KEGG   PATHWAY: lmut04217
Entry
lmut04217                   Pathway                                
Name
Necroptosis - Lagopus muta (rock ptarmigan)
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
lmut04217  Necroptosis
lmut04217

Organism
Lagopus muta (rock ptarmigan) [GN:lmut]
Gene
125684568  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
125684570  [KO:K11224]
125684885  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
125685168  PPIA; peptidyl-prolyl cis-trans isomerase A [KO:K03767] [EC:5.2.1.8]
125685190  CAMK2B; LOW QUALITY PROTEIN: calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
125685252  [KO:K04722]
125685277  CHMP7; charged multivesicular body protein 7 [KO:K15053]
125685303  [KO:K11251]
125685332  [KO:K04519]
125685344  VDAC3; voltage-dependent anion-selective channel protein 3 [KO:K15041]
125685562  STAT6; signal transducer and activator of transcription 6 isoform X1 [KO:K11225]
125685612  STAT2; LOW QUALITY PROTEIN: signal transducer and activator of transcription 2 [KO:K11221]
125685656  USP21; LOW QUALITY PROTEIN: ubiquitin carboxyl-terminal hydrolase 21 [KO:K21634] [EC:3.4.19.12]
125686210  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X1 [KO:K03158]
125686587  JAK2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
125686989  [KO:K05414]
125687151  HMGB1; high mobility group protein B1 [KO:K10802]
125687310  [KO:K05415]
125687311  [KO:K05414]
125687312  [KO:K05414]
125687313  [KO:K05414]
125687314  [KO:K05414]
125687315  [KO:K05414]
125687316  [KO:K05414]
125687523  RNF31; E3 ubiquitin-protein ligase RNF31 [KO:K11974] [EC:2.3.2.31]
125687688  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
125687724  JAK3; LOW QUALITY PROTEIN: tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
125687830  [KO:K11251]
125688071  IFNG; interferon gamma [KO:K04687]
125688413  SLC25A6; ADP/ATP translocase 3 [KO:K05863]
125688697  IFNGR1; interferon gamma receptor 1 [KO:K05132]
125688886  [KO:K00688] [EC:2.4.1.1]
125689287  TNFAIP3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
125689316  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
125689413  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
125689414  CAPN11; calpain-11 [KO:K01367] [EC:3.4.22.52]
125689845  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070]
125689920  EIF2AK2; interferon-induced, double-stranded RNA-activated protein kinase isoform X1 [KO:K16195] [EC:2.7.11.1]
125690047  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
125690121  [KO:K11251]
125690159  [KO:K11251]
125690168  [KO:K11251]
125690173  [KO:K11251]
125690176  [KO:K11251]
125690183  [KO:K11251]
125690190  [KO:K11251]
125690195  [KO:K11251]
125690198  [KO:K11251]
125690319  BID; BH3-interacting domain death agonist [KO:K04726]
125690379  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
125690420  CHMP4C; charged multivesicular body protein 4c [KO:K24782]
125690475  [KO:K08601] [EC:3.4.19.12]
125690650  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
125690875  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
125690894  VPS4B; vacuolar protein sorting-associated protein 4B [KO:K12196]
125690929  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
125691357  CHMP5; charged multivesicular body protein 5 [KO:K12198]
125691554  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
125691619  CHMP3; charged multivesicular body protein 3 [KO:K12193]
125691628  TLR3; toll-like receptor 3 isoform X1 [KO:K05401]
125691721  PPID; peptidyl-prolyl cis-trans isomerase D [KO:K05864] [EC:5.2.1.8]
125691793  [KO:K11251]
125692099  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
125692563  [KO:K11251]
125692621  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
125692643  [KO:K21421] [EC:1.-.-.-]
125692986  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
125693084  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
125693507  [KO:K04515] [EC:2.7.11.17]
125693517  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
125693580  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
125693715  GLUL; glutamine synthetase [KO:K01915] [EC:6.3.1.2]
125693721  [KO:K11251]
125693785  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
125694020  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
125694226  GLUD1; glutamate dehydrogenase 1, mitochondrial [KO:K00261] [EC:1.4.1.3]
125694668  [KO:K16342] [EC:3.1.1.4]
125694730  [KO:K16342] [EC:3.1.1.4]
125694734  [KO:K16342] [EC:3.1.1.4]
125694788  [KO:K16342] [EC:3.1.1.4]
125694965  IFNAR1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
125694980  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
125695071  PYGL; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
125695152  [KO:K16342] [EC:3.1.1.4]
125695153  [KO:K16342] [EC:3.1.1.4]
125695154  [KO:K16342] [EC:3.1.1.4]
125695237  PLA2G4F; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
125695241  FADD; FAS-associated death domain protein [KO:K02373]
125695396  FTH1; ferritin heavy chain [KO:K00522] [EC:1.16.3.1]
125695492  [KO:K11251]
125695540  [KO:K16342] [EC:3.1.1.4]
125695572  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
125695675  SMPD1; LOW QUALITY PROTEIN: sphingomyelin phosphodiesterase [KO:K12350] [EC:3.1.4.12]
125696902  CFLAR; CASP8 and FADD-like apoptosis regulator [KO:K04724]
125696903  [KO:K04398] [EC:3.4.22.61]
125696904  [KO:K04398] [EC:3.4.22.61]
125696993  STAT4; signal transducer and activator of transcription 4 [KO:K11222]
125697195  IFNGR2; interferon gamma receptor 2 [KO:K05133]
125697226  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
125697632  TNFSF10; tumor necrosis factor ligand superfamily member 10 isoform X1 [KO:K04721]
125698431  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
125698721  [KO:K11251]
125699072  MLKL; mixed lineage kinase domain-like protein [KO:K08849] [EC:2.7.11.1]
125699220  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
125699240  [KO:K17595]
125699245  VPS9D1; VPS9 domain-containing protein 1 isoform X1 [KO:K17595]
125699249  CHMP1A; charged multivesicular body protein 1a [KO:K12197]
125699257  VPS4A; vacuolar protein sorting-associated protein 4A [KO:K12196]
125699508  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:3.4.19.12]
125699616  AIFM1; apoptosis-inducing factor 1, mitochondrial [KO:K04727] [EC:1.-.-.-]
125699627  CHMP1B; charged multivesicular body protein 1b [KO:K12197]
125699651  [KO:K04725] [EC:2.3.2.27]
125699833  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
125700042  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
125700064  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
125700126  [KO:K11251]
125700173  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
125700294  SQSTM1; sequestosome-1 isoform X1 [KO:K14381]
125700436  CHMP2B; charged multivesicular body protein 2b [KO:K12192]
125700820  [KO:K11251]
125700834  [KO:K11251]
125701405  SPATA2; spermatogenesis-associated protein 2 isoform X1 [KO:K17595]
125701463  CHMP4B; charged multivesicular body protein 4b [KO:K12194]
125701587  PGAM5; serine/threonine-protein phosphatase PGAM5, mitochondrial isoform X1 [KO:K15637] [EC:3.1.3.16]
125702302  CHMP6; charged multivesicular body protein 6 [KO:K12195]
125702608  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
125702708  TLR4; toll-like receptor 4 [KO:K10160]
125702728  [KO:K01915] [EC:6.3.1.2]
125703079  [KO:K01370] [EC:3.4.22.36]
125703619  [KO:K11251]
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
lmut00250  Alanine, aspartate and glutamate metabolism
lmut04210  Apoptosis
KO pathway
ko04217   

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