KEGG   PATHWAY: atrc04621
Entry
atrc04621                   Pathway                                
Name
NOD-like receptor signaling pathway - Agelaius tricolor (tricolored blackbird)
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
atrc04621  NOD-like receptor signaling pathway
atrc04621

Organism
Agelaius tricolor (tricolored blackbird) [GN:atrc]
Gene
139585011  TXNIP; thioredoxin-interacting protein isoform X1 [KO:K20910]
139585184  IL1B; interleukin-1 beta isoform X1 [KO:K04519]
139585212  ANTXR1; anthrax toxin receptor 1 isoform X1 [KO:K20909]
139585453  [KO:K10630] [EC:2.3.2.31]
139585686  [KO:K04693]
139585926  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
139586234  IKBKG; NF-kappa-B essential modulator [KO:K07210]
139586360  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
139586434  RELA; transcription factor p65 isoform X1 [KO:K04735]
139586835  [KO:K05858] [EC:3.1.4.11]
139586853  [KO:K03156]
139587061  GABARAP; gamma-aminobutyric acid receptor-associated protein isoform X1 [KO:K08341]
139587374  RIPK2; receptor-interacting serine/threonine-protein kinase 2 isoform X1 [KO:K08846] [EC:2.7.11.1]
139587822  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
139587879  ITPR2; inositol 1,4,5-trisphosphate-gated calcium channel ITPR2 isoform X1 [KO:K04959]
139587901  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
139587972  TXN2; thioredoxin, mitochondrial [KO:K03671]
139588038  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
139588318  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
139588353  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
139588431  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
139588433  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
139588489  NAMPT; nicotinamide phosphoribosyltransferase isoform X1 [KO:K03462] [EC:2.4.2.12]
139588754  [KO:K05415]
139588780  ATG12; ubiquitin-like protein ATG12 [KO:K08336]
139588806  [KO:K03671]
139589161  ERBIN; erbin isoform X1 [KO:K12796]
139589349  [KO:K05415]
139589350  [KO:K05415]
139589352  [KO:K05415]
139589353  [KO:K05415]
139589354  [KO:K05415]
139589355  [KO:K05415]
139589356  [KO:K05415]
139589357  [KO:K05415]
139589358  [KO:K05415]
139589359  [KO:K05415]
139589360  [KO:K05415]
139589361  [KO:K05415]
139589363  [KO:K05415]
139589496  [KO:K05414]
139589751  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
139589763  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
139589789  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
139589958  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
139590148  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
139590236  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
139590269  IRF7; interferon regulatory factor 7 isoform X1 [KO:K09447]
139590399  [KO:K20865]
139590445  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
139590612  FADD; FAS-associated death domain protein [KO:K02373]
139590747  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
139590778  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
139591055  IL6; LOW QUALITY PROTEIN: interleukin-6 [KO:K05405]
139591131  GPRC6A; G-protein coupled receptor family C group 6 member A [KO:K04622]
139591169  NOD1; nucleotide-binding oligomerization domain-containing protein 1 [KO:K08727]
139591456  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
139591470  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
139591590  CYBB; cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
139591598  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
139592045  ANTXR2; anthrax toxin receptor 2 isoform X1 [KO:K20909]
139592107  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
139592250  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
139592589  [KO:K10030]
139592590  [KO:K10030]
139592591  [KO:K10030]
139592685  PANX1; pannexin-1 [KO:K03443]
139592744  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
139592863  CASR; extracellular calcium-sensing receptor [KO:K04612]
139593108  TNFAIP3; tumor necrosis factor alpha-induced protein 3 isoform X1 [KO:K11859] [EC:3.4.19.12]
139593348  [KO:K16060]
139593533  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
139593575  [KO:K04398] [EC:3.4.22.61]
139593578  [KO:K04398] [EC:3.4.22.61]
139593742  TANK; TRAF family member-associated NF-kappa-B activator isoform X1 [KO:K12650]
139594140  RNASEL; 2-5A-dependent ribonuclease [KO:K01165]
139594235  NEK7; LOW QUALITY PROTEIN: serine/threonine-protein kinase Nek7 [KO:K20876] [EC:2.7.11.34]
139594352  PKN2; serine/threonine-protein kinase N2 isoform X1 [KO:K23691]
139594554  JUN; transcription factor Jun [KO:K04448]
139594582  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
139594794  TRPM2; transient receptor potential cation channel subfamily M member 2 isoform X1 [KO:K04977] [EC:3.6.1.13]
139594860  ATG16L1; autophagy-related protein 16-1 isoform X1 [KO:K17890]
139595090  MFN1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
139595393  MCU; calcium uniporter protein, mitochondrial isoform X1 [KO:K20858]
139595416  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
139595474  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
139595531  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
139595584  ANTXRL; anthrax toxin receptor-like [KO:K20909]
139595591  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
139595734  ITPR1; inositol 1,4,5-trisphosphate-gated calcium channel ITPR1 isoform X1 [KO:K04958]
139595919  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
139595936  RHOA; transforming protein RhoA [KO:K04513]
139595990  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
139596295  [KO:K08846] [EC:2.7.11.1]
139596482  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
139596516  CYBA; cytochrome b-245 light chain [KO:K08009]
139596567  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
139596631  TP53BP1; TP53-binding protein 1 isoform X1 [KO:K20915]
139596843  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
139596963  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 [KO:K12804]
139597288  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
139597354  BRCC3; lys-63-specific deubiquitinase BRCC36 isoform X1 [KO:K11864] [EC:3.4.19.-]
139597661  VDAC1; non-selective voltage-gated ion channel VDAC1 [KO:K05862]
139597702  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
139597907  STING1; stimulator of interferon genes protein isoform X1 [KO:K12654]
139598700  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
139598943  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
139599422  ATG5; autophagy protein 5 isoform X1 [KO:K08339]
139599586  BCL2L1; bcl-2-like protein 1 [KO:K04570]
139599727  MAVS; mitochondrial antiviral-signaling protein [KO:K12648]
139599874  DHX33; LOW QUALITY PROTEIN: ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
139599878  [KO:K12499]
139599888  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
139599946  [KO:K04971]
139599986  YWHAE; 14-3-3 protein epsilon [KO:K06630]
139600035  [KO:K12499]
139600351  SUGT1; protein SGT1 homolog [KO:K12795]
139600778  MFN2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
139601044  NLRX1; NLR family member X1 [KO:K12653]
139601057  IL18; interleukin-18 isoform X1 [KO:K05482]
139601123  ITPR3; inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 isoform X1 [KO:K04960]
139601305  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
139601429  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
139601430  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
139602399  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
139602740  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
139603009  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
139603169  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
139603185  TLR4; toll-like receptor 4 [KO:K10160]
139603403  CARD9; caspase recruitment domain-containing protein 9 isoform X1 [KO:K12794]
139603809  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
139603816  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
139604287  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
139605068  CAMP; cathelicidin antimicrobial peptide [KO:K13916]
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
atrc04010  MAPK signaling pathway
atrc04140  Autophagy - animal
atrc04620  Toll-like receptor signaling pathway
KO pathway
ko04621   

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