Identifiers
receptor-interacting serine-threonine kinase 3
HUGO:RIPK3 HGNC:10021 ENTREZ:11035 UNIPROT:Q9Y572

Maps_Modules
HMC:RESISTING_CELL_DEATH
HMC:DEREGULATING_CELLULAR_ENERGETICS
 Regulated Cell Death   / APOPTOSIS 
 Regulated Cell Death   / CASPASES 
 Regulated Cell Death   / DEATH_RECEPTOR_PATHWAYS 
 Regulated Cell Death   / FAS_RESPONSE 
 Regulated Cell Death   / GLUTAMINE_METABOLISM 
 Regulated Cell Death   / MITOCHONDRIAL_METABOLISM 
 Regulated Cell Death   / NECROPTOSIS 
 Regulated Cell Death   / OXIDATIVE_PHOSPHOYLATION_AND_TCA_CYCLE 
 Regulated Cell Death   / TNF_RESPONSE 
 Regulated Cell Death   / TRAIL_RESPONSE 

References
PMID:23010170
PMID:27558815
PMID:23073834
PMID:19524512
PMID:19632174
PMID:19498109
PMID:19524513
The kinase activity of RIP3 is essential for necrosis execution.
PMID:26024392
The phosphorylation of Ser345 is not required for the interaction between RIPK3 and MLKL in the necrosome, but is essential for MLKL translocation, accumulation in the plasma membrane, and consequent necroptosis.
PMID:26900751
CHIP controls necroptosis through ubiquitylation- and lysosome-dependent degradation of RIPK3.

Maps_Modules
HMC:RESISTING_CELL_DEATH
HMC:DEREGULATING_CELLULAR_ENERGETICS
 Regulated Cell Death   / APOPTOSIS 
 Regulated Cell Death   / CASPASES 
 Regulated Cell Death   / DEATH_RECEPTOR_PATHWAYS 
 Regulated Cell Death   / FAS_RESPONSE 
 Regulated Cell Death   / GLUTAMINE_METABOLISM 
 Regulated Cell Death   / MITOCHONDRIAL_METABOLISM 
 Regulated Cell Death   / NECROPTOSIS 
 Regulated Cell Death   / OXIDATIVE_PHOSPHOYLATION_AND_TCA_CYCLE 
 Regulated Cell Death   / TNF_RESPONSE 
 Regulated Cell Death   / TRAIL_RESPONSE 

References
rc_re1649( Regulated Cell Death  ):
PMID:15760909
endogenous c-FLIP(L) functions primarily as an inhibitor of death receptor-mediated apoptosis

Maps_Modules
HMC:RESISTING_CELL_DEATH
HMC:DEREGULATING_CELLULAR_ENERGETICS
 Regulated Cell Death   / APOPTOSIS 
 Regulated Cell Death   / CASPASES 
 Regulated Cell Death   / DEATH_RECEPTOR_PATHWAYS 
 Regulated Cell Death   / FAS_RESPONSE 
 Regulated Cell Death   / GLUTAMINE_METABOLISM 
 Regulated Cell Death   / MITOCHONDRIAL_METABOLISM 
 Regulated Cell Death   / NECROPTOSIS 
 Regulated Cell Death   / OXIDATIVE_PHOSPHOYLATION_AND_TCA_CYCLE 
 Regulated Cell Death   / TNF_RESPONSE 
 Regulated Cell Death   / TRAIL_RESPONSE 

References
rc_re769:( Regulated Cell Death  ) PMID:19498109

Maps_Modules
HMC:RESISTING_CELL_DEATH
HMC:DEREGULATING_CELLULAR_ENERGETICS
 Regulated Cell Death   / APOPTOSIS 
 Regulated Cell Death   / CASPASES 
 Regulated Cell Death   / DEATH_RECEPTOR_PATHWAYS 
 Regulated Cell Death   / FAS_RESPONSE 
 Regulated Cell Death   / GLUTAMINE_METABOLISM 
 Regulated Cell Death   / MITOCHONDRIAL_METABOLISM 
 Regulated Cell Death   / NECROPTOSIS 
 Regulated Cell Death   / OXIDATIVE_PHOSPHOYLATION_AND_TCA_CYCLE 
 Regulated Cell Death   / TNF_RESPONSE 
 Regulated Cell Death   / TRAIL_RESPONSE 

References
rc_re1522:( Regulated Cell Death  ) PMID:23010170
rc_re1523( Regulated Cell Death  ):
PMID:23010170
RIP3 is known to be phosphotylated by itself
PMID:19524512
The kinase activity of RIP3 is essential for necrosis execution.

Maps_Modules
HMC:RESISTING_CELL_DEATH
HMC:DEREGULATING_CELLULAR_ENERGETICS
 Regulated Cell Death   / APOPTOSIS 
 Regulated Cell Death   / CASPASES 
 Regulated Cell Death   / DEATH_RECEPTOR_PATHWAYS 
 Regulated Cell Death   / FAS_RESPONSE 
 Regulated Cell Death   / GLUTAMINE_METABOLISM 
 Regulated Cell Death   / MITOCHONDRIAL_METABOLISM 
 Regulated Cell Death   / NECROPTOSIS 
 Regulated Cell Death   / OXIDATIVE_PHOSPHOYLATION_AND_TCA_CYCLE 
 Regulated Cell Death   / TNF_RESPONSE 
 Regulated Cell Death   / TRAIL_RESPONSE 

References
rc_re1522:( Regulated Cell Death  ) PMID:23010170
rc_re1525( Regulated Cell Death  ):
PMID:19498109
RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis.

1. RIPK3@Cytosol
2. RIPK3|​S199_pho@Cytosol

1. RIPK3@TNFRSF1 Receptor Complex
2. RIPK3|​S199_pho@TNFRSF1 Receptor Complex

1. RIPK1|​S161_pho:​RIPK3|​S199_pho@Cytosol
2. CFLAR:​Caspase8,10*|​ubi:​DR4/5*|​gly|​pal:​MLKL:​RIPK3@Cytosol
3. GLUD1:​GLUL:​MLKL|​S358_pho|​T357_pho:​PGAM5|​pho:​PYGL:​RIPK1|​S161_pho:​RIPK3|​S199_pho|​S227_pho@Cytosol

1. CFLAR:​Caspase8,10*|​ubi:​FADD:​FAF1:​FASLG:​FAS|​pal:​FLASH*:​MLKL:​RIPK1|​emp|​S161_pho:​RIPK3|​S199_pho@Endosome

1. RIPK3@Cytosol → RIPK3@TNFRSF1 Receptor Complex
2. RIPK3@TNFRSF1 Receptor Complex → cleaved~RIPK3*@TNFRSF1 Receptor Complex
3. RIPK3|​S199_pho@TNFRSF1 Receptor Complex → RIPK3|​S199_pho@Cytosol
4. RIPK3@TNFRSF1 Receptor Complex → RIPK3|​S199_pho@TNFRSF1 Receptor Complex
5. RIPK3|​S199_pho@TNFRSF1 Receptor Complex + RIPK1|​S161_pho@TNFRSF1 Receptor Complex + FADD@Cytosol → RIPK1|​S161_pho:​RIPK3|​S199_pho@Cytosol
6. RIPK1|​S161_pho:​RIPK3|​S199_pho@Cytosol + MLKL@Cytosol + GLUL@Cytosol + GLUD1@Cytosol + PYGL@Cytosol + PGAM5@Cytosol → GLUD1:​GLUL:​MLKL|​S358_pho|​T357_pho:​PGAM5|​pho:​PYGL:​RIPK1|​S161_pho:​RIPK3|​S199_pho|​S227_pho@Cytosol
7. GLUD1:​GLUL:​MLKL|​S358_pho|​T357_pho:​PGAM5|​pho:​PYGL:​RIPK1|​S161_pho:​RIPK3|​S199_pho|​S227_pho@Cytosol → Glycogen breakdown@Cytosol
8. GLUD1:​GLUL:​MLKL|​S358_pho|​T357_pho:​PGAM5|​pho:​PYGL:​RIPK1|​S161_pho:​RIPK3|​S199_pho|​S227_pho@Cytosol → Glutaminolysis@Cytosol
9. GLUD1:​GLUL:​MLKL|​S358_pho|​T357_pho:​PGAM5|​pho:​PYGL:​RIPK1|​S161_pho:​RIPK3|​S199_pho|​S227_pho@Cytosol → PARP activation@Cytosol
10. CUL3:​Caspase8,10*|​ubi:​DR4/5*|​gly|​pal:​RBX1@Cytosol + CFLAR@Cytosol + RIPK1@Cytosol + RIPK3@Cytosol + MLKL@Cytosol → CFLAR:​Caspase8,10*|​ubi:​DR4/5*|​gly|​pal:​MLKL:​RIPK3@Cytosol + CUL3:​RBX1@Cytosol
11. CFLAR:​Caspase8,10*|​ubi:​DR4/5*|​gly|​pal:​MLKL:​RIPK3@Cytosol → RIPK1|​S161_pho:​RIPK3|​S199_pho@Cytosol
12. Caspase8,10*|​ubi:​DAXX:​FADD:​FAF1:​FASLG:​FAS|​pal:​FLASH*:​RIPK1@Endosome → CFLAR:​Caspase8,10*|​ubi:​FADD:​FAF1:​FASLG:​FAS|​pal:​FLASH*:​MLKL:​RIPK1|​emp|​S161_pho:​RIPK3|​S199_pho@Endosome
13. CFLAR:​Caspase8,10*|​ubi:​FADD:​FAF1:​FASLG:​FAS|​pal:​FLASH*:​MLKL:​RIPK1|​emp|​S161_pho:​RIPK3|​S199_pho@Endosome → ASK1*:​CFLAR:​Caspase8,10*|​ubi:​DAXX:​FADD:​FAF1:​FASLG:​FAS|​pal:​FLASH*:​RIPK1|​emp|​K377_ubi:​TRAF2@Endosome
14. CFLAR:​Caspase8,10*|​ubi:​FADD:​FAF1:​FASLG:​FAS|​pal:​FLASH*:​MLKL:​RIPK1|​emp|​S161_pho:​RIPK3|​S199_pho@Endosome → RIPK1|​S161_pho:​RIPK3|​S199_pho@Cytosol
15. CFLAR:​Caspase8,10*|​ubi:​FADD:​FAF1:​FASLG:​FAS|​pal:​FLASH*:​MLKL:​RIPK1|​emp|​S161_pho:​RIPK3|​S199_pho@Endosome → Caspase8,10*|​ubi:​DAXX:​FADD:​FAF1:​FASLG:​FAS|​pal:​FLASH*:​RIPK1@Endosome
16. ASK1*:​CFLAR:​Caspase8,10*|​ubi:​DAXX:​FADD:​FAF1:​FASLG:​FAS|​pal:​FLASH*:​RIPK1|​emp|​K377_ubi:​TRAF2@Endosome → CFLAR:​Caspase8,10*|​ubi:​FADD:​FAF1:​FASLG:​FAS|​pal:​FLASH*:​MLKL:​RIPK1|​emp|​S161_pho:​RIPK3|​S199_pho@Endosome

1. ATP@Mitochondrial Matrix + ADP@Mitochondrial intermembrane space → ATP@Mitochondrial intermembrane space + ADP@Mitochondrial Matrix
2. GLUL|​unk@Cytosol → GLUL|​unk|​hm8@Cytosol
3. RIPK3@TNFRSF1 Receptor Complex → RIPK3|​S199_pho@TNFRSF1 Receptor Complex
4. RIPK1@TNFRSF1 Receptor Complex → RIPK1|​S161_pho@TNFRSF1 Receptor Complex
5. Drp1*|​pho@Cytosol → Drp1*@Cytosol
6. JNK1*@Cytosol → JNK1*|​pho|​active@Cytosol
7. GLUL@Cytosol → GLUL|​unk@Cytosol
8. GLUD1@Mitochondrial Matrix → GLUD1|​unk@Mitochondrial Matrix