KEGG   PATHWAY: fca04621
Entry
fca04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Felis catus (domestic cat)
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
fca04621  NOD-like receptor signaling pathway
fca04621

Organism
Felis catus (domestic cat) [GN:fca]
Gene
100127112  MCP-1; C-C motif chemokine 2 [KO:K14624]
100135767  CASP12; inactive caspase-12 [KO:K04741] [EC:3.4.22.-]
100142682  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X2 [KO:K07209] [EC:2.7.11.10]
100142683  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100142684  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
100302732  CASR; extracellular calcium-sensing receptor precursor [KO:K04612]
100533978  CAMP; cathelicidin antimicrobial peptide precursor [KO:K13916]
101081370  NAMPT; nicotinamide phosphoribosyltransferase isoform X1 [KO:K03462] [EC:2.4.2.12]
101081371  [KO:K05414]
101081653  PKN2; serine/threonine-protein kinase N2 isoform X1 [KO:K23691]
101081664  PANX1; pannexin-1 [KO:K03443]
101081984  [KO:K10435]
101082424  [KO:K20899]
101082884  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
101083061  ERBIN; erbin isoform X1 [KO:K12796]
101083444  [KO:K16060]
101083455  MCU; calcium uniporter protein, mitochondrial isoform X2 [KO:K20858]
101083505  RBCK1; ranBP-type and C3HC4-type zinc finger-containing protein 1 isoform X3 [KO:K10630] [EC:2.3.2.31]
101083606  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
101083682  TNFAIP3; tumor necrosis factor alpha-induced protein 3 isoform X2 [KO:K11859] [EC:3.4.19.12]
101083945  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
101084011  RHOA; transforming protein RhoA [KO:K04513]
101084060  IRF7; interferon regulatory factor 7 isoform X1 [KO:K09447]
101084377  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
101084561  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
101084765  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
101084873  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
101085164  NLRP12; NACHT, LRR and PYD domains-containing protein 12 isoform X1 [KO:K20865]
101085618  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
101085709  MAVS; mitochondrial antiviral-signaling protein isoform X1 [KO:K12648]
101086032  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
101086207  CYBB; cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
101086282  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
101086544  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
101086783  RIPK2; receptor-interacting serine/threonine-protein kinase 2 isoform X1 [KO:K08846] [EC:2.7.11.1]
101086963  NOD1; nucleotide-binding oligomerization domain-containing protein 1 isoform X1 [KO:K08727]
101087092  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
101087351  NLRP6; NACHT, LRR and PYD domains-containing protein 6 [KO:K20863]
101087614  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101087657  NLRC4; LOW QUALITY PROTEIN: NLR family CARD domain-containing protein 4 [KO:K12805]
101087663  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
101087716  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
101087871  FADD; FAS-associated death domain protein [KO:K02373]
101087875  OAS1; 2'-5'-oligoadenylate synthase 1 [KO:K14216] [EC:2.7.7.84]
101087958  MAPK3; mitogen-activated protein kinase 3 isoform X2 [KO:K04371] [EC:2.7.11.24]
101087993  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
101088116  OAS3; 2'-5'-oligoadenylate synthase 3 isoform X1 [KO:K14216] [EC:2.7.7.84]
101088440  [KO:K05414]
101088449  PYCARD; apoptosis-associated speck-like protein containing a CARD [KO:K12799]
101088808  SUGT1; protein SGT1 homolog [KO:K12795]
101089087  MFN1; mitofusin-1 isoform X1 [KO:K21356] [EC:3.6.5.-]
101089493  GSDMD; gasdermin-D [KO:K20917]
101090005  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
101090171  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
101090284  TRPM2; transient receptor potential cation channel subfamily M member 2 isoform X4 [KO:K04977] [EC:3.6.1.13]
101090285  IFNAR2; interferon alpha/beta receptor 2 [KO:K05131]
101090330  [KO:K12807]
101090594  [KO:K04725] [EC:2.3.2.27]
101090622  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
101090655  TXN; thioredoxin [KO:K03671]
101090659  DHX33; ATP-dependent RNA helicase DHX33 isoform X1 [KO:K17820] [EC:5.6.2.6]
101090737  STING1; stimulator of interferon genes protein isoform X1 [KO:K12654]
101090942  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
101091310  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
101091536  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
101091745  CYBA; cytochrome b-245 light chain [KO:K08009]
101091955  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
101092114  ATG5; autophagy protein 5 isoform X1 [KO:K08339]
101092262  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
101092535  IFNAR1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
101092579  NLRP3; NACHT, LRR and PYD domains-containing protein 3 isoform X1 [KO:K12800]
101092611  GPRC6A; G-protein coupled receptor family C group 6 member A [KO:K04622]
101092793  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
101092930  ANTXR1; anthrax toxin receptor 1 isoform X1 [KO:K20909]
101092961  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
101093152  CARD9; caspase recruitment domain-containing protein 9 isoform X1 [KO:K12794]
101093327  NEK7; serine/threonine-protein kinase Nek7 isoform X1 [KO:K20876] [EC:2.7.11.34]
101093701  [KO:K20899]
101093817  CARD8; caspase recruitment domain-containing protein 8 isoform X1 [KO:K12801]
101093854  [KO:K10030]
101093951  [KO:K20899]
101093972  TRPV2; transient receptor potential cation channel subfamily V member 2 [KO:K04971]
101094029  TXN2; thioredoxin, mitochondrial [KO:K03671]
101094063  [KO:K20864]
101094174  ANTXR2; anthrax toxin receptor 2 [KO:K20909]
101094189  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
101094195  GBP5; guanylate-binding protein 5 [KO:K20898]
101094318  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
101094469  TRIP6; thyroid receptor-interacting protein 6 isoform X1 [KO:K12792]
101094481  SHARPIN; sharpin isoform X2 [KO:K20894]
101094636  GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
101094857  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
101094867  TANK; TRAF family member-associated NF-kappa-B activator isoform X1 [KO:K12650]
101095177  TRPM7; transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
101095311  IFI16; gamma-interferon-inducible protein 16 isoform X10 [KO:K20914]
101095402  CARD6; caspase recruitment domain-containing protein 6 isoform X1 [KO:K12797]
101095617  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
101095705  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
101095825  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
101095899  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
101095934  IRF3; interferon regulatory factor 3 isoform X3 [KO:K05411]
101096259  NLRX1; NLR family member X1 isoform X1 [KO:K12653]
101096363  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
101096553  BRCC3; lys-63-specific deubiquitinase BRCC36 isoform X1 [KO:K11864] [EC:3.4.19.-]
101096604  RELA; transcription factor p65 [KO:K04735]
101096694  MEFV; pyrin isoform X1 [KO:K12803]
101096739  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
101096863  NOD2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165]
101097261  JUN; transcription factor AP-1 [KO:K04448]
101097365  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 isoform X2 [KO:K08341]
101097547  PKN1; serine/threonine-protein kinase N1 isoform X2 [KO:K06071] [EC:2.7.11.13]
101097560  GPSM3; G-protein-signaling modulator 3 isoform X1 [KO:K15838]
101097922  P2RX7; P2X purinoceptor 7 isoform X1 [KO:K05220]
101097985  RIPK3; receptor-interacting serine/threonine-protein kinase 3 isoform X1 [KO:K08847] [EC:2.7.11.1]
101098515  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
101098714  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
101098873  TP53BP1; TP53-binding protein 1 isoform X1 [KO:K20915]
101099117  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
101099224  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
101099259  NFKBIB; LOW QUALITY PROTEIN: NF-kappa-B inhibitor beta [KO:K02581]
101099739  TXNIP; thioredoxin-interacting protein [KO:K20910]
101099750  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
101100213  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 isoform X1 [KO:K12804]
101100225  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
101100546  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X2 [KO:K04958]
101100727  RNF31; E3 ubiquitin-protein ligase RNF31 isoform X1 [KO:K11974] [EC:2.3.2.31]
101100748  ATG16L1; autophagy-related protein 16-1 isoform X1 [KO:K17890]
101100938  ATG12; ubiquitin-like protein ATG12 isoform X1 [KO:K08336]
101100970  IRF9; interferon regulatory factor 9 [KO:K04693]
101101068  MFN2; mitofusin-2 isoform X2 [KO:K06030] [EC:3.6.5.-]
101101102  RNASEL; 2-5A-dependent ribonuclease [KO:K01165]
101101135  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101101212  [KO:K23126]
101101230  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
101101425  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
101101463  MAPK10; mitogen-activated protein kinase 10 isoform X3 [KO:K04440] [EC:2.7.11.24]
101101545  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
101101663  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
102899304  [KO:K05862]
102900654  [KO:K06630]
102901432  [KO:K05505]
102902352  [KO:K15041]
102902426  OAS2; 2'-5'-oligoadenylate synthase 2 isoform X2 [KO:K14216] [EC:2.7.7.84]
105260786  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
111556320  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
111557596  [KO:K05414]
111560177  [KO:K05505]
111560178  [KO:K05505]
123381775  [KO:K05414]
493648  IFNA8; interferon alpha-8 precursor [KO:K05414]
493653  IFNA7; interferon alpha precursor [KO:K05414]
493687  IL6; interleukin-6 precursor [KO:K05405]
493688  IL18; interleukin-18 [KO:K05482]
493689  CCL5; C-C motif chemokine 5 precursor [KO:K12499]
493698  TLR4; toll-like receptor 4 precursor [KO:K10160]
493701  BCL2L1; bcl-2-like protein 1 [KO:K04570]
493755  TNF; tumor necrosis factor precursor [KO:K03156]
493836  CXCL8; interleukin-8 precursor [KO:K10030]
493840  IFNA5; interferon alpha-5 [KO:K05414]
493849  IFNB1; interferon beta precursor [KO:K05415]
493934  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
493961  CASP4; caspase-1 [KO:K04394] [EC:3.4.22.57 3.4.22.64]
768274  IL1B; interleukin-1 beta [KO:K04519]
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
fca04010  MAPK signaling pathway
fca04064  NF-kappa B signaling pathway
fca04140  Autophagy - animal
fca04620  Toll-like receptor signaling pathway
KO pathway
ko04621   

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