KEGG   PATHWAY: cvf04621
Entry
cvf04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Charadrius vociferus (killdeer)
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
cvf04621  NOD-like receptor signaling pathway
cvf04621

Organism
Charadrius vociferus (killdeer) [GN:cvf]
Gene
104281567  NOD1; nucleotide-binding oligomerization domain-containing protein 1 [KO:K08727]
104287734  receptor-interacting serine/threonine-protein kinase 2-like [KO:K08846] [EC:2.7.11.1]
104292469  RIPK2; receptor-interacting serine/threonine-protein kinase 2 [KO:K08846] [EC:2.7.11.1]
104283555  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
104285155  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
104288240  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
104286863  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
104282130  interleukin-1 receptor antagonist protein-like [KO:K04519]
104284161  IL18; interleukin-18 isoform X1 [KO:K05482]
104281556  IL6; interleukin-6 [KO:K05405]
104288018  growth-regulated alpha protein-like [KO:K10030]
104288315  interleukin-8 isoform X1 [KO:K10030]
104288316  interleukin-8-like [KO:K10030]
104288319  interleukin-8-like [KO:K10030]
104289845  CCL5; C-C motif chemokine 5 [KO:K12499]
104289685  cathelicidin-3-like [KO:K13916]
104289686  CAMP; cathelicidin antimicrobial peptide [KO:K13916]
104289056  LOW QUALITY PROTEIN: antimicrobial peptide THP2-like [KO:K21100]
104288670  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
104288376  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
104284909  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
104285132  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793]
104289233  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
104285473  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
104289724  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
104293102  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
104292348  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
104292365  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
104285259  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
104285227  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
104286046  JUN; transcription factor AP-1 isoform X1 [KO:K04448]
104287793  ATG16L1; autophagy-related protein 16-1 isoform X1 [KO:K17890]
104294260  ATG5; autophagy protein 5 [KO:K08339]
104294473  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
104294543  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
104292705  MAP1LC3A; LOW QUALITY PROTEIN: microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
104290862  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
104294079  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
104296013  microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
104284150  SUGT1; suppressor of G2 allele of SKP1 homolog [KO:K12795]
104290206  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
104285734  ERBB2IP; protein LAP2 isoform X1 [KO:K12796]
104282068  LOW QUALITY PROTEIN: protein LAP2-like [KO:K12796]
104290315  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
104291072  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
104289397  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
104295805  TRAF6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
104292905  CARD9; caspase recruitment domain-containing protein 9 [KO:K12794]
104284020  TNFAIP3; tumor necrosis factor alpha-induced protein 3 isoform X1 [KO:K11859] [EC:3.4.19.12]
104284246  MAVS; LOW QUALITY PROTEIN: mitochondrial antiviral-signaling protein [KO:K12648]
104291770  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
104288935  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
104289285  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
104294928  TANK; TRAF family member-associated NF-kappa-B activator [KO:K12650]
104290298  IRF7; interferon regulatory factor 7 [KO:K09447]
104292172  interferon alpha-13-like [KO:K05414]
104296060  interferon beta-like [KO:K05414]
104287685  interferon-like [KO:K05415]
104284173  NLRX1; NLR family member X1 [KO:K12653]
104289809  ANTXRL; anthrax toxin receptor-like [KO:K20909]
104293470  ANTXR1; anthrax toxin receptor 1 [KO:K20909]
104289096  ANTXR2; anthrax toxin receptor 2 [KO:K20909]
104289860  caspase-1-like [KO:K01370] [EC:3.4.22.36]
104293864  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
104289047  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
104283089  PANX1; pannexin-1 [KO:K03443]
104282204  P2RX7; P2X purinoceptor 7 [KO:K05220]
104293566  TRPM2; LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13]
104287460  TRPM7; LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
104284383  TRPV2; transient receptor potential cation channel subfamily V member 2 [KO:K04971]
104293574  CASR; extracellular calcium-sensing receptor [KO:K04612]
104291277  GPRC6A; G-protein coupled receptor family C group 6 member A [KO:K04622]
104292993  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
104287337  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
104287385  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
104284516  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
104281650  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
104289376  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
104291600  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
104289665  VDAC2; voltage-dependent anion-selective channel protein 2 isoform X1 [KO:K15040]
104285151  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
104286998  MCU; calcium uniporter protein, mitochondrial [KO:K20858]
104293338  RNASEL; 2-5A-dependent ribonuclease [KO:K01165]
104286514  DHX33; putative ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
104295546  MFN1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
104290445  MFN2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
104286653  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
104290757  DNM1L; dynamin-1-like protein [KO:K17065] [EC:3.6.5.5]
104285147  NAMPT; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
104289422  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
104283782  TXNIP; thioredoxin-interacting protein [KO:K20910]
104283659  TXN2; thioredoxin, mitochondrial [KO:K03671]
104283889  TXN; LOW QUALITY PROTEIN: thioredoxin [KO:K03671]
104286219  NEK7; serine/threonine-protein kinase Nek7 [KO:K20876] [EC:2.7.11.34]
104282590  BRCC3; lys-63-specific deubiquitinase BRCC36 [KO:K11864] [EC:3.4.19.-]
104291797  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
104282329  HSP90AB1; heat shock protein HSP 90-beta isoform X1 [KO:K04079]
104293799  caspase recruitment domain-containing protein 8-like [KO:K12801]
104287940  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 [KO:K12804]
104290991  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
104287571  FADD; FAS-associated death domain protein [KO:K02373]
104293019  LOW QUALITY PROTEIN: NACHT, LRR and PYD domains-containing protein 12-like [KO:K20865]
104286673  NLRP12; NACHT, LRR and PYD domains-containing protein 12 [KO:K20865]
104286672  NAIP; LOW QUALITY PROTEIN: baculoviral IAP repeat-containing protein 1 [KO:K12807]
104282352  NLRC4; NLR family CARD domain-containing protein 4 [KO:K12805]
104291943  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
104286175  TP53BP1; tumor suppressor p53-binding protein 1 [KO:K20915]
104282962  RHOA; transforming protein RhoA [KO:K04513]
104286161  PKN2; serine/threonine-protein kinase N2 [KO:K23691] [EC:2.7.11.13]
104286555  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
104295200  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
104295176  IFNAR2; interferon alpha/beta receptor 2 [KO:K05131]
104285506  JAK1; LOW QUALITY PROTEIN: tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
104284773  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
104290959  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
104289137  TLR4; LOW QUALITY PROTEIN: toll-like receptor 4 [KO:K10160]
104295424  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
104291270  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
104282729  IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
104291456  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
cvf04010  MAPK signaling pathway
cvf04140  Autophagy - animal
cvf04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
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