KEGG   PATHWAY: cmac04217
Entry
cmac04217                   Pathway                                
Name
Necroptosis - Chlamydotis macqueenii (Macqueen's bustard)
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
cmac04217  Necroptosis
cmac04217

Organism
Chlamydotis macqueenii (Macqueen's bustard) [GN:cmac]
Gene
104479955  tumor necrosis factor receptor superfamily member 1A-like [KO:K03158]
104484025  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
104475837  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
104473441  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
104480789  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
104483745  inhibitor of apoptosis protein [KO:K16060]
104477815  LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase XIAP-like [KO:K04725] [EC:2.3.2.27]
104475247  SPATA2; spermatogenesis-associated protein 2 [KO:K17595]
104476320  uncharacterized protein LOC104476320 [KO:K17595]
104476903  ubiquitin carboxyl-terminal hydrolase CYLD-like [KO:K08601] [EC:3.4.19.12]
104482803  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD [KO:K08601] [EC:3.4.19.12]
104476173  FADD; LOW QUALITY PROTEIN: FAS-associated death domain protein [KO:K02373]
104478549  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
104485083  caspase-8-like [KO:K04398] [EC:3.4.22.61]
104483191  CFLAR; CASP8 and FADD-like apoptosis regulator [KO:K04724]
104477683  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
104479816  STK33; serine/threonine-protein kinase 33 [KO:K04515] [EC:2.7.11.17]
104486388  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
104482483  calcium/calmodulin-dependent protein kinase type II subunit gamma-like [KO:K04515] [EC:2.7.11.17]
104478447  ADP/ATP translocase 3-like [KO:K05863]
104484556  SLC25A31; LOW QUALITY PROTEIN: ADP/ATP translocase 4 [KO:K05863]
104484704  ADP/ATP translocase 2 [KO:K05863]
104485404  LOW QUALITY PROTEIN: ADP/ATP translocase 1-like [KO:K05863]
104484900  PPID; peptidyl-prolyl cis-trans isomerase D [KO:K05864] [EC:5.2.1.8]
104483087  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
104474950  VDAC2; voltage-dependent anion-selective channel protein 2 isoform X1 [KO:K15040]
104484701  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
104480892  LOW QUALITY PROTEIN: glutamate dehydrogenase 1, mitochondrial-like [KO:K00261] [EC:1.4.1.3]
104479947  GLUL; glutamine synthetase [KO:K01915] [EC:6.3.1.2]
104480411  glutamine synthetase [KO:K01915] [EC:6.3.1.2]
104476502  PYGB; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
104483661  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
104476736  mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
104482156  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
104477499  FTH1; ferritin heavy chain [KO:K00522] [EC:1.16.3.1]
104478126  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
104479676  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
104479677  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
104479783  cytosolic phospholipase A2 beta-like [KO:K16342] [EC:3.1.1.4]
104486295  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
104487005  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
104487006  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
104477947  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
104477948  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
104481933  calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
104483676  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
104484102  MLKL; mixed lineage kinase domain-like protein [KO:K08849] [EC:2.7.11.1]
104474815  PGAM5; serine/threonine-protein phosphatase PGAM5, mitochondrial [KO:K15637] [EC:3.1.3.16]
104473696  DNM1L; dynamin-1-like protein [KO:K17065] [EC:3.6.5.5]
104480664  NACHT, LRR and PYD domains-containing protein 3-like [KO:K12800]
104484947  caspase-1-like [KO:K01370] [EC:3.4.22.36]
104482028  LOW QUALITY PROTEIN: interleukin-1 beta-like [KO:K04519]
104484567  CHMP2B; charged multivesicular body protein 2b [KO:K12192]
104477760  CHMP3; charged multivesicular body protein 3 [KO:K12193]
104481357  CHMP4B; charged multivesicular body protein 4b [KO:K12194]
104480294  CHMP6; charged multivesicular body protein 6 [KO:K12195]
104475268  vacuolar protein sorting-associated protein 4B-like [KO:K12196]
104480583  CHMP1A; charged multivesicular body protein 1a [KO:K12197]
104476143  CHMP1B; charged multivesicular body protein 1b [KO:K12197]
104477949  CHMP5; charged multivesicular body protein 5 [KO:K12198]
104474053  CHMP7; charged multivesicular body protein 7 [KO:K15053]
104483248  HMGB1; high mobility group protein B1 [KO:K10802]
104476689  TNFSF10; LOW QUALITY PROTEIN: tumor necrosis factor ligand superfamily member 10 [KO:K04721]
104485149  tumor necrosis factor receptor superfamily member 10A-like [KO:K04722]
104477426  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
104476724  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
104478818  interferon omega-1-like [KO:K05414]
104475033  interferon-like [KO:K05415]
104480124  IFNG; interferon gamma [KO:K04687]
104473042  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
104475291  IFNAR2; interferon alpha/beta receptor 2 [KO:K05131]
104475444  IFNGR1; interferon gamma receptor 1 [KO:K05132]
104474922  IFNGR2; interferon gamma receptor 2 [KO:K05133]
104481714  LOW QUALITY PROTEIN: tyrosine-protein kinase JAK1-like [KO:K11217] [EC:2.7.10.2]
104476279  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
104485862  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
104476015  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
104478179  STAT4; signal transducer and activator of transcription 4 isoform X1 [KO:K11222]
104473908  EIF2AK2; interferon-induced, double-stranded RNA-activated protein kinase [KO:K16195] [EC:2.7.11.1]
104484970  TLR4; toll-like receptor 4 [KO:K10160]
104475890  TICAM2; LOW QUALITY PROTEIN: TIR domain-containing adapter molecule 2 [KO:K05409]
104474547  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
104481509  TLR3; toll-like receptor 3 [KO:K05401]
104474385  SQSTM1; sequestosome-1 [KO:K14381]
104485736  HSP90AA1; LOW QUALITY PROTEIN: heat shock protein HSP 90-alpha [KO:K04079]
104473984  HSP90AB1; heat shock protein HSP 90-beta isoform X1 [KO:K04079]
104486787  TNFAIP3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
104487477  PARP1; poly [ADP-ribose] polymerase 1 [KO:K24070] [EC:2.4.2.30]
104481489  BID; BH3-interacting domain death agonist [KO:K04726]
104483335  AIFM1; apoptosis-inducing factor 1, mitochondrial [KO:K04727] [EC:1.-.-.-]
104483475  histone H2A.V-like [KO:K11251]
104478945  core histone macro-H2A.1 isoform X1 [KO:K11251]
104476476  core histone macro-H2A.2 [KO:K11251]
104473604  histone H2A type 2-C [KO:K11251]
104486273  histone H2A-beta, sperm-like [KO:K11251]
104487228  histone H2A-beta, sperm-like [KO:K11251]
104487229  histone H2A-beta, sperm-like [KO:K11251]
104474894  histone H2A.Z [KO:K11251]
104487403  histone H2A type 2-C-like [KO:K11251]
104475170  peptidyl-prolyl cis-trans isomerase A [KO:K03767] [EC:5.2.1.8]
104485178  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
cmac00250  Alanine, aspartate and glutamate metabolism
cmac04210  Apoptosis
KO pathway
ko04217   
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