KEGG   PATHWAY: nnt04621
Entry
nnt04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Nestor notabilis (Kea)
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
nnt04621  NOD-like receptor signaling pathway
nnt04621

Organism
Nestor notabilis (Kea) [GN:nnt]
Gene
104410565  NOD1; nucleotide-binding oligomerization domain-containing protein 1 [KO:K08727]
104401235  receptor-interacting serine/threonine-protein kinase 2-like [KO:K08846] [EC:2.7.11.1]
104404382  receptor-interacting serine/threonine-protein kinase 2-like [KO:K08846] [EC:2.7.11.1]
104406104  CHUK; LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
104399565  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
104404537  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
104401714  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
104403914  interleukin-1 receptor antagonist protein-like [KO:K04519]
104411799  IL18; interleukin-18 [KO:K05482]
104411997  IL6; LOW QUALITY PROTEIN: interleukin-6 [KO:K05405]
104407495  interleukin-8-like [KO:K10030]
104407496  interleukin-8-like [KO:K10030]
104407500  interleukin-8-like [KO:K10030]
104407105  CCL5; C-C motif chemokine 5 [KO:K12499]
104409398  CAMP; cathelicidin antimicrobial peptide [KO:K13916]
104409399  cathelicidin-3-like [KO:K13916]
104400822  LOW QUALITY PROTEIN: antimicrobial peptide THP2-like [KO:K21100]
104400218  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
104400334  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
104402341  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
104407502  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793]
104408030  LOW QUALITY PROTEIN: mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
104408146  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
104402014  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
104406818  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
104400700  mitogen-activated protein kinase 11-like [KO:K04441] [EC:2.7.11.24]
104411368  mitogen-activated protein kinase 13-like [KO:K04441] [EC:2.7.11.24]
104411369  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
104411495  LOW QUALITY PROTEIN: mitogen-activated protein kinase 12-like [KO:K04441] [EC:2.7.11.24]
104401428  JUN; transcription factor AP-1 [KO:K04448]
104409431  ATG16L1; autophagy-related protein 16-1 isoform X1 [KO:K17890]
104409204  ATG5; autophagy protein 5 isoform X1 [KO:K08339]
104401392  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
104411865  gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
104413100  microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
104408622  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
104405857  microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
104401858  microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
104411314  SUGT1; suppressor of G2 allele of SKP1 homolog isoform X1 [KO:K12795]
104409037  E3 ubiquitin-protein ligase XIAP-like [KO:K04725] [EC:2.3.2.27]
104410591  ERBB2IP; protein LAP2 isoform X1 [KO:K12796]
104406446  inhibitor of apoptosis protein-like [KO:K16060]
104402074  TRAF2; LOW QUALITY PROTEIN: TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
104413671  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
104402000  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
104408062  CARD9; caspase recruitment domain-containing protein 9 [KO:K12794]
104406958  TNFAIP3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
104409820  MAVS; mitochondrial antiviral-signaling protein [KO:K12648]
104408547  TRAF3; TNF receptor-associated factor 3 [KO:K03174]
104399433  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
104413523  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
104406248  TRAF family member-associated NF-kappa-B activator-like [KO:K12650]
104411022  interferon beta-like [KO:K05414]
104400091  interferon-like [KO:K05415]
104405302  NLRX1; NLR family member X1 [KO:K12653]
104409406  ANTXR2; anthrax toxin receptor 2 [KO:K20909]
104410005  anthrax toxin receptor 1-like [KO:K20909]
104406469  ANTXR1; anthrax toxin receptor 1 [KO:K20909]
104399235  caspase-1-like [KO:K01370] [EC:3.4.22.36]
104401803  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
104412828  BCL2L1; bcl-2-like protein 1 [KO:K04570]
104412631  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
104409567  PANX1; pannexin-1 [KO:K03443]
104403338  TRPM2; LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13]
104404698  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
104406675  TRPV2; transient receptor potential cation channel subfamily V member 2 [KO:K04971]
104401542  CASR; extracellular calcium-sensing receptor [KO:K04612]
104410920  GPRC6A; G-protein coupled receptor family C group 6 member A [KO:K04622]
104407434  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
104407607  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
104408755  LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1-like [KO:K05858] [EC:3.1.4.11]
104407157  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
104401715  inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
104412975  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
104400318  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
104411577  VDAC2; voltage-dependent anion-selective channel protein 2 isoform X1 [KO:K15040]
104400836  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
104411062  MCU; calcium uniporter protein, mitochondrial [KO:K20858]
104413072  RNASEL; LOW QUALITY PROTEIN: 2-5A-dependent ribonuclease [KO:K01165]
104399192  DHX33; putative ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
104410557  MFN1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
104399660  MFN2; mitofusin-2 isoform X1 [KO:K06030] [EC:3.6.5.-]
104411630  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
104411456  DNM1L; dynamin-1-like protein [KO:K17065] [EC:3.6.5.5]
104413433  NAMPT; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
104404248  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
104409716  TXNIP; thioredoxin-interacting protein [KO:K20910]
104408433  TXN; thioredoxin [KO:K03671]
104411701  TXN2; thioredoxin, mitochondrial [KO:K03671]
104407455  NEK7; serine/threonine-protein kinase Nek7 [KO:K20876] [EC:2.7.11.34]
104410799  BRCC3; lys-63-specific deubiquitinase BRCC36 [KO:K11864] [EC:3.4.19.-]
104403625  heat shock protein HSP 90-beta [KO:K04079]
104411563  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
104410424  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 [KO:K12804]
104409396  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
104406622  caspase-8-like [KO:K04398] [EC:3.4.22.61]
104399843  FADD; FAS-associated death domain protein [KO:K02373]
104399035  NACHT, LRR and PYD domains-containing protein 3-like [KO:K20865]
104410700  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
104405782  TP53BP1; tumor suppressor p53-binding protein 1 [KO:K20915]
104401830  RHOA; transforming protein RhoA [KO:K04513]
104399964  PKN2; serine/threonine-protein kinase N2 [KO:K23691] [EC:2.7.11.13]
104406111  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
104406222  interferon-induced guanylate-binding protein 1-like [KO:K20899]
104409213  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
104407035  IFNAR2; interferon alpha/beta receptor 2 [KO:K05131]
104411815  JAK1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
104404294  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
104413420  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
104405963  TLR4; toll-like receptor 4 [KO:K10160]
104400449  TICAM1; LOW QUALITY PROTEIN: TIR domain-containing adapter molecule 1 [KO:K05842]
104410125  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
104399643  IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
104401859  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
nnt04010  MAPK signaling pathway
nnt04140  Autophagy - animal
nnt04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
LinkDB

DBGET integrated database retrieval system