KEGG   PATHWAY: npr04621
Entry
npr04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Nanorana parkeri (Xizang Plateau 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
npr04621  NOD-like receptor signaling pathway
npr04621

Organism
Nanorana parkeri (Xizang Plateau frog) [GN:npr]
Gene
108784114  RELA; transcription factor p65 [KO:K04735]
108784349  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
108784535  DHX33; putative ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
108784626  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
108784657  ATG5; autophagy protein 5 [KO:K08339]
108785356  ANTXR1; anthrax toxin receptor 1 [KO:K20909]
108785454  FADD; FAS-associated death domain protein [KO:K02373]
108785587  [KO:K04519]
108785600  [KO:K04519]
108785749  MFN1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
108786538  GPSM3; G-protein-signaling modulator 3 [KO:K15838]
108786558  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
108786686  [KO:K09447]
108786728  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
108786803  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
108786933  [KO:K16060]
108786979  BCL2L1; bcl-2-like protein 1 [KO:K04570]
108787232  [KO:K05220]
108787241  P2RX7; P2X purinoceptor 7 [KO:K05220]
108787259  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
108787281  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
108787306  PANX1; pannexin-1 [KO:K03443]
108787378  [KO:K04441] [EC:2.7.11.24]
108787622  [KO:K03671]
108787821  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
108787929  [KO:K04971]
108787939  [KO:K04971]
108788164  JUN; transcription factor AP-1 [KO:K04448]
108788240  [KO:K04441] [EC:2.7.11.24]
108788404  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
108788466  [KO:K12807]
108788467  [KO:K12807]
108788633  [KO:K04079]
108788768  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
108789059  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
108789229  [KO:K04513]
108789286  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
108789386  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
108789468  IRAK4; LOW QUALITY PROTEIN: interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
108789544  ATG12; ubiquitin-like protein ATG12 [KO:K08336]
108790253  SUGT1; protein SGT1 homolog [KO:K12795]
108790560  [KO:K04513]
108790750  TRAF3; TNF receptor-associated factor 3 [KO:K03174]
108790756  [KO:K04079]
108790769  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
108790873  [KO:K01370] [EC:3.4.22.36]
108791024  PKN2; serine/threonine-protein kinase N2 [KO:K23691]
108791352  IKBKG; NF-kappa-B essential modulator [KO:K07210]
108791445  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
108791446  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
108791510  [KO:K11221]
108791910  ITPR1; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
108792063  NOD1; nucleotide-binding oligomerization domain-containing protein 1 [KO:K08727]
108792287  [KO:K21421] [EC:1.-.-.-]
108792339  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
108792693  [KO:K04622]
108792765  [KO:K04622]
108792772  NOD2; nucleotide-binding oligomerization domain-containing protein 2 [KO:K10165]
108793109  CARD9; caspase recruitment domain-containing protein 9 [KO:K12794]
108793401  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
108793572  NEK7; serine/threonine-protein kinase Nek7 [KO:K20876] [EC:2.7.11.34]
108793666  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
108793697  TXN2; thioredoxin, mitochondrial [KO:K03671]
108793742  [KO:K03156]
108793965  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
108794147  [KO:K05130]
108794273  [KO:K10435]
108794648  [KO:K04440] [EC:2.7.11.24]
108794768  [KO:K10160]
108794863  [KO:K10030]
108794864  [KO:K10030]
108794889  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
108795080  [KO:K04398] [EC:3.4.22.61]
108795154  TNFAIP3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
108795169  [KO:K08846] [EC:2.7.11.1]
108795251  TP53BP1; tumor suppressor p53-binding protein 1 [KO:K20915]
108795338  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
108795396  [KO:K08341]
108795536  TANK; TRAF family member-associated NF-kappa-B activator [KO:K12650]
108795563  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
108795750  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
108796191  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 [KO:K12804]
108797062  NAMPT; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
108797293  [KO:K05405]
108797511  [KO:K05411]
108797512  [KO:K05411]
108797589  TRPM2; transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13]
108797654  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
108797661  ERBIN; erbin [KO:K12796]
108797721  [KO:K12800]
108797733  [KO:K12799]
108797915  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
108797919  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
108797950  RNF31; E3 ubiquitin-protein ligase RNF31 [KO:K11974] [EC:2.3.2.31]
108798164  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
108798410  [KO:K20899]
108798412  [KO:K20899]
108798426  MFN2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
108798433  TMEM173; stimulator of interferon genes protein [KO:K12654]
108798761  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
108798858  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
108799532  MCU; calcium uniporter protein, mitochondrial [KO:K20858]
108799665  NLRC4; NLR family CARD domain-containing protein 4 [KO:K12805]
108799853  ANTXR2; anthrax toxin receptor 2 isoform X1 [KO:K20909]
108799884  [KO:K04977] [EC:3.6.1.13]
108800110  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
108800165  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
108800285  [KO:K06071] [EC:2.7.11.13]
108800432  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
108800545  [KO:K12799]
108800546  [KO:K12799]
108800547  [KO:K12799]
108800706  NLRX1; NLR family member X1 [KO:K12653]
108800778  [KO:K04622]
108800779  [KO:K04622]
108800969  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
108801092  [KO:K20899]
108801096  [KO:K20899]
108801113  [KO:K20909]
108801744  [KO:K05482]
108801934  YWHAE; 14-3-3 protein epsilon [KO:K06630]
108801946  CASR; extracellular calcium-sensing receptor [KO:K04612]
108802101  RBCK1; ranBP-type and C3HC4-type zinc finger-containing protein 1 [KO:K10630] [EC:2.3.2.31]
108802186  [KO:K08009]
108802395  [KO:K12807]
108802396  [KO:K12807]
108803059  [KO:K20899]
108803432  [KO:K13916]
108803435  [KO:K13916]
108803647  [KO:K20899]
108804080  TXNIP; thioredoxin-interacting protein [KO:K20910]
108804455  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
108804463  [KO:K05862]
108804489  RIPK2; receptor-interacting serine/threonine-protein kinase 2 [KO:K08846] [EC:2.7.11.1]
108804572  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
108804799  [KO:K04982] [EC:2.7.11.1]
108804815  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
108804838  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
108804839  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
108805042  BRCC3; lys-63-specific deubiquitinase BRCC36 [KO:K11864] [EC:3.4.19.-]
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
npr04010  MAPK signaling pathway
npr04140  Autophagy - animal
npr04620  Toll-like receptor signaling pathway
KO pathway
ko04621   

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