KEGG   PATHWAY: xma04621
Entry
xma04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Xiphophorus maculatus (southern platyfish)
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
xma04621  NOD-like receptor signaling pathway
xma04621

Organism
Xiphophorus maculatus (southern platyfish) [GN:xma]
Gene
102231540  nod1; nucleotide-binding oligomerization domain-containing protein 1 isoform X1 [KO:K08727]
102234179  ripk2; receptor-interacting serine/threonine-protein kinase 2 [KO:K08846] [EC:2.7.11.1]
102233509  ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
102226088  inhibitor of nuclear factor kappa-B kinase subunit alpha-like [KO:K04467] [EC:2.7.11.10]
102221657  inhibitor of nuclear factor kappa-B kinase subunit alpha-like isoform X1 [KO:K04467] [EC:2.7.11.10]
102223773  ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
102228531  nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
102217801  NF-kappa-B inhibitor alpha-like [KO:K04734]
102218233  nfkb1; LOW QUALITY PROTEIN: nuclear factor NF-kappa-B p105 subunit [KO:K02580]
102219636  transcription factor p65-like isoform X1 [KO:K04735]
106700093  interleukin-1 beta isoform X1 [KO:K04519]
102231459  interleukin-1 beta [KO:K04519]
111610322  interleukin-1 beta-like [KO:K04519]
102222709  il18; interleukin-18 isoform X2 [KO:K05482]
102231253  tumor necrosis factor-like isoform X1 [KO:K03156]
111609466  tumor necrosis factor-like [KO:K03156]
102217177  interleukin-8-like [KO:K10030]
102217432  interleukin-8-like [KO:K10030]
102233259  permeability factor 2-like [KO:K10030]
102229465  nod2; nucleotide-binding oligomerization domain-containing protein 2 [KO:K10165]
102226534  map3k7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
102232287  mitogen-activated protein kinase kinase kinase 7-like isoform X1 [KO:K04427] [EC:2.7.11.25]
102220462  tab1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
102236763  tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
102235135  tab3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
102235941  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102237032  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
102237237  mitogen-activated protein kinase 9-like isoform X1 [KO:K04440] [EC:2.7.11.24]
102226476  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
102234094  mitogen-activated protein kinase 8-like isoform X3 [KO:K04440] [EC:2.7.11.24]
102221148  mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
102231047  mitogen-activated protein kinase 14A isoform X1 [KO:K04441] [EC:2.7.11.24]
102218102  mitogen-activated protein kinase 14A-like [KO:K04441] [EC:2.7.11.24]
102233918  mitogen-activated protein kinase 12-like [KO:K04441] [EC:2.7.11.24]
102223674  mitogen-activated protein kinase 11-like [KO:K04441] [EC:2.7.11.24]
102223422  mitogen-activated protein kinase 12-like [KO:K04441] [EC:2.7.11.24]
102233752  mitogen-activated protein kinase 12-like [KO:K04441] [EC:2.7.11.24]
102223477  mitogen-activated protein kinase 13-like [KO:K04441] [EC:2.7.11.24]
102234665  transcription factor AP-1-like [KO:K04448]
102230050  jun; transcription factor AP-1 [KO:K04448]
102217724  atg16l1; autophagy-related protein 16-1 isoform X1 [KO:K17890]
102217845  atg5; autophagy protein 5 [KO:K08339]
102221810  atg12; ubiquitin-like protein ATG12 isoform X1 [KO:K08336]
102223011  gabarapl2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
102218600  gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
102219827  gabarap; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
102217957  gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
102225513  microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
102227821  map1lc3a; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
102219544  microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
102231745  map1lc3c; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
102226352  sugt1; protein SGT1 homolog isoform X1 [KO:K12795]
102238252  sharpin; sharpin isoform X1 [KO:K20894]
102234963  rbck1; ranBP-type and C3HC4-type zinc finger-containing protein 1 [KO:K10630] [EC:2.3.2.31]
102226939  ranBP-type and C3HC4-type zinc finger-containing protein 1-like [KO:K10630] [EC:2.3.2.31]
102231972  rnf31; E3 ubiquitin-protein ligase RNF31 [KO:K11974] [EC:2.3.2.31]
111608983  E3 ubiquitin-protein ligase RNF31-like isoform X1 [KO:K11974] [EC:2.3.2.31]
102236946  E3 ubiquitin-protein ligase XIAP-like [KO:K04725] [EC:2.3.2.27]
102225203  trip6; thyroid receptor-interacting protein 6 isoform X3 [KO:K12792]
102228673  erbin; erbin isoform X1 [KO:K12796]
102228638  birc2; baculoviral IAP repeat-containing protein 2 isoform X2 [KO:K16060]
102233408  TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
102217350  TNF receptor-associated factor 2-like [KO:K03173] [EC:2.3.2.27]
102227944  TNF receptor-associated factor 2-like isoform X1 [KO:K03173] [EC:2.3.2.27]
102220826  traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
102238337  card9; caspase recruitment domain-containing protein 9 isoform X1 [KO:K12794]
102237440  tnfaip3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
102221226  mavs; mitochondrial antiviral-signaling protein [KO:K12648]
102234631  traf3; TNF receptor-associated factor 3 [KO:K03174]
102227107  tbk1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
102228722  inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
102237114  tank; TRAF family member-associated NF-kappa-B activator [KO:K12650]
102228854  interferon regulatory factor 3-like isoform X1 [KO:K05411]
102220023  irf7; interferon regulatory factor 7 isoform X2 [KO:K09447]
106699651  interferon a3-like [KO:K05414]
111609837  interferon a3-like [KO:K05414]
106700431  interferon a3-like [KO:K05414]
102220223  nlrx1; NLR family member X1 [KO:K12653]
102224328  anthrax toxin receptor 2-like [KO:K20909]
102230058  anthrax toxin receptor 1-like isoform X1 [KO:K20909]
102230168  anthrax toxin receptor 1-like [KO:K20909]
102226522  antxr2; anthrax toxin receptor 2 [KO:K20909]
102224771  anthrax toxin receptor 1-like [KO:K20909]
102217611  anthrax toxin receptor 1 [KO:K20909]
102235142  pycard; apoptosis-associated speck-like protein containing a CARD [KO:K12799]
111608209  uncharacterized protein LOC111608209 [KO:K12799]
102220624  caspase-1-like [KO:K01370] [EC:3.4.22.36]
102220363  caspase-1-like [KO:K01370] [EC:3.4.22.36]
102229031  caspase-1-like [KO:K01370] [EC:3.4.22.36]
111605766  caspase-1-like isoform X1 [KO:K01370] [EC:3.4.22.36]
102223266  bcl2; apoptosis regulator Bcl-2 [KO:K02161]
102221560  bcl-2-like protein 1 [KO:K04570]
102221225  bcl2l1; bcl-2-like protein 1 [KO:K04570]
102222087  cathepsin B-like [KO:K01363] [EC:3.4.22.1]
102226401  cathepsin B-like [KO:K01363] [EC:3.4.22.1]
102227499  panx1; pannexin-1 [KO:K03443]
102216528  pannexin-1-like [KO:K03443]
102233539  P2X purinoceptor 4 [KO:K05220]
102227598  trpm2; transient receptor potential cation channel subfamily M member 2 isoform X1 [KO:K04977] [EC:3.6.1.13]
102227852  transient receptor potential cation channel subfamily M member 2-like [KO:K04977] [EC:3.6.1.13]
102224766  trpm7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
102233243  casr; extracellular calcium-sensing receptor [KO:K04612]
102232187  G-protein coupled receptor family C group 6 member A-like isoform X1 [KO:K04622]
102217878  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1-like [KO:K05858] [EC:3.1.4.11]
102224078  plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
102219479  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3-like [KO:K05858] [EC:3.1.4.11]
102230660  plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
102223820  plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
102217419  inositol 1,4,5-trisphosphate receptor type 1-like isoform X1 [KO:K04958]
102227088  itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
102220160  itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
102237995  itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102230604  vdac1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
102226544  voltage-dependent anion-selective channel protein 2 [KO:K15040]
102231001  voltage-dependent anion-selective channel protein 2 [KO:K15040]
102233702  voltage-dependent anion-selective channel protein 3-like isoform X1 [KO:K15041]
102220558  mcu; calcium uniporter protein, mitochondrial [KO:K20858]
102222687  dhx33; putative ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
102232535  mfn1; mitofusin-1 isoform X2 [KO:K21356] [EC:3.6.5.-]
102223247  mitofusin-1-like [KO:K21356] [EC:3.6.5.-]
102236418  mfn2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
102226461  ripk1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
102226269  receptor-interacting serine/threonine-protein kinase 3-like isoform X1 [KO:K08847] [EC:2.7.11.1]
111612340  receptor-interacting serine/threonine-protein kinase 3-like isoform X1 [KO:K08847] [EC:2.7.11.1]
102234672  dynamin-1-like protein isoform X4 [KO:K17065] [EC:3.6.5.5]
102234804  dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
102237758  dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
102232015  nampt; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
102220339  nicotinamide phosphoribosyltransferase-like isoform X1 [KO:K03462] [EC:2.4.2.12]
102232835  cytochrome b-245 heavy chain isoform X2 [KO:K21421] [EC:1.-.-.-]
102219145  cytochrome b-245 light chain [KO:K08009]
102229818  thioredoxin-interacting protein-like [KO:K20910]
102231729  txnip; thioredoxin-interacting protein [KO:K20910]
102223468  txn2; thioredoxin, mitochondrial [KO:K03671]
102229876  thioredoxin-like [KO:K03671]
102230139  thioredoxin-like [KO:K03671]
102221821  nek7; serine/threonine-protein kinase Nek7 [KO:K20876] [EC:2.7.11.34]
102218136  brcc3; lys-63-specific deubiquitinase BRCC36 [KO:K11864] [EC:3.4.19.-]
102219317  heat shock protein HSP 90-beta [KO:K04079]
102218115  heat shock protein HSP 90-alpha [KO:K04079]
102218377  heat shock protein HSP 90-alpha 1 [KO:K04079]
102221102  proline-serine-threonine phosphatase-interacting protein 1 isoform X1 [KO:K12804]
102228179  proline-serine-threonine phosphatase-interacting protein 1-like [KO:K12804]
111608841  caspase-8-like [KO:K04398] [EC:3.4.22.61]
102236921  caspase-8-like [KO:K04398] [EC:3.4.22.61]
102237850  caspase-8-like isoform X1 [KO:K04398] [EC:3.4.22.61]
102237443  caspase-8-like isoform X1 [KO:K04398] [EC:3.4.22.61]
102230597  fadd; FAS-associated death domain protein [KO:K02373]
102232189  prkcd; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
102226327  tp53bp1; TP53-binding protein 1 isoform X1 [KO:K20915]
102225527  rho-related GTP-binding protein RhoA-B-like [KO:K04513]
102234531  rho-related GTP-binding protein RhoA-C [KO:K04513]
102222710  transforming protein RhoA [KO:K04513]
102229174  rho-related GTP-binding protein RhoA-D [KO:K04513]
102233685  transforming protein RhoA-like [KO:K04513]
102230198  serine/threonine-protein kinase N1-like isoform X3 [KO:K06071] [EC:2.7.11.13]
102238285  serine/threonine-protein kinase N1-like isoform X1 [KO:K06071] [EC:2.7.11.13]
102218787  pkn2; serine/threonine-protein kinase N2 [KO:K23691] [EC:2.7.11.13]
102236163  14-3-3 protein epsilon [KO:K06630]
102219021  14-3-3 protein epsilon isoform X1 [KO:K06630]
102219036  interferon alpha/beta receptor 2-like isoform X1 [KO:K05131]
102225542  jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
102232564  tyk2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
102225755  signal transducer and activator of transcription 1-like [KO:K11220]
102237914  signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
102236235  signal transducer and activator of transcription 1-alpha/beta [KO:K11221]
102232232  irf9; interferon regulatory factor 9 [KO:K04693]
102229375  TIR domain-containing adapter molecule 1-like [KO:K05842]
102234764  myd88; myeloid differentiation primary response protein MyD88 [KO:K04729]
102235789  irak4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
102235680  tmem173; stimulator of interferon genes protein [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
xma04010  MAPK signaling pathway
xma04140  Autophagy - animal
xma04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
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