KEGG   PATHWAY: achc04621
Entry
achc04621                   Pathway                                
Name
NOD-like receptor signaling pathway - Aquila chrysaetos chrysaetos (golden eagle)
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
achc04621  NOD-like receptor signaling pathway
achc04621

Organism
Aquila chrysaetos chrysaetos (golden eagle) [GN:achc]
Gene
115339005  NOD1; nucleotide-binding oligomerization domain-containing protein 1 isoform X1 [KO:K08727]
115340281  RIPK2; receptor-interacting serine/threonine-protein kinase 2 isoform X1 [KO:K08846] [EC:2.7.11.1]
115346445  LOW QUALITY PROTEIN: receptor-interacting serine/threonine-protein kinase 2-like [KO:K08846] [EC:2.7.11.1]
115348471  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
115350500  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
115338180  LOW QUALITY PROTEIN: NF-kappa-B inhibitor beta-like [KO:K02581]
115338184  NF-kappa-B inhibitor beta-like [KO:K02581]
115337413  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
115341473  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
115350114  interleukin-1 beta-like isoform X1 [KO:K04519]
115345010  IL18; interleukin-18 [KO:K05482]
115339802  IL6; LOW QUALITY PROTEIN: interleukin-6 [KO:K05405]
115340258  interleukin-8-like isoform X1 [KO:K10030]
115340259  interleukin-8-like [KO:K10030]
115340262  interleukin-8-like [KO:K10030]
115340268  C-X-C motif chemokine 5-like [KO:K10030]
115347274  C-C motif chemokine 5-like [KO:K12499]
115339568  LOW QUALITY PROTEIN: cathelicidin antimicrobial peptide [KO:K13916]
115339285  cathelicidin-3-like [KO:K13916]
115351305  antimicrobial peptide THP2 [KO:K21100]
115335051  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
115352340  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
115345137  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
115343621  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
115346261  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
115338798  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
115334063  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
115347976  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
115341623  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
115334823  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
115334828  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
115341838  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
115348746  JUN; transcription factor AP-1 [KO:K04448]
115346908  ATG16L1; autophagy-related protein 16-1 isoform X1 [KO:K17890]
115335250  ATG5; autophagy protein 5 isoform X1 [KO:K08339]
115336539  ATG12; ubiquitin-like protein ATG12 [KO:K08336]
115338362  gamma-aminobutyric acid receptor-associated protein [KO:K08341]
115345884  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
115352416  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
115350069  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
115345373  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
115339213  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
115348412  microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
115350632  SUGT1; protein SGT1 homolog isoform X1 [KO:K12795]
115340166  SHARPIN; sharpin isoform X2 [KO:K10630] [EC:2.3.2.31]
115333630  E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
115336604  ERBIN; erbin isoform X1 [KO:K12796]
121232390  erbin-like isoform X1 [KO:K12796]
115353209  inhibitor of apoptosis protein isoform X1 [KO:K16060]
115335375  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
115349818  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
115353383  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
115335451  CARD9; caspase recruitment domain-containing protein 9 isoform X8 [KO:K12794]
115345133  TNFAIP3; tumor necrosis factor alpha-induced protein 3 isoform X2 [KO:K11859] [EC:3.4.19.12]
115344346  MAVS; mitochondrial antiviral-signaling protein [KO:K12648]
115352265  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
115336293  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
115335388  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
115342910  TANK; TRAF family member-associated NF-kappa-B activator isoform X1 [KO:K12650]
115352198  IRF7; interferon regulatory factor 7 isoform X2 [KO:K09447]
115336480  interferon epsilon-like [KO:K05414]
115337094  interferon-like [KO:K05415]
115337096  interferon-like [KO:K05415]
115337097  interferon-like [KO:K05415]
115344958  NLRX1; NLR family member X1 isoform X2 [KO:K12653]
115350328  ANTXR1; anthrax toxin receptor 1 [KO:K20909]
115338773  ANTXR2; anthrax toxin receptor 2 isoform X1 [KO:K20909]
115348347  ANTXRL; anthrax toxin receptor-like [KO:K20909]
115346730  caspase-1-like [KO:K01370] [EC:3.4.22.36]
115353069  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
115339188  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
115350923  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
115353488  PANX1; pannexin-1 [KO:K03443]
115347589  TRPM2; transient receptor potential cation channel subfamily M member 2 isoform X2 [KO:K04977] [EC:3.6.1.13]
115341546  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
115346867  transient receptor potential cation channel subfamily V member 2-like isoform X1 [KO:K04971]
115344088  CASR; extracellular calcium-sensing receptor [KO:K04612]
115336190  GPRC6A; G-protein coupled receptor family C group 6 member A [KO:K04622]
115344237  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
115344678  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
115351830  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
115353680  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
115352454  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X2 [KO:K04959]
115334771  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
115334118  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
115348118  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
115350505  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
115347919  MCU; calcium uniporter protein, mitochondrial isoform X2 [KO:K20858]
115348753  RNASEL; 2-5A-dependent ribonuclease [KO:K01165]
115347026  DHX33; ATP-dependent RNA helicase DHX33 isoform X1 [KO:K17820] [EC:5.6.2.6]
115347306  MFN1; mitofusin-1 isoform X1 [KO:K21356] [EC:3.6.5.-]
115343147  MFN2; mitofusin-2 isoform X1 [KO:K06030] [EC:3.6.5.-]
115353096  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
115352290  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
115341445  NAMPT; nicotinamide phosphoribosyltransferase isoform X1 [KO:K03462] [EC:2.4.2.12]
115343583  cytochrome b-245 heavy chain isoform X1 [KO:K21421] [EC:1.-.-.-]
115345370  cytochrome b-245 light chain [KO:K08009]
115346288  thioredoxin-interacting protein [KO:K20910]
115336435  TXN; thioredoxin isoform X2 [KO:K03671]
115352362  TXN2; thioredoxin, mitochondrial [KO:K03671]
115348890  NEK7; serine/threonine-protein kinase Nek7 isoform X1 [KO:K20876] [EC:2.7.11.34]
115333475  BRCC3; lys-63-specific deubiquitinase BRCC36 isoform X1 [KO:K11864] [EC:3.4.19.-]
115350471  heat shock protein HSP 90-beta isoform X2 [KO:K04079]
115352316  HSP90AA1; heat shock protein HSP 90-alpha isoform X1 [KO:K04079]
115346362  NACHT, LRR and PYD domains-containing protein 1a-like isoform X1 [KO:K12801]
115342147  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 isoform X1 [KO:K12804]
115343326  caspase-8-like [KO:K04398] [EC:3.4.22.61]
115342550  caspase-8-like isoform X1 [KO:K04398] [EC:3.4.22.61]
115351998  FADD; FAS-associated death domain protein [KO:K02373]
115351564  NACHT, LRR and PYD domains-containing protein 3-like isoform X1 [KO:K20865]
115351833  NLRP6; NACHT, LRR and PYD domains-containing protein 6 isoform X1 [KO:K20865]
115350257  NLRC4; LOW QUALITY PROTEIN: NLR family CARD domain-containing protein 4 [KO:K12805]
115333335  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
115341450  TP53BP1; TP53-binding protein 1 isoform X1 [KO:K20915]
115353760  RHOA; transforming protein RhoA [KO:K04513]
115349194  PKN2; serine/threonine-protein kinase N2 isoform X1 [KO:K23691] [EC:2.7.11.13]
115346776  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
115348385  guanylate-binding protein 1-like isoform X1 [KO:K20899]
115343845  IFNAR1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
115343634  IFNAR2; interferon alpha/beta receptor 2 isoform X2 [KO:K05131]
115349347  JAK1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
115348242  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
115342511  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X2 [KO:K11220]
115351351  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
115335358  TLR4; toll-like receptor 4 [KO:K10160]
115349277  TICAM1; TIR domain-containing adapter molecule 1 isoform X1 [KO:K05842]
115339371  MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
115341041  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
115334319  STING1; stimulator of interferon genes protein isoform X2 [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
achc04010  MAPK signaling pathway
achc04140  Autophagy - animal
achc04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
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