KEGG   PATHWAY: csab04621
Entry
csab04621                   Pathway                                
Name
NOD-like receptor signaling pathway - Chlorocebus sabaeus (green monkey)
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
csab04621  NOD-like receptor signaling pathway
csab04621

Organism
Chlorocebus sabaeus (green monkey) [GN:csab]
Gene
103214484  SUGT1; SGT1 homolog, MIS12 kinetochore complex assembly cochaperone [KO:K12795]
103215179  CARD6; caspase recruitment domain family member 6 [KO:K12797]
103215301  [KO:K05230]
103215303  [KO:K05230]
103215304  DEFA1; defensin alpha 1 [KO:K05230]
103215308  DEFB4B; defensin beta 4B [KO:K21100]
103215309  [KO:K23126]
103215319  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
103215686  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
103215691  VDAC3; voltage dependent anion channel 3 [KO:K15041]
103215844  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
103215964  VDAC2; voltage dependent anion channel 2 [KO:K15040]
103216021  MCU; mitochondrial calcium uniporter [KO:K20858]
103216382  CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
103216875  IFNAR1; interferon alpha and beta receptor subunit 1 [KO:K05130]
103216889  IFNAR2; interferon alpha and beta receptor subunit 2 [KO:K05131]
103217178  TANK; TRAF family member associated NFKB activator [KO:K12650]
103217529  STAT1; signal transducer and activator of transcription 1 [KO:K11220]
103217637  CASP8; caspase 8 [KO:K04398] [EC:3.4.22.61]
103218104  ATG16L1; autophagy related 16 like 1 [KO:K17890]
103218578  GABARAPL1; GABA type A receptor associated protein like 1 [KO:K08341]
103218776  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
103218837  DNM1L; dynamin 1 like [KO:K17065] [EC:3.6.5.5]
103218937  TLR4; toll like receptor 4 [KO:K10160]
103219027  TXN; thioredoxin [KO:K03671]
103219366  [KO:K05414]
103219367  IFNA8; interferon alpha 8 [KO:K05414]
103219368  IFNA2; interferon alpha 2 [KO:K05414]
103219370  [KO:K05414]
103219372  [KO:K05414]
103219377  [KO:K05414]
103219378  [KO:K05414]
103219379  [KO:K05414]
103219381  [KO:K05414]
103219383  IFNB1; interferon beta 1 [KO:K05415]
103219813  TRPM2; transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13]
103219881  [KO:K10435]
103220113  ANTXR1; anthrax toxin receptor 1 [KO:K20909]
103220528  NLRC4; NLR family CARD domain containing 4 [KO:K12805]
103221064  MYD88; myeloid differentiation primary response 88 [KO:K04729]
103221210  MFN1; mitofusin 1 [KO:K21356] [EC:3.6.5.-]
103221232  [KO:K03671]
103221436  HSP90AB1; heat shock protein 90 alpha family class B member 1 [KO:K04079]
103221595  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
103221596  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
103221654  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
103221707  GPSM3; G-protein signaling modulator 3 [KO:K15838]
103222283  RIPK1; receptor interacting serine/threonine kinase 1 [KO:K02861] [EC:2.7.11.1]
103222413  ERBIN; erbb2 interacting protein [KO:K12796]
103222941  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103223247  TXN2; thioredoxin 2 [KO:K03671]
103223342  TAB1; TGF-beta activated kinase 1 (MAP3K7) binding protein 1 [KO:K04403]
103223551  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
103223553  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
103223764  AIM2; absent in melanoma 2 [KO:K12966]
103223767  IFI16; interferon gamma inducible protein 16 [KO:K20914]
103224057  TXNIP; thioredoxin interacting protein [KO:K20910]
103224469  [KO:K20899]
103224473  GBP7; guanylate binding protein 7 [KO:K20899]
103224476  GBP2; guanylate binding protein 2 [KO:K20897]
103224478  [KO:K20899]
103224480  GBP3; guanylate binding protein 3 [KO:K20899]
103224486  PKN2; protein kinase N2 [KO:K23691]
103224682  JAK1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]
103224726  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
103225132  NAIP; NLR family apoptosis inhibitory protein [KO:K12807]
103225593  MFN2; mitofusin 2 [KO:K06030] [EC:3.6.5.-]
103226003  IRF7; interferon regulatory factor 7 [KO:K09447]
103226280  NOD1; nucleotide binding oligomerization domain containing 1 [KO:K08727]
103226390  IL6; interleukin 6 [KO:K05405]
103226706  NAMPT; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
103227338  MEFV; MEFV, pyrin innate immunity regulator [KO:K12803]
103227364  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
103227575  CAMP; cathelicidin antimicrobial peptide [KO:K13916]
103227629  RHOA; ras homolog family member A [KO:K04513]
103227755  PRKCD; protein kinase C delta [KO:K06068] [EC:2.7.11.13]
103227941  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
103228191  CASR; calcium sensing receptor [KO:K04612]
103228710  IRF9; interferon regulatory factor 9 [KO:K04693]
103228711  RNF31; ring finger protein 31 [KO:K11974] [EC:2.3.2.31]
103228724  RIPK3; receptor interacting serine/threonine kinase 3 [KO:K08847] [EC:2.7.11.1]
103228823  NFKBIA; NFKB inhibitor alpha [KO:K04734]
103229726  HSP90AA1; heat shock protein 90 alpha family class A member 1 [KO:K04079]
103229744  TRAF3; TNF receptor associated factor 3 [KO:K03174]
103230138  TRAF5; TNF receptor associated factor 5 [KO:K09849]
103230198  IKBKE; inhibitor of nuclear factor kappa B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
103230368  NEK7; NIMA related kinase 7 [KO:K20876] [EC:2.7.11.34]
103230468  RNASEL; ribonuclease L [KO:K01165]
103230532  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103230861  MAP1LC3C; microtubule associated protein 1 light chain 3 gamma [KO:K10435]
103230928  NLRP3; NLR family pyrin domain containing 3 [KO:K12800]
103231198  [KO:K08341]
103231357  [KO:K12799]
103231769  TAB3; TGF-beta activated kinase 1/MAP3K7 binding protein 3 [KO:K12793]
103232735  NOD2; nucleotide binding oligomerization domain containing 2 [KO:K10165]
103232832  IKBKG; inhibitor of nuclear factor kappa B kinase subunit gamma [KO:K07210]
103232856  BRCC3; BRCA1/BRCA2-containing complex subunit 3 [KO:K11864] [EC:3.4.19.-]
103233299  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
103233317  GABARAPL2; GABA type A receptor associated protein like 2 [KO:K08341]
103233426  MAP1LC3B; microtubule associated protein 1 light chain 3 beta [KO:K10435]
103233451  [KO:K08009]
103233731  TICAM1; toll like receptor adaptor molecule 1 [KO:K05842]
103234039  PKN1; protein kinase N1 [KO:K06071] [EC:2.7.11.13]
103234360  TYK2; tyrosine kinase 2 [KO:K11219] [EC:2.7.10.2]
103234643  NFKBIB; NFKB inhibitor beta [KO:K02581]
103234962  CARD8; caspase recruitment domain family member 8 [KO:K12801]
103234965  [KO:K12801]
103235050  IRF3; interferon regulatory factor 3 [KO:K05411]
103235229  NLRP12; NLR family pyrin domain containing 12 [KO:K20865]
103235284  NLRP7; NLR family pyrin domain containing 7 [KO:K20864]
103235786  CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030]
103235789  CXCL1; C-X-C motif chemokine ligand 1 [KO:K05505]
103235792  [KO:K05505]
103235798  CXCL3; C-X-C motif chemokine ligand 3 [KO:K05505]
103235864  ANTXR2; anthrax toxin receptor 2 [KO:K20909]
103235918  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
103236047  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
103236665  [KO:K04079]
103236682  [KO:K05505]
103237096  RIPK2; receptor interacting serine/threonine kinase 2 [KO:K08846] [EC:2.7.11.1]
103237554  TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]
103237567  GSDMD; gasdermin D [KO:K20917]
103237608  SHARPIN; SHANK associated RH domain interactor [KO:K20894]
103238180  IRAK4; interleukin 1 receptor associated kinase 4 [KO:K04733] [EC:2.7.11.1]
103238525  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
103238638  TBK1; TANK binding kinase 1 [KO:K05410] [EC:2.7.11.10]
103239154  OAS1; 2'-5'-oligoadenylate synthetase 1 [KO:K14216] [EC:2.7.7.84]
103239155  OAS3; 2'-5'-oligoadenylate synthetase 3 [KO:K14216] [EC:2.7.7.84]
103239156  OAS2; 2'-5'-oligoadenylate synthetase 2 [KO:K14216] [EC:2.7.7.84]
103239277  P2RX7; purinergic receptor P2X 7 [KO:K05220]
103239600  TRAF2; TNF receptor associated factor 2 [KO:K03173] [EC:2.3.2.27]
103239631  CARD9; caspase recruitment domain family member 9 [KO:K12794]
103240115  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
103240159  TAB2; TGF-beta activated kinase 1/MAP3K7 binding protein 2 [KO:K04404]
103240296  TNFAIP3; TNF alpha induced protein 3 [KO:K11859] [EC:3.4.19.12]
103240498  GPRC6A; G protein-coupled receptor class C group 6 member A [KO:K04622]
103240649  ATG5; autophagy related 5 [KO:K08339]
103241278  IL1B; interleukin 1 beta [KO:K04519]
103241743  NLRP6; NLR family pyrin domain containing 6 [KO:K20863]
103241912  PYDC2; pyrin domain containing 2 [KO:K20911]
103242121  YWHAE; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon [KO:K06630]
103242241  NLRP1; NLR family pyrin domain containing 1 [KO:K12798]
103242281  GABARAP; GABA type A receptor-associated protein [KO:K08341]
103242446  TRPV2; transient receptor potential cation channel subfamily V member 2 [KO:K04971]
103242555  DHX33; DEAH-box helicase 33 [KO:K17820] [EC:5.6.2.6]
103242710  [KO:K14624]
103242750  CCL5; C-C motif chemokine ligand 5 [KO:K12499]
103244166  BCL2; BCL2, apoptosis regulator [KO:K02161]
103244369  ATG12; autophagy related 12 [KO:K08336]
103244541  VDAC1; voltage dependent anion channel 1 [KO:K05862]
103244640  TMEM173; transmembrane protein 173 [KO:K12654]
103245120  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
103245185  IRGM; immunity related GTPase M [KO:K14139] [EC:3.6.5.-]
103245274  PSTPIP1; proline-serine-threonine phosphatase interacting protein 1 [KO:K12804]
103245635  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
103245740  TP53BP1; tumor protein p53 binding protein 1 [KO:K20915]
103245758  FADD; Fas associated via death domain [KO:K02373]
103245842  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
103246591  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
103246657  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
103246715  TRIP6; thyroid hormone receptor interactor 6 [KO:K12792]
103247085  [KO:K05230]
103247087  [KO:K05230]
103247375  XIAP; X-linked inhibitor of apoptosis [KO:K04725] [EC:2.3.2.27]
103247465  CYBB; cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
103247611  MAVS; mitochondrial antiviral signaling protein [KO:K12648]
103247827  RBCK1; RANBP2-type and C3HC4-type zinc finger containing 1 [KO:K10630] [EC:2.3.2.31]
103248011  BCL2L1; BCL2 like 1 [KO:K04570]
103248248  PANX1; pannexin 1 [KO:K03443]
103248332  BIRC3; baculoviral IAP repeat containing 3 [KO:K16060]
103248333  BIRC2; baculoviral IAP repeat containing 2 [KO:K16060]
103248363  [KO:K01370] [EC:3.4.22.36]
103248364  CARD16; caspase recruitment domain family member 16 [KO:K12806]
103248365  CASP1; caspase 1 [KO:K01370] [EC:3.4.22.36]
103248366  [KO:K04395] [EC:3.4.22.58]
103248367  CASP4; caspase 4 [KO:K04394] [EC:3.4.22.57 3.4.22.64]
103248368  [KO:K04741] [EC:3.4.22.-]
103248464  IL18; interleukin 18 [KO:K05482]
103248628  NLRX1; NLR family member X1 [KO:K12653]
103248775  MAP1LC3A; microtubule associated protein 1 light chain 3 alpha [KO:K10435]
103248933  [KO:K01370] [EC:3.4.22.36]
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
csab04010  MAPK signaling pathway
csab04064  NF-kappa B signaling pathway
csab04140  Autophagy - animal
csab04620  Toll-like receptor signaling pathway
KO pathway
ko04621   

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