KEGG   PATHWAY: fch04217
Entry
fch04217                    Pathway                                
Name
Necroptosis - Falco cherrug (Saker falcon)
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
fch04217  Necroptosis
fch04217

Organism
Falco cherrug (Saker falcon) [GN:fch]
Gene
102045724  MLKL; mixed lineage kinase domain-like protein [KO:K08849] [EC:2.7.11.1]
102045859  CAPN11; calpain-11 [KO:K01367] [EC:3.4.22.52]
102045881  PGAM5; serine/threonine-protein phosphatase PGAM5, mitochondrial isoform X1 [KO:K15637] [EC:3.1.3.16]
102045899  GLUD1; glutamate dehydrogenase 1, mitochondrial [KO:K00261] [EC:1.4.1.3]
102046201  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
102046422  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
102046472  TNFAIP3; tumor necrosis factor alpha-induced protein 3 isoform X1 [KO:K11859] [EC:3.4.19.12]
102046544  VDAC1; voltage-dependent anion-selective channel protein 1 isoform X1 [KO:K05862]
102046752  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
102046784  [KO:K08601] [EC:3.4.19.12]
102047380  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
102047411  PYGB; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
102047522  PPID; peptidyl-prolyl cis-trans isomerase D [KO:K05864] [EC:5.2.1.8]
102047647  [KO:K10630] [EC:2.3.2.31]
102047662  IFNG; interferon gamma [KO:K04687]
102047699  TNFSF10; tumor necrosis factor ligand superfamily member 10 isoform X1 [KO:K04721]
102048105  CHMP2B; charged multivesicular body protein 2b [KO:K12192]
102048414  IFNGR1; LOW QUALITY PROTEIN: interferon gamma receptor 1 [KO:K05132]
102048431  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
102048640  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
102048655  JAK1; LOW QUALITY PROTEIN: tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
102049329  CHMP4C; charged multivesicular body protein 4c [KO:K24782]
102049466  [KO:K11251]
102049716  CHMP1B; charged multivesicular body protein 1b [KO:K12197]
102049796  VPS4A; vacuolar protein sorting-associated protein 4A [KO:K12196]
102050040  CHMP6; charged multivesicular body protein 6 [KO:K12195]
102050114  [KO:K11251]
102050179  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
102050391  CHMP2A; charged multivesicular body protein 2a [KO:K12191]
102050776  [KO:K04519]
102051116  [KO:K03767] [EC:5.2.1.8]
102051248  [KO:K00688] [EC:2.4.1.1]
102051371  [KO:K01370] [EC:3.4.22.36]
102051463  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
102051471  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
102051537  EIF2AK2; interferon-induced, double-stranded RNA-activated protein kinase [KO:K16195] [EC:2.7.11.1]
102051620  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
102051757  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
102051895  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD [KO:K08601] [EC:3.4.19.12]
102052104  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
102052173  SMPD1; LOW QUALITY PROTEIN: sphingomyelin phosphodiesterase [KO:K12350] [EC:3.1.4.12]
102052408  TICAM2; LOW QUALITY PROTEIN: TIR domain-containing adapter molecule 2 [KO:K05409]
102052695  CHMP4B; charged multivesicular body protein 4b [KO:K12194]
102052754  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
102052794  NLRP6; NACHT, LRR and PYD domains-containing protein 6 [KO:K12800]
102053015  TRAF5; LOW QUALITY PROTEIN: TNF receptor-associated factor 5 [KO:K09849]
102053134  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
102053169  [KO:K04722]
102053359  AIFM1; apoptosis-inducing factor 1, mitochondrial [KO:K04727] [EC:1.-.-.-]
102053408  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
102053609  [KO:K21421] [EC:1.-.-.-]
102053621  STAT6; signal transducer and activator of transcription 6 [KO:K11225]
102053699  [KO:K11224]
102053808  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
102053809  [KO:K16342] [EC:3.1.1.4]
102053879  BID; BH3-interacting domain death agonist isoform X1 [KO:K04726]
102053909  CHMP1A; charged multivesicular body protein 1a [KO:K12197]
102053934  SQSTM1; sequestosome-1 isoform X1 [KO:K14381]
102053985  [KO:K16342] [EC:3.1.1.4]
102054057  [KO:K11251]
102054155  [KO:K16342] [EC:3.1.1.4]
102054176  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
102054311  TLR3; toll-like receptor 3 [KO:K05401]
102054402  [KO:K11251]
102054435  VPS4B; vacuolar protein sorting-associated protein 4B [KO:K12196]
102054605  [KO:K11251]
102054682  [KO:K16342] [EC:3.1.1.4]
102054689  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
102054741  IFNGR2; interferon gamma receptor 2 [KO:K05133]
102054762  JAK3; tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
102054863  STAT4; signal transducer and activator of transcription 4 [KO:K11222]
102054913  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
102055091  [KO:K11251]
102055258  IFNAR2; interferon alpha/beta receptor 2 [KO:K05131]
102055286  FADD; FAS-associated death domain protein isoform X1 [KO:K02373]
102055451  [KO:K11251]
102055565  SPATA2; spermatogenesis-associated protein 2 [KO:K17595]
102055613  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
102055660  MAPK9; mitogen-activated protein kinase 9 isoform X2 [KO:K04440] [EC:2.7.11.24]
102055932  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
102055945  [KO:K11251]
102056426  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
102056440  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
102056470  [KO:K11251]
102056589  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
102056611  DNM1L; dynamin-1-like protein [KO:K17065] [EC:3.6.5.5]
102056614  [KO:K11251]
102056660  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
102057129  SLC25A6; ADP/ATP translocase 3 [KO:K05863]
102057229  [KO:K11251]
102057301  [KO:K16342] [EC:3.1.1.4]
102057417  [KO:K01915] [EC:6.3.1.2]
102057470  [KO:K16342] [EC:3.1.1.4]
102057472  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
102057623  [KO:K00688] [EC:2.4.1.1]
102057637  [KO:K16342] [EC:3.1.1.4]
102057647  [KO:K11251]
102057655  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
102057735  CHMP7; charged multivesicular body protein 7 isoform X1 [KO:K15053]
102057894  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
102058011  [KO:K12193]
102058424  FTH1; ferritin heavy chain [KO:K00522] [EC:1.16.3.2]
102058565  CAPN1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
102058589  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
102058611  SLC25A31; LOW QUALITY PROTEIN: ADP/ATP translocase 4 [KO:K05863]
102058622  [KO:K11251]
102058820  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
102059191  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070]
102059204  HMGB1; high mobility group protein B1 [KO:K10802]
102059225  GLUL; glutamine synthetase [KO:K01915] [EC:6.3.1.2]
102059593  [KO:K05414]
102059702  [KO:K11251]
102059920  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
102060267  CHMP5; charged multivesicular body protein 5 [KO:K12198]
106630923  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
106630990  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
106631028  SPATA2L; spermatogenesis-associated protein 2-like protein [KO:K17595]
106631313  [KO:K11251]
106631392  USP21; ubiquitin carboxyl-terminal hydrolase 21 [KO:K21634] [EC:3.4.19.12]
106631583  [KO:K17595]
114015105  [KO:K04982] [EC:2.7.11.1]
114015130  [KO:K11251]
114016448  IFNK; interferon kappa [KO:K05414]
114017752  [KO:K11251]
114017812  PLA2G4C; cytosolic phospholipase A2 gamma [KO:K16342] [EC:3.1.1.4]
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
fch00250  Alanine, aspartate and glutamate metabolism
fch04210  Apoptosis
KO pathway
ko04217   

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