KEGG   PATHWAY: pcao04621
Entry
pcao04621                   Pathway                                
Name
NOD-like receptor signaling pathway - Phalacrocorax carbo (great cormorant)
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
pcao04621  NOD-like receptor signaling pathway
pcao04621

Organism
Phalacrocorax carbo (great cormorant) [GN:pcao]
Gene
104048503  NOD1; nucleotide-binding oligomerization domain-containing protein 1 [KO:K08727]
104051864  receptor-interacting serine/threonine-protein kinase 2-like [KO:K08846] [EC:2.7.11.1]
104041028  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
104039708  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
104040479  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
104053716  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
104040362  IL18; interleukin-18 isoform X1 [KO:K05482]
104042564  IL6; interleukin-6 [KO:K05405]
104044191  interleukin-8-like [KO:K10030]
104051162  interleukin-8 [KO:K10030]
104051163  interleukin-8-like [KO:K10030]
104051164  LOW QUALITY PROTEIN: interleukin-8-like [KO:K10030]
104040509  CCL5; C-C motif chemokine 5 [KO:K12499]
104040114  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
104048535  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
104046505  TAB2; LOW QUALITY PROTEIN: TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
104049205  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793]
104043039  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
104053402  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
104043989  mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
104049434  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
104048216  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
104053513  mitogen-activated protein kinase 11-like [KO:K04441] [EC:2.7.11.24]
104045500  LOW QUALITY PROTEIN: mitogen-activated protein kinase 12-like [KO:K04441] [EC:2.7.11.24]
104051094  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
104042855  JUN; transcription factor AP-1 [KO:K04448]
104039789  ATG16L1; autophagy-related protein 16-1 isoform X1 [KO:K17890]
104044297  ATG5; autophagy protein 5 [KO:K08339]
104053199  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
104049093  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
104043675  microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
104045349  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
104041049  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
104046653  SUGT1; suppressor of G2 allele of SKP1 homolog [KO:K12795]
104052143  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
104044497  ERBB2IP; LOW QUALITY PROTEIN: protein LAP2 [KO:K12796]
104046076  inhibitor of apoptosis protein-like [KO:K16060]
104048946  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
104041089  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
104039330  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
104045459  CARD9; caspase recruitment domain-containing protein 9 [KO:K12794]
104053162  TNFAIP3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
104044683  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
104047645  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
104044932  TRAF family member-associated NF-kappa-B activator-like [KO:K12650]
104039528  interferon epsilon-like [KO:K05414]
104050721  interferon-like [KO:K05415]
104045550  NLRX1; LOW QUALITY PROTEIN: NLR family member X1 [KO:K12653]
104048160  anthrax toxin receptor 1-like [KO:K20909]
104050143  ANTXR1; anthrax toxin receptor 1 [KO:K20909]
104042148  ANTXR2; anthrax toxin receptor 2 [KO:K20909]
104051788  caspase-1-like [KO:K01370] [EC:3.4.22.36]
104041700  BCL2L1; bcl-2-like protein 1 [KO:K04570]
104041315  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
104041688  LOW QUALITY PROTEIN: NACHT, LRR and PYD domains-containing protein 3-like [KO:K12800]
104045092  PANX1; pannexin-1 [KO:K03443]
104051664  TRPM2; transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13]
104051668  transient receptor potential cation channel subfamily M member 7-like [KO:K04982] [EC:2.7.11.1]
104049595  TRPV2; transient receptor potential cation channel subfamily V member 2 [KO:K04971]
104050948  LOW QUALITY PROTEIN: extracellular calcium-sensing receptor-like [KO:K04612]
104047319  GPRC6A; G-protein coupled receptor family C group 6 member A [KO:K04622]
104042484  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
104042697  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
104045382  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
104042825  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
104053012  LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2-like [KO:K04959]
104053101  LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3-like [KO:K04960]
104041387  voltage-dependent anion-selective channel protein 1 [KO:K05862]
104040230  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
104040398  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
104047275  MCU; calcium uniporter protein, mitochondrial [KO:K20858]
104041831  RNASEL; 2-5A-dependent ribonuclease [KO:K01165]
104043385  DHX33; putative ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
104039765  MFN1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
104039739  MFN2; mitofusin-2 isoform X1 [KO:K06030] [EC:3.6.5.-]
104049000  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
104051800  DNM1L; dynamin-1-like protein [KO:K17065] [EC:3.6.5.5]
104044317  NAMPT; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
104039881  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
104042354  TXN2; thioredoxin, mitochondrial [KO:K03671]
104047366  TXN; thioredoxin [KO:K03671]
104044431  NEK7; serine/threonine-protein kinase Nek7 [KO:K20876] [EC:2.7.11.34]
104042323  BRCC3; lys-63-specific deubiquitinase BRCC36 [KO:K11864] [EC:3.4.19.-]
104044217  heat shock protein HSP 90-beta [KO:K04079]
104049806  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
104043051  caspase recruitment domain-containing protein 8-like [KO:K12801]
104050262  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 [KO:K12804]
104042978  caspase-8-like [KO:K04398] [EC:3.4.22.61]
104051994  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
104041064  FADD; FAS-associated death domain protein [KO:K02373]
104039513  NACHT, LRR and PYD domains-containing protein 3-like [KO:K20865]
104039912  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
104052617  TP53BP1; tumor suppressor p53-binding protein 1 [KO:K20915]
104044182  RHOA; transforming protein RhoA [KO:K04513]
104044287  PKN2; serine/threonine-protein kinase N2 [KO:K23691] [EC:2.7.11.13]
104040476  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
104049745  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
104048759  IFNAR2; interferon alpha/beta receptor 2 [KO:K05131]
104052406  LOW QUALITY PROTEIN: tyrosine-protein kinase JAK1-like [KO:K11217] [EC:2.7.10.2]
104041888  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
104052918  TLR4; toll-like receptor 4 [KO:K10160]
104052158  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
104045422  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
104051466  IRAK4; LOW QUALITY PROTEIN: interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
104053742  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
pcao04010  MAPK signaling pathway
pcao04140  Autophagy - animal
pcao04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
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