KEGG   PATHWAY: shr04621
Entry
shr04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Sarcophilus harrisii (Tasmanian devil)
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
shr04621  NOD-like receptor signaling pathway
shr04621

Organism
Sarcophilus harrisii (Tasmanian devil) [GN:shr]
Gene
100920057  NOD1; LOW QUALITY PROTEIN: nucleotide-binding oligomerization domain-containing protein 1 [KO:K08727]
100920956  RIPK2; receptor-interacting serine/threonine-protein kinase 2 isoform X1 [KO:K08846] [EC:2.7.11.1]
100926701  IKBKG; NF-kappa-B essential modulator isoform X3 [KO:K07210]
100913624  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
100928932  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
100919027  NFKBIA; LOW QUALITY PROTEIN: NF-kappa-B inhibitor alpha [KO:K04734]
100917619  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100932473  RELA; transcription factor p65 [KO:K04735]
100922350  IL1B; interleukin-1 beta [KO:K04519]
100919934  interleukin-18-like [KO:K05482]
100920716  IL18; interleukin-18 [KO:K05482]
111719790  interleukin-18-like [KO:K05482]
105750762  IL6; interleukin-6 [KO:K05405]
100921875  TNF; tumor necrosis factor [KO:K03156]
100933600  CXCL8; interleukin-8 [KO:K10030]
100915440  growth-regulated alpha protein [KO:K05505]
100918907  C-C motif chemokine 2 [KO:K14624]
100924204  CAMP; cathelicidin antimicrobial peptide isoform X1 [KO:K13916]
100929552  cathelicidin-2 [KO:K13916]
100919663  cathelicidin-6-like [KO:K13916]
100931118  cathelicidin-7 [KO:K13916]
100917839  cathelin [KO:K13916]
105749564  cathelicidin-3 [KO:K13916]
105749056  neutrophil antibiotic peptide NP-1-like [KO:K05230]
100919991  beta-defensin 103A [KO:K23126]
100931097  NOD2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165]
100920997  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
100917609  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
100930713  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
100920451  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793]
100934330  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100913231  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
100930815  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
100928480  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
100924267  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
100928729  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
100928990  MAPK11; LOW QUALITY PROTEIN: mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
100925013  MAPK14; mitogen-activated protein kinase 14 isoform X2 [KO:K04441] [EC:2.7.11.24]
100925447  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
116423739  JUN; transcription factor AP-1 [KO:K04448]
100915878  ATG16L1; autophagy-related protein 16-1 isoform X1 [KO:K17890]
100934445  ATG5; autophagy protein 5 isoform X1 [KO:K08339]
100923575  ATG12; ubiquitin-like protein ATG12 [KO:K08336]
100930358  GABARAP; gamma-aminobutyric acid receptor-associated protein isoform X1 [KO:K08341]
100931419  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
100931278  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
100914051  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
100928511  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
100927558  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
100918798  SUGT1; protein SGT1 homolog [KO:K12795]
100923314  sharpin [KO:K20894]
100919033  RBCK1; ranBP-type and C3HC4-type zinc finger-containing protein 1 [KO:K10630] [EC:2.3.2.31]
100915026  RNF31; E3 ubiquitin-protein ligase RNF31 [KO:K11974] [EC:2.3.2.31]
100928240  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
100931019  CARD6; caspase recruitment domain-containing protein 6 [KO:K12797]
100915260  TRIP6; thyroid receptor-interacting protein 6 isoform X1 [KO:K12792]
100920371  ERBIN; erbin isoform X1 [KO:K12796]
100914028  baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
100933131  baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060]
100934749  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
100926831  TRAF5; TNF receptor-associated factor 5 isoform X2 [KO:K09849]
100922331  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
100931004  CARD9; caspase recruitment domain-containing protein 9 [KO:K12794]
100919524  TNFAIP3; tumor necrosis factor alpha-induced protein 3 isoform X2 [KO:K11859] [EC:3.4.19.12]
100926796  MAVS; mitochondrial antiviral-signaling protein [KO:K12648]
100926344  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
100915362  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
100934784  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
100933472  TANK; TRAF family member-associated NF-kappa-B activator isoform X1 [KO:K12650]
100933650  interferon regulatory factor 3 [KO:K05411]
100914965  interferon tau-like [KO:K05414]
100920968  interferon tau-2-like [KO:K05414]
100914703  interferon tau-2-like [KO:K05414]
116420987  interferon omega-1-like [KO:K05414]
116420989  interferon omega-1-like [KO:K05414]
100914443  interferon beta [KO:K05415]
100921418  NLRX1; NLR family member X1 [KO:K12653]
100931607  ANTXR2; anthrax toxin receptor 2 isoform X1 [KO:K20909]
100913892  ANTXRL; anthrax toxin receptor-like [KO:K20909]
100924088  ANTXR1; anthrax toxin receptor 1 isoform X1 [KO:K20909]
100925851  PYCARD; apoptosis-associated speck-like protein containing a CARD [KO:K12799]
105749479  PYDC1; pyrin domain-containing protein 1 [KO:K12799]
100935043  caspase-1 isoform X1 [KO:K01370] [EC:3.4.22.36]
100934666  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
100915548  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
100920513  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
100923334  PANX1; pannexin-1 [KO:K03443]
100922617  P2RX7; P2X purinoceptor 7 isoform X1 [KO:K05220]
100922880  P2X purinoceptor 7 [KO:K05220]
100930450  TRPM2; transient receptor potential cation channel subfamily M member 2 isoform X1 [KO:K04977] [EC:3.6.1.13]
100934039  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
100915096  TRPV2; transient receptor potential cation channel subfamily V member 2 [KO:K04971]
100923241  CASR; extracellular calcium-sensing receptor [KO:K04612]
100932710  GPRC6A; G-protein coupled receptor family C group 6 member A isoform X2 [KO:K04622]
100922938  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
100934049  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
100934311  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
100929015  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
100918532  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X7 [KO:K04958]
100921270  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
100916996  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X2 [KO:K04960]
100927813  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
100920408  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
100923123  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X2 [KO:K15041]
100913360  MCU; calcium uniporter protein, mitochondrial [KO:K20858]
100928264  2'-5'-oligoadenylate synthase 1 isoform X1 [KO:K14216] [EC:2.7.7.84]
100928002  OAS3; LOW QUALITY PROTEIN: 2'-5'-oligoadenylate synthase 3 [KO:K14216] [EC:2.7.7.84]
105749342  2'-5'-oligoadenylate synthase 2 isoform X1 [KO:K14216] [EC:2.7.7.84]
116419074  RNASEL; 2-5A-dependent ribonuclease [KO:K01165]
100924480  DHX33; ATP-dependent RNA helicase DHX33 isoform X1 [KO:K17820] [EC:5.6.2.6]
100932357  MFN1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
100915154  MFN2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
100914177  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
100928220  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
100925196  NAMPT; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
100917667  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
100932491  cytochrome b-245 light chain isoform X1 [KO:K08009]
100916568  TXNIP; thioredoxin-interacting protein [KO:K20910]
100924684  TXN2; thioredoxin, mitochondrial [KO:K03671]
100913259  NEK7; serine/threonine-protein kinase Nek7 isoform X1 [KO:K20876] [EC:2.7.11.34]
100917032  BRCC3; lys-63-specific deubiquitinase BRCC36 isoform X1 [KO:K11864] [EC:3.4.19.-]
100927276  lys-63-specific deubiquitinase BRCC36 [KO:K11864] [EC:3.4.19.-]
100928900  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
100929957  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
100926052  GPSM3; G-protein-signaling modulator 3 isoform X1 [KO:K15838]
100933206  MEFV; pyrin isoform X3 [KO:K12803]
100923195  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 [KO:K12804]
100931580  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
100925732  FADD; FAS-associated death domain protein [KO:K02373]
100913862  caspase-4-like isoform X1 [KO:K04741] [EC:3.4.22.-]
100913330  caspase-12-like isoform X1 [KO:K04741] [EC:3.4.22.-]
100923423  NACHT, LRR and PYD domains-containing protein 12 [KO:K20865]
100925245  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
100921789  AIM2; interferon-inducible protein AIM2 [KO:K12966]
100927379  TP53BP1; TP53-binding protein 1 isoform X1 [KO:K20915]
100921931  RHOA; transforming protein RhoA [KO:K04513]
100921310  PKN1; serine/threonine-protein kinase N1 isoform X2 [KO:K06071] [EC:2.7.11.13]
100929232  PKN2; serine/threonine-protein kinase N2 isoform X1 [KO:K23691] [EC:2.7.11.13]
100922737  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
100928456  guanylate-binding protein 1 [KO:K20899]
100927683  guanylate-binding protein 1 [KO:K20899]
100922482  guanylate-binding protein 4 [KO:K20899]
100922739  guanylate-binding protein 1 [KO:K20899]
100923253  guanylate-binding protein 6 isoform X2 [KO:K20899]
116423785  guanylate-binding protein 1-like [KO:K20899]
116423787  guanylate-binding protein 4-like [KO:K20899]
100914382  caspase-13 [KO:K04394] [EC:3.4.22.57 3.4.22.64]
100914126  caspase-4 isoform X1 [KO:K04394] [EC:3.4.22.57 3.4.22.64]
100934670  gasdermin-D [KO:K20917]
100919064  IFNAR1; LOW QUALITY PROTEIN: interferon alpha/beta receptor 1 [KO:K05130]
105750087  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
100916991  JAK1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
100927743  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
105749862  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
100933167  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
100916853  IRF9; interferon regulatory factor 9 isoform X3 [KO:K04693]
100927125  TLR4; toll-like receptor 4 [KO:K10160]
100921575  TICAM1; TIR domain-containing adapter molecule 1 isoform X1 [KO:K05842]
100927751  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
100934112  IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
100932153  STING1; stimulator of interferon genes protein [KO:K12654]
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
shr04010  MAPK signaling pathway
shr04064  NF-kappa B signaling pathway
shr04140  Autophagy - animal
shr04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
LinkDB

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