KEGG   PATHWAY: nmel04621
Entry
nmel04621                   Pathway                                
Name
NOD-like receptor signaling pathway - Numida meleagris (helmeted guineafowl)
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
nmel04621  NOD-like receptor signaling pathway
nmel04621

Organism
Numida meleagris (helmeted guineafowl) [GN:nmel]
Gene
110394940  NOD1; nucleotide-binding oligomerization domain-containing protein 1 [KO:K08727]
110394065  RIPK2; receptor-interacting serine/threonine-protein kinase 2 [KO:K08846] [EC:2.7.11.1]
110404370  LOW QUALITY PROTEIN: receptor-interacting serine/threonine-protein kinase 2-like [KO:K08846] [EC:2.7.11.1]
110390496  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
110387184  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
110389114  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
110401359  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
110398425  NFKB1; LOW QUALITY PROTEIN: nuclear factor NF-kappa-B p105 subunit [KO:K02580]
110387108  interleukin-1 receptor antagonist protein-like [KO:K04519]
110387565  IL18; interleukin-18 isoform X1 [KO:K05482]
110394224  IL6; interleukin-6 [KO:K05405]
110398320  interleukin-8-like isoform X1 [KO:K10030]
110397580  interleukin-8-like [KO:K10030]
110398822  interleukin-8 [KO:K10030]
110407778  C-C motif chemokine 5-like [KO:K12499]
110394988  cathelicidin-1 [KO:K13916]
110390676  CAMP; cathelicidin antimicrobial peptide [KO:K13916]
110390539  cathelicidin-2-like [KO:K13916]
110390540  cathelicidin-2-like [KO:K13916]
110395011  cathelicidin-1-like [KO:K13916]
110396689  gallinacin-2 [KO:K21100]
110395624  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
110392579  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
110395593  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
110404188  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
110406180  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
110398630  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
110405490  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
110399325  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
110392503  mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
110392504  mitogen-activated protein kinase 12-like isoform X1 [KO:K04441] [EC:2.7.11.24]
110388127  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
110388128  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
110402812  JUN; transcription factor AP-1 [KO:K04448]
110397914  ATG16L1; autophagy-related protein 16-1 isoform X1 [KO:K17890]
110395341  ATG5; autophagy protein 5 [KO:K08339]
110389703  ATG12; ubiquitin-like protein ATG12 [KO:K08336]
110404464  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 isoform X1 [KO:K08341]
110397892  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
110391610  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
110395880  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
110404396  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
110387040  SUGT1; protein SGT1 homolog [KO:K12795]
110391473  ranBP-type and C3HC4-type zinc finger-containing protein 1-like [KO:K10630] [EC:2.3.2.31]
110403244  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
110389307  ERBIN; erbin isoform X1 [KO:K12796]
110389900  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
110406784  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
110396762  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
110401104  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
110406836  CARD9; caspase recruitment domain-containing protein 9 isoform X1 [KO:K12794]
110396285  TNFAIP3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
110397561  MAVS; mitochondrial antiviral-signaling protein isoform X1 [KO:K12648]
110401083  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
110392745  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
110388051  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
110399709  TANK; TRAF family member-associated NF-kappa-B activator isoform X1 [KO:K12650]
110402123  IRF7; interferon regulatory factor 7 isoform X1 [KO:K09447]
110390131  interferon kappa-like [KO:K05414]
110390553  interferon type B-like [KO:K05415]
110387779  NLRX1; NLR family member X1 isoform X1 [KO:K12653]
110399750  ANTXRL; anthrax toxin receptor-like isoform X1 [KO:K20909]
110387151  ANTXR1; anthrax toxin receptor 1 isoform X1 [KO:K20909]
110397874  ANTXR2; anthrax toxin receptor 2 isoform X1 [KO:K20909]
110391096  uncharacterized protein LOC110391096 isoform X1 [KO:K12799]
110407549  CARD16; caspase recruitment domain-containing protein 16 [KO:K01370] [EC:3.4.22.36]
110407545  caspase-1-like [KO:K01370] [EC:3.4.22.36]
110395041  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
110408466  BCL2L1; bcl-2-like protein 1 [KO:K04570]
110395601  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
110390516  PANX1; pannexin-1 isoform X1 [KO:K03443]
110406317  P2RX7; P2X purinoceptor 7 [KO:K05220]
110397643  TRPM2; transient receptor potential cation channel subfamily M member 2 isoform X1 [KO:K04977] [EC:3.6.1.13]
110403612  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
110407633  transient receptor potential cation channel subfamily V member 2-like isoform X1 [KO:K04971]
110398790  CASR; extracellular calcium-sensing receptor [KO:K04612]
110396434  GPRC6A; G-protein coupled receptor family C group 6 member A [KO:K04622]
110396662  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
110395536  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
110401183  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
110404652  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
110396437  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
110388144  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
110405202  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
110399852  VDAC2; voltage-dependent anion-selective channel protein 2 isoform X1 [KO:K15040]
110387188  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
110400250  MCU; calcium uniporter protein, mitochondrial isoform X1 [KO:K20858]
110402536  RNASEL; 2-5A-dependent ribonuclease isoform X1 [KO:K01165]
110407822  DHX33; putative ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
110399102  MFN1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
110408535  MFN2; mitofusin-2 isoform X1 [KO:K06030] [EC:3.6.5.-]
110392996  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
110394790  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
110392371  NAMPT; nicotinamide phosphoribosyltransferase isoform X1 [KO:K03462] [EC:2.4.2.12]
110404027  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
110404326  cytochrome b-245 light chain [KO:K08009]
110391031  TXNIP; thioredoxin-interacting protein [KO:K20910]
110390057  TXN; thioredoxin [KO:K03671]
110393356  TXN2; thioredoxin, mitochondrial [KO:K03671]
110402745  NEK7; serine/threonine-protein kinase Nek7 isoform X1 [KO:K20876] [EC:2.7.11.34]
110403359  BRCC3; lys-63-specific deubiquitinase BRCC36 [KO:K11864] [EC:3.4.19.-]
110395331  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
110400900  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
110406437  caspase recruitment domain-containing protein 8-like isoform X1 [KO:K12801]
110403573  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 isoform X1 [KO:K12804]
110400694  caspase-8-like [KO:K04398] [EC:3.4.22.61]
110399293  caspase-8-like [KO:K04398] [EC:3.4.22.61]
110401719  FADD; FAS-associated death domain protein [KO:K02373]
110401139  NLRP3; NACHT, LRR and PYD domains-containing protein 3 isoform X1 [KO:K20865]
110404811  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
110403636  TP53BP1; TP53-binding protein 1 isoform X1 [KO:K20915]
110404968  RHOA; transforming protein RhoA [KO:K04513]
110402251  PKN2; serine/threonine-protein kinase N2 isoform X1 [KO:K23691] [EC:2.7.11.13]
110407620  YWHAE; 14-3-3 protein epsilon [KO:K06630]
110392078  guanylate-binding protein 1-like [KO:K20899]
110405004  guanylate-binding protein 1-like isoform X1 [KO:K20899]
110387456  guanylate-binding protein 1-like [KO:K20899]
110391210  guanylate-binding protein 1-like isoform X1 [KO:K20899]
110391218  guanylate-binding protein 1-like [KO:K20899]
110402456  IFNAR1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
110402433  IFNAR2; interferon alpha/beta receptor 2 [KO:K05131]
110402219  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
110391543  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
110399457  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
110389141  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
110406939  TLR4; toll-like receptor 4 [KO:K10160]
110389069  TIR domain-containing adapter molecule 1-like isoform X1 [KO:K05842]
110394261  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
110392685  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
110405146  TMEM173; stimulator of interferon genes protein isoform X1 [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
nmel04010  MAPK signaling pathway
nmel04140  Autophagy - animal
nmel04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
LinkDB

DBGET integrated database retrieval system