KEGG   PATHWAY: loc04621
Entry
loc04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Lepisosteus oculatus (spotted gar)
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
loc04621  NOD-like receptor signaling pathway
loc04621

Organism
Lepisosteus oculatus (spotted gar) [GN:loc]
Gene
102697236  nod1; nucleotide-binding oligomerization domain-containing protein 1 [KO:K08727]
102695929  ripk2; receptor-interacting serine/threonine-protein kinase 2 [KO:K08846] [EC:2.7.11.1]
102682818  NF-kappa-B essential modulator-like isoform X1 [KO:K07210]
102691336  chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
102690045  ikbkb; LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
102689470  nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
102693746  nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
107078662  il6; interleukin-6 [KO:K05405]
107077132  interleukin-8-like [KO:K10030]
107077137  interleukin-8-like [KO:K10030]
107077138  interleukin-8-like isoform X1 [KO:K10030]
102689183  C-X-C motif chemokine 10-like [KO:K10030]
102684715  interleukin-8-like [KO:K10030]
107078213  cathelicidin-2-like [KO:K13916]
107078222  cathelicidin antimicrobial peptide-like [KO:K13916]
107078224  cathelicidin-1-like isoform X1 [KO:K13916]
102693991  map3k7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
102694529  tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
102688534  tab3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793]
102683764  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102687878  mapk10; mitogen-activated protein kinase 10 isoform X4 [KO:K04440] [EC:2.7.11.24]
102692400  mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
102691138  mitogen-activated protein kinase 9 isoform X4 [KO:K04440] [EC:2.7.11.24]
102698741  mitogen-activated protein kinase 14A isoform X2 [KO:K04441] [EC:2.7.11.24]
102695970  mitogen-activated protein kinase 13-like [KO:K04441] [EC:2.7.11.24]
102695733  mitogen-activated protein kinase 12-like [KO:K04441] [EC:2.7.11.24]
102695926  mitogen-activated protein kinase 11-like [KO:K04441] [EC:2.7.11.24]
102685390  mitogen-activated protein kinase 14A-like [KO:K04441] [EC:2.7.11.24]
102693762  jun; transcription factor AP-1 [KO:K04448]
102689161  transcription factor AP-1-like [KO:K04448]
102693910  atg16l1; autophagy-related protein 16-1 isoform X2 [KO:K17890]
102686863  atg5; autophagy protein 5 [KO:K08339]
102693463  atg12; ubiquitin-like protein ATG12 [KO:K08336]
102695187  gabarap; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
102692447  gabarapl2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
102692047  gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
102691899  microtubule-associated proteins 1A/1B light chain 3C-like isoform X2 [KO:K10435]
102692164  map1lc3a; microtubule-associated proteins 1A/1B light chain 3A isoform X1 [KO:K10435]
102686382  map1lc3b; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
102695099  sugt1; protein SGT1 homolog [KO:K12795]
102690636  rbck1; ranBP-type and C3HC4-type zinc finger-containing protein 1 [KO:K10630] [EC:2.3.2.31]
102691418  sharpin [KO:K10630] [EC:2.3.2.31]
107078305  uncharacterized protein LOC107078305 isoform X1 [KO:K11974] [EC:2.3.2.31]
102684651  xiap; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
102683501  lipoma-preferred partner homolog [KO:K12792]
102691922  erbb2ip; protein LAP2 [KO:K12796]
102688292  birc2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
107079892  TNF receptor-associated factor 1-like isoform X1 [KO:K03173] [EC:2.3.2.27]
102693526  traf2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
102695888  TNF receptor-associated factor 2-like isoform X2 [KO:K03173] [EC:2.3.2.27]
102698366  traf5; TNF receptor-associated factor 5 [KO:K09849]
102684182  traf6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
102698373  card9; caspase recruitment domain-containing protein 9 isoform X1 [KO:K12794]
102692234  tnfaip3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
107077521  tumor necrosis factor alpha-induced protein 3-like [KO:K11859] [EC:3.4.19.12]
107076971  mitochondrial antiviral-signaling protein-like [KO:K12648]
102685862  traf3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
102687024  tbk1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
102692331  ikbke; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
102694367  tank; TRAF family member-associated NF-kappa-B activator isoform X1 [KO:K12650]
107075358  irf3; interferon regulatory factor 3 [KO:K05411]
102698664  irf7; interferon regulatory factor 7 isoform X1 [KO:K09447]
107076357  uncharacterized protein LOC107076357 isoform X1 [KO:K05414]
102693774  interferon a3-like [KO:K05414]
107079271  interferon omega-2-like [KO:K05414]
107079272  interferon a3-like [KO:K05414]
102694188  nlrx1; NLR family member X1 isoform X1 [KO:K12653]
102688430  antxr2; anthrax toxin receptor 2 [KO:K20909]
102690920  anthrax toxin receptor 1-like [KO:K20909]
102687279  antxrl; anthrax toxin receptor-like [KO:K20909]
102686039  apoptosis-associated speck-like protein containing a CARD [KO:K12799]
102686244  apoptosis-associated speck-like protein containing a CARD [KO:K12799]
102696999  casp1; caspase-1 [KO:K01370] [EC:3.4.22.36]
102688855  caspase-13-like [KO:K01370] [EC:3.4.22.36]
102684940  bcl2; apoptosis regulator Bcl-2 [KO:K02161]
102691042  bcl2l1; bcl-2-like protein 1 isoform X2 [KO:K04570]
102698181  ctsb; cathepsin B [KO:K01363] [EC:3.4.22.1]
102688845  panx1; pannexin-1 [KO:K03443]
102693118  p2rx7; P2X purinoceptor 7 isoform X1 [KO:K05220]
102699238  trpm2; transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13]
102682361  trpm7; transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
102693201  casr; extracellular calcium-sensing receptor [KO:K04612]
102693668  gprc6a; G-protein coupled receptor family C group 6 member A [KO:K04622]
102686188  G-protein coupled receptor family C group 6 member A-like [KO:K04622]
102682149  plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
102691284  plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
102682351  plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
102694604  itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
102683319  itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
102696500  itpr3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
102694412  vdac1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
102694933  vdac2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
102690246  vdac3; voltage-dependent anion-selective channel protein 3 [KO:K15041]
102693549  mcu; calcium uniporter protein, mitochondrial [KO:K20858]
102696276  mfn1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
102686245  mfn2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
102691146  ripk1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
102688420  dnm1l; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
102697276  dynamin-1-like protein isoform X2 [KO:K17065] [EC:3.6.5.5]
102687550  nicotinamide phosphoribosyltransferase-like [KO:K03462] [EC:2.4.2.12]
102689605  nampt; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
102692101  cytochrome b-245 heavy chain isoform X1 [KO:K21421] [EC:1.-.-.-]
102687462  cytochrome b-245 light chain [KO:K08009]
102689562  txnip; thioredoxin-interacting protein [KO:K20910]
102692095  txn2; thioredoxin, mitochondrial [KO:K03671]
102685515  txn; thioredoxin [KO:K03671]
102684611  nek7; serine/threonine-protein kinase Nek7 isoform X1 [KO:K20876] [EC:2.7.11.34]
102691011  brcc3; lys-63-specific deubiquitinase BRCC36 [KO:K11864] [EC:3.4.19.-]
102698061  hsp90ab1; heat shock protein HSP 90-beta [KO:K04079]
102697884  hsp90aa1; heat shock protein HSP 90-alpha isoform X3 [KO:K04079]
102693534  heat shock protein HSP 90-alpha [KO:K04079]
102698401  pstpip1; proline-serine-threonine phosphatase-interacting protein 1 [KO:K12804]
102697635  caspase-8-like [KO:K04398] [EC:3.4.22.61]
102697443  casp8; caspase-8 [KO:K04398] [EC:3.4.22.61]
102697829  caspase-8-like [KO:K04398] [EC:3.4.22.61]
102690370  fadd; FAS-associated death domain protein [KO:K02373]
102684700  baculoviral IAP repeat-containing protein 1b-like [KO:K12807]
107079461  baculoviral IAP repeat-containing protein 1-like isoform X1 [KO:K12807]
102686781  baculoviral IAP repeat-containing protein 1e-like [KO:K12807]
102696211  nlrc4; NLR family CARD domain-containing protein 4 isoform X1 [KO:K12805]
102698207  prkcd; protein kinase C delta type isoform X3 [KO:K06068] [EC:2.7.11.13]
102695648  tp53bp1; tumor suppressor p53-binding protein 1 isoform X1 [KO:K20915]
102686749  transforming protein RhoA-like [KO:K04513]
102689455  rhoc; rho-related GTP-binding protein RhoC [KO:K04513]
102682211  rho-related GTP-binding protein RhoA-C [KO:K04513]
102695072  pkn1; serine/threonine-protein kinase N1 [KO:K06071] [EC:2.7.11.13]
102689813  pkn2; serine/threonine-protein kinase N2 isoform X1 [KO:K23691] [EC:2.7.11.13]
102698786  ywhae; 14-3-3 protein epsilon isoform X1 [KO:K06630]
102686393  guanylate-binding protein 1-like isoform X1 [KO:K20899]
102696936  guanylate-binding protein 1-like [KO:K20899]
102686298  guanylate-binding protein 1-like [KO:K20899]
102686500  guanylate-binding protein 1-like isoform X1 [KO:K20899]
102693969  interferon alpha/beta receptor 2-like [KO:K05131]
102694623  jak1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
102685935  tyk2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
102685821  stat1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
102698942  signal transducer and activator of transcription 1-alpha/beta-like [KO:K11221]
107075954  irf9; interferon regulatory factor 9 [KO:K04693]
102693850  tlr4; LOW QUALITY PROTEIN: toll-like receptor 4 [KO:K10160]
102691641  ticam1; TIR domain-containing adapter molecule 1 [KO:K05842]
102684939  myd88; myeloid differentiation primary response protein MyD88 [KO:K04729]
102693125  irak4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
102691936  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
loc04010  MAPK signaling pathway
loc04140  Autophagy - animal
loc04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
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