KEGG   PATHWAY: ola04621
Entry
ola04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Oryzias latipes (Japanese medaka)
Description
Specific families of pattern recognition receptors are responsible for detecting various pathogens and generating innate immune responses. The intracellular NOD-like receptor (NLR) family contains more than 20 members in mammals and plays a pivotal role in the recognition of intracellular ligands. NOD1 and NOD2, two prototypic NLRs, sense the cytosolic presence of the bacterial peptidoglycan fragments that escaped from endosomal compartments, driving the activation of NF-{kappa}B and MAPK, cytokine production and apoptosis. On the other hand, a different set of NLRs induces caspase-1 activation through the assembly of multiprotein complexes called inflammasomes. The activated of caspase-1 regulates maturation of the pro-inflammatory cytokines IL-1B, IL-18 and drives pyroptosis.
Class
Organismal Systems; Immune system
Pathway map
ola04621  NOD-like receptor signaling pathway
ola04621

Organism
Oryzias latipes (Japanese medaka) [GN:ola]
Gene
101170542  nod1; nucleotide-binding oligomerization domain-containing protein 1 [KO:K08727]
101161336  ripk2; receptor-interacting serine/threonine-protein kinase 2 [KO:K08846] [EC:2.7.11.1]
101162681  ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
101171857  inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
101159621  inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
101170684  ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
101168165  nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
101162015  NF-kappa-B inhibitor alpha [KO:K04734]
101167764  nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101158728  putative transcription factor p65 homolog [KO:K04735]
101169209  interleukin-1 beta [KO:K04519]
101172593  tumor necrosis factor-like [KO:K03156]
101162901  permeability factor 2 [KO:K10030]
101155802  interleukin-8 [KO:K10030]
101164467  nod2; nucleotide-binding oligomerization domain-containing protein 2 [KO:K10165]
101164271  map3k7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
105356874  mitogen-activated protein kinase kinase kinase 7-like [KO:K04427] [EC:2.7.11.25]
101163057  tab1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
101168511  tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
101170170  tab3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793]
101159747  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101162905  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101157952  mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
101168799  mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
101164997  mitogen-activated protein kinase 8 isoform X4 [KO:K04440] [EC:2.7.11.24]
101158978  mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
101171243  mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
101160731  mitogen-activated protein kinase 14A isoform X1 [KO:K04441] [EC:2.7.11.24]
101159668  mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
101162042  mitogen-activated protein kinase 14A isoform X1 [KO:K04441] [EC:2.7.11.24]
101172944  mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
101175696  mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
101154993  mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
101174822  transcription factor AP-1 [KO:K04448]
101173011  jun; transcription factor AP-1 [KO:K04448]
101160956  transcription factor AP-1 [KO:K04448]
100049389  atg5; autophagy protein 5 [KO:K08339]
101166739  atg12; ubiquitin-like protein ATG12 [KO:K08336]
101171396  gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
101168456  gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
101170049  gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
101158482  gabarap; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
105354249  map1lc3b; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
101162037  map1lc3a; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
101159112  microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
101162187  map1lc3c; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
101158053  sugt1; protein SGT1 homolog isoform X1 [KO:K12795]
101172531  sharpin [KO:K20894]
101166217  ranBP-type and C3HC4-type zinc finger-containing protein 1 [KO:K10630] [EC:2.3.2.31]
101169745  ranBP-type and C3HC4-type zinc finger-containing protein 1 [KO:K10630] [EC:2.3.2.31]
101174057  E3 ubiquitin-protein ligase RNF31 [KO:K11974] [EC:2.3.2.31]
101162956  E3 ubiquitin-protein ligase RNF31 isoform X1 [KO:K11974] [EC:2.3.2.31]
101155382  E3 ubiquitin-protein ligase RNF31 [KO:K11974] [EC:2.3.2.31]
101166883  E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
101164348  trip6; thyroid receptor-interacting protein 6 isoform X1 [KO:K12792]
101172095  erbin; erbin isoform X1 [KO:K12796]
101172600  baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
101159764  traf2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
101155367  TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
101167626  TNF receptor-associated factor 2 isoform X2 [KO:K03173] [EC:2.3.2.27]
101170323  TNF receptor-associated factor 5 [KO:K09849]
101161132  traf6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
101156662  card9; caspase recruitment domain-containing protein 9 isoform X1 [KO:K12794]
101160685  tnfaip3; tumor necrosis factor alpha-induced protein 3 isoform X2 [KO:K11859] [EC:3.4.19.12]
101167666  mavs; mitochondrial antiviral-signaling protein [KO:K12648]
101161601  traf3; TNF receptor-associated factor 3 [KO:K03174]
101168192  tbk1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
101168283  ikbke; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
101174711  tank; TRAF family member-associated NF-kappa-B activator [KO:K12650]
101158892  interferon regulatory factor 3 isoform X1 [KO:K05411]
110017164  interferon a3-like [KO:K05414]
110014574  interferon a3-like [KO:K05414]
111946454  interferon a3-like [KO:K05414]
101159274  antxr2; anthrax toxin receptor 2 isoform X1 [KO:K20909]
101159119  anthrax toxin receptor 2 isoform X1 [KO:K20909]
101165081  anthrax toxin receptor 1 [KO:K20909]
101167728  anthrax toxin receptor 1 [KO:K20909]
101163475  anthrax toxin receptor 1-like [KO:K20909]
101173554  antxr1; anthrax toxin receptor 1 isoform X2 [KO:K20909]
101161333  apoptosis-associated speck-like protein containing a CARD [KO:K12799]
101161579  apoptosis-associated speck-like protein containing a CARD [KO:K12799]
101170619  apoptosis-associated speck-like protein containing a CARD [KO:K12799]
101174762  caspase-1 [KO:K01370] [EC:3.4.22.36]
101163032  bcl2; apoptosis regulator Bcl-2 [KO:K02161]
101165300  bcl-2-like protein 1 isoform X1 [KO:K04570]
101159503  LOW QUALITY PROTEIN: bcl-2-like protein 1 [KO:K04570]
101165526  cathepsin B [KO:K01363] [EC:3.4.22.1]
101160638  ctsb; cathepsin B [KO:K01363] [EC:3.4.22.1]
101165456  pannexin-1 [KO:K03443]
101166974  pannexin-1 [KO:K03443]
101170060  trpm2; transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13]
101156483  trpm7; transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
101160185  casr; extracellular calcium-sensing receptor isoform X1 [KO:K04612]
101162627  G-protein coupled receptor family C group 6 member A [KO:K04622]
105357196  G-protein coupled receptor family C group 6 member A-like [KO:K04622]
100049465  plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
101175365  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
100049529  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
100049535  plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
101172698  plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
101155104  inositol 1,4,5-trisphosphate receptor type 1 isoform X3 [KO:K04958]
101167700  inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
101155191  itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
101170574  itpr3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
101173964  vdac1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
101173732  voltage-dependent anion-selective channel protein 2 [KO:K15040]
101154906  voltage-dependent anion-selective channel protein 2 [KO:K15040]
101170932  voltage-dependent anion-selective channel protein 2 isoform X2 [KO:K15041]
101162768  voltage-dependent anion-selective channel protein 2 isoform X2 [KO:K15041]
101162626  mcu; calcium uniporter protein, mitochondrial isoform X1 [KO:K20858]
101170865  dhx33; putative ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
101158009  mfn1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
101171942  mitofusin-1 isoform X6 [KO:K21356] [EC:3.6.5.-]
101170481  mfn2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
101167739  ripk1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
101168093  receptor-interacting serine/threonine-protein kinase 3-like [KO:K08847] [EC:2.7.11.1]
101168078  receptor-interacting serine/threonine-protein kinase 3-like [KO:K08847] [EC:2.7.11.1]
101168038  receptor-interacting serine/threonine-protein kinase 3 isoform X1 [KO:K08847] [EC:2.7.11.1]
101168285  receptor-interacting serine/threonine-protein kinase 3 [KO:K08847] [EC:2.7.11.1]
101159560  receptor-interacting serine/threonine-protein kinase 3 [KO:K08847] [EC:2.7.11.1]
110013360  receptor-interacting serine/threonine-protein kinase 3-like [KO:K08847] [EC:2.7.11.1]
101169210  dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
101168415  dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
101160650  dynamin-1-like protein isoform X4 [KO:K17065] [EC:3.6.5.5]
101156645  nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
101167087  nampt; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
101157756  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
101170577  cytochrome b-245 light chain [KO:K08009]
101163138  thioredoxin-interacting protein [KO:K20910]
101174114  txnip; thioredoxin-interacting protein [KO:K20910]
101164313  txn2; thioredoxin, mitochondrial isoform X2 [KO:K03671]
101173415  txn; thioredoxin [KO:K03671]
101170580  nek7; serine/threonine-protein kinase Nek7 [KO:K20876] [EC:2.7.11.34]
101158041  brcc3; lys-63-specific deubiquitinase BRCC36 [KO:K11864] [EC:3.4.19.-]
101169258  heat shock protein HSP 90-alpha 1 [KO:K04079]
101169506  heat shock protein HSP 90-alpha [KO:K04079]
100125466  hsp90ab1; heat shock protein HSP 90-beta isoform X2 [KO:K04079]
101174493  proline-serine-threonine phosphatase-interacting protein 1 [KO:K12804]
101156493  proline-serine-threonine phosphatase-interacting protein 1 [KO:K12804]
100049400  casp8; caspase-8 [KO:K04398] [EC:3.4.22.61]
100125536  caspase-8 [KO:K04398] [EC:3.4.22.61]
100049399  fadd; FAS-associated death domain protein [KO:K02373]
101174016  prkcd; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
101165871  tp53bp1; TP53-binding protein 1 isoform X5 [KO:K20915]
101155194  rho-related GTP-binding protein RhoA-C [KO:K04513]
101158607  transforming protein RhoA-like [KO:K04513]
101160539  rho-related GTP-binding protein RhoA-C [KO:K04513]
101167618  rho-related GTP-binding protein RhoA-B [KO:K04513]
101173444  transforming protein RhoA isoform X2 [KO:K04513]
101159676  serine/threonine-protein kinase N1 isoform X1 [KO:K06071] [EC:2.7.11.13]
101164700  pkn1; serine/threonine-protein kinase N1 isoform X3 [KO:K06071] [EC:2.7.11.13]
101158798  pkn2; serine/threonine-protein kinase N2 isoform X2 [KO:K23691] [EC:2.7.11.13]
101175099  14-3-3 protein epsilon isoform X1 [KO:K06630]
101165659  14-3-3 protein epsilon [KO:K06630]
101175389  jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
101155851  tyk2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
101154761  signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
101158490  signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
101173855  signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11221]
101173820  irf9; interferon regulatory factor 9 [KO:K04693]
101154981  TIR domain-containing adapter molecule 1 [KO:K05842]
101168580  myd88; myeloid differentiation primary response protein MyD88 isoform X2 [KO:K04729]
101158603  irak4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
101160004  tmem173; stimulator of interferon genes protein isoform X2 [KO:K12654]
Compound
C00002  ATP
C00076  Calcium cation
C00155  L-Homocysteine
C00238  Potassium cation
C00533  Nitric oxide
C01245  D-myo-Inositol 1,4,5-trisphosphate
Reference
PMID:23124073
  Authors
Vandenabeele P, Bertrand MJ
  Title
The role of the IAP E3 ubiquitin ligases in regulating pattern-recognition receptor signalling.
  Journal
Nat Rev Immunol 12:833-44 (2012)
DOI:10.1038/nri3325
Reference
PMID:16493424
  Authors
Strober W, Murray PJ, Kitani A, Watanabe T
  Title
Signalling pathways and molecular interactions of NOD1 and NOD2.
  Journal
Nat Rev Immunol 6:9-20 (2006)
DOI:10.1038/nri1747
Reference
PMID:24718315
  Authors
Estornes Y, Bertrand MJ
  Title
IAPs, regulators of innate immunity and inflammation.
  Journal
Semin Cell Dev Biol 39:106-14 (2015)
DOI:10.1016/j.semcdb.2014.03.035
Reference
PMID:24707857
  Authors
Jakopin Z
  Title
Nucleotide-binding oligomerization domain (NOD) inhibitors: a rational approach toward inhibition of NOD signaling pathway.
  Journal
J Med Chem 57:6897-918 (2014)
DOI:10.1021/jm401841p
Reference
PMID:25526305
  Authors
Caruso R, Warner N, Inohara N, Nunez G
  Title
NOD1 and NOD2: signaling, host defense, and inflammatory disease.
  Journal
Immunity 41:898-908 (2014)
DOI:10.1016/j.immuni.2014.12.010
Reference
PMID:19767725
  Authors
Murray PJ
  Title
Beyond peptidoglycan for Nod2.
  Journal
Nat Immunol 10:1053-4 (2009)
DOI:10.1038/ni1009-1053
Reference
PMID:20643110
  Authors
Lecat A, Piette J, Legrand-Poels S
  Title
The protein Nod2: an innate receptor more complex than previously assumed.
  Journal
Biochem Pharmacol 80:2021-31 (2010)
DOI:10.1016/j.bcp.2010.07.016
Reference
PMID:26655628
  Authors
Man SM, Kanneganti TD
  Title
Converging roles of caspases in inflammasome activation, cell death and innate immunity.
  Journal
Nat Rev Immunol 16:7-21 (2016)
DOI:10.1038/nri.2015.7
Reference
PMID:27291964
  Authors
Broz P, Dixit VM
  Title
Inflammasomes: mechanism of assembly, regulation and signalling.
  Journal
Nat Rev Immunol 16:407-20 (2016)
DOI:10.1038/nri.2016.58
Reference
PMID:25879280
  Authors
Man SM, Kanneganti TD
  Title
Regulation of inflammasome activation.
  Journal
Immunol Rev 265:6-21 (2015)
DOI:10.1111/imr.12296
Reference
PMID:26549800
  Authors
Jo EK, Kim JK, Shin DM, Sasakawa C
  Title
Molecular mechanisms regulating NLRP3 inflammasome activation.
  Journal
Cell Mol Immunol 13:148-59 (2016)
DOI:10.1038/cmi.2015.95
Reference
PMID:23846113
  Authors
Broz P, Monack DM
  Title
Newly described pattern recognition receptors team up against intracellular pathogens.
  Journal
Nat Rev Immunol 13:551-65 (2013)
DOI:10.1038/nri3479
Reference
PMID:22430786
  Authors
Rathinam VA, Vanaja SK, Fitzgerald KA
  Title
Regulation of inflammasome signaling.
  Journal
Nat Immunol 13:333-42 (2012)
DOI:10.1038/ni.2237
Reference
PMID:24840700
  Authors
Sutterwala FS, Haasken S, Cassel SL
  Title
Mechanism of NLRP3 inflammasome activation.
  Journal
Ann N Y Acad Sci 1319:82-95 (2014)
DOI:10.1111/nyas.12458
Reference
PMID:23702978
  Authors
Latz E, Xiao TS, Stutz A
  Title
Activation and regulation of the inflammasomes.
  Journal
Nat Rev Immunol 13:397-411 (2013)
DOI:10.1038/nri3452
Reference
PMID:25145756
  Authors
Blander JM
  Title
A long-awaited merger of the pathways mediating host defence and programmed cell death.
  Journal
Nat Rev Immunol 14:601-18 (2014)
DOI:10.1038/nri3720
Reference
PMID:23215645
  Authors
von Moltke J, Ayres JS, Kofoed EM, Chavarria-Smith J, Vance RE
  Title
Recognition of bacteria by inflammasomes.
  Journal
Annu Rev Immunol 31:73-106 (2013)
DOI:10.1146/annurev-immunol-032712-095944
Reference
PMID:25330206
  Authors
Abais JM, Xia M, Zhang Y, Boini KM, Li PL
  Title
Redox regulation of NLRP3 inflammasomes: ROS as trigger or effector?
  Journal
Antioxid Redox Signal 22:1111-29 (2015)
DOI:10.1089/ars.2014.5994
Reference
PMID:25879288
  Authors
Storek KM, Monack DM
  Title
Bacterial recognition pathways that lead to inflammasome activation.
  Journal
Immunol Rev 265:112-29 (2015)
DOI:10.1111/imr.12289
Reference
PMID:27012466
  Authors
Hu H, Sun SC
  Title
Ubiquitin signaling in immune responses.
  Journal
Cell Res 26:457-83 (2016)
DOI:10.1038/cr.2016.40
Reference
PMID:26121197
  Authors
Guo H, Callaway JB, Ting JP
  Title
Inflammasomes: mechanism of action, role in disease, and therapeutics.
  Journal
Nat Med 21:677-87 (2015)
DOI:10.1038/nm.3893
Reference
PMID:26482951
  Authors
Man SM, Kanneganti TD
  Title
Gasdermin D: the long-awaited executioner of pyroptosis.
  Journal
Cell Res 25:1183-4 (2015)
DOI:10.1038/cr.2015.124
Reference
PMID:22819539
  Authors
Rathinam VA, Vanaja SK, Waggoner L, Sokolovska A, Becker C, Stuart LM, Leong JM, Fitzgerald KA
  Title
TRIF licenses caspase-11-dependent NLRP3 inflammasome activation by gram-negative bacteria.
  Journal
Cell 150:606-19 (2012)
DOI:10.1016/j.cell.2012.07.007
Reference
PMID:21575908
  Authors
Kerur N, Veettil MV, Sharma-Walia N, Bottero V, Sadagopan S, Otageri P, Chandran B
  Title
IFI16 acts as a nuclear pathogen sensor to induce the inflammasome in response to Kaposi Sarcoma-associated herpesvirus infection.
  Journal
Cell Host Microbe 9:363-75 (2011)
DOI:10.1016/j.chom.2011.04.008
Reference
PMID:29148036
  Authors
Heilig R, Broz P
  Title
Function and mechanism of the pyrin inflammasome.
  Journal
Eur J Immunol 48:230-238 (2018)
DOI:10.1002/eji.201746947
Reference
PMID:25816776
  Authors
Chakrabarti A, Banerjee S, Franchi L, Loo YM, Gale M Jr, Nunez G, Silverman RH
  Title
RNase L activates the NLRP3 inflammasome during viral infections.
  Journal
Cell Host Microbe 17:466-77 (2015)
DOI:10.1016/j.chom.2015.02.010
Related
pathway
ola04010  MAPK signaling pathway
ola04140  Autophagy - animal
ola04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
LinkDB

DBGET integrated database retrieval system