KEGG   PATHWAY: esp04621
Entry
esp04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Etheostoma spectabile (orangethroat darter)
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
esp04621  NOD-like receptor signaling pathway
esp04621

Organism
Etheostoma spectabile (orangethroat darter) [GN:esp]
Gene
116690780  nod1; nucleotide-binding oligomerization domain-containing protein 1 isoform X1 [KO:K08727]
116699318  LOW QUALITY PROTEIN: receptor-interacting serine/threonine-protein kinase 2-like [KO:K08846] [EC:2.7.11.1]
116693209  ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
116705198  inhibitor of nuclear factor kappa-B kinase subunit alpha-like isoform X1 [KO:K04467] [EC:2.7.11.10]
116670894  inhibitor of nuclear factor kappa-B kinase subunit alpha-like [KO:K04467] [EC:2.7.11.10]
116688937  ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
116706183  NF-kappa-B inhibitor alpha-like [KO:K04734]
116670651  nfkbia; NF-kappa-B inhibitor alpha isoform X1 [KO:K04734]
116707180  putative transcription factor p65 homolog isoform X1 [KO:K04735]
116689682  il1b; interleukin-1 beta [KO:K04519]
116701753  interleukin-6-like [KO:K05405]
116702065  tumor necrosis factor-like [KO:K03156]
116706100  permeability factor 2-like [KO:K10030]
116707268  interleukin-8-like [KO:K10030]
116690303  nod2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165]
116706210  map3k7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
116669778  mitogen-activated protein kinase kinase kinase 7-like [KO:K04427] [EC:2.7.11.25]
116700613  tab1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
116705943  tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
116695153  tab3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
116690322  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
116703753  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
116697416  mitogen-activated protein kinase 9-like [KO:K04440] [EC:2.7.11.24]
116705432  mitogen-activated protein kinase 8-like isoform X1 [KO:K04440] [EC:2.7.11.24]
116671539  mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
116703876  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
116691890  mitogen-activated protein kinase 14A-like [KO:K04441] [EC:2.7.11.24]
116692206  mitogen-activated protein kinase 14A-like isoform X1 [KO:K04441] [EC:2.7.11.24]
116693198  mitogen-activated protein kinase 13-like [KO:K04441] [EC:2.7.11.24]
116693572  mitogen-activated protein kinase 12-like [KO:K04441] [EC:2.7.11.24]
116687835  mitogen-activated protein kinase 14A isoform X1 [KO:K04441] [EC:2.7.11.24]
116673128  mitogen-activated protein kinase 11-like isoform X1 [KO:K04441] [EC:2.7.11.24]
116673224  mitogen-activated protein kinase 12-like isoform X1 [KO:K04441] [EC:2.7.11.24]
116677748  transcription factor AP-1-like [KO:K04448]
116698745  transcription factor AP-1-like [KO:K04448]
116695201  transcription factor AP-1-like [KO:K04448]
116704060  transcription factor AP-1-like [KO:K04448]
116691436  atg5; autophagy protein 5 [KO:K08339]
116691548  atg12; ubiquitin-like protein ATG12 [KO:K08336]
116691314  gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
116686377  gabarap; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
116693480  gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
116693481  gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
116697266  map1lc3c; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
116693908  map1lc3b; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
116698770  sugt1; protein SGT1 homolog isoform X1 [KO:K12795]
116698668  sharpin; sharpin isoform X1 [KO:K20894]
116687739  rbck1; ranBP-type and C3HC4-type zinc finger-containing protein 1 [KO:K10630] [EC:2.3.2.31]
116672047  LOW QUALITY PROTEIN: ranBP-type and C3HC4-type zinc finger-containing protein 1-like [KO:K10630] [EC:2.3.2.31]
116672603  E3 ubiquitin-protein ligase RNF31-like [KO:K11974] [EC:2.3.2.31]
116678163  E3 ubiquitin-protein ligase RNF31-like [KO:K11974] [EC:2.3.2.31]
116699627  E3 ubiquitin-protein ligase RNF31-like isoform X1 [KO:K11974] [EC:2.3.2.31]
116697435  xiap; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
116686344  trip6; thyroid receptor-interacting protein 6 isoform X1 [KO:K12792]
116703862  erbin; erbin isoform X1 [KO:K12796]
116700009  inhibitor of apoptosis protein-like [KO:K16060]
116690145  LOW QUALITY PROTEIN: TNF receptor-associated factor 2-like [KO:K03173] [EC:2.3.2.27]
116704577  TNF receptor-associated factor 2-like [KO:K03173] [EC:2.3.2.27]
116703984  TNF receptor-associated factor 2-like [KO:K03173] [EC:2.3.2.27]
116689192  traf6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
116705091  tnfaip3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
116686108  proline-rich protein 36-like [KO:K12648]
116686116  LOW QUALITY PROTEIN: mitochondrial antiviral-signaling protein-like [KO:K12648]
116688334  ikbke; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
116698243  tank; TRAF family member-associated NF-kappa-B activator [KO:K12650]
116671420  interferon regulatory factor 3-like isoform X1 [KO:K05411]
116694062  irf7; interferon regulatory factor 7 [KO:K09447]
116670973  interferon a3-like [KO:K05414]
116674162  nlrx1; NLR family member X1 isoform X1 [KO:K12653]
116690192  antxr1; anthrax toxin receptor 1 [KO:K20909]
116705214  anthrax toxin receptor 1-like [KO:K20909]
116671520  anthrax toxin receptor 1-like [KO:K20909]
116689567  antxr2; anthrax toxin receptor 2 isoform X1 [KO:K20909]
116703891  anthrax toxin receptor 2-like [KO:K20909]
116691564  uncharacterized protein LOC116691564 [KO:K12799]
116672700  caspase-1-like [KO:K01370] [EC:3.4.22.36]
116698657  apoptosis regulator Bcl-2-like [KO:K02161]
116692614  bcl2l1; bcl-2-like protein 1 [KO:K04570]
116688562  bcl-2-like protein 1 [KO:K04570]
116706388  cathepsin B-like [KO:K01363] [EC:3.4.22.1]
116688443  cathepsin B-like [KO:K01363] [EC:3.4.22.1]
116682072  panx1; pannexin-1 [KO:K03443]
116695405  pannexin-1-like [KO:K03443]
116689166  p2rx7; P2X purinoceptor 7 isoform X1 [KO:K05220]
116697672  trpm2; transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13]
116674376  LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily M member 2-like [KO:K04977] [EC:3.6.1.13]
116677260  LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily M member 7-like [KO:K04982] [EC:2.7.11.1]
116700055  casr; extracellular calcium-sensing receptor [KO:K04612]
116706482  G-protein coupled receptor family C group 6 member A-like [KO:K04622]
116669917  G-protein coupled receptor family C group 6 member A-like [KO:K04622]
116705016  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1-like [KO:K05858] [EC:3.1.4.11]
116706249  plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
116706250  plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
116686556  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3-like [KO:K05858] [EC:3.1.4.11]
116670665  plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
116687305  inositol 1,4,5-trisphosphate receptor type 1-like isoform X1 [KO:K04958]
116687772  inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
116694480  itpr2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
116700318  vdac1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
116705243  voltage-dependent anion-selective channel protein 2 [KO:K15040]
116671390  voltage-dependent anion-selective channel protein 2-like isoform X1 [KO:K15040]
116688940  voltage-dependent anion-selective channel protein 2-like isoform X1 [KO:K15041]
116704016  voltage-dependent anion-selective channel protein 2-like isoform X1 [KO:K15041]
116705162  mcu; calcium uniporter protein, mitochondrial isoform X1 [KO:K20858]
116700455  dhx33; ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
116695745  mfn1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
116692635  mitofusin-2-like isoform X1 [KO:K06030] [EC:3.6.5.-]
116698944  ripk1; LOW QUALITY PROTEIN: receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
116676848  receptor-interacting serine/threonine-protein kinase 3-like isoform X1 [KO:K08847] [EC:2.7.11.1]
116678473  receptor-interacting serine/threonine-protein kinase 3-like [KO:K08847] [EC:2.7.11.1]
116684150  receptor-interacting serine/threonine-protein kinase 3-like [KO:K08847] [EC:2.7.11.1]
116707151  receptor-interacting serine/threonine-protein kinase 3-like isoform X1 [KO:K08847] [EC:2.7.11.1]
116694699  receptor-interacting serine/threonine-protein kinase 3-like [KO:K08847] [EC:2.7.11.1]
116702278  receptor-interacting serine/threonine-protein kinase 2-like [KO:K08847] [EC:2.7.11.1]
116690185  dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
116693901  dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
116673074  dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
116687964  nicotinamide phosphoribosyltransferase-like [KO:K03462] [EC:2.4.2.12]
116672787  nampt; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
116673729  cytochrome b-245 heavy chain isoform X1 [KO:K21421] [EC:1.-.-.-]
116692040  cytochrome b-245 light chain [KO:K08009]
116702157  txnip; thioredoxin-interacting protein [KO:K20910]
116707030  txn; thioredoxin [KO:K03671]
116702841  txn2; thioredoxin, mitochondrial [KO:K03671]
116695399  nek7; serine/threonine-protein kinase Nek7 [KO:K20876] [EC:2.7.11.34]
116704160  brcc3; lys-63-specific deubiquitinase BRCC36 [KO:K11864] [EC:3.4.19.-]
116706735  hsp90aa1; heat shock protein HSP 90-alpha isoform X1 [KO:K04079]
116690617  proline-serine-threonine phosphatase-interacting protein 1-like isoform X1 [KO:K12804]
116694070  proline-serine-threonine phosphatase-interacting protein 1-like isoform X1 [KO:K12804]
116698760  caspase-8-like [KO:K04398] [EC:3.4.22.61]
116698766  caspase-8-like isoform X1 [KO:K04398] [EC:3.4.22.61]
116690512  fadd; FAS-associated death domain protein [KO:K02373]
116688371  protein kinase C delta type-like [KO:K06068] [EC:2.7.11.13]
116688666  protein kinase C delta type-like [KO:K06068] [EC:2.7.11.13]
116685811  tp53bp1; TP53-binding protein 1 isoform X1 [KO:K20915]
116691940  rho-related GTP-binding protein RhoA-C [KO:K04513]
116692018  rho-related GTP-binding protein RhoA-B-like [KO:K04513]
116692455  rho-related GTP-binding protein RhoA-C-like isoform X1 [KO:K04513]
116687703  rho-related GTP-binding protein RhoA-B [KO:K04513]
116688259  rho-related GTP-binding protein RhoA-D isoform X1 [KO:K04513]
116705542  pkn1; LOW QUALITY PROTEIN: serine/threonine-protein kinase N1 [KO:K06071] [EC:2.7.11.13]
116702261  serine/threonine-protein kinase N2-like [KO:K06071] [EC:2.7.11.13]
116699743  pkn2; serine/threonine-protein kinase N2 isoform X1 [KO:K23691] [EC:2.7.11.13]
116674797  14-3-3 protein epsilon-like isoform X1 [KO:K06630]
116700739  14-3-3 protein epsilon isoform X1 [KO:K06630]
116698079  interferon lambda receptor 1-like [KO:K05131]
116696159  jak1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
116703721  tyk2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
116674022  stat1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
116698329  signal transducer and activator of transcription 1-alpha/beta-like isoform X1 [KO:K11220]
116688367  signal transducer and activator of transcription 1-alpha/beta-like isoform X1 [KO:K11221]
116699508  TIR domain-containing adapter molecule 1-like [KO:K05842]
116672056  myd88; myeloid differentiation primary response protein MyD88 [KO:K04729]
116694099  irak4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
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
esp04010  MAPK signaling pathway
esp04140  Autophagy - animal
esp04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
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