KEGG   PATHWAY: rkg04621
Entry
rkg04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Rhinichthys klamathensis goyatoka (western speckled dace)
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
rkg04621  NOD-like receptor signaling pathway
rkg04621

Organism
Rhinichthys klamathensis goyatoka (western speckled dace) [GN:rkg]
Gene
130069051  il6; interleukin-6 [KO:K05405]
130069316  antxr1d; anthrax toxin receptor 1 isoform X1 [KO:K20909]
130069579  mapk12b; mitogen-activated protein kinase 12b [KO:K04441] [EC:2.7.11.24]
130069580  mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
130069756  nod2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165]
130069886  traf3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
130069939  ikbke; inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
130070256  [KO:K20899]
130070257  gbp2; guanylate-binding protein 1 [KO:K20899]
130070258  [KO:K20899]
130070260  [KO:K20899]
130070273  [KO:K20899]
130070289  [KO:K20899]
130070297  ifnphi1; interferon phi 1 [KO:K05414]
130070313  ifnphi3; interferon phi 3 [KO:K05414]
130070769  zgc:56493; thioredoxin-like [KO:K03671]
130070957  pkn2a; serine/threonine-protein kinase N2 [KO:K23691]
130071070  rela; transcription factor p65 [KO:K04735]
130071099  ripk3; receptor-interacting serine/threonine-protein kinase 3 [KO:K08847] [EC:2.7.11.1]
130071236  gabarapa; GABA(A) receptor-associated protein a [KO:K08341]
130071353  mapk8b; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
130071384  cxcl8a; interleukin-8 isoform X1 [KO:K10030]
130071446  mfn1b; mitofusin-1b [KO:K21356] [EC:3.6.5.-]
130071804  mapk14b; mitogen-activated protein kinase 14B isoform X1 [KO:K04441] [EC:2.7.11.24]
130071976  nek7; serine/threonine-protein kinase Nek7 [KO:K20876] [EC:2.7.11.34]
130072368  p2rx7; P2X purinoceptor 7 [KO:K05220]
130072558  stat1b; signal transducer and activator of transcription 1b isoform X1 [KO:K11220]
130072594  [KO:K11220]
130072636  panx1b; pannexin-1b [KO:K03443]
130072666  card9; LOW QUALITY PROTEIN: caspase recruitment domain-containing protein 9 [KO:K12794]
130072741  [KO:K04513]
130073603  brcc3; lys-63-specific deubiquitinase BRCC36 [KO:K11864] [EC:3.4.19.-]
130075331  tbk1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
130075600  xiap; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
130075635  gabarapb; GABA(A) receptor-associated protein b [KO:K08341]
130075650  sugt1; protein SGT1 homolog isoform X1 [KO:K12795]
130075742  ctsbb; cathepsin Bb [KO:K01363] [EC:3.4.22.1]
130075784  [KO:K05858] [EC:3.1.4.11]
130075785  [KO:K05858] [EC:3.1.4.11]
130075956  nampt2; nicotinamide phosphoribosyltransferase 2 [KO:K03462] [EC:2.4.2.12]
130076052  si:dkey-181m9.8; uncharacterized protein si:dkey-181m9.8 isoform X1 [KO:K11974] [EC:2.3.2.31]
130076560  erbin; erbin isoform X1 [KO:K12796]
130076949  june; junE proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
130077123  traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
130077242  casp10; caspase-8 [KO:K04398] [EC:3.4.22.61]
130077325  rbck1; ranBP-type and C3HC4-type zinc finger-containing protein 1 isoform X1 [KO:K10630] [EC:2.3.2.31]
130077416  dhx33; ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
130077464  tank; TRAF family member-associated NF-kappa-B activator [KO:K12650]
130077514  trpm7; transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
130077656  atg16l1; autophagy-related protein 16-1 isoform X1 [KO:K17890]
130077856  tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
130078051  plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
130078072  irf9; interferon regulatory factor 9 [KO:K04693]
130078405  antxr1b; anthrax toxin receptor 1 [KO:K20909]
130078463  [KO:K15040]
130080053  nampt1; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
130080583  irf3; interferon regulatory factor 3 isoform X1 [KO:K05411]
130080640  antxr1c; anthrax toxin receptor 1 [KO:K20909]
130081257  pkn2b; serine/threonine-protein kinase N2 isoform X1 [KO:K23691]
130081696  bcl2l1; bcl-2-like protein 1 [KO:K04570]
130081706  ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
130081725  cxcl8b.3; interleukin-8b.3 [KO:K10030]
130081727  cxcl19; C-X-C motif chemokine 19 [KO:K10030]
130082042  mfn2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
130082079  antxr1a; anthrax toxin receptor 1 [KO:K20909]
130082086  si:dkey-32e23.4; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
130082323  hsp90aa1.2; heat shock protein 90, alpha (cytosolic), class A member 1, tandem duplicate 2 [KO:K04079]
130082324  hsp90aa1.1; heat shock protein HSP 90-alpha 1 [KO:K04079]
130082525  casr; extracellular calcium-sensing receptor [KO:K04612]
130083058  mavs; mitochondrial antiviral-signaling protein [KO:K12648]
130083093  tlr4bb; toll-like receptor 4b, duplicate b [KO:K10160]
130083094  tlr4al; toll-like receptor 4a, like [KO:K10160]
130083095  [KO:K10160]
130083111  vdac2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
130083516  itpr1b; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
130083832  myd88; myeloid differentiation primary response protein MyD88 [KO:K04729]
130084029  bcl2a; apoptosis regulator Bcl-2a [KO:K02161]
130084299  mcu; calcium uniporter protein, mitochondrial [KO:K20858]
130084652  zgc:171775; STKc_p38 domain-containing protein [KO:K04441] [EC:2.7.11.24]
130084762  sting1; stimulator of interferon genes protein [KO:K12654]
130084925  pkn1a; serine/threonine-protein kinase N1 isoform X1 [KO:K06071] [EC:2.7.11.13]
130085012  antxr2a; ANTXR cell adhesion molecule 2a [KO:K20909]
130085192  map1lc3b; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
130085553  [KO:K21421] [EC:1.-.-.-]
130085587  map1lc3a; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
130085702  plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
130085991  gabarapl2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
130086007  irf7; interferon regulatory factor 7 isoform X1 [KO:K09447]
130086130  tab3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793]
130086199  itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
130086517  irak4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
130086585  tyk2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
130086710  prkcdb; protein kinase C, delta b [KO:K06068] [EC:2.7.11.13]
130086886  [KO:K08009]
130087150  antxr2b; ANTXR cell adhesion molecule 2b [KO:K20909]
130087502  prkcda; protein kinase C, delta a [KO:K06068] [EC:2.7.11.13]
130087534  itpr1a; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
130087560  stat2; signal transducer and activator of transcription 2 [KO:K11221]
130087928  tnfa; tumor necrosis factor a (TNF superfamily, member 2) [KO:K03156]
130087968  txnipa; thioredoxin interacting protein a [KO:K20910]
130088093  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
130088204  [KO:K03173] [EC:2.3.2.27]
130088368  [KO:K04622]
130088928  pstpip1a; proline-serine-threonine phosphatase-interacting protein 1a [KO:K12804]
130089381  [KO:K11974] [EC:2.3.2.31]
130089640  chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
130089726  map1lc3cl; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
130089827  traf2a; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
130090475  ywhae2; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide 2 [KO:K06630]
130090659  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
130090761  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
130090899  gprc6a; G-protein coupled receptor family C group 6 member A [KO:K04622]
130091126  jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
130091214  tp53bp1; TP53-binding protein 1 isoform X1 [KO:K20915]
130091441  trip6; thyroid receptor-interacting protein 6 isoform X1 [KO:K12792]
130091525  nod1; nucleotide-binding oligomerization domain-containing protein 1 [KO:K08727]
130091644  rhoaa; rho-related GTP-binding protein RhoA-A [KO:K04513]
130091708  mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
130091778  map3k7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
130091915  casp22; caspase-22 [KO:K04398] [EC:3.4.22.61]
130091951  [KO:K04622]
130094564  rhoab; rho-related GTP-binding protein RhoA-B [KO:K04513]
130094565  rhocb; rho-related GTP-binding protein RhoA-D [KO:K04513]
130094634  mapk14a; mitogen-activated protein kinase 14A isoform X1 [KO:K04441] [EC:2.7.11.24]
130094764  itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
130094797  mapk12a; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
130094933  il1b; interleukin-1 beta [KO:K04519]
130095213  tnfaip3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
130095375  mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
130095637  nfkb1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
130096089  nfkbiaa; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha a [KO:K04734]
130096106  jun; transcription factor AP-1 [KO:K04448]
130096170  hsp90ab1; heat shock protein HSP 90-beta [KO:K04079]
130096507  birc2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
130096571  bcl2b; apoptosis regulator Bcl-2 [KO:K02161]
130096743  nlrx1; NLR family member X1 [KO:K12653]
130096781  ywhae1; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide 1 isoform X1 [KO:K06630]
130096828  [KO:K11217] [EC:2.7.10.2]
130096845  vdac1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
130097217  ripk2; receptor-interacting serine/threonine-protein kinase 2 [KO:K08846] [EC:2.7.11.1]
130097277  fadd; protein FADD [KO:K02373]
130097724  panx1a; pannexin-1a isoform X1 [KO:K03443]
130098389  mfn1a; mitofusin-1 isoform X1 [KO:K21356] [EC:3.6.5.-]
130099645  sharpin; ranBP-type and C3HC4-type zinc finger-containing protein 1 [KO:K20894]
130099777  ripk1l; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
130100395  stat1a; signal transducer and activator of transcription 1a [KO:K11220]
130100672  pycard; apoptosis-associated speck-like protein containing a CARD [KO:K12799]
130100674  caspa; caspase a [KO:K01370] [EC:3.4.22.36]
130100712  txnipb; thioredoxin interacting protein b isoform X1 [KO:K20910]
130100776  ctsba; LOW QUALITY PROTEIN: cathepsin B [KO:K01363] [EC:3.4.22.1]
130101234  casp20; caspase 20, apoptosis-related cysteine peptidase isoform X1 [KO:K04398] [EC:3.4.22.61]
130101272  [KO:K04398] [EC:3.4.22.61]
130101352  [KO:K04398] [EC:3.4.22.61]
130101563  pstpip1b; proline-serine-threonine phosphatase-interacting protein 1b [KO:K12804]
130101978  traf5; TNF receptor-associated factor 5 [KO:K09849]
130102420  crfb2; cytokine receptor family member b2 [KO:K05131]
130102648  txn; thioredoxin [KO:K03671]
130103666  zgc:92606; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
130103997  atg12; ubiquitin-like protein ATG12 [KO:K08336]
130104170  rhoca; ras homolog family member Ca [KO:K04513]
130104215  rhoac; rho-related GTP-binding protein RhoA-C [KO:K04513]
130104409  dnm1l; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
130105388  trpm2; transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13]
130106311  txn2; thioredoxin, mitochondrial [KO:K03671]
130106313  pkn1b; serine/threonine-protein kinase N1b isoform X1 [KO:K06071] [EC:2.7.11.13]
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
rkg04010  MAPK signaling pathway
rkg04140  Autophagy - animal
rkg04620  Toll-like receptor signaling pathway
KO pathway
ko04621   

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