KEGG   PATHWAY: brhi04621
Entry
brhi04621                   Pathway                                
Name
NOD-like receptor signaling pathway - Buceros rhinoceros silvestris (rhinoceros hornbill)
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
brhi04621  NOD-like receptor signaling pathway
brhi04621

Organism
Buceros rhinoceros silvestris (rhinoceros hornbill) [GN:brhi]
Gene
104495681  NOD1; nucleotide-binding oligomerization domain-containing protein 1 [KO:K08727]
104490207  RIPK2; receptor-interacting serine/threonine-protein kinase 2 [KO:K08846] [EC:2.7.11.1]
104496480  receptor-interacting serine/threonine-protein kinase 2-like [KO:K08846] [EC:2.7.11.1]
104488253  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
104487936  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
104495174  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
104491277  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
104500195  IL1B; interleukin-1 beta [KO:K04519]
104496434  IL18; interleukin-18 [KO:K05482]
104488697  IL6; interleukin-6 [KO:K05405]
104494403  LOW QUALITY PROTEIN: interleukin-8-like [KO:K10030]
104494404  interleukin-8-like [KO:K10030]
104494405  interleukin-8-like [KO:K10030]
104492872  CCL5; C-C motif chemokine 5 [KO:K12499]
104501669  cathelicidin-3-like [KO:K13916]
104490812  antimicrobial peptide THP2-like [KO:K21100]
104498814  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
104493970  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
104496992  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
104495911  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793]
104490261  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
104494032  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
104490313  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
104495861  mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
104500087  mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
104491252  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
104492731  mitogen-activated protein kinase 11-like [KO:K04441] [EC:2.7.11.24]
104489576  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
104496282  JUN; transcription factor AP-1 isoform X1 [KO:K04448]
104491617  ATG16L1; autophagy-related protein 16-1 isoform X1 [KO:K17890]
104495422  ATG5; autophagy protein 5 isoform X1 [KO:K08339]
104493059  ATG12; ubiquitin-like protein ATG12 [KO:K08336]
104489678  gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
104500387  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
104494120  MAP1LC3A; LOW QUALITY PROTEIN: microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
104490926  microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
104496998  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
104500282  SUGT1; suppressor of G2 allele of SKP1 homolog [KO:K12795]
104488620  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
104490475  ERBB2IP; protein LAP2 [KO:K12796]
104498416  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
104491295  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
104495856  TRAF6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
104500467  CARD9; caspase recruitment domain-containing protein 9 [KO:K12794]
104494708  TNFAIP3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
104493585  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
104489937  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
104493706  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
104498151  TANK; TRAF family member-associated NF-kappa-B activator [KO:K12650]
104498037  interferon epsilon-like [KO:K05414]
104488934  interferon omega-1-like [KO:K05414]
104488763  NLRX1; NLR family member X1 [KO:K12653]
104500426  anthrax toxin receptor 1-like [KO:K20909]
104496637  ANTXR2; anthrax toxin receptor 2 [KO:K20909]
104498709  anthrax toxin receptor 1-like [KO:K20909]
104493687  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
104489459  BCL2L1; bcl-2-like protein 1 [KO:K04570]
104500753  PANX1; pannexin-1 [KO:K03443]
104494341  TRPM2; LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13]
104501210  TRPM7; LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
104495668  TRPV2; transient receptor potential cation channel subfamily V member 2 [KO:K04971]
104500225  CASR; extracellular calcium-sensing receptor [KO:K04612]
104490463  GPRC6A; G-protein coupled receptor family C group 6 member A [KO:K04622]
104500775  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
104502280  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
104499999  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
104493057  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
104488324  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
104493738  VDAC2; voltage-dependent anion-selective channel protein 2 isoform X1 [KO:K15040]
104488264  VDAC3; voltage-dependent anion-selective channel protein 3 [KO:K15041]
104501183  MCU; calcium uniporter protein, mitochondrial [KO:K20858]
104492562  RNASEL; 2-5A-dependent ribonuclease [KO:K01165]
104487980  DHX33; putative ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
104490337  MFN1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
104490039  MFN2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
104492700  receptor-interacting serine/threonine-protein kinase 1-like [KO:K02861] [EC:2.7.11.1]
104492246  DNM1L; dynamin-1-like protein [KO:K17065] [EC:3.6.5.5]
104499657  NAMPT; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
104488623  TXN; thioredoxin [KO:K03671]
104496202  TXN2; thioredoxin, mitochondrial [KO:K03671]
104489011  NEK7; serine/threonine-protein kinase Nek7 [KO:K20876] [EC:2.7.11.34]
104499481  BRCC3; lys-63-specific deubiquitinase BRCC36 [KO:K11864] [EC:3.4.19.-]
104491958  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
104491363  proline-serine-threonine phosphatase-interacting protein 1-like [KO:K12804]
104500748  caspase-8-like [KO:K04398] [EC:3.4.22.61]
104492696  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
104488312  FADD; FAS-associated death domain protein [KO:K02373]
104490479  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
104499372  TP53BP1; tumor suppressor p53-binding protein 1 [KO:K20915]
104494849  RHOA; transforming protein RhoA [KO:K04513]
104492443  PKN2; serine/threonine-protein kinase N2 [KO:K23691] [EC:2.7.11.13]
104498839  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
104501093  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
104495604  IFNAR2; interferon alpha/beta receptor 2 [KO:K05131]
104494851  JAK1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
104491544  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
104494590  TLR4; toll-like receptor 4 [KO:K10160]
104496118  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
104489844  IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
104495235  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
brhi04010  MAPK signaling pathway
brhi04140  Autophagy - animal
brhi04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
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