KEGG   PATHWAY: arow04621
Entry
arow04621                   Pathway                                
Name
NOD-like receptor signaling pathway - Apteryx rowi (Okarito brown kiwi)
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
arow04621  NOD-like receptor signaling pathway
arow04621

Organism
Apteryx rowi (Okarito brown kiwi) [GN:arow]
Gene
112967142  NOD1; nucleotide-binding oligomerization domain-containing protein 1 isoform X1 [KO:K08727]
112964082  RIPK2; receptor-interacting serine/threonine-protein kinase 2 [KO:K08846] [EC:2.7.11.1]
112961084  receptor-interacting serine/threonine-protein kinase 2-like [KO:K08846] [EC:2.7.11.1]
112977217  inhibitor of nuclear factor kappa-B kinase subunit alpha-like [KO:K04467] [EC:2.7.11.10]
112962239  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
112974186  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
112977918  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
112972215  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
112975327  interleukin-1 beta-like isoform X1 [KO:K04519]
112967461  IL18; interleukin-18 [KO:K05482]
112974163  IL6; interleukin-6 [KO:K05405]
112977596  interleukin-8-like [KO:K10030]
112977599  platelet factor 4-like [KO:K10030]
112977640  interleukin-8-like [KO:K10030]
112968624  C-C motif chemokine 5-like [KO:K12499]
112968638  C-C motif chemokine 5-like [KO:K12499]
112977398  cathelicidin-2-like [KO:K13916]
112961572  antimicrobial peptide THP2 [KO:K21100]
112963613  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
112965723  TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
112974544  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
112967666  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
112978378  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
112963855  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
112964950  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
112967355  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
112961437  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
112961439  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
112973525  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
112973531  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
112967663  JUN; transcription factor AP-1 [KO:K04448]
112972879  ATG16L1; autophagy-related protein 16-1 isoform X1 [KO:K17890]
112966061  ATG5; autophagy protein 5 isoform X1 [KO:K08339]
112967864  ATG12; ubiquitin-like protein ATG12 [KO:K08336]
112973331  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
112963113  gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
112976939  microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
112978492  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B isoform X1 [KO:K10435]
112973810  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
112974642  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A isoform X1 [KO:K10435]
112962610  SUGT1; protein SGT1 homolog isoform X1 [KO:K12795]
112976666  sharpin [KO:K10630] [EC:2.3.2.31]
112977305  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
112961337  ERBIN; erbin isoform X1 [KO:K12796]
112971955  BIRC2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
112969740  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
112969242  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
112960908  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
112964351  CARD9; caspase recruitment domain-containing protein 9 isoform X1 [KO:K12794]
112971132  TNFAIP3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
112969435  MAVS; mitochondrial antiviral-signaling protein isoform X1 [KO:K12648]
112972701  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
112968150  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
112971687  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
112972028  TANK; TRAF family member-associated NF-kappa-B activator isoform X1 [KO:K12650]
112962692  IRF7; interferon regulatory factor 7 [KO:K09447]
112969822  interferon alpha-10-like [KO:K05414]
112978363  interferon beta-like [KO:K05414]
112976152  interferon-like [KO:K05415]
112967468  NLRX1; NLR family member X1 [KO:K12653]
112963885  ANTXRL; anthrax toxin receptor-like [KO:K20909]
112973582  ANTXR2; anthrax toxin receptor 2 isoform X1 [KO:K20909]
112973635  ANTXR1; anthrax toxin receptor 1 [KO:K20909]
112966225  apoptosis-associated speck-like protein containing a CARD [KO:K12799]
112965025  caspase-1-like isoform X1 [KO:K01370] [EC:3.4.22.36]
112972797  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
112965948  BCL2L1; bcl-2-like protein 1 [KO:K04570]
112963755  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
112969059  PANX1; pannexin-1 isoform X1 [KO:K03443]
112962564  P2RX7; P2X purinoceptor 7 [KO:K05220]
112971718  TRPM2; transient receptor potential cation channel subfamily M member 2 isoform X1 [KO:K04977] [EC:3.6.1.13]
112963477  TRPM7; transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
112960734  TRPV2; transient receptor potential cation channel subfamily V member 2 isoform X1 [KO:K04971]
112963960  CASR; extracellular calcium-sensing receptor isoform X1 [KO:K04612]
112966166  GPRC6A; G-protein coupled receptor family C group 6 member A [KO:K04622]
112969665  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
112965294  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
112965307  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
112970422  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
112966593  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
112961456  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
112964883  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
112961045  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
112974191  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
112969799  MCU; calcium uniporter protein, mitochondrial [KO:K20858]
112975073  RNASEL; 2-5A-dependent ribonuclease [KO:K01165]
112965043  DHX33; ATP-dependent RNA helicase DHX33 isoform X1 [KO:K17820] [EC:5.6.2.6]
112964269  MFN1; mitofusin-1 isoform X1 [KO:K21356] [EC:3.6.5.-]
112970127  MFN2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
112968039  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
112974961  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
112962648  NAMPT; nicotinamide phosphoribosyltransferase isoform X1 [KO:K03462] [EC:2.4.2.12]
112969450  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
112978482  cytochrome b-245 light chain [KO:K08009]
112975514  TXNIP; thioredoxin-interacting protein isoform X1 [KO:K20910]
112963989  thioredoxin isoform X1 [KO:K03671]
112971479  TXN2; thioredoxin, mitochondrial [KO:K03671]
112976511  NEK7; serine/threonine-protein kinase Nek7 isoform X1 [KO:K20876] [EC:2.7.11.34]
112966276  BRCC3; lys-63-specific deubiquitinase BRCC36 [KO:K11864] [EC:3.4.19.-]
112972749  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
112973400  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
112973906  caspase recruitment domain-containing protein 8-like isoform X1 [KO:K12801]
112967280  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 [KO:K12804]
112976408  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
112976426  caspase-8-like isoform X1 [KO:K04398] [EC:3.4.22.61]
112977257  FADD; FAS-associated death domain protein [KO:K02373]
112969687  NACHT, LRR and PYD domains-containing protein 3-like [KO:K20865]
112964219  NACHT, LRR and PYD domains-containing protein 3-like isoform X1 [KO:K20865]
112973774  NLRP6; NACHT, LRR and PYD domains-containing protein 6 [KO:K20865]
112972980  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
112976288  TP53BP1; TP53-binding protein 1 isoform X1 [KO:K20915]
112975194  RHOA; transforming protein RhoA [KO:K04513]
112961852  PKN2; serine/threonine-protein kinase N2 isoform X1 [KO:K23691] [EC:2.7.11.13]
112960685  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
112971829  IFNAR1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
112971838  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
112970278  JAK1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
112962009  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
112978333  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
112974309  STAT2; LOW QUALITY PROTEIN: signal transducer and activator of transcription 2 [KO:K11221]
112963054  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
112966772  TIR domain-containing adapter molecule 1-like isoform X1 [KO:K05842]
112978275  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
112976393  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
112967099  TMEM173; stimulator of interferon genes protein [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
arow04010  MAPK signaling pathway
arow04140  Autophagy - animal
arow04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
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