KEGG   PATHWAY: fab04621
Entry
fab04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Ficedula albicollis (collared flycatcher)
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
fab04621  NOD-like receptor signaling pathway
fab04621

Organism
Ficedula albicollis (collared flycatcher) [GN:fab]
Gene
101805718  NOD1; nucleotide binding oligomerization domain containing 1 [KO:K08727]
101810818  receptor-interacting serine/threonine-protein kinase 2-like [KO:K08846] [EC:2.7.11.1]
101819872  RIPK2; receptor interacting serine/threonine kinase 2 [KO:K08846] [EC:2.7.11.1]
101821038  uncharacterized LOC101821038 [KO:K07210]
101812706  CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
101809821  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
101816754  NFKBIA; NFKB inhibitor alpha [KO:K04734]
101815528  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
101819115  IL1B; interleukin-1 beta [KO:K04519]
101819906  IL18; interleukin-18 [KO:K05482]
101806545  IL6; interleukin 6 [KO:K05405]
101808020  interleukin-8-like [KO:K10030]
101807822  interleukin-8-like [KO:K10030]
101808210  interleukin-8-like [KO:K10030]
107604613  CAMP; cathelicidin antimicrobial peptide [KO:K13916]
101814600  gallinacin-2 [KO:K21100]
101814532  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
101806997  TAB1; TGF-beta activated kinase 1 (MAP3K7) binding protein 1 [KO:K04403]
101808905  TAB2; TGF-beta activated kinase 1/MAP3K7 binding protein 2 [KO:K04404]
101818348  TAB3; TGF-beta activated kinase 1/MAP3K7 binding protein 3 [KO:K12793]
101815088  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101809052  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
101819306  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
101817339  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
101819980  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
101817434  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
101807358  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
101814783  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
101816255  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
101809920  ATG16L1; autophagy related 16 like 1 [KO:K17890]
101820801  ATG5; autophagy related 5 [KO:K08339]
101814814  GABARAPL2; GABA type A receptor associated protein like 2 [KO:K08341]
101806792  GABARAPL1; GABA type A receptor associated protein like 1 [KO:K08341]
101816774  MAP1LC3B; microtubule associated protein 1 light chain 3 beta [KO:K10435]
101814765  MAP1LC3A; microtubule associated protein 1 light chain 3 alpha [KO:K10435]
101809903  MAP1LC3C; microtubule associated protein 1 light chain 3 gamma [KO:K10435]
101821497  SUGT1; SGT1 homolog, MIS12 kinetochore complex assembly cochaperone [KO:K12795]
101821219  RNF31; ring finger protein 31 [KO:K11974] [EC:2.3.2.31]
101819741  XIAP; X-linked inhibitor of apoptosis [KO:K04725] [EC:2.3.2.27]
101818682  ERBIN; erbb2 interacting protein [KO:K12796]
101821374  BIRC2; baculoviral IAP repeat containing 2 [KO:K16060]
101807272  TRAF2; TNF receptor associated factor 2 [KO:K03173] [EC:2.3.2.27]
101821791  TRAF5; TNF receptor associated factor 5 [KO:K09849]
101817601  TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]
101815228  CARD9; caspase recruitment domain family member 9 [KO:K12794]
101817397  TNFAIP3; TNF alpha induced protein 3 [KO:K11859] [EC:3.4.19.12]
101816643  MAVS; mitochondrial antiviral signaling protein [KO:K12648]
101807381  TRAF3; TNF receptor associated factor 3 [KO:K03174]
101809300  TBK1; TANK binding kinase 1 [KO:K05410] [EC:2.7.11.10]
101814828  IKBKE; inhibitor of nuclear factor kappa B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
101812044  TANK; TRAF family member associated NFKB activator [KO:K12650]
101807197  IRF7; interferon regulatory factor 7 [KO:K09447]
101811547  IFNW1; interferon omega-1 [KO:K05414]
101815751  interferon-like [KO:K05414]
101815236  NLRX1; NLR family member X1 [KO:K12653]
101816756  ANTXRL; anthrax toxin receptor-like [KO:K20909]
101819707  ANTXR1; anthrax toxin receptor 1 [KO:K20909]
101818228  BCL2; BCL2, apoptosis regulator [KO:K02161]
101814183  BCL2L1; BCL2 like 1 [KO:K04570]
101815778  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
101816027  PANX1; pannexin 1 [KO:K03443]
101813560  TRPM2; transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13]
101813566  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
101821682  TRPV2; transient receptor potential cation channel subfamily V member 2 [KO:K04971]
101816726  CASR; calcium sensing receptor [KO:K04612]
101811760  GPRC6A; G protein-coupled receptor class C group 6 member A [KO:K04622]
101816169  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
101812094  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
101806047  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
101816592  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
101811180  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
101809694  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
101813252  VDAC1; voltage dependent anion channel 1 [KO:K05862]
101810113  VDAC2; voltage dependent anion channel 2 [KO:K15040]
101819191  VDAC3; voltage dependent anion channel 3 [KO:K15041]
101811915  MCU; mitochondrial calcium uniporter [KO:K20858]
101812172  RNASEL; ribonuclease L [KO:K01165]
101814181  DHX33; DEAH-box helicase 33 [KO:K17820] [EC:5.6.2.6]
101813563  MFN1; mitofusin 1 [KO:K21356] [EC:3.6.5.-]
101815947  MFN2; mitofusin 2 [KO:K06030] [EC:3.6.5.-]
101806351  RIPK1; receptor interacting serine/threonine kinase 1 [KO:K02861] [EC:2.7.11.1]
101821576  DNM1L; dynamin 1 like [KO:K17065] [EC:3.6.5.5]
101808963  NAMPT; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
101813268  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
101819099  cytochrome b-245 light chain [KO:K08009]
101821036  thioredoxin [KO:K03671]
101813878  TXN2; thioredoxin 2 [KO:K03671]
101819179  NME9; NME/NM23 family member 9 [KO:K03671]
101817284  NEK7; NIMA related kinase 7 [KO:K20876] [EC:2.7.11.34]
101808413  BRCC3; BRCA1/BRCA2-containing complex subunit 3 [KO:K11864] [EC:3.4.19.-]
101814465  HSP90AB1; heat shock protein 90 alpha family class B member 1 [KO:K04079]
101820609  HSP90AA1; heat shock protein 90 alpha family class A member 1 [KO:K04079]
101805745  PSTPIP1; proline-serine-threonine phosphatase interacting protein 1 [KO:K12804]
101815602  caspase-8-like [KO:K04398] [EC:3.4.22.61]
101814031  caspase-8-like [KO:K04398] [EC:3.4.22.61]
101806236  FADD; Fas associated via death domain [KO:K02373]
101819678  NACHT, LRR and PYD domains-containing protein 12-like [KO:K20865]
101806370  PRKCD; protein kinase C delta [KO:K06068] [EC:2.7.11.13]
101809343  TP53BP1; tumor protein p53 binding protein 1 [KO:K20915]
101806310  RHOA; ras homolog family member A [KO:K04513]
101816126  PKN2; protein kinase N2 [KO:K23691] [EC:2.7.11.13]
101807403  YWHAE; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon [KO:K06630]
101814442  IFNAR1; interferon alpha and beta receptor subunit 1 [KO:K05130]
101814062  IFNAR2; interferon alpha and beta receptor subunit 2 [KO:K05131]
101805872  JAK1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]
101811260  STAT1; signal transducer and activator of transcription 1 [KO:K11220]
101821433  nascent polypeptide-associated complex subunit alpha, muscle-specific form-like [KO:K11221]
101813378  TLR4; toll like receptor 4 [KO:K10160]
101819322  TICAM1; toll like receptor adaptor molecule 1 [KO:K05842]
101805645  MYD88; myeloid differentiation primary response 88 [KO:K04729]
101816877  IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
101815614  TMEM173; transmembrane protein 173 [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
fab04010  MAPK signaling pathway
fab04140  Autophagy - animal
fab04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
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