KEGG   PATHWAY: afz04621
Entry
afz04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Antechinus flavipes (yellow-footed antechinus)
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
afz04621  NOD-like receptor signaling pathway
afz04621

Organism
Antechinus flavipes (yellow-footed antechinus) [GN:afz]
Gene
127539293  nucleotide-binding oligomerization domain-containing protein 1 isoform X1 [KO:K08727]
127544264  receptor-interacting serine/threonine-protein kinase 2 isoform X1 [KO:K08846] [EC:2.7.11.1]
127542289  NF-kappa-B essential modulator isoform X1 [KO:K07210]
127548272  inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
127556146  NF-kappa-B inhibitor beta [KO:K02581]
127549751  NF-kappa-B inhibitor alpha [KO:K04734]
127541094  nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
127540746  transcription factor p65 isoform X1 [KO:K04735]
127547601  interleukin-1 beta [KO:K04519]
127557357  interleukin-18-like [KO:K05482]
127554992  interleukin-18-like [KO:K05482]
127559172  tumor necrosis factor [KO:K03156]
127540720  interleukin-8 [KO:K10030]
127540718  permeability factor 2-like [KO:K05505]
127540719  permeability factor 2-like [KO:K05505]
127548531  neutrophil antibiotic peptide NP-1-like isoform X1 [KO:K05230]
127548533  neutrophil antibiotic peptide NP-1-like [KO:K05230]
127552425  beta-defensin 103A-like [KO:K23126]
127550701  nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165]
127562007  mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
127538308  TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
127562312  TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
127553936  TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793]
127556083  mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
127545795  mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
127542137  mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
127550306  mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
127551815  mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
127538834  mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
127538838  mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
127561225  mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
127561226  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
127563247  transcription factor Jun [KO:K04448]
127563084  autophagy-related protein 16-1 isoform X1 [KO:K17890]
127562048  autophagy protein 5 isoform X1 [KO:K08339]
127563934  gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
127543884  gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
127547705  gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
127560908  gamma-aminobutyric acid receptor-associated protein [KO:K08341]
127550340  microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
127559598  microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
127547815  microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
127553280  protein SGT1 homolog [KO:K12795]
127544618  sharpin [KO:K20894]
127550477  ranBP-type and C3HC4-type zinc finger-containing protein 1 [KO:K10630] [EC:2.3.2.31]
127551081  E3 ubiquitin-protein ligase RNF31 [KO:K11974] [EC:2.3.2.31]
127543223  E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
127556815  LOW QUALITY PROTEIN: caspase recruitment domain-containing protein 6 [KO:K12797]
127560965  LOW QUALITY PROTEIN: thyroid receptor-interacting protein 6 [KO:K12792]
127558168  erbin isoform X1 [KO:K12796]
127554917  baculoviral IAP repeat-containing protein 2-like [KO:K16060]
127554918  baculoviral IAP repeat-containing protein 3-like isoform X1 [KO:K16060]
127549124  TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
127562587  TNF receptor-associated factor 5 [KO:K09849]
127542124  LOW QUALITY PROTEIN: TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
127550984  caspase recruitment domain-containing protein 9 [KO:K12794]
127562255  tumor necrosis factor alpha-induced protein 3 isoform X1 [KO:K11859] [EC:3.4.19.12]
127547414  mitochondrial antiviral-signaling protein [KO:K12648]
127549887  TNF receptor-associated factor 3 [KO:K03174]
127539419  serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
127562632  inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
127554619  TRAF family member-associated NF-kappa-B activator isoform X1 [KO:K12650]
127556561  interferon regulatory factor 3 [KO:K05411]
127541173  interferon regulatory factor 7 isoform X1 [KO:K09447]
127544839  interferon tau-like [KO:K05414]
127544846  interferon tau-like [KO:K05414]
127552476  interferon alpha-16-like [KO:K05414]
127552756  interferon alpha-1-like [KO:K05414]
127552856  interferon omega-1-like [KO:K05414]
127552925  interferon beta-like [KO:K05415]
127551822  anthrax toxin receptor-like [KO:K20909]
127548178  anthrax toxin receptor 1 [KO:K20909]
127540979  anthrax toxin receptor 2 [KO:K20909]
127561114  apoptosis-associated speck-like protein containing a CARD [KO:K12799]
127554938  LOW QUALITY PROTEIN: caspase-1-like [KO:K01370] [EC:3.4.22.36]
127543678  apoptosis regulator Bcl-2 [KO:K02161]
127550456  bcl-2-like protein 1 isoform X1 [KO:K04570]
127543788  cathepsin B-like [KO:K01363] [EC:3.4.22.1]
127548524  cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
127556924  LOW QUALITY PROTEIN: NACHT, LRR and PYD domains-containing protein 3-like [KO:K12800]
127545452  P2X purinoceptor 7-like [KO:K05220]
127545453  P2X purinoceptor 7-like [KO:K05220]
127562457  transient receptor potential cation channel subfamily M member 2 isoform X1 [KO:K04977] [EC:3.6.1.13]
127551146  transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
127558768  transient receptor potential cation channel subfamily V member 2 [KO:K04971]
127554131  extracellular calcium-sensing receptor [KO:K04612]
127559507  G-protein coupled receptor family C group 6 member A [KO:K04622]
127549225  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
127539641  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
127548499  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
127548500  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
127551451  inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
127539174  inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
127561144  inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
127549828  voltage-dependent anion-selective channel protein 1 [KO:K05862]
127541140  LOW QUALITY PROTEIN: voltage-dependent anion-selective channel protein 1-like [KO:K05862]
127551885  voltage-dependent anion-selective channel protein 2 [KO:K15040]
127548278  voltage-dependent anion-selective channel protein 3 [KO:K15041]
127551934  calcium uniporter protein, mitochondrial [KO:K20858]
127548517  LOW QUALITY PROTEIN: 2'-5'-oligoadenylate synthase 1 [KO:K14216] [EC:2.7.7.84]
127548527  LOW QUALITY PROTEIN: 2'-5'-oligoadenylate synthase 3 [KO:K14216] [EC:2.7.7.84]
127548539  2'-5'-oligoadenylate synthase 2 [KO:K14216] [EC:2.7.7.84]
127562824  2-5A-dependent ribonuclease [KO:K01165]
127558242  ATP-dependent RNA helicase DHX33 isoform X1 [KO:K17820] [EC:5.6.2.6]
127552895  mitofusin-1 [KO:K21356] [EC:3.6.5.-]
127555858  mitofusin-2 [KO:K06030] [EC:3.6.5.-]
127544228  receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
127542324  dynamin-1-like protein [KO:K17065] [EC:3.6.5.5]
127542327  dynamin-1-like protein [KO:K17065] [EC:3.6.5.5]
127542328  dynamin-1-like protein [KO:K17065] [EC:3.6.5.5]
127542339  dynamin-1-like protein [KO:K17065] [EC:3.6.5.5]
127542784  dynamin-1-like protein [KO:K17065] [EC:3.6.5.5]
127538930  dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
127538533  nicotinamide phosphoribosyltransferase-like [KO:K03462] [EC:2.4.2.12]
127539424  nicotinamide phosphoribosyltransferase isoform X1 [KO:K03462] [EC:2.4.2.12]
127553929  cytochrome b-245 heavy chain isoform X1 [KO:K21421] [EC:1.-.-.-]
127547797  cytochrome b-245 light chain [KO:K08009]
127559157  thioredoxin-interacting protein [KO:K20910]
127542864  thioredoxin, mitochondrial-like [KO:K03671]
127538124  thioredoxin, mitochondrial [KO:K03671]
127538781  thioredoxin [KO:K03671]
127561590  serine/threonine-protein kinase Nek7 [KO:K20876] [EC:2.7.11.34]
127542950  lys-63-specific deubiquitinase BRCC36 [KO:K11864] [EC:3.4.19.-]
127559273  lys-63-specific deubiquitinase BRCC36 [KO:K11864] [EC:3.4.19.-]
127549897  LOW QUALITY PROTEIN: heat shock protein HSP 90-alpha [KO:K04079]
127561796  heat shock protein HSP 90-beta [KO:K04079]
127561109  G-protein-signaling modulator 3 [KO:K15838]
127542445  pyrin [KO:K12803]
127552066  proline-serine-threonine phosphatase-interacting protein 1 [KO:K12804]
127553228  caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
127540264  FAS-associated death domain protein [KO:K02373]
127554934  caspase-12-like isoform X1 [KO:K04741] [EC:3.4.22.-]
127555279  LOW QUALITY PROTEIN: NACHT, LRR and PYD domains-containing protein 12-like [KO:K20865]
127555281  NACHT, LRR and PYD domains-containing protein 3-like [KO:K20865]
127556742  NACHT, LRR and PYD domains-containing protein 12-like [KO:K20865]
127553769  protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
127559733  interferon-inducible protein AIM2-like [KO:K12966]
127549298  TP53-binding protein 1 isoform X1 [KO:K20915]
127541249  transforming protein RhoA-like isoform X1 [KO:K04513]
127549354  transforming protein RhoA-like [KO:K04513]
127554850  transforming protein RhoA [KO:K04513]
127544843  serine/threonine-protein kinase N1 isoform X1 [KO:K06071] [EC:2.7.11.13]
127563096  serine/threonine-protein kinase N2 isoform X1 [KO:K23691] [EC:2.7.11.13]
127558846  14-3-3 protein epsilon isoform X1 [KO:K06630]
127563505  guanylate-binding protein 4-like isoform X1 [KO:K20899]
127563506  guanylate-binding protein 4-like [KO:K20899]
127563507  guanylate-binding protein 1-like [KO:K20899]
127563508  guanylate-binding protein 1-like [KO:K20899]
127563509  guanylate-binding protein 7-like [KO:K20899]
127563097  guanylate-binding protein 4-like isoform X1 [KO:K20899]
127563099  guanylate-binding protein 1-like [KO:K20899]
127554936  caspase-13-like [KO:K04394] [EC:3.4.22.57 3.4.22.64]
127554937  caspase-13-like [KO:K04394] [EC:3.4.22.57 3.4.22.64]
127554939  caspase-1-like [KO:K04394] [EC:3.4.22.57 3.4.22.64]
127554940  caspase-1-like [KO:K04394] [EC:3.4.22.57 3.4.22.64]
127544537  gasdermin-D-like [KO:K20917]
127553873  interferon alpha/beta receptor 1 [KO:K05130]
127553875  interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
127563200  tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
127544720  non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
127554459  signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
127564177  signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
127551086  interferon regulatory factor 9 isoform X1 [KO:K04693]
127550519  toll-like receptor 4 [KO:K10160]
127541566  TIR domain-containing adapter molecule 1 [KO:K05842]
127550351  myeloid differentiation primary response protein MyD88 [KO:K04729]
127538287  interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
127549981  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
afz04010  MAPK signaling pathway
afz04064  NF-kappa B signaling pathway
afz04140  Autophagy - animal
afz04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
LinkDB

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