KEGG   PATHWAY: aang04217
Entry
aang04217                   Pathway                                
Name
Necroptosis - Anguilla anguilla (European eel)
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
aang04217  Necroptosis
aang04217

Organism
Anguilla anguilla (European eel) [GN:aang]
Gene
118207705  si:ch211-112c15.8; tumor necrosis factor receptor superfamily member 1A isoform X1 [KO:K03158]
118220060  tnfrsf1a; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
118227505  tradd; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
118206207  TNF receptor-associated factor 2-like [KO:K03173] [EC:2.3.2.27]
118212933  traf2b; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
118213211  TNF receptor-associated factor 2-like isoform X1 [KO:K03173] [EC:2.3.2.27]
118221762  traf5; TNF receptor-associated factor 5 [KO:K09849]
118226129  receptor-interacting serine/threonine-protein kinase 1-like isoform X1 [KO:K02861] [EC:2.7.11.1]
118234395  ripk1l; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
118236782  birc2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
118224103  xiap; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
118211197  rbck1; ranBP-type and C3HC4-type zinc finger-containing protein 1 [KO:K10630] [EC:2.3.2.31]
118225147  shrprbck1r; LOW QUALITY PROTEIN: ranBP-type and C3HC4-type zinc finger-containing protein 1 [KO:K10630] [EC:2.3.2.31]
118234561  E3 ubiquitin-protein ligase RNF31 [KO:K11974] [EC:2.3.2.31]
118232756  si:dkey-181m9.8; uncharacterized protein si:dkey-181m9.8 isoform X1 [KO:K11974] [EC:2.3.2.31]
118224942  E3 ubiquitin-protein ligase RNF31-like isoform X1 [KO:K11974] [EC:2.3.2.31]
118234651  ranBP-type and C3HC4-type zinc finger-containing protein 1-like isoform X1 [KO:K20894]
118228534  uncharacterized protein LOC118228534 [KO:K17595]
118211444  spermatogenesis-associated protein 2-like [KO:K17595]
118208280  spata2; spermatogenesis-associated protein 2 [KO:K17595]
118228041  spata2l; spermatogenesis-associated protein 2-like protein isoform X1 [KO:K17595]
118215262  cylda; ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:3.4.19.12]
118232298  si:cabz01101003.1; ubiquitin carboxyl-terminal hydrolase CYLD [KO:K08601] [EC:3.4.19.12]
118226682  fadd; FAS-associated death domain protein [KO:K02373]
118222448  caspase-8-like [KO:K04398] [EC:3.4.22.61]
118214013  caspase-8-like isoform X1 [KO:K04398] [EC:3.4.22.61]
118222872  CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
118213703  CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
118231452  ripk3; receptor-interacting serine/threonine-protein kinase 4 [KO:K08847] [EC:2.7.11.1]
118214260  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
118235731  calcium/calmodulin-dependent protein kinase type II subunit alpha-like isoform X1 [KO:K04515] [EC:2.7.11.17]
118224113  calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
118217801  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
118231172  camk2d1; calcium/calmodulin-dependent protein kinase type II delta 1 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
118206365  calcium/calmodulin-dependent protein kinase type II subunit beta-like isoform X1 [KO:K04515] [EC:2.7.11.17]
118212497  calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
118220819  calcium/calmodulin-dependent protein kinase type II subunit gamma-like isoform X1 [KO:K04515] [EC:2.7.11.17]
118223362  slc25a5; ADP/ATP translocase 2 [KO:K05863]
118213965  slc25a6; ADP/ATP translocase 3 [KO:K05863]
118227167  slc25a4; ADP/ATP translocase 1 [KO:K05863]
118235005  ADP/ATP translocase 2-like [KO:K05863]
118227289  ppid; peptidyl-prolyl cis-trans isomerase D [KO:K05864] [EC:5.2.1.8]
118223048  voltage-dependent anion-selective channel protein 1-like [KO:K05862]
118236558  vdac1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
118219694  vdac2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
118207050  vdac3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
118213425  voltage-dependent anion-selective channel protein 2-like isoform X1 [KO:K15041]
118218030  glutamate dehydrogenase, mitochondrial-like [KO:K00261] [EC:1.4.1.3]
118220970  glutamate dehydrogenase, mitochondrial [KO:K00261] [EC:1.4.1.3]
118229510  glula; glutamate-ammonia ligase (glutamine synthase) a [KO:K01915] [EC:6.3.1.2]
118224530  glulb; glutamine synthetase [KO:K01915] [EC:6.3.1.2]
118213116  glutamine synthetase-like [KO:K01915] [EC:6.3.1.2]
118223638  glycogen phosphorylase, muscle form-like [KO:K00688] [EC:2.4.1.1]
118217614  pygb; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
118225920  pygl; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
118234927  glycogen phosphorylase, muscle form-like [KO:K00688] [EC:2.4.1.1]
118236139  mitogen-activated protein kinase 9-like [KO:K04440] [EC:2.7.11.24]
118223663  mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
118217861  mapk8a; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
118212863  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
118220848  mapk8b; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
118215390  ferritin, heavy subunit [KO:K00522] [EC:1.16.3.1]
118216669  ferritin, middle subunit-like [KO:K00522] [EC:1.16.3.1]
118221599  ferritin, middle subunit [KO:K00522] [EC:1.16.3.1]
118221833  zgc:56095; ferritin, heavy subunit [KO:K00522] [EC:1.16.3.1]
118230091  pla2g4aa; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
118225096  pla2g4ab; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
118233579  cytosolic phospholipase A2-like [KO:K16342] [EC:3.1.1.4]
118233574  cytosolic phospholipase A2 zeta-like [KO:K16342] [EC:3.1.1.4]
118217792  capn1a; calpain 1, (mu/I) large subunit a [KO:K01367] [EC:3.4.22.52]
118220681  calpain-1 catalytic subunit-like [KO:K01367] [EC:3.4.22.52]
118221077  calpain-14-like [KO:K01367] [EC:3.4.22.52]
118234986  si:dkeyp-50d11.2; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
118217793  capn2a; calpain 2, (m/II) large subunit a [KO:K03853] [EC:3.4.22.53]
118218445  calpain-2 catalytic subunit-like [KO:K03853] [EC:3.4.22.53]
118218446  capn8; calpain-8 [KO:K03853] [EC:3.4.22.53]
118212877  calpain-2 catalytic subunit-like [KO:K03853] [EC:3.4.22.53]
118212878  calpain-2 catalytic subunit-like [KO:K03853] [EC:3.4.22.53]
118220682  calpain-2 catalytic subunit-like [KO:K03853] [EC:3.4.22.53]
118220959  calpain-2 catalytic subunit-like [KO:K03853] [EC:3.4.22.53]
118235627  smpd1; sphingomyelin phosphodiesterase [KO:K12350] [EC:3.1.4.12]
118214717  mixed lineage kinase domain-like protein [KO:K08849] [EC:2.7.11.1]
118206166  pgam5; serine/threonine-protein phosphatase PGAM5, mitochondrial isoform X1 [KO:K15637] [EC:3.1.3.16]
118219268  dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
118232319  dnm1l; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
118237280  si:dkey-32e23.4; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
118223809  pycard; apoptosis-associated speck-like protein containing a CARD [KO:K12799]
118227695  apoptosis-associated speck-like protein containing a CARD [KO:K12799]
118227697  apoptosis-associated speck-like protein containing a CARD [KO:K12799]
118210370  caspase-1-like [KO:K01370] [EC:3.4.22.36]
118212525  il1b; interleukin-1 beta isoform X1 [KO:K04519]
118207102  interleukin-1 beta-like [KO:K04519]
118226133  chmp2a; charged multivesicular body protein 2a [KO:K12191]
118224107  charged multivesicular body protein 2b-A-like [KO:K12192]
118214589  chmp2ba; charged multivesicular body protein 2Ba [KO:K12192]
118231753  charged multivesicular body protein 3 isoform X1 [KO:K12193]
118227303  charged multivesicular body protein 3-like [KO:K12193]
118227478  charged multivesicular body protein 3-like [KO:K12193]
118211330  chmp4ba; charged multivesicular body protein 4b [KO:K12194]
118208049  charged multivesicular body protein 4b-like [KO:K12194]
118224538  chmp4c; charged multivesicular body protein 4c [KO:K24782]
118217208  charged multivesicular body protein 6-like [KO:K12195]
118228533  vacuolar protein sorting-associated protein 4A isoform X1 [KO:K12196]
118225301  vacuolar protein sorting-associated protein 4B-like [KO:K12196]
118233080  vps4b; vacuolar protein sorting-associated protein 4B isoform X1 [KO:K12196]
118215068  vps4a; vacuolar protein sorting-associated protein 4A [KO:K12196]
118215824  chmp1a; charged multivesicular body protein 1a [KO:K12197]
118224001  charged multivesicular body protein 1b [KO:K12197]
118236473  charged multivesicular body protein 1b-like [KO:K12197]
118225217  chmp5b; charged multivesicular body protein 5 [KO:K12198]
118232919  charged multivesicular body protein 5-like [KO:K12198]
118207053  chmp7; charged multivesicular body protein 7 [KO:K15053]
118215450  transient receptor potential cation channel subfamily M member 7-like isoform X1 [KO:K04982] [EC:2.7.11.1]
118227349  trpm7; transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
118236432  high mobility group protein B1-like [KO:K10802]
118229086  tumor necrosis factor ligand superfamily member 10-like [KO:K04721]
118226119  tumor necrosis factor ligand superfamily member 10-like [KO:K04721]
118206564  hdr; hematopoietic death receptor isoform X1 [KO:K04722]
118213458  tumor necrosis factor receptor superfamily member 10B-like [KO:K04722]
118224955  faslg; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
118221088  fas; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
118215933  interferon a3-like [KO:K05414]
118216116  interferon a3-like [KO:K05414]
118217094  interferon a3-like [KO:K05414]
118221758  interferon alpha-7-like [KO:K05414]
118218838  interferon gamma 1-like [KO:K04687]
118218015  interferon gamma receptor 1-like isoform X1 [KO:K05132]
118218069  ifngr1; interferon gamma receptor 1 isoform X1 [KO:K05132]
118214504  interferon alpha/beta receptor 1-like [KO:K05133]
118229660  tyrosine-protein kinase JAK1-like isoform X1 [KO:K11217] [EC:2.7.10.2]
118225684  jak1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
118212588  tyrosine-protein kinase JAK2-like isoform X1 [KO:K04447] [EC:2.7.10.2]
118226427  jak3; tyrosine-protein kinase JAK2 [KO:K11218] [EC:2.7.10.2]
118216638  tyk2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
118223245  signal transducer and activator of transcription 1-like [KO:K11220]
118214287  signal transducer and activator of transcription 1-alpha/beta-like [KO:K11220]
118210889  stat2; signal transducer and activator of transcription 2 [KO:K11221]
118216486  signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
118220792  stat3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
118223247  stat4; signal transducer and activator of transcription 4 [KO:K11222]
118214570  signal transducer and activator of transcription 4-like isoform X1 [KO:K11222]
118220791  stat5a; signal transducer and activator of transcription 5A [KO:K11224]
118207476  stat6; signal transducer and activator of transcription 6 isoform X1 [KO:K11225]
118225170  irf9; interferon regulatory factor 9 isoform X1 [KO:K04693]
118218399  eif2ak2; interferon-induced, double-stranded RNA-activated protein kinase isoform X1 [KO:K16195] [EC:2.7.11.1]
118224595  ticam1; TIR domain-containing adapter molecule 1 isoform X1 [KO:K05842]
118227723  tlr3; toll-like receptor 3 isoform X1 [KO:K05401]
118211354  usp21; ubiquitin carboxyl-terminal hydrolase 21 isoform X1 [KO:K21634] [EC:3.4.19.12]
118223874  sqstm1; sequestosome-1 [KO:K14381]
118229338  heat shock protein HSP 90-alpha [KO:K04079]
118229339  heat shock protein HSP 90-alpha 1-like [KO:K04079]
118230802  hsp90ab1; heat shock protein HSP 90-beta [KO:K04079]
118213512  heat shock protein HSP 90-alpha [KO:K04079]
118220277  heat shock protein HSP 90-alpha 1 [KO:K04079]
118218217  tnfaip3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
118206810  tumor necrosis factor alpha-induced protein 3-like [KO:K11859] [EC:3.4.19.12]
118220328  tumor necrosis factor alpha-induced protein 3-like isoform X1 [KO:K11859] [EC:3.4.19.12]
118221581  tumor necrosis factor alpha-induced protein 3-like isoform X1 [KO:K11859] [EC:3.4.19.12]
118230631  parp1; poly [ADP-ribose] polymerase 1 [KO:K24070] [EC:2.4.2.30]
118231019  bida; BH3 interacting domain death agonist [KO:K04726]
118217377  baxa; BCL2 associated X, apoptosis regulator a [KO:K02159]
118214689  zgc:153993; apoptosis regulator BAX [KO:K02159]
118221131  apoptosis regulator BAX-like isoform X1 [KO:K02159]
118235791  aifm1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
118236388  core histone macro-H2A.1 isoform X1 [KO:K11251]
118209516  histone H2A-like [KO:K11251]
118235553  histone H2AX [KO:K11251]
118235662  histone H2A [KO:K11251]
118216305  histone H2A-like [KO:K11251]
118216306  histone H2A-like [KO:K11251]
118216312  histone H2A [KO:K11251]
118216313  histone H2A-like [KO:K11251]
118217642  core histone macro-H2A.2 [KO:K11251]
118231304  histone H2A.Z [KO:K11251]
118206221  histone H2A.V [KO:K11251]
118212323  histone H2A-like [KO:K11251]
118212478  histone H2A.V [KO:K11251]
118219655  histone H2A [KO:K11251]
118219656  histone H2A [KO:K11251]
118219657  histone H2A [KO:K11251]
118220017  histone H2A [KO:K11251]
118220018  histone H2A [KO:K11251]
118220019  histone H2A [KO:K11251]
118220021  histone H2A [KO:K11251]
118226988  histone H2A.Z [KO:K11251]
118233721  histone H2A-like [KO:K11251]
118234365  late histone H2A.2.2-like [KO:K11251]
118234370  late histone H2A.2.2 [KO:K11251]
118214982  histone H2A-like [KO:K11251]
118214983  histone H2A [KO:K11251]
118215115  histone H2A [KO:K11251]
118221646  histone H2A-like [KO:K11251]
118221651  histone H2A-like [KO:K11251]
118206455  peptidyl-prolyl cis-trans isomerase-like isoform X1 [KO:K03767] [EC:5.2.1.8]
118212614  ppiab; peptidylprolyl isomerase Ab (cyclophilin A) [KO:K03767] [EC:5.2.1.8]
118225426  apoptosis regulator Bcl-2-like [KO:K02161]
118233789  apoptosis regulator Bcl-2-like [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
PMID:20823910
  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
PMID:26008591
  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
PMID:26775689
  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
PMID:24129419
  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
PMID:27158445
  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
PMID:24452471
  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
PMID:27368376
  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
PMID:27746097
  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
PMID:27984721
  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
PMID:28138137
  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
PMID:20354226
  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
PMID:22075985
  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
PMID:23913919
  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
PMID:25146926
  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
PMID:28126382
  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
PMID:27545878
  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
PMID:27219062
  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
PMID:19910467
  Authors
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