KEGG   PATHWAY: llv04621
Entry
llv04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Lutra lutra (Eurasian river otter)
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
llv04621  NOD-like receptor signaling pathway
llv04621

Organism
Lutra lutra (Eurasian river otter) [GN:llv]
Gene
125080753  nucleotide-binding oligomerization domain-containing protein 1-like isoform X1 [KO:K08727]
125098185  receptor-interacting serine/threonine-protein kinase 2 isoform X1 [KO:K08846] [EC:2.7.11.1]
125091312  NF-kappa-B essential modulator isoform X1 [KO:K07210]
125084339  LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit alpha-like [KO:K04467] [EC:2.7.11.10]
125094028  inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
125088499  NF-kappa-B inhibitor beta isoform X1 [KO:K02581]
125105211  NF-kappa-B inhibitor alpha [KO:K04734]
125093224  nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
125078405  transcription factor p65 isoform X1 [KO:K04735]
125109148  interleukin-1 beta [KO:K04519]
125110334  interleukin-18-like [KO:K05482]
125081177  interleukin-6 [KO:K05405]
125103142  tumor necrosis factor isoform X1 [KO:K03156]
125094403  interleukin-8 [KO:K10030]
125093820  growth-regulated protein homolog gamma-like isoform X1 [KO:K05505]
125093821  LOW QUALITY PROTEIN: growth-regulated alpha protein-like [KO:K05505]
125093822  growth-regulated alpha protein-like [KO:K05505]
125088018  C-C motif chemokine 2 [KO:K14624]
125087970  C-C motif chemokine 5 [KO:K12499]
125090436  cathelicidin-6-like [KO:K13916]
125094398  enteric beta-defensin-like [KO:K21100]
125094408  beta-defensin 103A-like [KO:K23126]
125089231  nucleotide-binding oligomerization domain-containing protein 2-like isoform X1 [KO:K10165]
125102400  LOW QUALITY PROTEIN: mitogen-activated protein kinase kinase kinase 7-like [KO:K04427] [EC:2.7.11.25]
125106336  TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
125101867  TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
125091696  TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
125081690  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
125090203  mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
125099732  mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
125084526  mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
125093137  mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
125101777  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
125103018  mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
125096321  mitogen-activated protein kinase 13-like [KO:K04441] [EC:2.7.11.24]
125106184  mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
125106185  mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
125098159  transcription factor Jun [KO:K04448]
125095227  autophagy-related protein 16-1 isoform X1 [KO:K17890]
125102644  autophagy protein 5 isoform X1 [KO:K08339]
125099790  ubiquitin-like protein ATG12 isoform X1 [KO:K08336]
125080657  gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
125087813  gamma-aminobutyric acid receptor-associated protein [KO:K08341]
125089849  gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
125107167  gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
125109681  microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
125086434  microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
125079924  microtubule-associated proteins 1A/1B light chain 3B-like [KO:K10435]
125089822  microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
125094658  protein SGT1 homolog [KO:K12795]
125097462  sharpin-like isoform X1 [KO:K20894]
125108516  LOW QUALITY PROTEIN: ranBP-type and C3HC4-type zinc finger-containing protein 1-like [KO:K10630] [EC:2.3.2.31]
125104308  E3 ubiquitin-protein ligase RNF31 isoform X1 [KO:K11974] [EC:2.3.2.31]
125091577  E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
125100164  caspase recruitment domain-containing protein 6-like isoform X1 [KO:K12797]
125090318  thyroid receptor-interacting protein 6 [KO:K12792]
125099743  erbin isoform X1 [KO:K12796]
125079331  LOW QUALITY PROTEIN: baculoviral IAP repeat-containing protein 2-like [KO:K16060]
125079332  baculoviral IAP repeat-containing protein 3-like [KO:K16060]
125083298  TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
125085695  TNF receptor-associated factor 5 isoform X1 [KO:K09849]
125078866  TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
125082910  caspase recruitment domain-containing protein 9-like isoform X1 [KO:K12794]
125102704  tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
125108204  mitochondrial antiviral-signaling protein-like [KO:K12648]
125103668  TNF receptor-associated factor 3 isoform X1 [KO:K03174]
125106807  serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
125085960  inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
125095469  TRAF family member-associated NF-kappa-B activator isoform X1 [KO:K12650]
125088511  interferon regulatory factor 3-like isoform X1 [KO:K05411]
125078240  interferon regulatory factor 7-like isoform X1 [KO:K09447]
125083482  interferon alpha-1/2-like [KO:K05414]
125083790  interferon alpha-2-like [KO:K05414]
125084017  interferon alpha-like [KO:K05414]
125084018  interferon alpha-1/2-like [KO:K05414]
125082970  interferon alpha-1/2-like [KO:K05414]
125083068  interferon alpha-1/2-like [KO:K05414]
125083069  interferon alpha-1/2-like [KO:K05414]
125083072  interferon alpha-1/2-like [KO:K05414]
125083073  interferon alpha-1/2-like [KO:K05414]
125083074  interferon alpha-1/2-like [KO:K05414]
125083075  interferon alpha-1/2-like [KO:K05414]
125083077  interferon alpha-1/2-like [KO:K05414]
125083078  interferon alpha-1/2-like [KO:K05414]
125083082  interferon alpha-1/2-like [KO:K05414]
125083083  interferon alpha-1/2-like [KO:K05414]
125083084  interferon alpha-1/2-like [KO:K05414]
125083789  interferon beta-like [KO:K05415]
125079132  NLR family member X1 isoform X1 [KO:K12653]
125108696  anthrax toxin receptor 1 isoform X1 [KO:K20909]
125093903  anthrax toxin receptor 2 isoform X1 [KO:K20909]
125087375  NACHT, LRR and PYD domains-containing protein 1-like isoform X1 [KO:K12798]
125091174  apoptosis-associated speck-like protein containing a CARD isoform X1 [KO:K12799]
125081686  apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
125108270  bcl-2-like protein 1 [KO:K04570]
125092926  cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
125100831  LOW QUALITY PROTEIN: NACHT, LRR and PYD domains-containing protein 3-like [KO:K12800]
125079017  pannexin-1-like [KO:K03443]
125081679  P2X purinoceptor 7-like [KO:K05220]
125093441  transient receptor potential cation channel subfamily M member 2-like isoform X1 [KO:K04977] [EC:3.6.1.13]
125103869  transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
125087238  transient receptor potential cation channel subfamily V member 2-like [KO:K04971]
125103649  extracellular calcium-sensing receptor isoform X1 [KO:K04612]
125102613  G-protein coupled receptor family C group 6 member A [KO:K04622]
125108695  LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1-like [KO:K05858] [EC:3.1.4.11]
125108926  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
125110237  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
125105190  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
125109360  inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
125107116  inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
125103123  inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
125100315  voltage-dependent anion-selective channel protein 1 [KO:K05862]
125081242  voltage-dependent anion-selective channel protein 1 [KO:K05862]
125084591  voltage-dependent anion-selective channel protein 2 [KO:K15040]
125092799  voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
125084524  calcium uniporter protein, mitochondrial [KO:K20858]
125082013  2'-5'-oligoadenylate synthase 3-like isoform X1 [KO:K14216] [EC:2.7.7.84]
125082014  LOW QUALITY PROTEIN: 2'-5'-oligoadenylate synthase 2-like [KO:K14216] [EC:2.7.7.84]
125082372  LOW QUALITY PROTEIN: 2'-5'-oligoadenylate synthase 1-like [KO:K14216] [EC:2.7.7.84]
125085907  2-5A-dependent ribonuclease-like isoform X1 [KO:K01165]
125087379  ATP-dependent RNA helicase DHX33 isoform X1 [KO:K17820] [EC:5.6.2.6]
125100641  mitofusin-1 isoform X1 [KO:K21356] [EC:3.6.5.-]
125098037  mitofusin-2 isoform X1 [KO:K06030] [EC:3.6.5.-]
125103136  receptor-interacting serine/threonine-protein kinase 1-like [KO:K02861] [EC:2.7.11.1]
125104721  receptor-interacting serine/threonine-protein kinase 3-like isoform X1 [KO:K08847] [EC:2.7.11.1]
125106039  dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
125081189  nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
125091990  LOW QUALITY PROTEIN: cytochrome b-245 heavy chain-like [KO:K21421] [EC:1.-.-.-]
125088746  cytochrome b-245 light chain [KO:K08009]
125097920  thioredoxin-interacting protein [KO:K20910]
125083570  thioredoxin [KO:K03671]
125106659  thioredoxin, mitochondrial [KO:K03671]
125085643  LOW QUALITY PROTEIN: serine/threonine-protein kinase Nek7-like [KO:K20876] [EC:2.7.11.34]
125092432  lys-63-specific deubiquitinase BRCC36 isoform X1 [KO:K11864] [EC:3.4.19.-]
125092011  heat shock protein HSP 90-alpha-like [KO:K04079]
125101710  heat shock protein HSP 90-beta [KO:K04079]
125104755  heat shock protein HSP 90-alpha [KO:K04079]
125098939  heat shock protein HSP 90-alpha-like [KO:K04079]
125089316  caspase recruitment domain-containing protein 8-like isoform X1 [KO:K12801]
125103215  G-protein-signaling modulator 3-like [KO:K15838]
125100152  LOW QUALITY PROTEIN: immunity-related GTPase family M protein 1-like [KO:K14139] [EC:3.6.5.-]
125100153  LOW QUALITY PROTEIN: immunity-related GTPase family M protein 1-like [KO:K14139] [EC:3.6.5.-]
125100697  immunity-related GTPase family M protein-like [KO:K14139] [EC:3.6.5.-]
125090754  pyrin-like isoform X1 [KO:K12803]
125104664  proline-serine-threonine phosphatase-interacting protein 1 isoform X1 [KO:K12804]
125094998  caspase-8-like isoform X1 [KO:K04398] [EC:3.4.22.61]
125079328  FAS-associated death domain protein-like [KO:K02373]
125078536  caspase-12-like isoform X1 [KO:K04741] [EC:3.4.22.-]
125079916  NACHT, LRR and PYD domains-containing protein 6-like [KO:K20863]
125088582  LOW QUALITY PROTEIN: NACHT, LRR and PYD domains-containing protein 7-like [KO:K20864]
125089406  LOW QUALITY PROTEIN: NACHT, LRR and PYD domains-containing protein 12-like [KO:K20865]
125078754  protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
125085700  interferon-activable protein 203-like isoform X1 [KO:K20914]
125104129  TP53-binding protein 1 isoform X1 [KO:K20915]
125080203  transforming protein RhoA [KO:K04513]
125083405  serine/threonine-protein kinase N1 isoform X1 [KO:K06071] [EC:2.7.11.13]
125097193  serine/threonine-protein kinase N2 [KO:K23691] [EC:2.7.11.13]
125107588  14-3-3 protein epsilon [KO:K06630]
125108683  14-3-3 protein epsilon-like [KO:K06630]
125087039  14-3-3 protein epsilon isoform X1 [KO:K06630]
125097366  guanylate-binding protein 4-like [KO:K20899]
125097491  guanylate-binding protein 4-like isoform X1 [KO:K20899]
125098708  LOW QUALITY PROTEIN: guanylate-binding protein 1-like [KO:K20899]
125078537  LOW QUALITY PROTEIN: caspase-13-like [KO:K04394] [EC:3.4.22.57 3.4.22.64]
125097200  gasdermin-D-like [KO:K20917]
125095023  interferon alpha/beta receptor 1-like [KO:K05130]
125095032  interferon alpha/beta receptor 2-like isoform X1 [KO:K05131]
125097987  tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
125084878  non-receptor tyrosine-protein kinase TYK2-like isoform X1 [KO:K11219] [EC:2.7.10.2]
125095018  signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
125106747  signal transducer and activator of transcription 2-like isoform X1 [KO:K11221]
125104318  interferon regulatory factor 9-like [KO:K04693]
125083203  toll-like receptor 4 [KO:K10160]
125088060  TIR domain-containing adapter molecule 1-like [KO:K05842]
125106441  myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
125106124  interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
125099664  stimulator of interferon genes protein-like [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
llv04010  MAPK signaling pathway
llv04064  NF-kappa B signaling pathway
llv04140  Autophagy - animal
llv04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
LinkDB

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