KEGG   PATHWAY: cata04217
Entry
cata04217                   Pathway                                
Name
Necroptosis - Cygnus atratus (black swan)
Description
Necroptosis is a programmed form of necrosis. It can be initiated by different stimuli, such as tumor necrosis factor (TNF), TNF-related apoptosis-inducing ligand (TRAIL), Fas ligand (FasL), interferon (IFN), LPS, viral DNA or RNA, DNA-damage agent and requires the kinase activity of receptor-interacting protein 1 (RIPK1) and RIPK3. Its execution involves ROS generation, calcium overload, the opening of the mitochondrial permeability transition pore, mitochondrial fission, inflammatory response and chromatinolysis. Necroptosis participates in many pathogenesis of diseases, including neurological diseases, retinal disorders, acute kidney injury, inflammatory diseases and microbial infections.
Class
Cellular Processes; Cell growth and death
Pathway map
cata04217  Necroptosis
cata04217

Organism
Cygnus atratus (black swan) [GN:cata]
Gene
118245101  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
118246384  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
118260735  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
118253382  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
118251009  RIPK1; LOW QUALITY PROTEIN: receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
118245864  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
118245486  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
118248941  SPATA2; spermatogenesis-associated protein 2 isoform X1 [KO:K17595]
118257863  SPATA2L; spermatogenesis-associated protein 2-like protein [KO:K17595]
118246425  spermatogenesis-associated protein 2-like [KO:K17595]
118257908  ubiquitin carboxyl-terminal hydrolase CYLD-like [KO:K08601] [EC:3.4.19.12]
118246274  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:3.4.19.12]
118250793  FADD; FAS-associated death domain protein isoform X1 [KO:K02373]
118243184  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
118243190  caspase-8-like [KO:K04398] [EC:3.4.22.61]
118243189  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
118245830  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
118247368  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
118247750  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X2 [KO:K04515] [EC:2.7.11.17]
118260559  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
118253487  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
118245267  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
118245691  SLC25A6; ADP/ATP translocase 3 [KO:K05863]
118248699  PPID; peptidyl-prolyl cis-trans isomerase D [KO:K05864] [EC:5.2.1.8]
118254955  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
118253391  VDAC2; voltage-dependent anion-selective channel protein 2 isoform X1 [KO:K15040]
118256067  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
118254457  glutamate dehydrogenase 1, mitochondrial-like [KO:K00261] [EC:1.4.1.3]
118246885  GLUD1; glutamate dehydrogenase 1, mitochondrial isoform X1 [KO:K00261] [EC:1.4.1.3]
118243277  GLUL; glutamine synthetase [KO:K01915] [EC:6.3.1.2]
118257087  glutamine synthetase [KO:K01915] [EC:6.3.1.2]
118253331  PYGB; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
118250234  PYGL; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
118254865  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
118248962  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
118243928  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
118249731  FTH1; ferritin heavy chain [KO:K00522] [EC:1.16.3.1]
118243262  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
118244227  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
118244782  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
118244261  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
118244481  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
118244496  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
118244543  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
118244781  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
118244827  PLA2G4B; cytosolic phospholipase A2 beta isoform X2 [KO:K16342] [EC:3.1.1.4]
118255178  CAPN11; calpain-11 isoform X1 [KO:K01367] [EC:3.4.22.52]
118261398  CAPN1; calpain-1 catalytic subunit isoform X1 [KO:K01367] [EC:3.4.22.52]
118252991  calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
118259767  SMPD1; sphingomyelin phosphodiesterase [KO:K12350] [EC:3.1.4.12]
118246405  MLKL; mixed lineage kinase domain-like protein isoform X1 [KO:K08849] [EC:2.7.11.1]
118253026  PGAM5; serine/threonine-protein phosphatase PGAM5, mitochondrial isoform X1 [KO:K15637] [EC:3.1.3.16]
118250049  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
118254061  caspase-1-like isoform X1 [KO:K01370] [EC:3.4.22.36]
118261248  interleukin-1 beta-like [KO:K04519]
118245023  CHMP2B; charged multivesicular body protein 2b [KO:K12192]
118248947  CHMP4B; charged multivesicular body protein 4b [KO:K12194]
118247822  CHMP4C; charged multivesicular body protein 4c [KO:K24782]
118259295  CHMP6; charged multivesicular body protein 6 [KO:K12195]
118250968  VPS4B; vacuolar protein sorting-associated protein 4B [KO:K12196]
118257880  VPS4A; vacuolar protein sorting-associated protein 4A [KO:K12196]
126913730  charged multivesicular body protein 1b [KO:K12197]
118245611  charged multivesicular body protein 1b [KO:K12197]
118257806  CHMP1A; charged multivesicular body protein 1a [KO:K12197]
118250036  CHMP5; charged multivesicular body protein 5 [KO:K12198]
118256092  CHMP7; charged multivesicular body protein 7 [KO:K15053]
118251976  TRPM7; transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
118245957  HMGB1; high mobility group protein B1 [KO:K10802]
118253207  TNFSF10; tumor necrosis factor ligand superfamily member 10 isoform X1 [KO:K04721]
118255990  tumor necrosis factor receptor superfamily member 10A-like isoform X1 [KO:K04722]
118243636  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
118243457  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
118253811  interferon kappa-like [KO:K05414]
118257698  interferon-like [KO:K05415]
118257699  LOW QUALITY PROTEIN: interferon [KO:K05415]
118257700  interferon [KO:K05415]
118257701  LOW QUALITY PROTEIN: interferon [KO:K05415]
118257702  interferon [KO:K05415]
118257703  interferon [KO:K05415]
118257704  interferon-like [KO:K05415]
126913675  interferon [KO:K05415]
126913676  interferon [KO:K05415]
118246753  IFNG; interferon gamma [KO:K04687]
118247660  IFNAR1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
118247624  IFNAR2; interferon alpha/beta receptor 2 isoform X2 [KO:K05131]
118244196  IFNGR1; interferon gamma receptor 1 [KO:K05132]
118247661  IFNGR2; interferon gamma receptor 2 [KO:K05133]
118256994  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
118258704  JAK2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
118259912  JAK3; tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
118261546  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
118260153  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
118259131  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
118261542  STAT4; signal transducer and activator of transcription 4 [KO:K11222]
118259130  signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
118260162  STAT6; signal transducer and activator of transcription 6 isoform X1 [KO:K11225]
118256378  EIF2AK2; interferon-induced, double-stranded RNA-activated protein kinase [KO:K16195] [EC:2.7.11.1]
118252184  TLR4; toll-like receptor 4 [KO:K10160]
118258726  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
118253475  TLR3; toll-like receptor 3 [KO:K05401]
118260433  USP21; LOW QUALITY PROTEIN: ubiquitin carboxyl-terminal hydrolase 21 [KO:K21634] [EC:3.4.19.12]
118260565  SQSTM1; sequestosome-1 isoform X3 [KO:K14381]
118250314  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
118252736  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
118243941  TNFAIP3; tumor necrosis factor alpha-induced protein 3 isoform X1 [KO:K11859] [EC:3.4.19.12]
118255864  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070] [EC:2.4.2.30]
118250088  BID; BH3-interacting domain death agonist [KO:K04726]
118245279  AIFM1; apoptosis-inducing factor 1, mitochondrial isoform X2 [KO:K04727] [EC:1.-.-.-]
118259370  histone H2A.V [KO:K11251]
118253579  histone H2A-beta, sperm-like [KO:K11251]
118253580  histone H2A type 2-B-like [KO:K11251]
118248204  histone H2A type 2-B [KO:K11251]
118254903  core histone macro-H2A.1 isoform X1 [KO:K11251]
118261485  histone H2A type 2-C-like [KO:K11251]
118247779  LOW QUALITY PROTEIN: uncharacterized protein LOC118247779 [KO:K11251]
118244275  histone H2A.Z [KO:K11251]
118250601  histone H2A-IV [KO:K11251]
118250603  histone H2A-IV [KO:K11251]
118250604  histone H2A type 2-C [KO:K11251]
118250605  histone H2A.J [KO:K11251]
126913098  histone H2A type 2-C [KO:K11251]
118250606  histone H2A-IV [KO:K11251]
118250607  histone H2A-IV [KO:K11251]
118250608  histone H2A [KO:K11251]
118246206  core histone macro-H2A.2 [KO:K11251]
118252406  histone H2A [KO:K11251]
118246793  LOW QUALITY PROTEIN: histone H2A-IV-like [KO:K11251]
118250974  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
Compound
C00002  ATP
C00027  Hydrogen peroxide
C00076  Calcium cation
C00195  N-Acylsphingosine
C00219  Arachidonate
C00305  Magnesium cation
C00319  Sphingosine
C00550  Sphingomyelin
C14592  N-Methyl-N'-nitro-N-nitrosoguanidine
C16844  Hydroxyl radical
Reference
  Authors
Vandenabeele P, Galluzzi L, Vanden Berghe T, Kroemer G
  Title
Molecular mechanisms of necroptosis: an ordered cellular explosion.
  Journal
Nat Rev Mol Cell Biol 11:700-14 (2010)
DOI:10.1038/nrm2970
Reference
  Authors
Brenner D, Blaser H, Mak TW
  Title
Regulation of tumour necrosis factor signalling: live or let die.
  Journal
Nat Rev Immunol 15:362-74 (2015)
DOI:10.1038/nri3834
Reference
  Authors
Conrad M, Angeli JP, Vandenabeele P, Stockwell BR
  Title
Regulated necrosis: disease relevance and therapeutic opportunities.
  Journal
Nat Rev Drug Discov 15:348-66 (2016)
DOI:10.1038/nrd.2015.6
Reference
  Authors
Ofengeim D, Yuan J
  Title
Regulation of RIP1 kinase signalling at the crossroads of inflammation and cell death.
  Journal
Nat Rev Mol Cell Biol 14:727-36 (2013)
DOI:10.1038/nrm3683
Reference
  Authors
Murphy JM, Vince JE
  Title
Post-translational control of RIPK3 and MLKL mediated necroptotic cell death.
  Journal
F1000Res 4:F1000 Faculty Rev-1297 (2015)
DOI:10.12688/f1000research.7046.1
Reference
  Authors
Vanden Berghe T, Linkermann A, Jouan-Lanhouet S, Walczak H, Vandenabeele P
  Title
Regulated necrosis: the expanding network of non-apoptotic cell death pathways.
  Journal
Nat Rev Mol Cell Biol 15:135-47 (2014)
DOI:10.1038/nrm3737
Reference
  Authors
Dondelinger Y, Hulpiau P, Saeys Y, Bertrand MJ, Vandenabeele P
  Title
An evolutionary perspective on the necroptotic pathway.
  Journal
Trends Cell Biol 26:721-32 (2016)
DOI:10.1016/j.tcb.2016.06.004
Reference
  Authors
Thapa RJ, Ingram JP, Ragan KB, Nogusa S, Boyd DF, Benitez AA, Sridharan H, Kosoff R, Shubina M, Landsteiner VJ, Andrake M, Vogel P, Sigal LJ, tenOever BR, Thomas PG, Upton JW, Balachandran S
  Title
DAI Senses Influenza A Virus Genomic RNA and Activates RIPK3-Dependent Cell Death.
  Journal
Cell Host Microbe 20:674-681 (2016)
DOI:10.1016/j.chom.2016.09.014
Reference
  Authors
Yuan J, Najafov A, Py BF
  Title
Roles of Caspases in Necrotic Cell Death.
  Journal
Cell 167:1693-1704 (2016)
DOI:10.1016/j.cell.2016.11.047
Reference
  Authors
Jorgensen I, Rayamajhi M, Miao EA
  Title
Programmed cell death as a defence against infection.
  Journal
Nat Rev Immunol 17:151-164 (2017)
DOI:10.1038/nri.2016.147
Reference
  Authors
Vandenabeele P, Declercq W, Van Herreweghe F, Vanden Berghe T
  Title
The role of the kinases RIP1 and RIP3 in TNF-induced necrosis.
  Journal
Sci Signal 3:re4 (2010)
DOI:10.1126/scisignal.3115re4
Reference
  Authors
Vanlangenakker N, Vanden Berghe T, Vandenabeele P
  Title
Many stimuli pull the necrotic trigger, an overview.
  Journal
Cell Death Differ 19:75-86 (2012)
DOI:10.1038/cdd.2011.164
Reference
  Authors
Moriwaki K, Chan FK
  Title
RIP3: a molecular switch for necrosis and inflammation.
  Journal
Genes Dev 27:1640-9 (2013)
DOI:10.1101/gad.223321.113
Reference
  Authors
Humphries F, Yang S, Wang B, Moynagh PN
  Title
RIP kinases: key decision makers in cell death and innate immunity.
  Journal
Cell Death Differ 22:225-36 (2015)
DOI:10.1038/cdd.2014.126
Reference
  Authors
Wegner KW, Saleh D, Degterev A
  Title
Complex Pathologic Roles of RIPK1 and RIPK3: Moving Beyond Necroptosis.
  Journal
Trends Pharmacol Sci 38:202-225 (2017)
DOI:10.1016/j.tips.2016.12.005
Reference
  Authors
Kupka S, De Miguel D, Draber P, Martino L, Surinova S, Rittinger K, Walczak H
  Title
SPATA2-Mediated Binding of CYLD to HOIP Enables CYLD Recruitment to Signaling Complexes.
  Journal
Cell Rep 16:2271-80 (2016)
DOI:10.1016/j.celrep.2016.07.086
Reference
  Authors
Goodall ML, Fitzwalter BE, Zahedi S, Wu M, Rodriguez D, Mulcahy-Levy JM, Green DR, Morgan M, Cramer SD, Thorburn A
  Title
The Autophagy Machinery Controls Cell Death Switching between Apoptosis and Necroptosis.
  Journal
Dev Cell 37:337-49 (2016)
DOI:10.1016/j.devcel.2016.04.018
Reference
  Authors
Xu G, Tan X, Wang H, Sun W, Shi Y, Burlingame S, Gu X, Cao G, Zhang T, Qin J, Yang J
  Title
Ubiquitin-specific peptidase 21 inhibits tumor necrosis factor alpha-induced nuclear factor kappaB activation via binding to and deubiquitinating receptor-interacting protein 1.
  Journal
J Biol Chem 285:969-78 (2010)
DOI:10.1074/jbc.M109.042689
Reference
  Authors
Jacobsen AV, Silke J
  Title
The importance of being chaperoned: HSP90 and necroptosis.
  Journal
Cell Chem Biol 23:205-7 (2016)
DOI:10.1016/j.chembiol.2016.02.003
Reference
  Authors
Gurung P, Man SM, Kanneganti TD
  Title
A20 is a regulator of necroptosis.
  Journal
Nat Immunol 16:596-7 (2015)
DOI:10.1038/ni.3174
Reference
  Authors
Feng N, Anderson ME
  Title
CaMKII is a nodal signal for multiple programmed cell death pathways in heart.
  Journal
J Mol Cell Cardiol 103:102-109 (2017)
DOI:10.1016/j.yjmcc.2016.12.007
Reference
  Authors
Zhivotovsky B, Galluzzi L, Kepp O, Kroemer G
  Title
Adenine nucleotide translocase: a component of the phylogenetically conserved cell death machinery.
  Journal
Cell Death Differ 16:1419-25 (2009)
DOI:10.1038/cdd.2009.118
Reference
  Authors
Thapa RJ, Nogusa S, Chen P, Maki JL, Lerro A, Andrake M, Rall GF, Degterev A, Balachandran S
  Title
Interferon-induced RIP1/RIP3-mediated necrosis requires PKR and is licensed by FADD and caspases.
  Journal
Proc Natl Acad Sci U S A 110:E3109-18 (2013)
DOI:10.1073/pnas.1301218110
Reference
  Authors
Thapa RJ, Basagoudanavar SH, Nogusa S, Irrinki K, Mallilankaraman K, Slifker MJ, Beg AA, Madesh M, Balachandran S
  Title
NF-kappaB protects cells from gamma interferon-induced RIP1-dependent necroptosis.
  Journal
Mol Cell Biol 31:2934-46 (2011)
DOI:10.1128/MCB.05445-11
Reference
  Authors
Sridharan H, Upton JW
  Title
Programmed necrosis in microbial pathogenesis.
  Journal
Trends Microbiol 22:199-207 (2014)
DOI:10.1016/j.tim.2014.01.005
Reference
  Authors
Cabon L, Galan-Malo P, Bouharrour A, Delavallee L, Brunelle-Navas MN, Lorenzo HK, Gross A, Susin SA
  Title
BID regulates AIF-mediated caspase-independent necroptosis by promoting BAX activation.
  Journal
Cell Death Differ 19:245-56 (2012)
DOI:10.1038/cdd.2011.91
Reference
  Authors
Baritaud M, Boujrad H, Lorenzo HK, Krantic S, Susin SA
  Title
Histone H2AX: The missing link in AIF-mediated caspase-independent programmed necrosis.
  Journal
Cell Cycle 9:3166-73 (2010)
DOI:10.4161/cc.9.16.12887
Reference
  Authors
Upton JW, Kaiser WJ
  Title
DAI Another Way: Necroptotic Control of Viral Infection.
  Journal
Cell Host Microbe 21:290-293 (2017)
DOI:10.1016/j.chom.2017.01.016
Reference
  Authors
Silke J, Rickard JA, Gerlic M
  Title
The diverse role of RIP kinases in necroptosis and inflammation.
  Journal
Nat Immunol 16:689-97 (2015)
DOI:10.1038/ni.3206
Reference
  Authors
Guo H, Kaiser WJ
  Title
ESCRTing Necroptosis.
  Journal
Cell 169:186-187 (2017)
DOI:10.1016/j.cell.2017.03.030
Reference
  Authors
Gong YN, Guy C, Olauson H, Becker JU, Yang M, Fitzgerald P, Linkermann A, Green DR
  Title
ESCRT-III Acts Downstream of MLKL to Regulate Necroptotic Cell Death and Its Consequences.
  Journal
Cell 169:286-300.e16 (2017)
DOI:10.1016/j.cell.2017.03.020
Reference
  Authors
Petrie EJ, Hildebrand JM, Murphy JM
  Title
Insane in the membrane: a structural perspective of MLKL function in necroptosis.
  Journal
Immunol Cell Biol 95:152-159 (2017)
DOI:10.1038/icb.2016.125
Reference
  Authors
Cai Z, Jitkaew S, Zhao J, Chiang HC, Choksi S, Liu J, Ward Y, Wu LG, Liu ZG
  Title
Plasma membrane translocation of trimerized MLKL protein is required for TNF-induced necroptosis.
  Journal
Nat Cell Biol 16:55-65 (2014)
DOI:10.1038/ncb2883
Reference
  Authors
Lawlor KE, Khan N, Mildenhall A, Gerlic M, Croker BA, D'Cruz AA, Hall C, Kaur Spall S, Anderton H, Masters SL, Rashidi M, Wicks IP, Alexander WS, Mitsuuchi Y, Benetatos CA, Condon SM, Wong WW, Silke J, Vaux DL, Vince JE
  Title
RIPK3 promotes cell death and NLRP3 inflammasome activation in the absence of MLKL.
  Journal
Nat Commun 6:6282 (2015)
DOI:10.1038/ncomms7282
Reference
  Authors
Shlomovitz I, Zargrian S, Gerlic M
  Title
Mechanisms of RIPK3-induced inflammation.
  Journal
Immunol Cell Biol 95:166-172 (2017)
DOI:10.1038/icb.2016.124
Related
pathway
cata00250  Alanine, aspartate and glutamate metabolism
cata04210  Apoptosis
KO pathway
ko04217   
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