KEGG   PATHWAY: ssc04621
Entry
ssc04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Sus scrofa (pig)
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
ssc04621  NOD-like receptor signaling pathway
ssc04621

Organism
Sus scrofa (pig) [GN:ssc]
Gene
100037289  IRF7; interferon regulatory factor 7 [KO:K09447]
100037290  MAVS; mitochondrial antiviral-signaling protein [KO:K12648]
100037300  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
100037961  CTSB; cathepsin B precursor [KO:K01363] [EC:3.4.22.1]
100048946  RNASEL; 2-5A-dependent ribonuclease [KO:K01165]
100049703  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
100101471  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
100125828  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
100125838  NOD2; nucleotide-binding oligomerization domain-containing protein 2 [KO:K10165]
100127166  IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
100127355  IKBKG; NF-kappa-B essential modulator [KO:K07210]
100135660  NOD1; nucleotide-binding oligomerization domain-containing protein 1 [KO:K08727]
100135662  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
100135663  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
100135665  RELA; transcription factor p65 [KO:K04735]
100144483  NPG1; protegrin-1 precursor [KO:K13916]
100144533  GPSM3; G-protein-signaling modulator 3 [KO:K15838]
100151938  GBP1; interferon-induced guanylate-binding protein 1 [KO:K20899]
100152099  GPRC6A; G-protein coupled receptor family C group 6 member A [KO:K04622]
100152100  IFN-ALPHA-13; uncharacterized protein LOC100152100 precursor [KO:K05414]
100152504  IFN-ALPHA-15; uncharacterized protein LOC100152504 precursor [KO:K05414]
100152628  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 [KO:K12804]
100152679  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
100153137  GBP2; interferon-induced guanylate-binding protein 2 [KO:K20897]
100153263  RIPK3; receptor-interacting serine/threonine-protein kinase 3 [KO:K08847] [EC:2.7.11.1]
100153325  [KO:K05414]
100153661  [KO:K05414]
100153724  IFN-ALPHA-8; uncharacterized protein LOC100153724 precursor [KO:K05414]
100153785  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
100153794  MCU; calcium uniporter protein, mitochondrial isoform X1 [KO:K20858]
100153927  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100154766  PKN2; serine/threonine-protein kinase N2 isoform X3 [KO:K23691]
100154938  IFN-ALPHA-17; uncharacterized protein LOC100154938 precursor [KO:K05414]
100155015  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
100155195  [KO:K20899]
100155841  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
100156073  [KO:K20914]
100156182  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
100156366  TANK; LOW QUALITY PROTEIN: TRAF family member-associated NF-kappa-B activator [KO:K12650]
100156561  IFN-ALPHA-10; interferon-alpha-10 precursor [KO:K05414]
100156630  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
100156936  [KO:K05414]
100156979  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
100157352  IFN-ALPHA-1; interferon-alpha-1 precursor [KO:K05414]
100157641  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
100157735  IFN-ALPHA-16; uncharacterized protein LOC100157735 precursor [KO:K05414]
100157766  IFN-ALPHA-9; uncharacterized protein LOC100157766 precursor [KO:K05414]
100158080  TXN2; thioredoxin, mitochondrial [KO:K03671]
100169932  TRPM7; transient receptor potential cation channel subfamily M member 7 isoform X2 [KO:K04982] [EC:2.7.11.1]
100170124  PMAP-36; antibacterial peptide PMAP-36 precursor [KO:K13916]
100217389  TMEM173; stimulator of interferon genes protein [KO:K12654]
100303758  IFN-ALPHA-5; interferon, alpha 5 precursor [KO:K05414]
100310806  IFN-ALPHAOMEGA; interferon-alphaomega precursor [KO:K05414]
100322893  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
100462745  ATG12; ubiquitin-like protein ATG12 [KO:K08336]
100462746  ATG16L1; autophagy-related protein 16-1 isoform 1 [KO:K17890]
100462751  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
100462752  GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
100462754  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
100511418  ERBIN; erbin isoform X20 [KO:K12796]
100512354  MFN2; mitofusin-2 isoform X2 [KO:K06030] [EC:3.6.5.-]
100512852  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
100513840  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
100513853  ANTXR1; anthrax toxin receptor 1 [KO:K20909]
100514416  ANTXR2; anthrax toxin receptor 2 [KO:K20909]
100514823  NLRP3; NACHT, LRR and PYD domains-containing protein 3 [KO:K12800]
100515078  NLRC4; LOW QUALITY PROTEIN: NLR family CARD domain-containing protein 4 [KO:K12805]
100515528  PKN1; serine/threonine-protein kinase N1 isoform X1 [KO:K06071] [EC:2.7.11.13]
100515607  GSDMD; gasdermin-D [KO:K20917]
100516581  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
100516741  NLRP7; NACHT, LRR and PYD domains-containing protein 7 [KO:K20864]
100516948  BRCC3; lys-63-specific deubiquitinase BRCC36 [KO:K11864] [EC:3.4.19.-]
100517279  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
100517333  MEFV; pyrin isoform X1 [KO:K12803]
100517796  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793]
100518678  NLRX1; NLR family member X1 [KO:K12653]
100518835  RIPK2; receptor-interacting serine/threonine-protein kinase 2 isoform X2 [KO:K08846] [EC:2.7.11.1]
100519245  NLRP6; NACHT, LRR and PYD domains-containing protein 6 isoform X1 [KO:K20863]
100519508  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
100519985  RBCK1; ranBP-type and C3HC4-type zinc finger-containing protein 1 isoform X1 [KO:K10630] [EC:2.3.2.31]
100520655  TP53BP1; tumor suppressor p53-binding protein 1 isoform X1 [KO:K20915]
100520980  CASR; extracellular calcium-sensing receptor precursor [KO:K04612]
100521736  MAPK10; mitogen-activated protein kinase 10 isoform X3 [KO:K04440] [EC:2.7.11.24]
100521742  NEK7; serine/threonine-protein kinase Nek7 isoform X1 [KO:K20876] [EC:2.7.11.34]
100521968  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
100522011  [KO:K12799]
100522887  [KO:K04394] [EC:3.4.22.57 3.4.22.64]
100523066  NLRP12; NACHT, LRR and PYD domains-containing protein 12 isoform X1 [KO:K20865]
100523492  [KO:K20898]
100523638  TRPV2; transient receptor potential cation channel subfamily V member 2 isoform X2 [KO:K04971]
100523668  [KO:K20897]
100524751  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
100525148  PLCB3; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
100525396  [KO:K05505]
100526216  SHARPIN; sharpin isoform X2 [KO:K20894]
100533555  IFNAR2; interferon alpha/beta receptor 2 [KO:K05131]
100620600  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
100620791  TRIP6; thyroid receptor-interacting protein 6 [KO:K12792]
100621111  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
100622032  TRPM2; transient receptor potential cation channel subfamily M member 2 isoform X1 [KO:K04977] [EC:3.6.1.13]
100622156  TNFAIP3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
100622590  BIRC3; LOW QUALITY PROTEIN: baculoviral IAP repeat-containing protein 3 [KO:K16060]
100622859  [KO:K16060]
100622955  PRKCD; protein kinase C delta type isoform X2 [KO:K06068] [EC:2.7.11.13]
100623776  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
100624497  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
100627238  CARD6; LOW QUALITY PROTEIN: caspase recruitment domain-containing protein 6 [KO:K12797]
100627612  MFN1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
100736854  SUGT1; protein SGT1 homolog [KO:K12795]
100737904  [KO:K05414]
100738603  PANX1; pannexin-1 [KO:K03443]
100739102  ATG5; autophagy protein 5 isoform X1 [KO:K08339]
102159373  [KO:K13916]
102164352  NAIP; LOW QUALITY PROTEIN: baculoviral IAP repeat-containing protein 1 [KO:K12807]
110255221  [KO:K13916]
110256098  NLRP1; NACHT, LRR and PYD domains-containing protein 1 isoform X1 [KO:K12798]
110256102  DHX33; LOW QUALITY PROTEIN: putative ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
110256441  [KO:K13916]
110258075  CARD9; caspase recruitment domain-containing protein 9 isoform X1 [KO:K12794]
110258648  [KO:K13916]
110258649  [KO:K13916]
110258650  [KO:K13916]
110258651  [KO:K13916]
110260605  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
396565  IL1B2; interleukin 1, beta [KO:K04519]
396609  MAPK9; mitogen-activated protein kinase 9 isoform X4 [KO:K04440] [EC:2.7.11.24]
396610  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
396613  CCL5; C-C motif chemokine 5 precursor [KO:K12499]
396616  TRAF5; TNF receptor-associated factor 5 isoform X2 [KO:K09849]
396629  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
396646  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
396655  STAT1; signal transducer and activator of transcription 1 [KO:K11220]
396656  IRF3; interferon regulatory factor 3 [KO:K05411]
396658  IFNAR1; interferon alpha/beta receptor 1 precursor [KO:K05130]
396742  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
396819  DEFB1; beta-defensin 1 precursor [KO:K21100]
396849  RHOA; transforming protein RhoA [KO:K04513]
396880  CXCL8; interleukin-8 precursor [KO:K10030]
396913  JUN; transcription factor AP-1 [KO:K04448]
396923  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
397010  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
397028  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
397057  IL18; interleukin-18 precursor [KO:K05482]
397086  TNF; tumor necrosis factor [KO:K03156]
397108  GP91-PHOX; cytochrome b-245 heavy chain precursor [KO:K21421] [EC:1.-.-.-]
397122  IL1B; interleukin-1 beta precursor [KO:K04519]
397202  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
397319  CASP1; caspase-1 [KO:K01370] [EC:3.4.22.36]
397363  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
397422  CCL2; C-C motif chemokine 2 precursor [KO:K14624]
397454  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
397507  CYBA; cytochrome b-245 light chain [KO:K08009]
397536  BCL2L1; bcl-2-like protein 1 [KO:K04570]
397570  OAS1; LOW QUALITY PROTEIN: 2'-5'-oligoadenylate synthase 1 [KO:K14216] [EC:2.7.7.84]
397581  TXN; thioredoxin [KO:K03671]
397651  VDAC3; voltage-dependent anion-selective channel protein 3 [KO:K15041]
397659  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
397686  IFNA1; interferon alpha-1 precursor [KO:K05414]
399500  IL6; interleukin-6 precursor [KO:K05405]
399541  TLR4; toll-like receptor 4 isoform 1 precursor [KO:K10160]
404703  [KO:K23126]
406188  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
407610  PR39; antibacterial protein PR-39 precursor [KO:K13916]
414904  CXCL2; C-X-C motif chemokine 2 precursor [KO:K05505]
445013  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
445459  IFNB1; interferon beta precursor [KO:K05415]
497623  P2RX7; P2X purinoceptor 7 isoform X1 [KO:K05220]
574062  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
595105  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
595123  NAMPT; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
595128  OAS2; 2'-5'-oligoadenylate synthase 2 [KO:K14216] [EC:2.7.7.84]
595129  FADD; FAS-associated death domain protein [KO:K02373]
733688  TXNIP; thioredoxin-interacting protein [KO:K20910]
751869  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
780415  IRF9; interferon regulatory factor 9 [KO:K04693]
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
ssc04010  MAPK signaling pathway
ssc04064  NF-kappa B signaling pathway
ssc04140  Autophagy - animal
ssc04620  Toll-like receptor signaling pathway
KO pathway
ko04621   

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