KEGG   PATHWAY: sfm04217
Entry
sfm04217                    Pathway                                
Name
Necroptosis - Scleropages formosus (Asian bonytongue)
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
sfm04217  Necroptosis
sfm04217

Organism
Scleropages formosus (Asian bonytongue) [GN:sfm]
Gene
108935614  tumor necrosis factor-like [KO:K03156]
108925658  tnfrsf1a; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
108918966  tradd; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
108922584  TNF receptor-associated factor 2-like isoform X1 [KO:K03173] [EC:2.3.2.27]
108929927  TNF receptor-associated factor 2-like [KO:K03173] [EC:2.3.2.27]
108938148  TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
108933531  traf5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
108937518  receptor-interacting serine/threonine-protein kinase 1-like [KO:K02861] [EC:2.7.11.1]
108939327  ripk1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
108934246  baculoviral IAP repeat-containing protein 3-like [KO:K16060]
108925196  E3 ubiquitin-protein ligase XIAP-like [KO:K04725] [EC:2.3.2.27]
108936338  rbck1; ranBP-type and C3HC4-type zinc finger-containing protein 1 [KO:K10630] [EC:2.3.2.31]
108939041  ranBP-type and C3HC4-type zinc finger-containing protein 1-like isoform X1 [KO:K10630] [EC:2.3.2.31]
108938335  sharpin [KO:K10630] [EC:2.3.2.31]
108927796  E3 ubiquitin-protein ligase RNF31-like isoform X1 [KO:K11974] [EC:2.3.2.31]
108937533  uncharacterized protein LOC108937533 isoform X1 [KO:K11974] [EC:2.3.2.31]
108923311  E3 ubiquitin-protein ligase RNF31-like isoform X1 [KO:K11974] [EC:2.3.2.31]
108926413  spermatogenesis-associated protein 2-like [KO:K17595]
108937026  spata2; spermatogenesis-associated protein 2 [KO:K17595]
108934568  spermatogenesis-associated protein 2-like [KO:K17595]
108933980  spermatogenesis-associated protein 2-like protein isoform X1 [KO:K17595]
108927465  ubiquitin carboxyl-terminal hydrolase CYLD-like [KO:K08601] [EC:3.4.19.12]
108932976  cyld; ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:3.4.19.12]
108926381  ubiquitin carboxyl-terminal hydrolase CYLD-like [KO:K08601] [EC:3.4.19.12]
108930644  ubiquitin carboxyl-terminal hydrolase CYLD-like [KO:K08601] [EC:3.4.19.12]
114911833  ubiquitin carboxyl-terminal hydrolase CYLD-like [KO:K08601] [EC:3.4.19.12]
108941100  fadd; FAS-associated death domain protein [KO:K02373]
108920619  casp8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
108918550  caspase-8-like [KO:K04398] [EC:3.4.22.61]
108918555  caspase-8-like [KO:K04398] [EC:3.4.22.61]
108932283  caspase-8-like [KO:K04398] [EC:3.4.22.61]
108920617  caspase-8-like isoform X1 [KO:K04398] [EC:3.4.22.61]
108942112  cflar; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
108930640  receptor-interacting serine/threonine-protein kinase 4-like [KO:K08847] [EC:2.7.11.1]
114911906  receptor-interacting serine/threonine-protein kinase 3-like [KO:K08847] [EC:2.7.11.1]
108933209  cytochrome b-245 heavy chain isoform X1 [KO:K21421] [EC:1.-.-.-]
108923134  calcium/calmodulin-dependent protein kinase type II subunit alpha-like isoform X1 [KO:K04515] [EC:2.7.11.17]
108925892  calcium/calmodulin-dependent protein kinase type II delta chain-like isoform X1 [KO:K04515] [EC:2.7.11.17]
108920687  calcium/calmodulin-dependent protein kinase type II delta 1 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
108934409  calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
108932918  calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
108942762  camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
108940337  calcium/calmodulin-dependent protein kinase type II subunit beta-like isoform X1 [KO:K04515] [EC:2.7.11.17]
108934887  calcium/calmodulin-dependent protein kinase type II subunit gamma-like isoform X1 [KO:K04515] [EC:2.7.11.17]
108930987  ADP/ATP translocase 2 [KO:K05863]
108923172  ADP/ATP translocase 1 [KO:K05863]
108926465  ADP/ATP translocase 2 [KO:K05863]
108924561  slc25a4; ADP/ATP translocase 1 [KO:K05863]
108924536  ppid; peptidyl-prolyl cis-trans isomerase D [KO:K05864] [EC:5.2.1.8]
108934477  voltage-dependent anion-selective channel protein 1 [KO:K05862]
108920963  voltage-dependent anion-selective channel protein 2-like [KO:K15040]
108939729  voltage-dependent anion-selective channel protein 2 [KO:K15040]
108939530  voltage-dependent anion-selective channel protein 2-like [KO:K15040]
108934648  voltage-dependent anion-selective channel protein 2-like isoform X1 [KO:K15041]
108920171  voltage-dependent anion-selective channel protein 2 isoform X1 [KO:K15041]
108918124  glud1; glutamate dehydrogenase 1, mitochondrial [KO:K00261] [EC:1.4.1.3]
108934891  glutamate dehydrogenase, mitochondrial [KO:K00261] [EC:1.4.1.3]
108923843  glul; glutamine synthetase [KO:K01915] [EC:6.3.1.2]
108922580  glutamine synthetase-like isoform X1 [KO:K01915] [EC:6.3.1.2]
108918096  pygb; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
108919616  pygl; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
108934411  glycogen phosphorylase, muscle form-like [KO:K00688] [EC:2.4.1.1]
108918109  mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
108918907  mitogen-activated protein kinase 8B isoform X1 [KO:K04440] [EC:2.7.11.24]
108936860  mitogen-activated protein kinase 9-like isoform X1 [KO:K04440] [EC:2.7.11.24]
108934371  mitogen-activated protein kinase 9-like isoform X1 [KO:K04440] [EC:2.7.11.24]
108935733  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
108925135  ferritin, middle subunit-like [KO:K00522] [EC:1.16.3.1]
108941220  ferritin, heavy subunit [KO:K00522] [EC:1.16.3.1]
108923953  ferritin, middle subunit [KO:K00522] [EC:1.16.3.1]
108923956  ferritin, heavy subunit-like [KO:K00522] [EC:1.16.3.1]
108923957  ferritin, middle subunit-like [KO:K00522] [EC:1.16.3.1]
108941628  ferritin, middle subunit-like [KO:K00522] [EC:1.16.3.1]
114911041  ferritin, middle subunit-like [KO:K00522] [EC:1.16.3.1]
114909202  ferritin, middle subunit-like [KO:K00522] [EC:1.16.3.1]
114909208  ferritin, middle subunit-like [KO:K00522] [EC:1.16.3.1]
108935146  cytosolic phospholipase A2-like [KO:K16342] [EC:3.1.1.4]
108937528  cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
108942720  cytosolic phospholipase A2 zeta-like isoform X1 [KO:K16342] [EC:3.1.1.4]
108927995  cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
108927996  cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
114909784  cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
114909785  cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
114909787  LOW QUALITY PROTEIN: cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
114910935  cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
114910936  cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
114910937  cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
108934318  calpain-1 catalytic subunit-like [KO:K01367] [EC:3.4.22.52]
108933741  calpain-1 catalytic subunit-like [KO:K01367] [EC:3.4.22.52]
108927110  calpain-1 catalytic subunit-like [KO:K01367] [EC:3.4.22.52]
108921654  calpain-9-like [KO:K01367] [EC:3.4.22.52]
108927097  calpain-2 catalytic subunit-like [KO:K03853] [EC:3.4.22.53]
108927098  calpain-2 catalytic subunit-like [KO:K03853] [EC:3.4.22.53]
108927128  calpain-2 catalytic subunit-like [KO:K03853] [EC:3.4.22.53]
108933713  calpain-2 catalytic subunit-like [KO:K03853] [EC:3.4.22.53]
108933714  calpain-2 catalytic subunit-like [KO:K03853] [EC:3.4.22.53]
108921160  smpd1; sphingomyelin phosphodiesterase [KO:K12350] [EC:3.1.4.12]
108940805  mlkl; mixed lineage kinase domain-like protein [KO:K08849] [EC:2.7.11.1]
108940311  pgam5; serine/threonine-protein phosphatase PGAM5, mitochondrial isoform X3 [KO:K15637] [EC:3.1.3.16]
108933123  serine/threonine-protein phosphatase PGAM5, mitochondrial-like [KO:K15637] [EC:3.1.3.16]
108921023  dynamin-1-like protein isoform X2 [KO:K17065] [EC:3.6.5.5]
108929543  dynamin-1-like protein isoform X2 [KO:K17065] [EC:3.6.5.5]
108931665  dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
108919109  pycard; apoptosis-associated speck-like protein containing a CARD [KO:K12799]
108922456  caspase-1-A-like [KO:K01370] [EC:3.4.22.36]
108940319  interleukin-1 beta-like [KO:K04519]
108932396  interleukin-1 beta [KO:K04519]
114909774  LOW QUALITY PROTEIN: interleukin-1 beta-like [KO:K04519]
108918709  chmp2a; charged multivesicular body protein 2a [KO:K12191]
108920441  charged multivesicular body protein 2b-like [KO:K12192]
108927663  chmp2b; charged multivesicular body protein 2b [KO:K12192]
108920745  chmp3; charged multivesicular body protein 3 [KO:K12193]
108928336  chmp4b; charged multivesicular body protein 4b [KO:K12194]
108930437  charged multivesicular body protein 4b-like [KO:K12194]
108937069  charged multivesicular body protein 4c-like [KO:K24782]
108930169  chmp6; charged multivesicular body protein 6 [KO:K12195]
108937243  charged multivesicular body protein 6-like [KO:K12195]
108926621  vps4a; vacuolar protein sorting-associated protein 4A [KO:K12196]
108937480  vps4b; vacuolar protein sorting-associated protein 4B isoform X1 [KO:K12196]
108920108  charged multivesicular body protein 1b [KO:K12197]
108926523  chmp1a; charged multivesicular body protein 1a [KO:K12197]
108925197  charged multivesicular body protein 1b-like [KO:K12197]
108937062  charged multivesicular body protein 5 [KO:K12198]
108937726  charged multivesicular body protein 5-like [KO:K12198]
108929460  chmp7; charged multivesicular body protein 7 isoform X1 [KO:K15053]
108942028  transient receptor potential cation channel subfamily M member 7-like isoform X1 [KO:K04982] [EC:2.7.11.1]
108941140  trpm7; transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
108936270  high mobility group protein B1-like [KO:K10802]
108941932  high mobility group protein B1-like [KO:K10802]
108935283  tnfsf10; tumor necrosis factor ligand superfamily member 10 isoform X1 [KO:K04721]
108931028  CD40 ligand-like [KO:K04721]
108927788  tumor necrosis factor ligand superfamily member 10-like isoform X1 [KO:K04721]
108925009  tumor necrosis factor receptor superfamily member 10A-like isoform X1 [KO:K04722]
108940401  tumor necrosis factor receptor superfamily member 10A-like isoform X1 [KO:K04722]
108923469  tumor necrosis factor ligand superfamily member 6-like [KO:K04389]
114911301  tumor necrosis factor ligand superfamily member 6-like [KO:K04389]
108939520  fas; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
108924755  interferon alpha-6-like [KO:K05414]
114911089  interferon beta-like [KO:K05414]
114909445  interferon gamma 1-like [KO:K04687]
108929004  interferon alpha/beta receptor 1b-like isoform X1 [KO:K05130]
108922254  uncharacterized protein LOC108922254 [KO:K05131]
108932840  ifngr1l; interferon gamma receptor 1-like precursor [KO:K05132]
108918633  interferon gamma receptor 1-like isoform X1 [KO:K05132]
108922312  ifngr2; interferon gamma receptor 2 precursor [KO:K05133]
108935121  tyrosine-protein kinase JAK1-like [KO:K11217] [EC:2.7.10.2]
108935468  jak1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
108930978  tyrosine-protein kinase JAK2-like [KO:K04447] [EC:2.7.10.2]
108934741  jak2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
108930599  jak3; tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
108935860  tyk2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
108924273  signal transducer and activator of transcription 1-alpha/beta-like [KO:K11220]
108929360  signal transducer and activator of transcription 1-like isoform X1 [KO:K11220]
108918442  signal transducer and activator of transcription 1-alpha/beta-like isoform X1 [KO:K11221]
108941723  signal transducer and activator of transcription 3-like [KO:K04692]
108919563  signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
108924290  signal transducer and activator of transcription 4-like [KO:K11222]
108929374  signal transducer and activator of transcription 4-like [KO:K11222]
108919537  signal transducer and activator of transcription 5B-like isoform X1 [KO:K11224]
108941722  signal transducer and activator of transcription 5B-like [KO:K11224]
108918572  signal transducer and activator of transcription 6-like isoform X2 [KO:K11225]
108939311  signal transducer and activator of transcription 5B-like isoform X1 [KO:K11225]
108927799  irf9; interferon regulatory factor 9 isoform X1 [KO:K04693]
108927142  interferon-induced, double-stranded RNA-activated protein kinase-like isoform X1 [KO:K16195] [EC:2.7.11.1]
108938967  TIR domain-containing adapter molecule 1-like [KO:K05842]
108924320  tlr3; toll-like receptor 3 [KO:K05401]
108918465  ubiquitin carboxyl-terminal hydrolase 21-like [KO:K21634] [EC:3.4.19.12]
108925413  sqstm1; sequestosome-1 isoform X1 [KO:K14381]
108929331  hsp90ab1; heat shock protein HSP 90-beta [KO:K04079]
108930816  heat shock protein HSP 90-alpha [KO:K04079]
108941499  heat shock protein HSP 90-alpha-like isoform X1 [KO:K04079]
108941510  heat shock protein HSP 90-alpha 1 [KO:K04079]
108931280  tumor necrosis factor alpha-induced protein 3-like [KO:K11859] [EC:3.4.19.12]
108932919  tnfaip3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
108923980  parp1; poly [ADP-ribose] polymerase 1 [KO:K24070] [EC:2.4.2.30]
108941669  bax; apoptosis regulator BAX isoform X1 [KO:K02159]
108923902  apoptosis regulator BAX-like [KO:K02159]
108931051  aifm1; apoptosis-inducing factor 1, mitochondrial isoform X1 [KO:K04727] [EC:1.-.-.-]
108920354  core histone macro-H2A.1 isoform X1 [KO:K11251]
108922055  histone H2A [KO:K11251]
108927817  histone H2A.Z [KO:K11251]
108928798  histone H2AX-like [KO:K11251]
108928940  histone H2A [KO:K11251]
108931955  histone H2A, sperm-like [KO:K11251]
108930827  histone H2A-like [KO:K11251]
108936076  histone H2A-like [KO:K11251]
108936082  histone H2AX [KO:K11251]
108933313  histone H2A.V [KO:K11251]
108918040  core histone macro-H2A.2 isoform X1 [KO:K11251]
108926490  histone H2A-like [KO:K11251]
108940363  histone H2A.V [KO:K11251]
114910265  histone H2A-like [KO:K11251]
114910266  histone H2A-like [KO:K11251]
114910268  histone H2A-like [KO:K11251]
114910269  histone H2A-like [KO:K11251]
108936330  peptidyl-prolyl cis-trans isomerase [KO:K03767] [EC:5.2.1.8]
108940358  peptidyl-prolyl cis-trans isomerase-like [KO:K03767] [EC:5.2.1.8]
108931633  apoptosis regulator Bcl-2-like [KO:K02161]
108937589  apoptosis regulator Bcl-2-like isoform X1 [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)
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pathway
sfm00250  Alanine, aspartate and glutamate metabolism
sfm04210  Apoptosis
KO pathway
ko04217   
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