KEGG   PATHWAY: bbub04621
Entry
bbub04621                   Pathway                                
Name
NOD-like receptor signaling pathway - Bubalus bubalis (water buffalo)
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
bbub04621  NOD-like receptor signaling pathway
bbub04621

Organism
Bubalus bubalis (water buffalo) [GN:bbub]
Gene
102389823  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
102389945  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
102390227  NOD2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165]
102390391  PKN2; serine/threonine-protein kinase N2 isoform X2 [KO:K23691]
102391059  [KO:K20899]
102391402  [KO:K20899]
102391970  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
102392112  TNF; tumor necrosis factor isoform X1 [KO:K03156]
102392185  DNM1L; dynamin-1-like protein isoform X10 [KO:K17065] [EC:3.6.5.5]
102392310  CCL5; C-C motif chemokine 5 isoform X1 [KO:K12499]
102392614  MAP1LC3C; LOW QUALITY PROTEIN: microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
102392713  [KO:K20899]
102393086  [KO:K20910]
102393091  ATG16L1; autophagy-related protein 16-1 isoform X3 [KO:K17890]
102393434  MAPK8; mitogen-activated protein kinase 8 isoform X2 [KO:K04440] [EC:2.7.11.24]
102393445  ANTXR1; anthrax toxin receptor 1 [KO:K20909]
102393505  TRPM2; transient receptor potential cation channel subfamily M member 2 isoform X1 [KO:K04977] [EC:3.6.1.13]
102393701  [KO:K05414]
102393748  GSDMD; gasdermin-D isoform X1 [KO:K20917]
102393818  [KO:K05414]
102394110  BIRC3; baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060]
102394317  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
102394663  RNF31; E3 ubiquitin-protein ligase RNF31 isoform X1 [KO:K11974] [EC:2.3.2.31]
102394706  IKBKG; NF-kappa-B essential modulator isoform X6 [KO:K07210]
102394850  [KO:K16060]
102394938  P2RX7; P2X purinoceptor 7 isoform X1 [KO:K05220]
102394946  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
102394992  [KO:K04394] [EC:3.4.22.57 3.4.22.64]
102395129  TRAF2; TNF receptor-associated factor 2 isoform X2 [KO:K03173] [EC:2.3.2.27]
102395411  IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]
102395598  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X2 [KO:K04403]
102395643  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X2 [KO:K12793]
102395839  CASP1; caspase-1 [KO:K01370] [EC:3.4.22.36]
102396206  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
102396209  PKN1; serine/threonine-protein kinase N1 isoform X2 [KO:K06071] [EC:2.7.11.13]
102396262  IL1B; interleukin-1 beta isoform X1 [KO:K04519]
102396314  TRIP6; thyroid receptor-interacting protein 6 isoform X1 [KO:K12792]
102396572  MAPK10; mitogen-activated protein kinase 10 isoform X2 [KO:K04440] [EC:2.7.11.24]
102396674  IRF3; interferon regulatory factor 3 isoform X1 [KO:K05411]
102396688  SHARPIN; sharpin isoform X2 [KO:K20894]
102396769  TRPM7; transient receptor potential cation channel subfamily M member 7 isoform X3 [KO:K04982] [EC:2.7.11.1]
102397052  TANK; TRAF family member-associated NF-kappa-B activator isoform X1 [KO:K12650]
102397143  [KO:K12799]
102397149  MAPK14; mitogen-activated protein kinase 14 isoform X4 [KO:K04441] [EC:2.7.11.24]
102397482  [KO:K20899]
102397694  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
102397938  RELA; transcription factor P65 [KO:K04735]
102397948  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
102397985  FADD; FAS-associated death domain protein [KO:K02373]
102398022  [KO:K20898]
102398090  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
102398335  TP53BP1; TP53-binding protein 1 isoform X1 [KO:K20915]
102398355  MEFV; pyrin isoform X1 [KO:K12803]
102398468  MFN2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
102398481  TRPV2; transient receptor potential cation channel subfamily V member 2 isoform X1 [KO:K04971]
102398659  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X4 [KO:K07211] [EC:2.7.11.10]
102398886  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
102399138  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
102399202  [KO:K20899]
102399262  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 isoform X3 [KO:K08341]
102399580  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
102399613  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X3 [KO:K04467] [EC:2.7.11.10]
102399652  MFN1; mitofusin-1 isoform X1 [KO:K21356] [EC:3.6.5.-]
102399768  SUGT1; protein SGT1 homolog isoform X1 [KO:K12795]
102400092  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X2 [KO:K15041]
102401062  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X2 [KO:K04959]
102401432  IL18; interleukin-18 isoform X1 [KO:K05482]
102402025  RHOA; transforming protein RhoA [KO:K04513]
102402056  [KO:K05415]
102402077  BCL2; apoptosis regulator Bcl-2 isoform X3 [KO:K02161]
102402213  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
102402262  TRAF3; TNF receptor-associated factor 3 isoform X2 [KO:K03174]
102402367  [KO:K05415]
102402381  [KO:K13916]
102402697  [KO:K05415]
102402789  [KO:K05414]
102402850  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
102402911  NLRP1; NACHT, LRR and PYD domains-containing protein 1 isoform X3 [KO:K12798]
102402933  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
102403296  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102403416  CARD6; caspase recruitment domain-containing protein 6 isoform X1 [KO:K12797]
102403452  MAPK9; mitogen-activated protein kinase 9 isoform X5 [KO:K04440] [EC:2.7.11.24]
102403644  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
102403930  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X2 [KO:K02580]
102404023  [KO:K04725] [EC:2.3.2.27]
102404882  NLRP6; NACHT, LRR and PYD domains-containing protein 6 [KO:K20863]
102405083  DHX33; ATP-dependent RNA helicase DHX33 isoform X1 [KO:K17820] [EC:5.6.2.6]
102405176  NLRC4; NLR family CARD domain-containing protein 4 [KO:K12805]
102405224  JUN; transcription factor AP-1 [KO:K04448]
102405285  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
102405788  ATG12; ubiquitin-like protein ATG12 [KO:K08336]
102405830  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X2 [KO:K05858] [EC:3.1.4.11]
102406103  NLRP12; NACHT, LRR and PYD domains-containing protein 12 isoform X2 [KO:K20865]
102406400  [KO:K04079]
102406758  RBCK1; ranBP-type and C3HC4-type zinc finger-containing protein 1 isoform X1 [KO:K10630] [EC:2.3.2.31]
102407022  TLR4; toll-like receptor 4 precursor [KO:K10160]
102407094  [KO:K14216] [EC:2.7.7.84]
102407178  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
102407215  RIPK2; receptor-interacting serine/threonine-protein kinase 2 isoform X1 [KO:K08846] [EC:2.7.11.1]
102407491  PRKCD; protein kinase C delta type isoform X4 [KO:K06068] [EC:2.7.11.13]
102407635  NLRX1; NLR family member X1 isoform X3 [KO:K12653]
102407872  [KO:K12807]
102407958  CASR; extracellular calcium-sensing receptor isoform X2 [KO:K04612]
102408391  [KO:K14216] [EC:2.7.7.84]
102408434  [KO:K05415]
102408706  TXN; thioredoxin [KO:K03671]
102408809  ANTXR2; anthrax toxin receptor 2 [KO:K20909]
102408947  NLRP3; NACHT, LRR and PYD domains-containing protein 3 isoform X3 [KO:K12800]
102408963  [KO:K14624]
102409463  MAVS; mitochondrial antiviral-signaling protein isoform X5 [KO:K12648]
102409656  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
102409665  MAPK12; mitogen-activated protein kinase 12 isoform X3 [KO:K04441] [EC:2.7.11.24]
102409744  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
102409793  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
102409833  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
102409842  [KO:K08341]
102410738  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
102410871  [KO:K04079]
102411013  [KO:K04570]
102411493  TXN2; thioredoxin, mitochondrial [KO:K03671]
102411526  NAMPT; nicotinamide phosphoribosyltransferase isoform X1 [KO:K03462] [EC:2.4.2.12]
102412133  TNFAIP3; tumor necrosis factor alpha-induced protein 3 isoform X2 [KO:K11859] [EC:3.4.19.12]
102412320  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858] [EC:3.1.4.11]
102412377  [KO:K20914]
102412452  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X8 [KO:K04958]
102412615  CARD9; caspase recruitment domain-containing protein 9 isoform X1 [KO:K12794]
102412626  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
102412929  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
102412933  CXCL8; interleukin-8 precursor [KO:K10030]
102412937  MCU; calcium uniporter protein, mitochondrial isoform X1 [KO:K20858]
102412940  BRCC3; lys-63-specific deubiquitinase BRCC36 isoform X1 [KO:K11864] [EC:3.4.19.-]
102412955  PANX1; pannexin-1 [KO:K03443]
102413072  [KO:K08009]
102413198  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
102413293  [KO:K13916]
102413357  ATG5; autophagy protein 5 isoform X4 [KO:K08339]
102413359  NOD1; nucleotide-binding oligomerization domain-containing protein 1 isoform X1 [KO:K08727]
102413623  [KO:K13916]
102413748  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
102413796  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
102414314  STAT2; signal transducer and activator of transcription 2 isoform X2 [KO:K11221]
102414434  [KO:K05414]
102414555  [KO:K23126]
102414912  [KO:K12966]
102414941  [KO:K13916]
102415101  IL6; interleukin-6 isoform X1 [KO:K05405]
102415113  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X4 [KO:K04427] [EC:2.7.11.25]
102415114  [KO:K05414]
102415247  [KO:K05505]
102415288  [KO:K21421] [EC:1.-.-.-]
102415500  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X2 [KO:K11220]
102415742  GPRC6A; LOW QUALITY PROTEIN: G-protein coupled receptor family C group 6 member A [KO:K04622]
102415899  [KO:K05505]
102416135  ERBIN; erbin isoform X2 [KO:K12796]
102416177  STING1; stimulator of interferon genes protein isoform X1 [KO:K12654]
102416204  [KO:K05414]
102416225  [KO:K05505]
102416386  RNASEL; 2-5A-dependent ribonuclease [KO:K01165]
102416535  NEK7; serine/threonine-protein kinase Nek7 isoform X3 [KO:K20876] [EC:2.7.11.34]
102416581  BCL2L1; bcl-2-like protein 1 [KO:K04570]
102416670  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 isoform X2 [KO:K12804]
112577733  [KO:K13916]
112577736  [KO:K05414]
112578537  [KO:K21100]
112581107  [KO:K13916]
112583541  [KO:K05414]
112583544  [KO:K05414]
112583545  [KO:K05414]
112583546  [KO:K05414]
112583548  [KO:K05414]
112583867  [KO:K05414]
112583876  [KO:K05414]
112583880  [KO:K05414]
112583883  [KO:K05415]
112583884  [KO:K05415]
112583885  [KO:K05415]
112583886  [KO:K05415]
112585628  [KO:K20899]
123332559  [KO:K21100]
123332581  [KO:K21100]
123332785  [KO:K05415]
123334066  [KO:K20899]
123334067  [KO:K20899]
123464561  [KO:K13916]
123464880  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A isoform X2 [KO:K10435]
123465155  [KO:K20864]
123465246  [KO:K13916]
123465262  MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
123465472  [KO:K03671]
123465588  [KO:K05415]
123465589  [KO:K05415]
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
bbub04010  MAPK signaling pathway
bbub04064  NF-kappa B signaling pathway
bbub04140  Autophagy - animal
bbub04620  Toll-like receptor signaling pathway
KO pathway
ko04621   

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