KEGG   PATHWAY: xgl04621
Entry
xgl04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Xiphias gladius (swordfish)
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
xgl04621  NOD-like receptor signaling pathway
xgl04621

Organism
Xiphias gladius (swordfish) [GN:xgl]
Gene
120782944  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
120783001  ikbke; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
120783057  map1lc3a; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
120783113  rbck1; ranBP-type and C3HC4-type zinc finger-containing protein 1 isoform X1 [KO:K10630] [EC:2.3.2.31]
120783176  [KO:K04570]
120783206  mapk14b; mitogen-activated protein kinase 14B isoform X1 [KO:K04441] [EC:2.7.11.24]
120783672  [KO:K20910]
120783989  zgc:92606; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
120784018  pycard; apoptosis-associated speck-like protein containing a CARD [KO:K12799]
120784031  atg12; ubiquitin-like protein ATG12 [KO:K08336]
120784189  atg5; autophagy protein 5 isoform X1 [KO:K08339]
120784263  nod1; nucleotide-binding oligomerization domain-containing protein 1 isoform X1 [KO:K08727]
120784265  tnfb; tumor necrosis factor b (TNF superfamily, member 2) [KO:K03156]
120784271  [KO:K05414]
120784276  [KO:K05414]
120784439  gprc6a; G-protein coupled receptor family C group 6 member A [KO:K04622]
120784446  [KO:K12798]
120784811  pkn1b; serine/threonine-protein kinase N1b isoform X1 [KO:K06071] [EC:2.7.11.13]
120784894  sting1; stimulator of interferon genes protein [KO:K12654]
120785165  [KO:K02580]
120785237  map1lc3cl; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
120785433  mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
120785816  [KO:K04725] [EC:2.3.2.27]
120786357  tnfa; tumor necrosis factor a (TNF superfamily, member 2) [KO:K03156]
120786412  [KO:K05405]
120786882  txnipa; thioredoxin interacting protein a [KO:K20910]
120787384  nlrx1; NLR family member X1 isoform X1 [KO:K12653]
120787513  card9; caspase recruitment domain-containing protein 9 [KO:K12794]
120787843  [KO:K04734]
120788362  txn2; thioredoxin, mitochondrial [KO:K03671]
120788678  [KO:K05858] [EC:3.1.4.11]
120788717  traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
120788739  map3k7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
120788807  hsp90ab1; heat shock protein HSP 90-beta [KO:K04079]
120789004  [KO:K05858] [EC:3.1.4.11]
120789016  tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
120789083  ctsbb; cathepsin Bb [KO:K01363] [EC:3.4.22.1]
120789116  hsp90aa1.2; heat shock protein 90, alpha (cytosolic), class A member 1, tandem duplicate 2 [KO:K04079]
120789117  hsp90aa1.1; heat shock protein HSP 90-alpha 1 [KO:K04079]
120789330  [KO:K04622]
120789383  [KO:K04622]
120789782  [KO:K04729]
120789832  [KO:K11974] [EC:2.3.2.31]
120789833  irf9; interferon regulatory factor 9 isoform X1 [KO:K04693]
120789915  [KO:K02161]
120789938  shrprbck1r; ranBP-type and C3HC4-type zinc finger-containing protein 1 [KO:K10630] [EC:2.3.2.31]
120790858  trpm7; transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
120790882  [KO:K21356] [EC:3.6.5.-]
120790916  nek7; serine/threonine-protein kinase Nek7 [KO:K20876] [EC:2.7.11.34]
120791244  tab3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793]
120791293  jun; transcription factor AP-1 isoform X1 [KO:K04448]
120791353  jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
120791532  atg16l1; autophagy-related protein 16-1 isoform X1 [KO:K17890]
120791656  [KO:K08009]
120791689  tp53bp1; TP53-binding protein 1 isoform X1 [KO:K20915]
120791739  [KO:K01370] [EC:3.4.22.36]
120791861  ywhae1; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide 1 isoform X1 [KO:K06630]
120792572  [KO:K03443]
120792776  [KO:K08847] [EC:2.7.11.1]
120792797  mapk12a; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
120792799  itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
120792944  gabarapl2; gamma-aminobutyric acid receptor-associated protein-like 2 isoform X1 [KO:K08341]
120792961  irf7; interferon regulatory factor 7 [KO:K09447]
120792990  irak4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
120793083  pstpip1a; proline-serine-threonine phosphatase-interacting protein 1a isoform X1 [KO:K12804]
120793273  map1lc3b; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
120793680  dnm1l; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
120793796  [KO:K12804]
120793811  [KO:K08341]
120794257  [KO:K04467] [EC:2.7.11.10]
120794262  irf3; interferon regulatory factor 3 isoform X1 [KO:K05411]
120794394  mapk8b; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
120794508  [KO:K05414]
120794519  [KO:K05414]
120794529  antxr1c; anthrax toxin receptor 1 [KO:K20909]
120794839  [KO:K15040]
120794981  [KO:K04622]
120795051  [KO:K04427] [EC:2.7.11.25]
120795368  traf3; TNF receptor-associated factor 3 [KO:K03174]
120795579  plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
120795761  nod2; nucleotide-binding oligomerization domain-containing protein 2 [KO:K10165]
120795821  nfkbiab; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha b [KO:K04734]
120795827  mavs; mitochondrial antiviral-signaling protein isoform X1 [KO:K12648]
120796054  [KO:K04467] [EC:2.7.11.10]
120796128  ctsba; LOW QUALITY PROTEIN: cathepsin B [KO:K01363] [EC:3.4.22.1]
120796162  mcu; calcium uniporter protein, mitochondrial isoform X1 [KO:K20858]
120796205  mapk8a; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
120796244  antxr1d; anthrax toxin receptor 1 [KO:K20909]
120796336  vdac2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
120796457  [KO:K05858] [EC:3.1.4.11]
120796570  tnfaip3; tumor necrosis factor alpha-induced protein 3 isoform X1 [KO:K11859] [EC:3.4.19.12]
120797023  ripk3; receptor-interacting serine/threonine-protein kinase 3 [KO:K08847] [EC:2.7.11.1]
120797026  rela; transcription factor p65 isoform X1 [KO:K04735]
120797191  plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
120797365  txn; thioredoxin [KO:K03671]
120797480  [KO:K10030]
120797524  cxcl19; C-X-C motif chemokine 19 [KO:K10030]
120797563  trip6; thyroid receptor-interacting protein 6 isoform X1 [KO:K12792]
120797761  gabarapa; GABA(A) receptor-associated protein a [KO:K08341]
120797916  [KO:K21421] [EC:1.-.-.-]
120798154  stat1a; signal transducer and activator of transcription 1a isoform X1 [KO:K11220]
120798581  ticam1; TIR domain-containing adapter molecule 1 [KO:K05842]
120798605  mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
120798669  pkn2a; serine/threonine-protein kinase N2 isoform X1 [KO:K23691]
120798672  [KO:K20894]
120798903  sugt1; protein SGT1 homolog isoform X1 [KO:K12795]
120799083  casp8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
120799085  [KO:K04398] [EC:3.4.22.61]
120799207  [KO:K08846] [EC:2.7.11.1]
120799277  bcl2b; apoptosis regulator Bcl-2 [KO:K02161]
120799349  ripk1l; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
120799354  [KO:K11974] [EC:2.3.2.31]
120799405  [KO:K04448]
120799678  [KO:K11974] [EC:2.3.2.31]
120799710  [KO:K10030]
120799791  traf5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
120799949  pkn1a; serine/threonine-protein kinase N1 isoform X1 [KO:K06071] [EC:2.7.11.13]
120800101  [KO:K10030]
120800214  [KO:K04441] [EC:2.7.11.24]
120800317  map1lc3c; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
120800421  tbk1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
120800498  fadd; protein FADD [KO:K02373]
120800512  [KO:K03443]
120800783  tab1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
120800849  [KO:K17065] [EC:3.6.5.5]
120800855  mfn1a; mitofusin-1 isoform X1 [KO:K21356] [EC:3.6.5.-]
120801517  trpm2; LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13]
120801616  [KO:K11220]
120801861  casp10; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
120801939  tank; TRAF family member-associated NF-kappa-B activator [KO:K12650]
120802251  dhx33; ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
120802438  [KO:K06630]
120802729  vdac1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
120802747  casr; extracellular calcium-sensing receptor [KO:K04612]
120802962  birc2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
120803408  mfn2; mitofusin-2 isoform X1 [KO:K06030] [EC:3.6.5.-]
120803427  ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
120803515  [KO:K04513]
120803517  [KO:K04513]
120803582  rhoab; rho-related GTP-binding protein RhoA-B [KO:K04513]
120803636  itpr3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
120803799  bcl2l1; bcl-2-like protein 1 [KO:K04570]
120803801  mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
120803829  zgc:171775; STKc_p38 domain-containing protein [KO:K04441] [EC:2.7.11.24]
120803885  mapk14a; mitogen-activated protein kinase 14A isoform X1 [KO:K04441] [EC:2.7.11.24]
120803897  rhoaa; rho-related GTP-binding protein RhoA-A [KO:K04513]
120804225  nampt1; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
120805086  ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
120805088  vdac3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
120805165  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
120805168  traf2a; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
120805225  si:dkey-32e23.4; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
120805320  [KO:K04519]
120805321  [KO:K04519]
120805375  antxr2a; ANTXR cell adhesion molecule 2a [KO:K20909]
120805406  [KO:K20909]
120805623  p2rx7; P2X purinoceptor 7 isoform X1 [KO:K05220]
120805930  brcc3; lys-63-specific deubiquitinase BRCC36 [KO:K11864] [EC:3.4.19.-]
120806001  [KO:K20909]
120806021  il1b; interleukin-1 beta [KO:K04519]
120806102  antxr1b; anthrax toxin receptor 1 [KO:K20909]
120806199  traf2b; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
120806563  [KO:K03173] [EC:2.3.2.27]
120806589  zgc:56235; voltage-dependent anion-selective channel protein 2 isoform X1 [KO:K15041]
120806714  erbin; erbin [KO:K12796]
120806753  mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
120807153  rhoca; ras homolog family member Ca [KO:K04513]
120807228  tyk2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
120807293  [KO:K04513]
120807379  stat2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
120807423  nampt2; nicotinamide phosphoribosyltransferase 2 isoform X1 [KO:K03462] [EC:2.4.2.12]
120807463  [KO:K04958]
120807519  prkcda; protein kinase C, delta a [KO:K06068] [EC:2.7.11.13]
120807595  itpr1b; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
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
xgl04010  MAPK signaling pathway
xgl04140  Autophagy - animal
xgl04620  Toll-like receptor signaling pathway
KO pathway
ko04621   

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