KEGG   PATHWAY: tsr04621
Entry
tsr04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Thamnophis sirtalis (common garter snake)
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
tsr04621  NOD-like receptor signaling pathway
tsr04621

Organism
Thamnophis sirtalis (common garter snake) [GN:tsr]
Gene
106545486  NOD1; nucleotide-binding oligomerization domain-containing protein 1 [KO:K08727]
106545514  RIPK2; receptor-interacting serine/threonine-protein kinase 2 [KO:K08846] [EC:2.7.11.1]
106541579  receptor-interacting serine/threonine-protein kinase 2-like [KO:K08846] [EC:2.7.11.1]
106548462  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
106550867  inhibitor of nuclear factor kappa-B kinase subunit beta-like isoform X1 [KO:K07209] [EC:2.7.11.10]
106547318  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
106551236  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
106548335  nuclear factor NF-kappa-B p105 subunit-like [KO:K02580]
106545771  nuclear factor NF-kappa-B p105 subunit-like [KO:K02580]
106556843  RELA; transcription factor p65 [KO:K04735]
106544675  interleukin-1 beta-like [KO:K04519]
106544745  tumor necrosis factor-like [KO:K03156]
106550154  interleukin-8-like [KO:K10030]
106550186  interleukin-8-like [KO:K10030]
106545361  cathelicidin-related peptide Oh-Cath-like [KO:K13916]
106554358  cathelicidin-related peptide Oh-Cath-like [KO:K13916]
106541515  cathelicidin-related peptide Oh-Cath-like [KO:K13916]
106538153  crotamine CRO3-like [KO:K23126]
106549515  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
106551715  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
106552457  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
106541886  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793]
106554657  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
106539801  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
106547350  mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
106550161  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
106539258  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
106539876  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
106556039  mitogen-activated protein kinase 11-like [KO:K04441] [EC:2.7.11.24]
106539166  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
106539167  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
106545185  JUN; transcription factor AP-1 [KO:K04448]
106555287  ATG16L1; autophagy-related protein 16-1 isoform X1 [KO:K17890]
106546857  ATG5; autophagy protein 5 [KO:K08339]
106545002  ATG12; ubiquitin-like protein ATG12 [KO:K08336]
106542412  GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
106539679  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
106553436  microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
106553437  microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
106542233  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
106541518  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
106538620  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
106555687  microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
106550246  sharpin [KO:K10630] [EC:2.3.2.31]
106549808  ranBP-type and C3HC4-type zinc finger-containing protein 1-like [KO:K10630] [EC:2.3.2.31]
106546987  thyroid receptor-interacting protein 6-like [KO:K12792]
106546712  ERBB2IP; protein LAP2 [KO:K12796]
106549668  inhibitor of apoptosis protein-like [KO:K16060]
106541963  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
106552805  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
106556967  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
106540449  CARD9; caspase recruitment domain-containing protein 9 [KO:K12794]
106547167  TNFAIP3; tumor necrosis factor alpha-induced protein 3 isoform X1 [KO:K11859] [EC:3.4.19.12]
106540064  TRAF3; TNF receptor-associated factor 3 [KO:K03174]
106548060  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
106542037  TANK; TRAF family member-associated NF-kappa-B activator [KO:K12650]
106553402  IRF3; interferon regulatory factor 3 [KO:K05411]
106546498  IRF7; interferon regulatory factor 7 [KO:K09447]
106542110  interferon alpha-21-like [KO:K05414]
106552265  NLRX1; NLR family member X1 [KO:K12653]
106538249  anthrax toxin receptor 1-like [KO:K20909]
106538133  apoptosis-associated speck-like protein containing a CARD [KO:K12799]
106538147  apoptosis-associated speck-like protein containing a CARD [KO:K12799]
106551867  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
106546569  BCL2L1; bcl-2-like protein 1 [KO:K04570]
106546573  cathepsin B-like [KO:K01363] [EC:3.4.22.1]
106546575  cathepsin B-like [KO:K01363] [EC:3.4.22.1]
106554133  PANX1; pannexin-1 [KO:K03443]
106537600  TRPM2; transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13]
106546390  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
106550537  CASR; extracellular calcium-sensing receptor [KO:K04612]
106540398  GPRC6A; G-protein coupled receptor family C group 6 member A isoform X1 [KO:K04622]
106544747  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
106543825  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
106550123  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2-like [KO:K05858] [EC:3.1.4.11]
106542534  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
106553941  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3-like [KO:K05858] [EC:3.1.4.11]
106541049  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
106541215  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
106542639  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
106537461  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
106550868  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
106555359  MCU; calcium uniporter protein, mitochondrial [KO:K20858]
106554335  2'-5'-oligoadenylate synthase 3-like [KO:K14216] [EC:2.7.7.84]
106541233  RNASEL; 2-5A-dependent ribonuclease [KO:K01165]
106556393  LOW QUALITY PROTEIN: putative ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
106544961  DHX33; putative ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
106541176  mitofusin-1-like [KO:K21356] [EC:3.6.5.-]
106544402  MFN2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
106553353  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
106549301  receptor-interacting serine/threonine-protein kinase 3-like [KO:K08847] [EC:2.7.11.1]
106538589  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
106548954  NAMPT; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
106557320  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
106549747  cytochrome b-245 light chain [KO:K08009]
106554918  TXNIP; thioredoxin-interacting protein isoform X1 [KO:K20910]
106552056  TXN2; thioredoxin, mitochondrial [KO:K03671]
106555383  TXN; thioredoxin [KO:K03671]
106544884  NEK7; serine/threonine-protein kinase Nek7 [KO:K20876] [EC:2.7.11.34]
106554901  BRCC3; lys-63-specific deubiquitinase BRCC36 [KO:K11864] [EC:3.4.19.-]
106539342  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
106538122  heat shock protein HSP 90-alpha [KO:K04079]
106553560  G-protein-signaling modulator 3-like [KO:K15838]
106546194  FADD; FAS-associated death domain protein isoform X1 [KO:K02373]
106548379  NACHT, LRR and PYD domains-containing protein 3-like [KO:K20865]
106546505  NAIP; baculoviral IAP repeat-containing protein 1 [KO:K12807]
106544562  NLRC4; NLR family CARD domain-containing protein 4 [KO:K12805]
106543897  TP53BP1; tumor suppressor p53-binding protein 1 isoform X1 [KO:K20915]
106552511  transforming protein RhoA-like isoform X1 [KO:K04513]
106539135  RHOA; transforming protein RhoA [KO:K04513]
106540810  serine/threonine-protein kinase N1-like [KO:K06071] [EC:2.7.11.13]
106551057  PKN1; serine/threonine-protein kinase N1 [KO:K06071] [EC:2.7.11.13]
106546788  PKN2; serine/threonine-protein kinase N2 [KO:K23691] [EC:2.7.11.13]
106543395  YWHAE; 14-3-3 protein epsilon [KO:K06630]
106549942  interferon-induced guanylate-binding protein 1-like [KO:K20899]
106543180  interferon-induced guanylate-binding protein 1-like [KO:K20899]
106555375  interferon-induced guanylate-binding protein 1-like [KO:K20899]
106556607  interferon-induced guanylate-binding protein 1-like [KO:K20899]
106550452  interferon alpha/beta receptor 2-like [KO:K05131]
106550876  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
106542268  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
106537889  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
106544441  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
106542752  interferon regulatory factor 9-like [KO:K04693]
106546496  TLR4; toll-like receptor 4 [KO:K10160]
106552723  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
106539892  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
106556721  interleukin-1 receptor-associated kinase 4-like [KO:K04733] [EC:2.7.11.1]
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
tsr04010  MAPK signaling pathway
tsr04140  Autophagy - animal
tsr04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
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