KEGG   PATHWAY: etf04621
Entry
etf04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Echinops telfairi (small Madagascar hedgehog)
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
etf04621  NOD-like receptor signaling pathway
etf04621

Organism
Echinops telfairi (small Madagascar hedgehog) [GN:etf]
Gene
101652070  NOD1; nucleotide-binding oligomerization domain-containing protein 1 [KO:K08727]
101659564  RIPK2; receptor-interacting serine/threonine-protein kinase 2 [KO:K08846] [EC:2.7.11.1]
101648136  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
101649582  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
101657011  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
101647906  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
101656238  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
101662652  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101663870  RELA; transcription factor p65 [KO:K04735]
101639333  IL1B; interleukin-1 beta [KO:K04519]
105978242  IL18; interleukin-18 [KO:K05482]
123522712  interleukin-6-like [KO:K05405]
101644240  IL6; interleukin-6 [KO:K05405]
101654642  TNF; tumor necrosis factor [KO:K03156]
101664548  CXCL8; interleukin-8 [KO:K10030]
101648039  growth-regulated protein homolog gamma-like [KO:K05505]
101647727  growth-regulated protein homolog gamma-like [KO:K05505]
101641002  C-C motif chemokine 2-like isoform X1 [KO:K14624]
101662141  monocyte chemotactic protein 1B-like [KO:K14624]
101645531  CCL5; C-C motif chemokine 5 [KO:K12499]
101641205  cathelicidin antimicrobial peptide [KO:K13916]
101659125  neutrophil defensin 6-like [KO:K05230]
115868308  beta-defensin 103A-like [KO:K23126]
101661310  NOD2; nucleotide-binding oligomerization domain-containing protein 2 [KO:K10165]
101647452  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
101649684  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
101642439  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
101640111  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793]
101648971  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101661786  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101654493  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
101653598  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
101645489  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
101657745  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
101656204  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101653430  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
101653940  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
101656959  JUN; transcription factor AP-1 [KO:K04448]
101659819  ATG16L1; LOW QUALITY PROTEIN: autophagy-related protein 16-1 [KO:K17890]
101655379  ATG5; autophagy protein 5 [KO:K08339]
101650353  ATG12; ubiquitin-like protein ATG12 isoform X1 [KO:K08336]
101653429  gamma-aminobutyric acid receptor-associated protein-like [KO:K08341]
105978814  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
101646927  gamma-aminobutyric acid receptor-associated protein [KO:K08341]
101640345  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
101661311  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
105978339  microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
101664062  microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
101662715  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
101655770  SUGT1; protein SGT1 homolog [KO:K12795]
101654451  sharpin [KO:K20894]
101649553  RBCK1; ranBP-type and C3HC4-type zinc finger-containing protein 1 [KO:K10630] [EC:2.3.2.31]
101641682  RNF31; E3 ubiquitin-protein ligase RNF31 [KO:K11974] [EC:2.3.2.31]
101662600  E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
101654991  CARD6; caspase recruitment domain-containing protein 6 [KO:K12797]
101650131  TRIP6; thyroid receptor-interacting protein 6 [KO:K12792]
101640478  ERBIN; erbin [KO:K12796]
101655890  baculoviral IAP repeat-containing protein 3 [KO:K16060]
101659133  baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
115869468  baculoviral IAP repeat-containing protein 2 [KO:K16060]
101643556  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
101655200  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
101658809  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
101651114  CARD9; caspase recruitment domain-containing protein 9 isoform X1 [KO:K12794]
101651870  TNFAIP3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
101663462  MAVS; mitochondrial antiviral-signaling protein [KO:K12648]
101663779  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
101649686  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
101647812  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
101651972  TANK; TRAF family member-associated NF-kappa-B activator [KO:K12650]
101651495  IRF3; interferon regulatory factor 3 isoform X1 [KO:K05411]
101647709  IRF7; interferon regulatory factor 7 [KO:K09447]
101650862  interferon alpha-2-like [KO:K05414]
101650550  IFNB1; interferon beta [KO:K05415]
101658507  NLRX1; NLR family member X1 [KO:K12653]
101661956  ANTXR1; anthrax toxin receptor 1 [KO:K20909]
101662435  ANTXR2; anthrax toxin receptor 2 [KO:K20909]
101656036  NLRP1; NACHT, LRR and PYD domains-containing protein 1 [KO:K12798]
101660779  apoptosis-associated speck-like protein containing a CARD [KO:K12799]
101653570  caspase-1 [KO:K01370] [EC:3.4.22.36]
101659722  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
101644838  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
101659262  bcl-2-like protein 1 [KO:K04570]
101644265  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
101662492  NLRP3; NACHT, LRR and PYD domains-containing protein 3 [KO:K12800]
101638177  PANX1; pannexin-1 [KO:K03443]
101639980  P2RX7; P2X purinoceptor 7 isoform X1 [KO:K05220]
101644187  TRPM2; transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13]
101660894  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
101649940  TRPV2; transient receptor potential cation channel subfamily V member 2 isoform X2 [KO:K04971]
101644174  CASR; extracellular calcium-sensing receptor [KO:K04612]
101641402  GPRC6A; G-protein coupled receptor family C group 6 member A isoform X1 [KO:K04622]
101651304  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
101650582  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
101647679  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
101656854  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858] [EC:3.1.4.11]
101654141  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
101638553  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
101657031  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
101656727  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
101653907  voltage-dependent anion-selective channel protein 1-like [KO:K05862]
101649902  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
101642569  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X2 [KO:K15041]
101640880  MCU; calcium uniporter protein, mitochondrial [KO:K20858]
101643318  2'-5'-oligoadenylate synthase 3 [KO:K14216] [EC:2.7.7.84]
101643629  OAS2; 2'-5'-oligoadenylate synthase 2 [KO:K14216] [EC:2.7.7.84]
101662447  RNASEL; 2-5A-dependent ribonuclease [KO:K01165]
101641379  DHX33; ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
101657627  MFN1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
101661936  MFN2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
101652750  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
101639698  RIPK3; receptor-interacting serine/threonine-protein kinase 3 [KO:K08847] [EC:2.7.11.1]
101650823  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
101661399  NAMPT; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
101640739  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
101658151  cytochrome b-245 light chain [KO:K08009]
101656257  thioredoxin-interacting protein [KO:K20910]
101660138  thioredoxin-like [KO:K03671]
123522433  TXN; thioredoxin [KO:K03671]
105978839  thioredoxin-like [KO:K03671]
105979871  thioredoxin-like [KO:K03671]
101648249  thioredoxin-like isoform X1 [KO:K03671]
101663538  thioredoxin, mitochondrial-like [KO:K03671]
105979981  thioredoxin [KO:K03671]
101662809  thioredoxin-like [KO:K03671]
101661085  thioredoxin-like [KO:K03671]
101660941  thioredoxin-like [KO:K03671]
101644798  thioredoxin-like [KO:K03671]
101658544  TXN2; thioredoxin, mitochondrial [KO:K03671]
101645150  thioredoxin-like [KO:K03671]
101655097  NEK7; serine/threonine-protein kinase Nek7 isoform X1 [KO:K20876] [EC:2.7.11.34]
101661998  lys-63-specific deubiquitinase BRCC36-like [KO:K11864] [EC:3.4.19.-]
101641396  BRCC3; lys-63-specific deubiquitinase BRCC36 isoform X1 [KO:K11864] [EC:3.4.19.-]
101649746  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
101650153  LOW QUALITY PROTEIN: heat shock protein HSP 90-beta-like [KO:K04079]
101639274  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
101643213  CARD8; LOW QUALITY PROTEIN: caspase recruitment domain-containing protein 8 [KO:K12801]
101664367  GPSM3; G-protein-signaling modulator 3 isoform X2 [KO:K15838]
101639790  immunity-related GTPase family M protein 1-like [KO:K14139] [EC:3.6.5.-]
101641044  immunity-related GTPase family M protein-like [KO:K14139] [EC:3.6.5.-]
101659213  MEFV; pyrin [KO:K12803]
101641657  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 [KO:K12804]
101638051  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
101653369  caspase-12 [KO:K04741] [EC:3.4.22.-]
101643271  NLRP6; NACHT, LRR and PYD domains-containing protein 6 [KO:K20863]
101640753  NLRP12; NACHT, LRR and PYD domains-containing protein 12 [KO:K20865]
101662239  baculoviral IAP repeat-containing protein 1 [KO:K12807]
101662272  NLRC4; NLR family CARD domain-containing protein 4 [KO:K12805]
101650810  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
101662405  guanylate-binding protein 1-like [KO:K20897]
101661252  AIM2; LOW QUALITY PROTEIN: interferon-inducible protein AIM2 [KO:K12966]
101643206  TP53BP1; TP53-binding protein 1 isoform X1 [KO:K20915]
101662299  RHOA; transforming protein RhoA [KO:K04513]
101645165  PKN1; serine/threonine-protein kinase N1 [KO:K06071] [EC:2.7.11.13]
101663373  PKN2; LOW QUALITY PROTEIN: serine/threonine-protein kinase N2 [KO:K23691] [EC:2.7.11.13]
101644365  YWHAE; 14-3-3 protein epsilon [KO:K06630]
101642829  GBP1; guanylate-binding protein 1 [KO:K20899]
101662091  guanylate-binding protein 4 [KO:K20899]
101653056  caspase-4 isoform X1 [KO:K04394] [EC:3.4.22.57 3.4.22.64]
101661042  GSDMD; gasdermin-D [KO:K20917]
101640204  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
101639566  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
101664197  JAK1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
101663486  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
101650838  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
101661602  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
101663983  IRF9; LOW QUALITY PROTEIN: interferon regulatory factor 9 [KO:K04693]
101660600  TLR4; toll-like receptor 4 [KO:K10160]
101649346  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
115873309  LOW QUALITY PROTEIN: TIR domain-containing adapter molecule 1-like [KO:K05842]
101644448  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
101643108  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X2 [KO:K04733] [EC:2.7.11.1]
101649228  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
etf04010  MAPK signaling pathway
etf04064  NF-kappa B signaling pathway
etf04140  Autophagy - animal
etf04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
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