KEGG   PATHWAY: scan04621
Entry
scan04621                   Pathway                                
Name
NOD-like receptor signaling pathway - Serinus canaria (common canary)
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
scan04621  NOD-like receptor signaling pathway
scan04621

Organism
Serinus canaria (common canary) [GN:scan]
Gene
103812959  NOD1; nucleotide-binding oligomerization domain-containing protein 1 isoform X1 [KO:K08727]
103816814  receptor-interacting serine/threonine-protein kinase 2-like isoform X1 [KO:K08846] [EC:2.7.11.1]
103813399  RIPK2; receptor-interacting serine/threonine-protein kinase 2 isoform X1 [KO:K08846] [EC:2.7.11.1]
103814234  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X2 [KO:K04467] [EC:2.7.11.10]
103822735  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
103826549  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
103826026  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
103822662  IL1B; interleukin-1 beta isoform X2 [KO:K04519]
103822985  IL18; interleukin-18 isoform X1 [KO:K05482]
103813132  IL6; interleukin-6 [KO:K05405]
103823445  interleukin-8-like [KO:K10030]
103823470  interleukin-8-like [KO:K10030]
103823472  interleukin-8-like [KO:K10030]
103823469  alveolar macrophage chemotactic factor-like [KO:K05505]
103820036  C-C motif chemokine 5-like isoform X1 [KO:K12499]
103812672  CAMP; LOW QUALITY PROTEIN: cathelicidin antimicrobial peptide [KO:K13916]
103813032  cathelicidin-B1-like [KO:K13916]
103823292  gallinacin-2 [KO:K21100]
103819102  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X5 [KO:K04427] [EC:2.7.11.25]
103813611  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
103818533  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
103815792  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
103818074  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103817284  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
103813947  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
103826066  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
103813699  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
103823281  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
103823282  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
103813488  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
103815057  JUN; transcription factor AP-1 [KO:K04448]
103815461  ATG16L1; autophagy-related protein 16-1 isoform X2 [KO:K17890]
103818829  ATG5; autophagy protein 5 isoform X1 [KO:K08339]
103821471  ATG12; ubiquitin-like protein ATG12 [KO:K08336]
103816785  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
103819569  gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
103825386  GABARAP; LOW QUALITY PROTEIN: gamma-aminobutyric acid receptor-associated protein [KO:K08341]
103816874  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
103818582  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
103818531  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
103812584  SUGT1; protein SGT1 homolog [KO:K12795]
103816388  XIAP; E3 ubiquitin-protein ligase XIAP isoform X2 [KO:K04725] [EC:2.3.2.27]
103823132  ERBIN; erbin isoform X1 [KO:K12796]
103827281  inhibitor of apoptosis protein [KO:K16060]
103819084  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
103821528  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
103826724  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
103819122  CARD9; caspase recruitment domain-containing protein 9 isoform X1 [KO:K12794]
103818470  TNFAIP3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
103823098  MAVS; mitochondrial antiviral-signaling protein [KO:K12648]
103826414  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
103820400  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
103822391  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X3 [KO:K07211] [EC:2.7.11.10]
103814384  TANK; TRAF family member-associated NF-kappa-B activator isoform X2 [KO:K12650]
103824089  IRF7; interferon regulatory factor 7 [KO:K09447]
103819513  interferon kappa-like [KO:K05414]
115485133  IFNK; interferon kappa [KO:K05414]
108962800  LOW QUALITY PROTEIN: interferon-like [KO:K05415]
103823038  NLRX1; NLR family member X1 [KO:K12653]
103814189  ANTXRL; anthrax toxin receptor-like [KO:K20909]
103823449  ANTXR2; anthrax toxin receptor 2 isoform X1 [KO:K20909]
103822728  ANTXR1; anthrax toxin receptor 1 [KO:K20909]
108964924  BCL2; apoptosis regulator Bcl-2 isoform X2 [KO:K02161]
103818674  BCL2L1; bcl-2-like protein 1 [KO:K04570]
103821275  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
103812509  PANX1; pannexin-1 [KO:K03443]
103815520  TRPM2; transient receptor potential cation channel subfamily M member 2 isoform X1 [KO:K04977] [EC:3.6.1.13]
103816033  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
103820148  transient receptor potential cation channel subfamily V member 2 isoform X2 [KO:K04971]
103827139  CASR; extracellular calcium-sensing receptor isoform X1 [KO:K04612]
103818399  GPRC6A; G-protein coupled receptor family C group 6 member A [KO:K04622]
103822183  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
103819233  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
103819309  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
103823703  ITPR1; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
103819592  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
103823305  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
103817251  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
103814011  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
103822679  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
103823735  MCU; calcium uniporter protein, mitochondrial [KO:K20858]
103823366  RNASEL; 2-5A-dependent ribonuclease [KO:K01165]
103820063  DHX33; ATP-dependent RNA helicase DHX33 isoform X1 [KO:K17820] [EC:5.6.2.6]
103815307  MFN1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
103820843  MFN2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
103817591  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
103819631  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
103813725  NAMPT; nicotinamide phosphoribosyltransferase isoform X1 [KO:K03462] [EC:2.4.2.12]
103815785  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
103816882  cytochrome b-245 light chain [KO:K08009]
103824013  TXNIP; thioredoxin-interacting protein isoform X1 [KO:K20910]
103821826  TXN; thioredoxin [KO:K03671]
103813217  TXN2; thioredoxin, mitochondrial [KO:K03671]
103814835  NEK7; serine/threonine-protein kinase Nek7 [KO:K20876] [EC:2.7.11.34]
103824253  BRCC3; lys-63-specific deubiquitinase BRCC36 [KO:K11864] [EC:3.4.19.-]
103817905  HSP90AB1; heat shock protein HSP 90-beta isoform X1 [KO:K04079]
103826421  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
103823176  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 isoform X1 [KO:K12804]
103814506  caspase-8-like [KO:K04398] [EC:3.4.22.61]
103814507  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
103822220  FADD; FAS-associated death domain protein [KO:K02373]
103822288  NACHT, LRR and PYD domains-containing protein 12-like isoform X1 [KO:K20865]
103816971  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
103816291  TP53BP1; TP53-binding protein 1 isoform X1 [KO:K20915]
103816985  RHOA; transforming protein RhoA [KO:K04513]
103814908  PKN2; serine/threonine-protein kinase N2 isoform X1 [KO:K23691] [EC:2.7.11.13]
103820105  YWHAE; 14-3-3 protein epsilon [KO:K06630]
103824810  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
103824806  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
103815217  tyrosine-protein kinase JAK1-like [KO:K11217] [EC:2.7.10.2]
103815215  tyrosine-protein kinase JAK1-like [KO:K11217] [EC:2.7.10.2]
103825008  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
103814539  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
103819051  TLR4; toll-like receptor 4 [KO:K10160]
103821959  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
103813055  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
103820377  IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
103817453  TMEM173; stimulator of interferon genes protein isoform X1 [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
scan04010  MAPK signaling pathway
scan04140  Autophagy - animal
scan04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
LinkDB

DBGET integrated database retrieval system