYS 
 Regulated Cell Death   / DEPENDANCE_RECEPTORS 
 Regulated Cell Death   / MOMP_REGULATION 
 Regulated Cell Death   / RCD_GENES 

References
rc_re1704( Regulated Cell Death  ):
PMID:22679284
Patched dependence receptor triggers apoptosis through ubiquitination of caspase-9

References
su_mpk1_mpk1_re32( Survival  ):
Caspase9 is phosphorylated on Thr125 in a MEK1/2-dependent manner in vivo. Furthermore caspase9 is efficiently phosphorylated on Thr125 by ERK in vitro suggesting that it is targeted directly by ERK in vivo. This is one of the ways ERK plays its anti-apoptotic role.
PMID:12792650
su_mpk1_mpk1_re34( Survival  ):
Activated caspase-9 cleaves and activates caspase-3 leading to apoptosis.
PMID:9390557
su_akt1_s_akt1_re132( Survival  ):
PMID:19788417
PMID:16977332
su_akt1_s_akt1_re134:( Survival  ) PMID:9812896

References
su_mpk1_mpk1_re32( Survival  ):
Caspase9 is phosphorylated on Thr125 in a MEK1/2-dependent manner in vivo. Furthermore caspase9 is efficiently phosphorylated on Thr125 by ERK in vitro suggesting that it is targeted directly by ERK in vivo. This is one of the ways ERK plays its anti-apoptotic role.
PMID:12792650

References
s_akt1_re134:( Survival  ) PMID:9812896

1. Caspase9*@Cytoplasm
2. Caspase9*@Cytoplasm
3. Caspase9*|​pho@Cytoplasm
4. Caspase9*|​pho@Cytoplasm

1. Caspase9*@Cytosol
2. Caspase9*|​pho@Cytosol
3. Caspase9*|​K63_ubi@Cytosol
4. Caspase9*|​S196_unk|​S144_unk|​Y153_unk@Cytosol
5. Caspase9*|​S196_unk|​T125_unk|​S144_unk@Cytosol
6. Caspase9*|​S196_unk|​T125_unk|​Y153_unk@Cytosol
7. Caspase9*|​T125_unk|​S144_unk|​Y153_unk@Cytosol
8. Caspase9*|​S196_pho|​T125_unk|​S144_unk|​Y153_unk@Cytosol
9. Caspase9*|​S196_unk|​T125_pho|​S144_unk|​Y153_unk@Cytosol
10. Caspase9*|​S196_unk|​T125_unk|​S144_pho|​Y153_unk@Cytosol
11. Caspase9*|​S196_unk|​T125_unk|​S144_unk|​Y153_pho@Cytosol
12. Caspase9*|​S196_unk|​T125_unk|​S144_unk|​Y153_unk@Cytosol
13. Caspase9*|​S196_unk|​T125_unk|​S144_unk|​Y153_unk|​ubi@Cytosol
14. Caspase9*|​S196_unk|​T125_unk|​S144_unk|​Y153_unk|​-SNO@Cytosol

1. Caspase9*@Mitochondrial intermembrane space

1. APAF1:​Caspase9*@Cytoplasm
2. APAF1:​Caspase9*:​Cytochrome_C*:​dATP/ATP@Cytoplasm

1. Caspase9*|​S196_unk|​T125_unk|​S144_unk|​Y153_unk:​XIAP|​S87_unk|​hm2@Cytosol
2. APPL2:​Caspase9*:​Cleaved DCC*@Cytosol

1. Caspase9*:​HAX1@Mitochondrial intermembrane space

1. Caspase9*@Cytosol → Caspase9*|​pho@Cytosol
2. Caspase9*|​S196_unk|​T125_unk|​S144_unk|​Y153_unk@Cytosol + NO@Cytosol → Caspase9*|​S196_unk|​T125_unk|​S144_unk|​Y153_unk|​-SNO@Cytosol
3. Caspase9*@Mitochondrial intermembrane space + HAX1@Mitochondrial intermembrane space → Caspase9*:​HAX1@Mitochondrial intermembrane space
4. Caspase9*@Mitochondrial intermembrane space + H_sub_2_endsub_O_sub_2_endsub_@Mitochondrial intermembrane space → rc_s934
5. APPL2:​Caspase9*:​Cleaved DCC*@Cytosol → APPL2:​Cleaved DCC*:​cleaved~Caspase9*@Cytosol
6. APPL2@Cytosol + Cleaved DCC*@Cytosol + Caspase9*@Cytosol → APPL2:​Caspase9*:​Cleaved DCC*@Cytosol
7. Caspase9*@Cytosol → Caspase9*|​K63_ubi@Cytosol
8. rCaspase9*@Nucleus → Caspase9*@Cytosol
9. Caspase9*@Cytosol → cleaved~Caspase9*@Cytosol
10. Caspase9*@Cytosol → cleaved~Caspase9*@Cytosol
11. Caspase9*|​T125_unk|​S144_unk|​Y153_unk@Cytosol → Caspase9*|​S196_pho|​T125_unk|​S144_unk|​Y153_unk@Cytosol
12. Caspase9*@Cytosol → Caspase9*|​T125_unk|​S144_unk|​Y153_unk@Cytosol
13. Caspase9*|​S196_unk|​T125_unk|​Y153_unk@Cytosol → Caspase9*|​S196_unk|​T125_unk|​S144_pho|​Y153_unk@Cytosol
14. Caspase9*|​S196_unk|​T125_unk|​S144_pho|​Y153_unk@Cytosol → Caspase9*|​S196_unk|​T125_unk|​Y153_unk@Cytosol
15. Caspase9*@Cytosol → Caspase9*|​S196_unk|​T125_unk|​Y153_unk@Cytosol
16. Caspase9*|​S196_unk|​S144_unk|​Y153_unk@Cytosol → Caspase9*|​S196_unk|​T125_pho|​S144_unk|​Y153_unk@Cytosol
17. Caspase9*|​S196_unk|​T125_pho|​S144_unk|​Y153_unk@Cytosol → Caspase9*|​S196_unk|​S144_unk|​Y153_unk@Cytosol
18. Caspase9*@Mitochondrial intermembrane space → Caspase9*@Cytosol
19. Caspase9*@Cytosol → Caspase9*|​S196_unk|​S144_unk|​Y153_unk@Cytosol
20. Caspase9*|​S196_unk|​T125_unk|​S144_unk@Cytosol → Caspase9*|​S196_unk|​T125_unk|​S144_unk|​Y153_pho@Cytosol
21. Caspase9*@Cytosol → Caspase9*|​S196_unk|​T125_unk|​S144_unk@Cytosol
22. Caspase9*|​S196_unk|​T125_unk|​S144_unk|​Y153_pho@Cytosol → cleaved~Caspase9*@Cytosol
23. Caspase9*@Cytosol → Caspase9*|​S196_unk|​T125_unk|​S144_unk|​Y153_unk@Cytosol
24. XIAP|​S87_unk@Cytosol + Caspase9*|​S196_unk|​T125_unk|​S144_unk|​Y153_unk@Cytosol → Caspase9*|​S196_unk|​T125_unk|​S144_unk|​Y153_unk:​XIAP|​S87_unk|​hm2@Cytosol
25. Caspase9*|​S196_unk|​T125_unk|​S144_unk|​Y153_unk@Cytosol → degraded
26. Caspase9*|​S196_unk|​T125_unk|​S144_unk|​Y153_unk@Cytosol → Caspase9*|​S196_unk|​T125_unk|​S144_unk|​Y153_unk|​ubi@Cytosol
27. Caspase9*|​S196_unk|​T125_unk|​S144_unk|​Y153_unk|​ubi@Cytosol → degraded
28. rCaspase9*@Nucleus → Caspase9*@Cytosol
29. Caspase9*@Cytoplasm → Caspase9__sub_TRUNC_endsub_*@Cytoplasm
30. Caspase9*@Cytoplasm → Caspase9*|​pho@Cytoplasm
31. dATP/ATP@Cytoplasm + APAF1:​Caspase9*@Cytoplasm + Cytochrome_C*@Cytoplasm → APAF1:​Caspase9*:​Cytochrome_C*:​dATP/ATP@Cytoplasm
32. Caspase9*@Cytoplasm → Caspase9*|​pho@Cytoplasm
33. PTCH*@Cytosol + DRAL*@Cytosol + TUCAN*@Cytosol + Caspase9*@Cytosol → su_shh1_s_shh3_s137

1. Caspase9*@Cytoplasm → Caspase9__sub_TRUNC_endsub_*@Cytoplasm
2. Caspase3*@Cytoplasm → Caspase3_sub_TRUNC_endsub_*@Cytoplasm