KEGG   PATHWAY: ppad04621
Entry
ppad04621                   Pathway                                
Name
NOD-like receptor signaling pathway - Panthera pardus (leopard)
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
ppad04621  NOD-like receptor signaling pathway
ppad04621

Organism
Panthera pardus (leopard) [GN:ppad]
Gene
109263918  NOD1; nucleotide-binding oligomerization domain-containing protein 1 isoform X1 [KO:K08727]
109269456  RIPK2; receptor-interacting serine/threonine-protein kinase 2 [KO:K08846] [EC:2.7.11.1]
109261148  IKBKG; NF-kappa-B essential modulator [KO:K07210]
109261721  NF-kappa-B essential modulator-like [KO:K07210]
109272766  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
109262264  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
109269589  LOW QUALITY PROTEIN: NF-kappa-B inhibitor beta-like [KO:K02581]
109256623  NFKBIB; NF-kappa-B inhibitor beta isoform X1 [KO:K02581]
109253320  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
109247385  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
109246747  RELA; transcription factor p65 isoform X1 [KO:K04735]
109264508  IL1B; interleukin-1 beta [KO:K04519]
109278654  IL18; interleukin-18 isoform X1 [KO:K05482]
109263814  IL6; interleukin-6 isoform X1 [KO:K05405]
109260532  TNF; tumor necrosis factor [KO:K03156]
109277765  interleukin-8 [KO:K10030]
109277737  growth-regulated alpha protein-like isoform X1 [KO:K05505]
109251929  C-C motif chemokine 2 [KO:K14624]
109251958  CCL5; C-C motif chemokine 5 [KO:K12499]
109247748  CAMP; cathelicidin antimicrobial peptide [KO:K13916]
109260741  beta-defensin 103A-like [KO:K23126]
109270946  NOD2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165]
109263420  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
109265583  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
109252493  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
109249383  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
109259699  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
109261343  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
109278973  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
109276314  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
109264550  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
109265257  MAPK11; LOW QUALITY PROTEIN: mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
109265767  mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
109271512  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
109271515  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
109266785  JUN; transcription factor AP-1 [KO:K04448]
109264886  ATG16L1; autophagy-related protein 16-1 isoform X1 [KO:K17890]
109263482  ATG5; autophagy protein 5 isoform X1 [KO:K08339]
109278919  ATG12; ubiquitin-like protein ATG12 [KO:K08336]
109245686  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 isoform X1 [KO:K08341]
109259070  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
109245976  GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
109251424  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
109245565  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
109250512  microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
109272536  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
109265864  SUGT1; protein SGT1 homolog [KO:K12795]
109258333  SHARPIN; sharpin isoform X1 [KO:K20894]
109272618  RBCK1; ranBP-type and C3HC4-type zinc finger-containing protein 1 isoform X1 [KO:K10630] [EC:2.3.2.31]
109254989  RNF31; E3 ubiquitin-protein ligase RNF31 [KO:K11974] [EC:2.3.2.31]
109250719  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
109275845  CARD6; caspase recruitment domain-containing protein 6 [KO:K12797]
109251310  TRIP6; thyroid receptor-interacting protein 6 isoform X1 [KO:K12792]
109246406  ERBIN; erbin isoform X1 [KO:K12796]
109257521  baculoviral IAP repeat-containing protein 3-like [KO:K16060]
109257526  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
109258781  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
109254870  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
109279193  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
109258814  CARD9; caspase recruitment domain-containing protein 9 isoform X1 [KO:K12794]
109249867  TNFAIP3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
109274754  MAVS; mitochondrial antiviral-signaling protein isoform X1 [KO:K12648]
109274594  TNF receptor-associated factor 3 isoform X1 [KO:K03174]
109270431  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
109257640  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
109271895  TANK; TRAF family member-associated NF-kappa-B activator isoform X1 [KO:K12650]
109253050  IRF3; interferon regulatory factor 3 isoform X1 [KO:K05411]
109259807  IRF7; interferon regulatory factor 7 isoform X1 [KO:K09447]
109247112  interferon alpha-2-like [KO:K05414]
109247120  interferon alpha-like [KO:K05414]
109247123  interferon alpha-like [KO:K05414]
109261306  interferon alpha-like [KO:K05414]
109261307  interferon alpha [KO:K05414]
109247124  IFNB1; interferon beta [KO:K05415]
109278526  NLRX1; NLR family member X1 [KO:K12653]
109277079  ANTXR2; anthrax toxin receptor 2 [KO:K20909]
109262217  ANTXR1; anthrax toxin receptor 1 isoform X1 [KO:K20909]
109259036  apoptosis-associated speck-like protein containing a CARD [KO:K12799]
109275625  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
109272592  BCL2L1; bcl-2-like protein 1 [KO:K04570]
109262395  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
109260338  NLRP3; NACHT, LRR and PYD domains-containing protein 3 isoform X1 [KO:K12800]
109267357  PANX1; pannexin-1 [KO:K03443]
109277675  P2RX7; P2X purinoceptor 7 isoform X1 [KO:K05220]
109256926  TRPM2; transient receptor potential cation channel subfamily M member 2 isoform X1 [KO:K04977] [EC:3.6.1.13]
109262997  TRPM7; transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
109245822  TRPV2; transient receptor potential cation channel subfamily V member 2 [KO:K04971]
109266471  CASR; extracellular calcium-sensing receptor isoform X1 [KO:K04612]
109248459  GPRC6A; G-protein coupled receptor family C group 6 member A [KO:K04622]
109246661  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
109274721  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
109274722  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
109263166  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
109254652  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
109268756  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
109271454  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
109250866  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
109264442  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
109262260  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
109264395  MCU; calcium uniporter protein, mitochondrial isoform X1 [KO:K20858]
109277795  OAS3; LOW QUALITY PROTEIN: 2'-5'-oligoadenylate synthase 3 [KO:K14216] [EC:2.7.7.84]
109277626  OAS1; 2'-5'-oligoadenylate synthase 1 [KO:K14216] [EC:2.7.7.84]
109254076  RNASEL; 2-5A-dependent ribonuclease isoform X1 [KO:K01165]
109246026  DHX33; putative ATP-dependent RNA helicase DHX33 isoform X1 [KO:K17820] [EC:5.6.2.6]
109275163  MFN1; mitofusin-1 isoform X1 [KO:K21356] [EC:3.6.5.-]
109274124  MFN2; mitofusin-2 isoform X1 [KO:K06030] [EC:3.6.5.-]
109249466  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
109254967  RIPK3; receptor-interacting serine/threonine-protein kinase 3 isoform X1 [KO:K08847] [EC:2.7.11.1]
109268813  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
109268084  NAMPT; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
109248000  cytochrome b-245 heavy chain isoform X1 [KO:K21421] [EC:1.-.-.-]
109245544  cytochrome b-245 light chain [KO:K08009]
109259165  TXNIP; thioredoxin-interacting protein [KO:K20910]
109269986  TXN; thioredoxin [KO:K03671]
109265506  TXN2; thioredoxin, mitochondrial [KO:K03671]
109255767  NEK7; serine/threonine-protein kinase Nek7 isoform X1 [KO:K20876] [EC:2.7.11.34]
109260883  BRCC3; lys-63-specific deubiquitinase BRCC36 isoform X1 [KO:K11864] [EC:3.4.19.-]
109271683  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
109274576  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
109253143  CARD8; caspase recruitment domain-containing protein 8 isoform X1 [KO:K12801]
109260566  GPSM3; G-protein-signaling modulator 3 isoform X1 [KO:K15838]
109260635  IRGM; LOW QUALITY PROTEIN: immunity-related GTPase family M protein [KO:K14139] [EC:3.6.5.-]
109278214  MEFV; pyrin isoform X1 [KO:K12803]
109262645  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 isoform X1 [KO:K12804]
109260762  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
109246999  FADD; FAS-associated death domain protein [KO:K02373]
109258466  caspase-12-like isoform X1 [KO:K04741] [EC:3.4.22.-]
109259815  NLRP6; NACHT, LRR and PYD domains-containing protein 6 isoform X1 [KO:K20863]
109259894  LOW QUALITY PROTEIN: NACHT, LRR and PYD domains-containing protein 7-like [KO:K20864]
109259286  NLRP12; NACHT, LRR and PYD domains-containing protein 12 isoform X1 [KO:K20865]
109275037  NAIP; baculoviral IAP repeat-containing protein 1 [KO:K12807]
109266166  NLRC4; NLR family CARD domain-containing protein 4 [KO:K12805]
109247926  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
109246241  guanylate-binding protein 5-like [KO:K20898]
109261618  guanylate-binding protein 5-like [KO:K20898]
109257229  IFI16; gamma-interferon-inducible protein 16 isoform X1 [KO:K20914]
109263082  TP53BP1; tumor suppressor p53-binding protein 1 isoform X1 [KO:K20915]
109247805  RHOA; transforming protein RhoA [KO:K04513]
109253977  PKN1; serine/threonine-protein kinase N1 isoform X1 [KO:K06071] [EC:2.7.11.13]
109246228  PKN2; serine/threonine-protein kinase N2 isoform X1 [KO:K23691] [EC:2.7.11.13]
109255159  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
109246234  guanylate-binding protein 1-like [KO:K20899]
109246237  guanylate-binding protein 4-like isoform X1 [KO:K20899]
109246239  guanylate-binding protein 4-like [KO:K20899]
109258467  caspase-1 isoform X1 [KO:K04394] [EC:3.4.22.57 3.4.22.64]
109258300  GSDMD; gasdermin-D [KO:K20917]
109249714  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
109249711  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
109266731  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
109254113  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
109274693  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
109270329  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
109254992  IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]
109269905  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
109255994  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
109248749  MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
109248991  IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
109252151  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
ppad04010  MAPK signaling pathway
ppad04064  NF-kappa B signaling pathway
ppad04140  Autophagy - animal
ppad04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
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