KEGG   PATHWAY: mui04621
Entry
mui04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Mesitornis unicolor (brown roatelo)
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
mui04621  NOD-like receptor signaling pathway
mui04621

Organism
Mesitornis unicolor (brown roatelo) [GN:mui]
Gene
104547108  NOD1; nucleotide-binding oligomerization domain-containing protein 1 [KO:K08727]
104539630  RIPK2; receptor-interacting serine/threonine-protein kinase 2 [KO:K08846] [EC:2.7.11.1]
104545071  receptor-interacting serine/threonine-protein kinase 2-like [KO:K08846] [EC:2.7.11.1]
104535310  receptor-interacting serine/threonine-protein kinase 2-like [KO:K08846] [EC:2.7.11.1]
104546789  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
104533819  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
104538960  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
104537709  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
104548801  interleukin-1 receptor antagonist protein-like [KO:K04519]
104546623  IL18; interleukin-18 [KO:K05482]
104535351  IL6; interleukin-6 [KO:K05405]
104538275  interleukin-8-like [KO:K10030]
104538276  interleukin-8 [KO:K10030]
104539281  CCL5; C-C motif chemokine 5 [KO:K12499]
104539198  LOW QUALITY PROTEIN: cathelicidin-3-like [KO:K13916]
104536541  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
104541594  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
104536892  TAB2; LOW QUALITY PROTEIN: TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
104544731  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793]
104534766  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
104544253  mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
104534693  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
104538133  mitogen-activated protein kinase 11-like [KO:K04441] [EC:2.7.11.24]
104544084  mitogen-activated protein kinase 12-like [KO:K04441] [EC:2.7.11.24]
104539184  mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
104547036  mitogen-activated protein kinase 13-like [KO:K04441] [EC:2.7.11.24]
104535854  JUN; transcription factor AP-1 [KO:K04448]
104533952  ATG16L1; autophagy-related protein 16-1 isoform X1 [KO:K17890]
104539913  ATG5; autophagy protein 5 [KO:K08339]
104536128  ATG12; ubiquitin-like protein ATG12 [KO:K08336]
104535364  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
104533507  gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
104539404  microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
104535282  microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
104534943  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
104533612  microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
104548144  SUGT1; suppressor of G2 allele of SKP1 homolog [KO:K12795]
104537250  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
104542104  LOW QUALITY PROTEIN: protein LAP2-like [KO:K12796]
104548263  ERBB2IP; protein LAP2 [KO:K12796]
104533966  inhibitor of apoptosis protein [KO:K16060]
104546430  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
104535949  TRAF5; LOW QUALITY PROTEIN: TNF receptor-associated factor 5 [KO:K09849]
104548272  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
104540037  LOW QUALITY PROTEIN: caspase recruitment domain-containing protein 9-like [KO:K12794]
104546684  TNFAIP3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
104537675  MAVS; mitochondrial antiviral-signaling protein [KO:K12648]
104537198  TRAF3; TNF receptor-associated factor 3 [KO:K03174]
104534147  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
104538090  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
104546579  TANK; TRAF family member-associated NF-kappa-B activator [KO:K12650]
104542263  IRF7; interferon regulatory factor 7 [KO:K09447]
104539464  LOW QUALITY PROTEIN: interferon beta-like [KO:K05414]
104533588  interferon epsilon-like [KO:K05414]
104542485  LOW QUALITY PROTEIN: interferon-like [KO:K05415]
104543783  NLRX1; NLR family member X1 [KO:K12653]
104536044  ANTXR2; anthrax toxin receptor 2 [KO:K20909]
104539877  anthrax toxin receptor 1-like [KO:K20909]
104537796  anthrax toxin receptor 1-like [KO:K20909]
104546136  caspase-1-like [KO:K01370] [EC:3.4.22.36]
104537605  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
104548769  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
104543324  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
104541916  PANX1; pannexin-1 [KO:K03443]
104545198  TRPM2; transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13]
104545710  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
104536717  TRPV2; LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily V member 2 [KO:K04971]
104545028  CASR; extracellular calcium-sensing receptor [KO:K04612]
104546678  GPRC6A; G-protein coupled receptor family C group 6 member A [KO:K04622]
104545723  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
104540768  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
104547733  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
104537163  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
104534556  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
104535115  VDAC2; voltage-dependent anion-selective channel protein 2 isoform X1 [KO:K15040]
104534789  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
104544564  MCU; LOW QUALITY PROTEIN: calcium uniporter protein, mitochondrial [KO:K20858]
104547612  RNASEL; 2-5A-dependent ribonuclease [KO:K01165]
104548438  DHX33; putative ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
104541968  MFN1; LOW QUALITY PROTEIN: mitofusin-1 [KO:K21356] [EC:3.6.5.-]
104545988  MFN2; mitofusin-2 isoform X1 [KO:K06030] [EC:3.6.5.-]
104538113  receptor-interacting serine/threonine-protein kinase 1-like [KO:K02861] [EC:2.7.11.1]
104533958  DNM1L; dynamin-1-like protein [KO:K17065] [EC:3.6.5.5]
104544690  nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
104539845  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
104548181  LOW QUALITY PROTEIN: cytochrome b-245 light chain [KO:K08009]
104545813  TXNIP; thioredoxin-interacting protein [KO:K20910]
104542720  TXN2; thioredoxin, mitochondrial [KO:K03671]
104537759  TXN; thioredoxin [KO:K03671]
104543396  NEK7; serine/threonine-protein kinase Nek7 [KO:K20876] [EC:2.7.11.34]
104539063  HSP90AB1; LOW QUALITY PROTEIN: heat shock protein HSP 90-beta [KO:K04079]
104534415  heat shock protein HSP 90-alpha [KO:K04079]
104545192  NACHT, LRR and PYD domains-containing protein 1-like [KO:K12801]
104539673  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 [KO:K12804]
104536360  caspase-8-like [KO:K04398] [EC:3.4.22.61]
104536361  caspase-8-like [KO:K04398] [EC:3.4.22.61]
104543590  FADD; FAS-associated death domain protein [KO:K02373]
104539217  LOW QUALITY PROTEIN: NACHT, LRR and PYD domains-containing protein 12-like [KO:K20865]
104539980  NACHT, LRR and PYD domains-containing protein 3-like [KO:K20865]
104541201  LOW QUALITY PROTEIN: NACHT, LRR and PYD domains-containing protein 12-like [KO:K20865]
104537245  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
104534059  TP53BP1; tumor suppressor p53-binding protein 1 [KO:K20915]
104535946  transforming protein RhoA [KO:K04513]
104538125  PKN2; serine/threonine-protein kinase N2 [KO:K23691] [EC:2.7.11.13]
104544571  YWHAE; 14-3-3 protein epsilon [KO:K06630]
104546766  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
104535604  IFNAR2; interferon alpha/beta receptor 2 [KO:K05131]
104536595  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
104544870  signal transducer and activator of transcription 1-like [KO:K11220]
104547901  TLR4; toll-like receptor 4 [KO:K10160]
104534833  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
104545424  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
104534214  IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
104533350  TMEM173; 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
mui04010  MAPK signaling pathway
mui04140  Autophagy - animal
mui04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
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