ENTRY ko04621 Pathway NAME NOD-like receptor signaling pathway 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 ko04621 NOD-like receptor signaling pathway DRUG D05706 Raxibacumab (USAN/INN) ORTHOLOGY K08727 nucleotide-binding oligomerization domain-containing protein 1 K08846 receptor-interacting serine/threonine-protein kinase 2 [EC:2.7.11.1] K07210 inhibitor of nuclear factor kappa-B kinase subunit gamma K04467 inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10] K07209 inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10] K02581 NF-kappa-B inhibitor beta K04734 NF-kappa-B inhibitor alpha K02580 nuclear factor NF-kappa-B p105 subunit K04735 transcription factor p65 K04519 interleukin 1 beta K05482 interleukin 18 K05405 interleukin 6 K03156 tumor necrosis factor superfamily, member 2 K10030 interleukin 8 K05505 C-X-C motif chemokine 1/2/3 K14624 C-C motif chemokine 2 K12499 C-C motif chemokine 5 K13916 cathelicidin antimicrobial peptide K05230 defensin, alpha K21100 beta-defensin 4 K23126 beta-defensin 103 K10165 nucleotide-binding oligomerization domain-containing protein 2 K04427 mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25] K04403 TAK1-binding protein 1 K04404 TAK1-binding protein 2 K12793 TAK1-binding protein 3 K04371 mitogen-activated protein kinase 1/3 [EC:2.7.11.24] K04440 mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24] K04441 p38 MAP kinase [EC:2.7.11.24] K04448 transcription factor AP-1 K17890 autophagy-related protein 16-1 K08339 autophagy-related protein 5 K08336 ubiquitin-like protein ATG12 K08341 GABA(A) receptor-associated protein K10435 microtubule-associated protein 1 light chain K12795 suppressor of G2 allele of SKP1 K20894 shank-associated RH domain-interacting protein K10630 RanBP-type and C3HC4-type zinc finger-containing protein 1 [EC:2.3.2.31] K11974 E3 ubiquitin-protein ligase RNF31 [EC:2.3.2.31] K04725 E3 ubiquitin-protein ligase XIAP [EC:2.3.2.27] K12797 caspase recruitment domain-containing protein 6 K12792 thyroid receptor-interacting protein 6 K12796 erbb2-interacting protein K16060 baculoviral IAP repeat-containing protein 2/3 K03173 TNF receptor-associated factor 2 [EC:2.3.2.27] K09849 TNF receptor-associated factor 5 K03175 TNF receptor-associated factor 6 [EC:2.3.2.27] K12794 caspase recruitment domain-containing protein 9 K11859 tumor necrosis factor, alpha-induced protein 3 [EC:3.4.19.12] K12648 mitochondrial antiviral-signaling protein K03174 TNF receptor-associated factor 3 K05410 TANK-binding kinase 1 [EC:2.7.11.10] K07211 inhibitor of nuclear factor kappa-B kinase subunit epsilon [EC:2.7.11.10] K12650 TRAF family member-associated NF-kappa-B activator K05411 interferon regulatory factor 3 K09447 interferon regulatory factor 7 K05414 interferon alpha K05415 interferon beta K12653 NLR family member X1 K08645 anthrax lethal toxin endopeptidase [EC:3.4.24.83] K11030 protective antigen K20909 anthrax toxin receptor K12798 NACHT, LRR and PYD domains-containing protein 1 K12799 apoptosis-associated speck-like protein containing a CARD K01370 caspase 1 [EC:3.4.22.36] K02161 apoptosis regulator Bcl-2 K04570 Bcl-2-like 1 (apoptosis regulator Bcl-X) K01363 cathepsin B [EC:3.4.22.1] K12800 NACHT, LRR and PYD domains-containing protein 3 K03443 pannexin 1 K05220 P2X purinoceptor 7 K04977 transient receptor potential cation channel subfamily M member 2 [EC:3.6.1.13] K04982 transient receptor potential cation channel subfamily M member 7 [EC:2.7.11.1] K04971 transient receptor potential cation channel subfamily V member 2 K04612 calcium-sensing receptor K04622 G protein-coupled receptor family C group 6 member A K05858 phosphatidylinositol phospholipase C, beta [EC:3.1.4.11] K04958 inositol 1,4,5-triphosphate receptor type 1 K04959 inositol 1,4,5-triphosphate receptor type 2 K04960 inositol 1,4,5-triphosphate receptor type 3 K05862 voltage-dependent anion channel protein 1 K15040 voltage-dependent anion channel protein 2 K15041 voltage-dependent anion channel protein 3 K20858 calcium uniporter protein, mitochondrial K14216 2'-5'-oligoadenylate synthetase [EC:2.7.7.84] K01165 ribonuclease L K17820 ATP-dependent RNA helicase DHX33 [EC:5.6.2.6] K21356 mitofusin 1 [EC:3.6.5.-] K06030 mitofusin 2 [EC:3.6.5.-] K02861 receptor-interacting serine/threonine-protein kinase 1 [EC:2.7.11.1] K08847 receptor-interacting serine/threonine-protein kinase 3 [EC:2.7.11.1] K17065 dynamin 1-like protein [EC:3.6.5.5] K03462 nicotinamide phosphoribosyltransferase [EC:2.4.2.12] K21421 NADPH oxidase 2 [EC:1.-.-.-] K08009 cytochrome b-245, alpha polypeptide K20910 thioredoxin-interacting protein K03671 thioredoxin K20876 serine/threonine-protein kinase Nek7 [EC:2.7.11.34] K11864 BRCA1/BRCA2-containing complex subunit 3 [EC:3.4.19.-] K04079 molecular chaperone HtpG K12801 caspase recruitment domain-containing protein 8 K15838 G-protein signaling modulator 3 K14139 immunity-related GTPase family M protein [EC:3.6.5.-] K12802 pyrin domain-containing protein 1 K20911 pyrin domain-containing protein 2 K12803 pyrin K12804 proline-serine-threonine phosphatase interacting protein 1 K04398 caspase 8 [EC:3.4.22.61] K02373 FAS-associated death domain protein K04741 caspase 12 [EC:3.4.22.-] K12806 caspase recruitment domain-containing protein 16/17/18 K20863 NACHT, LRR and PYD domains-containing protein 6 K20864 NACHT, LRR and PYD domains-containing protein 7 K08598 YopJ protease family K20865 NACHT, LRR and PYD domains-containing protein 12 K02406 flagellin K12807 baculoviral IAP repeat-containing protein 1 K12805 NLR family CARD domain-containing protein 4 K06068 novel protein kinase C delta type [EC:2.7.11.13] K20897 guanylate-binding protein 2 K20898 guanylate-binding protein 5 K12966 absent in melanoma 2 K20914 gamma-interferon-inducible protein 16 K20915 tumor suppressor p53-binding protein 1 K20916 pyrin domain-only protein 3 K04513 Ras homolog gene family, member A K06071 serine/threonine-protein kinase N1 [EC:2.7.11.13] K23691 serine/threonine-protein kinase N2 [EC:2.7.11.13] K06630 14-3-3 protein epsilon K20899 guanylate-binding protein 1/3/4/7 K04395 caspase 5 [EC:3.4.22.58] K04394 caspase 4 [EC:3.4.22.57 3.4.22.64] K20917 gasdermin-D K05130 interferon receptor 1 K05131 interferon receptor 2 K11217 Janus kinase 1 [EC:2.7.10.2] K11219 non-receptor tyrosine-protein kinase TYK2 [EC:2.7.10.2] K11220 signal transducer and activator of transcription 1 K11221 signal transducer and activator of transcription 2 K04693 interferon regulatory factor 9 K10160 toll-like receptor 4 K05842 toll-like receptor adapter molecule 1 K04729 myeloid differentiation primary response protein MyD88 K04733 interleukin-1 receptor-associated kinase 4 [EC:2.7.11.1] K12654 stimulator of interferon genes protein 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 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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 REL_PATHWAY ko00550 Peptidoglycan biosynthesis ko03070 Bacterial secretion system ko04010 MAPK signaling pathway ko04064 NF-kappa B signaling pathway ko04140 Autophagy - animal ko04620 Toll-like receptor signaling pathway ///