KEGG   PATHWAY: cfa04621
Entry
cfa04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Canis lupus familiaris (dog)
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
cfa04621  NOD-like receptor signaling pathway
cfa04621

Organism
Canis lupus familiaris (dog) [GN:cfa]
Gene
100135059  DEFB4A; beta-defensin 2 precursor [KO:K21100]
100170103  CBD103; beta-defensin 14 precursor [KO:K23126]
100682977  [KO:K05414]
100683045  [KO:K05414]
100683567  [KO:K05414]
100684769  [KO:K14139] [EC:3.6.5.-]
100685213  [KO:K05414]
100686162  [KO:K05414]
100687242  [KO:K04079]
100688005  [KO:K05414]
100688084  [KO:K05414]
100688110  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
100688481  CARD6; caspase recruitment domain-containing protein 6 isoform X1 [KO:K12797]
100855742  NLRP12; NACHT, LRR and PYD domains-containing protein 12 isoform X1 [KO:K20865]
100855877  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100856182  ERBIN; erbin isoform X1 [KO:K12796]
100856190  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
100856347  PYCARD; apoptosis-associated speck-like protein containing a CARD isoform X1 [KO:K12799]
100856398  PKN1; serine/threonine-protein kinase N1 isoform X3 [KO:K06071] [EC:2.7.11.13]
100856408  TRPM2; transient receptor potential cation channel subfamily M member 2 isoform X9 [KO:K04977] [EC:3.6.1.13]
100856468  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
100856598  NAMPT; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
102152063  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
102152873  [KO:K05862]
102153882  [KO:K12805]
102155674  [KO:K12795]
102156745  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
119864198  IRF7; interferon regulatory factor 7 isoform X1 [KO:K09447]
119874472  [KO:K05505]
119876918  [KO:K05505]
403416  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
403417  TLR4; toll-like receptor 4 precursor [KO:K10160]
403522  CCL5; C-C motif chemokine 5 precursor [KO:K12499]
403618  BCL2L1; bcl-2-like protein 1 [KO:K04570]
403724  CASP4; caspase-1 [KO:K04394] [EC:3.4.22.57 3.4.22.64]
403796  IL18; interleukin-18 precursor [KO:K05482]
403850  CXCL8; interleukin-8 precursor [KO:K10030]
403856  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
403922  TNF; tumor necrosis factor [KO:K03156]
403954  RHOA; transforming protein RhoA [KO:K04513]
403974  IL1B; interleukin-1 beta [KO:K04519]
403981  CCL2; C-C motif chemokine 2 precursor [KO:K14624]
403985  IL6; interleukin-6 precursor [KO:K05405]
442859  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
442934  IFNA5; interferon alpha-3 precursor [KO:K05414]
442947  CAMP; cathelicidin antimicrobial peptide precursor [KO:K13916]
442952  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
442989  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
448778  P2RX7; P2X purinoceptor 7 [KO:K05220]
474181  IFNA7; interferon alpha-1/2 precursor [KO:K05414]
474519  TXN2; thioredoxin, mitochondrial [KO:K03671]
474636  ATG12; ubiquitin-like protein ATG12 isoform X2 [KO:K08336]
474652  MAPK9; mitogen-activated protein kinase 9 isoform X4 [KO:K04440] [EC:2.7.11.24]
474681  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
474798  TXN; thioredoxin [KO:K03671]
474919  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
475122  [KO:K20894]
475829  TXNIP; thioredoxin-interacting protein [KO:K20910]
476034  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X2 [KO:K05858] [EC:3.1.4.11]
476412  IRF3; interferon regulatory factor 3 isoform X2 [KO:K05411]
476548  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
476714  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
477024  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
477160  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
477201  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
477412  ATG16L1; autophagy-related protein 16-1 isoform X1 [KO:K17890]
477490  OAS3; 2'-5'-oligoadenylate synthase 3 [KO:K14216] [EC:2.7.7.84]
477575  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
477649  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
477746  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
477796  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X3 [KO:K04467] [EC:2.7.11.10]
477936  RIPK2; receptor-interacting serine/threonine-protein kinase 2 isoform X1 [KO:K08846] [EC:2.7.11.1]
478274  TP53BP1; TP53-binding protein 1 isoform X2 [KO:K20915]
478300  TRPM7; transient receptor potential cation channel subfamily M member 7 isoform X12 [KO:K04982] [EC:2.7.11.1]
478464  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
478950  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
479255  VDAC2; voltage-dependent anion-selective channel protein 2 isoform X1 [KO:K15040]
479458  CASP12; caspase-12 [KO:K04741] [EC:3.4.22.-]
479464  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
479479  GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
479619  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B isoform X1 [KO:K10435]
479646  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 isoform X1 [KO:K08341]
479732  TRIP6; thyroid receptor-interacting protein 6 isoform X2 [KO:K12792]
480008  NEK7; serine/threonine-protein kinase Nek7 isoform X1 [KO:K20876] [EC:2.7.11.34]
480019  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
480259  RNF31; E3 ubiquitin-protein ligase RNF31 isoform X1 [KO:K11974] [EC:2.3.2.31]
480291  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
480438  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
480645  YWHAE; 14-3-3 protein epsilon isoform X2 [KO:K06630]
480673  TRAF2; TNF receptor-associated factor 2 isoform X2 [KO:K03173] [EC:2.3.2.27]
481111  STAT2; signal transducer and activator of transcription 2 isoform X2 [KO:K11221]
481145  TBK1; serine/threonine-protein kinase TBK1 isoform X2 [KO:K05410] [EC:2.7.11.10]
481245  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
481473  [KO:K14139] [EC:3.6.5.-]
481558  IFNB1; interferon beta precursor [KO:K05415]
481746  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
482382  NOD1; nucleotide-binding oligomerization domain-containing protein 1 isoform X1 [KO:K08727]
482839  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
483394  NLRP6; NACHT, LRR and PYD domains-containing protein 6 [KO:K20863]
483729  RELA; transcription factor p65 isoform X2 [KO:K04735]
484006  TNFAIP3; tumor necrosis factor alpha-induced protein 3 isoform X2 [KO:K11859] [EC:3.4.19.12]
484028  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X2 [KO:K04404]
484095  GPRC6A; G-protein coupled receptor family C group 6 member A [KO:K04622]
484411  CARD8; LOW QUALITY PROTEIN: caspase recruitment domain-containing protein 8 isoform X7 [KO:K12801]
484519  NFKBIB; NF-kappa-B inhibitor beta isoform X2 [KO:K02581]
485773  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
485789  MAVS; mitochondrial antiviral-signaling protein [KO:K12648]
485818  RBCK1; ranBP-type and C3HC4-type zinc finger-containing protein 1 isoform X2 [KO:K10630] [EC:2.3.2.31]
486077  CTSB; cathepsin B isoform X2 [KO:K01363] [EC:3.4.22.1]
486601  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X2 [KO:K04733] [EC:2.7.11.1]
486628  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X2 [KO:K04959]
487286  NOD2; nucleotide-binding oligomerization domain-containing protein 2 [KO:K10165]
487439  MFN2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
487821  ANTXR2; anthrax toxin receptor 2 isoform X2 [KO:K20909]
488007  CASR; extracellular calcium-sensing receptor precursor [KO:K04612]
488086  MFN1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
488449  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
488473  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
488622  [KO:K20914]
489042  MCU; calcium uniporter protein, mitochondrial isoform X1 [KO:K20858]
489370  NLRX1; NLR family member X1 isoform X1 [KO:K12653]
489433  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
489449  NLRP1; NACHT, LRR and PYD domains-containing protein 1 isoform X4 [KO:K12798]
489522  TRPV2; transient receptor potential cation channel subfamily V member 2 [KO:K04971]
489664  CYBA; cytochrome b-245 alpha chain [KO:K08009]
490170  GBP5; guanylate-binding protein 5 [KO:K20898]
490172  GBP1; LOW QUALITY PROTEIN: guanylate-binding protein 1 [KO:K20899]
490174  PKN2; serine/threonine-protein kinase N2 isoform X1 [KO:K23691]
490310  RNASEL; 2-5A-dependent ribonuclease [KO:K01165]
490576  NLRP3; NACHT, LRR and PYD domains-containing protein 3 isoform X2 [KO:K12800]
490867  TRAF3; TNF receptor-associated factor 3 [KO:K03174]
491807  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
491825  CYBB; cytochrome b-245, beta polypeptide [KO:K21421] [EC:1.-.-.-]
494005  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
606815  STING1; stimulator of interferon genes protein isoform X1 [KO:K12654]
606863  [KO:K14139] [EC:3.6.5.-]
606963  VDAC3; voltage-dependent anion-selective channel protein 3 isoform 1 [KO:K15041]
607019  MAPK11; mitogen-activated protein kinase 11 isoform X2 [KO:K04441] [EC:2.7.11.24]
607023  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
607226  DHX33; ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
607492  CARD9; caspase recruitment domain-containing protein 9 isoform X2 [KO:K12794]
607532  PANX1; pannexin-1 isoform X3 [KO:K03443]
607687  GPSM3; G-protein-signaling modulator 3 isoform X1 [KO:K15838]
607899  IRF9; interferon regulatory factor 9 [KO:K04693]
608092  TANK; TRAF family member-associated NF-kappa-B activator isoform X1 [KO:K12650]
608486  RIPK3; receptor-interacting serine/threonine-protein kinase 3 isoform X8 [KO:K08847] [EC:2.7.11.1]
608573  [KO:K06630]
608778  OAS1; 2'-5'-oligoadenylate synthase 1 [KO:K14216] [EC:2.7.7.84]
609395  GSDMD; gasdermin-D [KO:K20917]
609429  JUN; transcription factor AP-1 [KO:K04448]
609605  SUGT1; protein SGT1 homolog isoform X2 [KO:K12795]
609830  IFNAR1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
610150  [KO:K11864] [EC:3.4.19.-]
610868  ATG5; autophagy protein 5 isoform X1 [KO:K08339]
611051  OAS2; 2'-5'-oligoadenylate synthase 2 [KO:K14216] [EC:2.7.7.84]
611406  [KO:K05414]
611659  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
611694  FADD; FAS-associated death domain protein isoform X1 [KO:K02373]
611757  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 isoform X1 [KO:K12804]
611852  TICAM1; TIR domain-containing adapter molecule 1 isoform X5 [KO:K05842]
612601  ANTXR1; anthrax toxin receptor 1 isoform X1 [KO:K20909]
612642  BRCC3; lys-63-specific deubiquitinase BRCC36 isoform X4 [KO:K11864] [EC:3.4.19.-]
612821  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
612919  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
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
cfa04010  MAPK signaling pathway
cfa04064  NF-kappa B signaling pathway
cfa04140  Autophagy - animal
cfa04620  Toll-like receptor signaling pathway
KO pathway
ko04621   

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