KEGG   PATHWAY: oor04621
Entry
oor04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Orcinus orca (killer whale)
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
oor04621  NOD-like receptor signaling pathway
oor04621

Organism
Orcinus orca (killer whale) [GN:oor]
Gene
101269212  MAPK13; mitogen-activated protein kinase 13 isoform X7 [KO:K04441] [EC:2.7.11.24]
101269256  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
101269458  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101269870  TNF; tumor necrosis factor [KO:K03156]
101270095  [KO:K20864]
101270140  MCU; calcium uniporter protein, mitochondrial isoform X3 [KO:K20858]
101270342  RELA; transcription factor p65 isoform X1 [KO:K04735]
101270529  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
101270537  NLRX1; NLR family member X1 isoform X3 [KO:K12653]
101270548  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
101270809  PKN1; serine/threonine-protein kinase N1 isoform X1 [KO:K06071] [EC:2.7.11.13]
101270961  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
101271249  [KO:K04079]
101271274  IL18; interleukin-18 isoform X1 [KO:K05482]
101271374  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
101271817  ATG5; autophagy protein 5 isoform X1 [KO:K08339]
101271819  NOD2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165]
101272168  IRF3; interferon regulatory factor 3 [KO:K05411]
101272236  GSDMD; gasdermin-D isoform X2 [KO:K20917]
101272428  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
101272458  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
101272806  [KO:K21356] [EC:3.6.5.-]
101272815  IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]
101272962  FADD; FAS-associated death domain protein isoform X1 [KO:K02373]
101272972  [KO:K04741] [EC:3.4.22.-]
101273068  RNF31; E3 ubiquitin-protein ligase RNF31 isoform X6 [KO:K11974] [EC:2.3.2.31]
101273094  RIPK2; receptor-interacting serine/threonine-protein kinase 2 isoform X1 [KO:K08846] [EC:2.7.11.1]
101273287  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
101273673  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X4 [KO:K07211] [EC:2.7.11.10]
101273776  [KO:K12499]
101273830  RHOA; transforming protein RhoA [KO:K04513]
101274009  GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
101274041  [KO:K05414]
101274139  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793]
101274282  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 isoform X3 [KO:K12804]
101274558  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
101274897  PANX1; pannexin-1 [KO:K03443]
101274948  [KO:K08009]
101275016  [KO:K05414]
101275275  [KO:K05414]
101275303  TNFAIP3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
101275325  GPSM3; G-protein-signaling modulator 3 [KO:K15838]
101275383  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
101275504  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
101275571  TANK; TRAF family member-associated NF-kappa-B activator isoform X1 [KO:K12650]
101275617  ANTXR1; LOW QUALITY PROTEIN: anthrax toxin receptor 1 [KO:K20909]
101275839  TRIP6; thyroid receptor-interacting protein 6 [KO:K12792]
101275872  STING1; stimulator of interferon genes protein isoform X1 [KO:K12654]
101275998  TXN; thioredoxin [KO:K03671]
101276394  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
101276520  VDAC2; voltage-dependent anion-selective channel protein 2 isoform X3 [KO:K15040]
101276622  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
101276649  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
101276750  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
101277391  [KO:K05505]
101277458  IRF7; interferon regulatory factor 7 isoform X1 [KO:K09447]
101277553  TRAF6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
101277583  MFN1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
101277656  MAPK10; mitogen-activated protein kinase 10 isoform X4 [KO:K04440] [EC:2.7.11.24]
101277730  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
101277868  OAS2; LOW QUALITY PROTEIN: 2'-5'-oligoadenylate synthase 2 [KO:K14216] [EC:2.7.7.84]
101278129  CXCL8; interleukin-8 [KO:K10030]
101278136  [KO:K20914]
101278346  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X2 [KO:K11219] [EC:2.7.10.2]
101278395  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
101278425  MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
101278630  NEK7; serine/threonine-protein kinase Nek7 isoform X6 [KO:K20876] [EC:2.7.11.34]
101278758  ATG16L1; autophagy-related protein 16-1 isoform X3 [KO:K17890]
101278806  NOD1; nucleotide-binding oligomerization domain-containing protein 1 isoform X1 [KO:K08727]
101279174  [KO:K21421] [EC:1.-.-.-]
101279469  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
101279660  NLRP6; LOW QUALITY PROTEIN: NACHT, LRR and PYD domains-containing protein 6 [KO:K20863]
101279857  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101279981  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
101280074  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
101280755  [KO:K08341]
101280877  [KO:K13916]
101280894  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
101281072  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
101281155  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
101281228  MAPK8; mitogen-activated protein kinase 8 isoform X2 [KO:K04440] [EC:2.7.11.24]
101281303  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
101281343  SUGT1; protein SGT1 homolog [KO:K12795]
101281417  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X9 [KO:K05858] [EC:3.1.4.11]
101281591  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
101281780  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
101281783  IL6; LOW QUALITY PROTEIN: interleukin-6 [KO:K05405]
101282000  NLRP3; NACHT, LRR and PYD domains-containing protein 3 isoform X1 [KO:K12800]
101282011  ANTXR2; anthrax toxin receptor 2 isoform X1 [KO:K20909]
101282217  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
101282675  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X2 [KO:K04403]
101282698  [KO:K13916]
101282737  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X2 [KO:K04958]
101282948  [KO:K13916]
101283001  P2RX7; P2X purinoceptor 7 isoform X1 [KO:K05220]
101283081  ERBIN; erbin isoform X8 [KO:K12796]
101283121  NAMPT; nicotinamide phosphoribosyltransferase isoform X1 [KO:K03462] [EC:2.4.2.12]
101283238  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
101283436  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
101283958  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
101283961  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
101284215  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
101284278  TRPM7; transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
101284365  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
101284483  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
101284534  PKN2; serine/threonine-protein kinase N2 isoform X1 [KO:K23691]
101284551  SHARPIN; sharpin isoform X2 [KO:K20894]
101284556  MAVS; mitochondrial antiviral-signaling protein isoform X4 [KO:K12648]
101284630  TRPM2; transient receptor potential cation channel subfamily M member 2 isoform X1 [KO:K04977] [EC:3.6.1.13]
101284636  CARD9; caspase recruitment domain-containing protein 9 isoform X2 [KO:K12794]
101284673  TP53BP1; TP53-binding protein 1 isoform X1 [KO:K20915]
101284892  IL1B; interleukin-1 beta isoform X2 [KO:K04519]
101285036  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
101285237  [KO:K05505]
101285270  RBCK1; ranBP-type and C3HC4-type zinc finger-containing protein 1 isoform X2 [KO:K10630] [EC:2.3.2.31]
101285302  [KO:K20899]
101285413  TXNIP; thioredoxin-interacting protein [KO:K20910]
101285495  [KO:K05505]
101285669  BRCC3; lys-63-specific deubiquitinase BRCC36 isoform X1 [KO:K11864] [EC:3.4.19.-]
101285763  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
101285765  [KO:K12797]
101285818  [KO:K20898]
101286130  RNASEL; 2-5A-dependent ribonuclease isoform X2 [KO:K01165]
101286422  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
101286450  MEFV; pyrin isoform X2 [KO:K12803]
101287122  PYCARD; apoptosis-associated speck-like protein containing a CARD [KO:K12799]
101287367  [KO:K05414]
101287377  NLRC4; NLR family CARD domain-containing protein 4 isoform X1 [KO:K12805]
101287453  DHX33; ATP-dependent RNA helicase DHX33 isoform X1 [KO:K17820] [EC:5.6.2.6]
101287492  TXN2; thioredoxin, mitochondrial [KO:K03671]
101287579  [KO:K04441] [EC:2.7.11.24]
101287701  MAPK9; mitogen-activated protein kinase 9 isoform X5 [KO:K04440] [EC:2.7.11.24]
101287833  [KO:K04441] [EC:2.7.11.24]
101287874  TRPV2; transient receptor potential cation channel subfamily V member 2 isoform X1 [KO:K04971]
101288019  [KO:K20899]
101288063  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
101288065  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
101288184  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
101288913  JUN; transcription factor Jun [KO:K04448]
101289058  IFNB1; interferon beta [KO:K05415]
101289192  [KO:K14216] [EC:2.7.7.84]
101289394  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101289477  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
101289484  MFN2; mitofusin-2 isoform X1 [KO:K06030] [EC:3.6.5.-]
101289504  CASR; extracellular calcium-sensing receptor [KO:K04612]
101289706  [KO:K14624]
101289751  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X2 [KO:K02861] [EC:2.7.11.1]
101289850  CASP1; caspase-1 [KO:K01370] [EC:3.4.22.36]
101289999  VDAC1; voltage-dependent anion-selective channel protein 1 isoform X1 [KO:K05862]
101290090  [KO:K04394] [EC:3.4.22.57 3.4.22.64]
101290315  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
101290359  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
117197019  [KO:K23126]
117198145  [KO:K13916]
117198239  [KO:K08336]
125964698  [KO:K05414]
125964699  [KO:K05414]
125964701  [KO:K05414]
125964702  [KO:K05414]
125964703  [KO:K05414]
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
oor04010  MAPK signaling pathway
oor04064  NF-kappa B signaling pathway
oor04140  Autophagy - animal
oor04620  Toll-like receptor signaling pathway
KO pathway
ko04621   

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