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KEGG   PATHWAY: xtr04621
Entry
xtr04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Xenopus tropicalis (tropical clawed frog)
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
xtr04621  NOD-like receptor signaling pathway
xtr04621

Organism
Xenopus tropicalis (tropical clawed frog) [GN:xtr]
Gene
100036616  rnf31; E3 ubiquitin-protein ligase RNF31 [KO:K11974] [EC:2.3.2.31]
100037849  tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
100038172  jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
100101764  map3k7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
100101766  mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
100124748  itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
100124749  itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
100124999  trpm2; transient receptor potential cation channel subfamily M member 2 isoform X1 [KO:K04977] [EC:3.6.1.13]
100125098  plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
100125141  gabarapl2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
100127621  sting1; stimulator of interferon genes protein [KO:K12654]
100127742  pycard; PYD and CARD domain containing [KO:K12799]
100134991  tnf; tumor necrosis factor [KO:K03156]
100144715  mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
100145045  [KO:K04441] [EC:2.7.11.24]
100145270  ikbkg; NF-kappa-B essential modulator [KO:K07210]
100145295  gbp5; guanylate binding protein 5 [KO:K20899]
100145327  card9; caspase recruitment domain-containing protein 9 [KO:K12794]
100145795  gbp6; guanylate binding protein family member 6 [KO:K20899]
100158556  antxr2; anthrax toxin receptor 2 precursor [KO:K20909]
100170174  stat2; signal transducer and activator of transcription 2 [KO:K11221]
100170194  mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
100170420  [KO:K03671]
100170428  [KO:K03671]
100170451  mcu; calcium uniporter protein, mitochondrial [KO:K20858]
100170473  panx1; pannexin-1 [KO:K03443]
100216212  tbk1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
100329113  trpm7; transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
100379705  pstpip1; proline-serine-threonine phosphatase-interacting protein 1 isoform X2 [KO:K12804]
100379789  fadd; FAS-associated death domain protein [KO:K02373]
100379847  pkn1; serine/threonine-protein kinase N1 isoform X1 [KO:K06071] [EC:2.7.11.13]
100380103  gprc6a; G-protein coupled receptor family C group 6 member A [KO:K04622]
100485267  bcl2; apoptosis regulator Bcl-2 [KO:K02161]
100485739  [KO:K23691]
100485829  mavs; mitochondrial antiviral-signaling protein isoform X1 [KO:K12648]
100486083  nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100486218  tank; TRAF family member-associated NF-kappa-B activator [KO:K12650]
100486418  antxr1; anthrax toxin receptor 1 [KO:K20909]
100487038  il1b; interleukin-1 beta [KO:K04519]
100487158  irf9; interferon regulatory factor 9 isoform X1 [KO:K04693]
100487267  plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
100487682  trpv2; transient receptor potential cation channel subfamily V member 1 [KO:K04971]
100487744  ikbke; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
100487890  [KO:K04622]
100488013  [KO:K20899]
100488164  nod1; nucleotide-binding oligomerization domain-containing protein 1 [KO:K08727]
100488854  pkn2; serine/threonine-protein kinase N2 [KO:K23691]
100489432  tyk2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
100489572  nlrx1; NLR family member X1 [KO:K12653]
100489592  gbp3; guanylate-binding protein 1 [KO:K20899]
100490124  tp53bp1; TP53-binding protein 1 isoform X1 [KO:K20915]
100490493  ripk3.2; receptor-interacting serine/threonine-protein kinase 3 [KO:K08847] [EC:2.7.11.1]
100490662  p2rx7; P2X purinoceptor 4 [KO:K05220]
100490828  [KO:K05220]
100491139  trpm2l; transient receptor potential cation channel subfamily M member 2 isoform X1 [KO:K04977] [EC:3.6.1.13]
100491169  ripk3.1; receptor-interacting serine/threonine-protein kinase 3 [KO:K08847] [EC:2.7.11.1]
100491300  rbck1; ranBP-type and C3HC4-type zinc finger-containing protein 1 [KO:K10630] [EC:2.3.2.31]
100491460  [KO:K05505]
100491604  traf5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
100491605  casp1; caspase-1-A isoform X1 [KO:K01370] [EC:3.4.22.36]
100492126  txnip; thioredoxin-interacting protein [KO:K20910]
100493341  itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X10 [KO:K04958]
100493403  atg12; ubiquitin-like protein ATG12 [KO:K08336]
100493742  [KO:K06071] [EC:2.7.11.13]
100493911  jun; transcription factor AP-1 [KO:K04448]
100493927  il6; interleukin-6 [KO:K05405]
100494415  traf2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
100494576  dnm1l; dynamin-1-like protein [KO:K17065] [EC:3.6.5.5]
100495158  tab3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
100495160  [KO:K20899]
100495168  [KO:K23691]
100495471  casp8; caspase-8 [KO:K04398] [EC:3.4.22.61]
100496120  [KO:K23691]
100496229  [KO:K10435]
100496395  irf7; interferon regulatory factor 7 [KO:K09447]
100496505  casr; extracellular calcium-sensing receptor [KO:K04612]
100496523  ccl5; C-C motif chemokine 5 isoform X3 [KO:K12499]
100496716  [KO:K05482]
100496810  gbp7; guanylate-binding protein 1 [KO:K20899]
100496877  ifnar2.2; interferon alpha/beta receptor 2 [KO:K05131]
100496958  ripk2; receptor-interacting serine/threonine-protein kinase 2 isoform X1 [KO:K08846] [EC:2.7.11.1]
100497374  [KO:K08847] [EC:2.7.11.1]
100497855  [KO:K04982] [EC:2.7.11.1]
100497910  [KO:K03671]
100498011  antxrl; anthrax toxin receptor 1 isoform X1 [KO:K20909]
100498017  cxcl2; interleukin-8 [KO:K10030]
100498068  [KO:K03671]
100498216  traf3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
100498224  [KO:K03671]
100498234  [KO:K10030]
100498389  [KO:K10030]
100498551  cxcl8; interleukin-8 [KO:K10030]
100498552  ifnar1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
101730379  [KO:K10030]
101730448  [KO:K23691]
101731161  camp; cathelicidin antimicrobial peptide [KO:K13916]
101731964  gpsm3; G-protein-signaling modulator 3 [KO:K15838]
101732196  [KO:K12799]
101732593  [KO:K13916]
101732991  [KO:K23691]
101733632  [KO:K04622]
101733659  [KO:K05842]
101733742  [KO:K04622]
101734275  irf3; interferon regulatory factor 3 [KO:K05411]
101734935  plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
101735006  [KO:K06071] [EC:2.7.11.13]
105945198  [KO:K05414]
105948304  [KO:K23691]
108645367  [KO:K06071] [EC:2.7.11.13]
108645541  [KO:K06071] [EC:2.7.11.13]
108645636  [KO:K23691]
108645640  [KO:K23691]
108648098  il18; interleukin-18 [KO:K05482]
116406436  [KO:K12807]
116406699  [KO:K23691]
116406784  [KO:K06071] [EC:2.7.11.13]
116407520  [KO:K06068] [EC:2.7.11.13]
116407562  [KO:K12801]
116407627  [KO:K20899]
116407652  [KO:K20899]
116407843  [KO:K06071] [EC:2.7.11.13]
116407924  [KO:K05414]
116407962  [KO:K23691]
116408002  [KO:K23691]
116408033  [KO:K05414]
116408267  [KO:K23691]
116408342  [KO:K06071] [EC:2.7.11.13]
116409784  [KO:K04519]
116410967  [KO:K04622]
116411623  [KO:K23691]
116412350  [KO:K06068] [EC:2.7.11.13]
116412413  [KO:K23691]
116412446  [KO:K06071] [EC:2.7.11.13]
116412457  [KO:K23691]
394833  ctsb; cathepsin B precursor [KO:K01363] [EC:3.4.22.1]
394972  map1lc3b; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
407869  rela; transcription factor p65 [KO:K04735]
447985  dhx33; ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
447991  bcl2l1; BCL2 like 1 [KO:K04570]
448041  birc2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
448080  rhoa; transforming protein RhoA [KO:K04513]
448125  ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
448138  nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
448296  mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
493344  map1lc3a; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
493518  ywhae; 14-3-3 protein epsilon [KO:K06630]
493523  txn2; thioredoxin, mitochondrial [KO:K03671]
493524  traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
496541  txn; thioredoxin [KO:K03671]
496614  gabarapl1; GABA(A) receptor-associated protein like 1 [KO:K08341]
496695  vdac3; voltage-dependent anion-selective channel protein 3 [KO:K15041]
496856  nampt; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
548910  sugt1; protein SGT1 homolog [KO:K12795]
548943  mfn1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
548947  vdac2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
549036  hsp90aa1.1; heat shock protein 90kDa alpha family class A member 1 [KO:K04079]
549199  atg5; autophagy protein 5 [KO:K08339]
549211  brcc3; lys-63-specific deubiquitinase BRCC36 [KO:K11864] [EC:3.4.19.-]
549217  tab1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
549234  cyba; cytochrome b-245 alpha polypeptide [KO:K08009]
549246  vdac1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
549268  mfn2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
549323  rhoc; rho-related GTP-binding protein RhoC [KO:K04513]
549402  rhoa.2; ras homolog gene family, member A, gene 2 [KO:K04513]
549527  gbp1; guanylate binding protein 1, interferon-inducible [KO:K20899]
549591  myd88; myeloid differentiation primary response protein MyD88 [KO:K04729]
549654  chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
549834  mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
549881  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
550097  atg16l1; autophagy-related protein 16 [KO:K17890]
594971  xiap; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
595008  gbp4; guanylate binding protein 4 [KO:K20899]
595040  gabarapl1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
595047  hsp90ab1; heat shock protein HSP 90-beta [KO:K04079]
595081  cybb; cytochrome b-245, beta polypeptide [KO:K21421] [EC:1.-.-.-]
733738  irak4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
733756  prkcd; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
733779  map1lc3c; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
733844  nlrc4; NLR family CARD domain-containing protein 4 [KO:K12805]
734027  erbin; erbin isoform X3 [KO:K12796]
779515  mapk10; mitogen-activated protein kinase 10 isoform 2 [KO:K04440] [EC:2.7.11.24]
779720  gbp2; guanylate binding protein 2, interferon-inducible [KO:K20899]
779845  ifnar2.1; interferon (alpha, beta and omega) receptor 2, gene 1 precursor [KO:K05131]
779958  ripk1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
780029  nek7; serine/threonine-protein kinase Nek7 [KO:K20876] [EC:2.7.11.34]
780222  hsp90aa1.2; heat shock protein 90kDa alpha (cytosolic), class A member 1, gene 2 [KO:K04079]
780394  plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
780397  stat1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
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
xtr04010  MAPK signaling pathway
xtr04140  Autophagy - animal
xtr04620  Toll-like receptor signaling pathway
KO pathway
ko04621   

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