KEGG   PATHWAY: oma04621
Entry
oma04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Oenanthe melanoleuca (Eastern black-eared wheatear)
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
oma04621  NOD-like receptor signaling pathway
oma04621

Organism
Oenanthe melanoleuca (Eastern black-eared wheatear) [GN:oma]
Gene
130250067  NOD1; nucleotide-binding oligomerization domain-containing protein 1 isoform X1 [KO:K08727]
130258053  receptor-interacting serine/threonine-protein kinase 2-like isoform X1 [KO:K08846] [EC:2.7.11.1]
130249264  RIPK2; receptor-interacting serine/threonine-protein kinase 2 isoform X1 [KO:K08846] [EC:2.7.11.1]
130266109  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
130255162  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
130261961  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
130262792  NFKBIB; LOW QUALITY PROTEIN: NF-kappa-B inhibitor beta [KO:K02581]
130254071  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
130252126  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
130262766  RELA; transcription factor p65 isoform X1 [KO:K04735]
130266786  interleukin-1 beta-like [KO:K04519]
130262009  interleukin-1 beta-like [KO:K04519]
130262481  interleukin-18-like isoform X1 [KO:K05482]
130248751  IL6; interleukin-6 [KO:K05405]
130252725  interleukin-8-like [KO:K10030]
130252726  interleukin-8-like [KO:K10030]
130252727  interleukin-8-like isoform X1 [KO:K10030]
130250382  cathelicidin-2-like isoform X1 [KO:K13916]
130250383  cathelicidin-2-like [KO:K13916]
130251001  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
130263507  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
130250537  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
130255091  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
130259590  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
130252708  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
130254720  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
130258632  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
130263680  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
130263682  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
130248642  MAPK11; LOW QUALITY PROTEIN: mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
130248643  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
130256017  JUN; transcription factor Jun [KO:K04448]
130256815  ATG16L1; autophagy-related protein 16-1 isoform X1 [KO:K17890]
130250699  ATG5; autophagy protein 5 isoform X1 [KO:K08339]
130264677  ATG12; ubiquitin-like protein ATG12 [KO:K08336]
130266761  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
130261472  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
130250540  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C isoform X1 [KO:K10435]
130261206  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A isoform X1 [KO:K10435]
130257960  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
130254440  SUGT1; protein SGT1 homolog [KO:K12795]
130250284  SHARPIN; sharpin isoform X1 [KO:K10630] [EC:2.3.2.31]
130264473  RNF31; E3 ubiquitin-protein ligase RNF31 isoform X1 [KO:K11974] [EC:2.3.2.31]
130253075  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
130264825  ERBIN; erbin isoform X1 [KO:K12796]
130250579  inhibitor of apoptosis protein-like [KO:K16060]
130260219  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
130251003  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
130253546  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
130260282  CARD9; caspase recruitment domain-containing protein 9 isoform X1 [KO:K12794]
130251644  TNFAIP3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
130252064  MAVS; mitochondrial antiviral-signaling protein [KO:K12648]
130254031  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
130267074  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
130263556  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
130255656  TANK; TRAF family member-associated NF-kappa-B activator [KO:K12650]
130253702  IRF7; interferon regulatory factor 7 isoform X1 [KO:K09447]
130265253  interferon omega-1-like [KO:K05414]
130265549  interferon-like [KO:K05415]
130265550  interferon-like [KO:K05415]
130262499  NLRX1; NLR family member X1 isoform X1 [KO:K12653]
130252213  ANTXR2; anthrax toxin receptor 2 [KO:K20909]
130261887  ANTXR1; LOW QUALITY PROTEIN: anthrax toxin receptor 1 [KO:K20909]
130254931  ANTXRL; anthrax toxin receptor-like [KO:K20909]
130249137  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
130261540  BCL2L1; bcl-2-like protein 1 [KO:K04570]
130250789  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
130257344  PANX1; pannexin-1 [KO:K03443]
130256578  TRPM2; transient receptor potential cation channel subfamily M member 2 isoform X1 [KO:K04977] [EC:3.6.1.13]
130257531  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
130266859  transient receptor potential cation channel subfamily V member 2-like [KO:K04971]
130258689  CASR; extracellular calcium-sensing receptor [KO:K04612]
130251062  GPRC6A; LOW QUALITY PROTEIN: G-protein coupled receptor family C group 6 member A [KO:K04622]
130250780  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
130251914  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
130254499  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
130258144  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
130265231  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
130263660  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
130258530  VDAC1; voltage-dependent anion-selective channel protein 1 isoform X1 [KO:K05862]
130255073  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
130261964  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
130255198  MCU; calcium uniporter protein, mitochondrial isoform X1 [KO:K20858]
130256510  RNASEL; 2-5A-dependent ribonuclease isoform X1 [KO:K01165]
130260893  DHX33; ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
130256738  MFN1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
130261718  MFN2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
130250432  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
130266631  NAMPT; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
130254202  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
130257716  cytochrome b-245 light chain [KO:K08009]
130263428  TXNIP; LOW QUALITY PROTEIN: thioredoxin-interacting protein [KO:K20910]
130264863  thioredoxin [KO:K03671]
130265244  TXN2; thioredoxin, mitochondrial [KO:K03671]
130256147  NEK7; serine/threonine-protein kinase Nek7 [KO:K20876] [EC:2.7.11.34]
130253197  BRCC3; lys-63-specific deubiquitinase BRCC36 [KO:K11864] [EC:3.4.19.-]
130251200  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
130253553  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
130257454  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 [KO:K12804]
130255261  caspase-8-like [KO:K04398] [EC:3.4.22.61]
130255263  caspase-8-like [KO:K04398] [EC:3.4.22.61]
130254053  FADD; FAS-associated death domain protein [KO:K02373]
130254535  NACHT, LRR and PYD domains-containing protein 12-like [KO:K20865]
130258495  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
130257517  TP53BP1; TP53-binding protein 1 isoform X1 [KO:K20915]
130258181  RHOA; transforming protein RhoA [KO:K04513]
130256207  PKN2; serine/threonine-protein kinase N2 [KO:K23691] [EC:2.7.11.13]
130260943  YWHAE; 14-3-3 protein epsilon [KO:K06630]
130251879  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
130251888  IFNAR2; interferon alpha/beta receptor 2 [KO:K05131]
130256302  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
130262633  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
130255273  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
130265681  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
130260187  TLR4; toll-like receptor 4 [KO:K10160]
130264539  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
130249978  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
130262891  IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
130258650  STING1; stimulator of interferon genes protein isoform X1 [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
oma04010  MAPK signaling pathway
oma04140  Autophagy - animal
oma04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
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