KEGG   PATHWAY: lcat04621
Entry
lcat04621                   Pathway                                
Name
NOD-like receptor signaling pathway - Lemur catta (Ring-tailed lemur)
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
lcat04621  NOD-like receptor signaling pathway
lcat04621

Organism
Lemur catta (Ring-tailed lemur) [GN:lcat]
Gene
123620186  [KO:K14624]
123620350  CCL5; C-C motif chemokine 5 [KO:K12499]
123620707  YWHAE; 14-3-3 protein epsilon [KO:K06630]
123621073  TRPV2; transient receptor potential cation channel subfamily V member 2 isoform X1 [KO:K04971]
123621799  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
123621883  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
123622057  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
123622065  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
123622409  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
123622419  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
123622556  MAVS; mitochondrial antiviral-signaling protein isoform X1 [KO:K12648]
123622635  TRPM7; transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
123622846  BCL2L1; bcl-2-like protein 1 [KO:K04570]
123622872  RBCK1; ranBP-type and C3HC4-type zinc finger-containing protein 1 isoform X1 [KO:K10630] [EC:2.3.2.31]
123623170  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
123623278  RHOA; transforming protein RhoA [KO:K04513]
123623322  [KO:K13916]
123623574  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
123623813  IRF3; interferon regulatory factor 3 isoform X1 [KO:K05411]
123624110  [KO:K05505]
123624184  NLRP12; LOW QUALITY PROTEIN: NACHT, LRR and PYD domains-containing protein 12 [KO:K20865]
123624357  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
123624366  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
123624520  CXCL8; interleukin-8 [KO:K10030]
123624660  [KO:K20864]
123624689  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 isoform X1 [KO:K12804]
123624714  [KO:K05505]
123624715  [KO:K05505]
123625037  NOD2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165]
123625343  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
123625377  [KO:K08009]
123625419  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
123625980  OAS3; 2'-5'-oligoadenylate synthase 3 [KO:K14216] [EC:2.7.7.84]
123626026  OAS2; 2'-5'-oligoadenylate synthase 2 [KO:K14216] [EC:2.7.7.84]
123626027  OAS1; 2'-5'-oligoadenylate synthase 1 [KO:K14216] [EC:2.7.7.84]
123626078  P2RX7; P2X purinoceptor 7 isoform X1 [KO:K05220]
123626228  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
123626546  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
123626561  [KO:K23126]
123626562  [KO:K05230]
123626563  [KO:K05230]
123626606  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
123626609  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
123626913  RNASEL; 2-5A-dependent ribonuclease [KO:K01165]
123627048  NEK7; serine/threonine-protein kinase Nek7 [KO:K20876] [EC:2.7.11.34]
123627059  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
123627128  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
123627174  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
123627206  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
123627295  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
123627368  ANTXR2; anthrax toxin receptor 2 isoform X1 [KO:K20909]
123627462  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
123628501  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
123628616  [KO:K04725] [EC:2.3.2.27]
123628906  BRCC3; lys-63-specific deubiquitinase BRCC36 isoform X1 [KO:K11864] [EC:3.4.19.-]
123630283  MFN1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
123630387  TP53BP1; TP53-binding protein 1 isoform X1 [KO:K20915]
123630694  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
123630696  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
123630805  TRPM2; transient receptor potential cation channel subfamily M member 2 isoform X1 [KO:K04977] [EC:3.6.1.13]
123631550  [KO:K03671]
123631647  TRIP6; thyroid receptor-interacting protein 6 [KO:K12792]
123631724  TNF; tumor necrosis factor [KO:K03156]
123631784  GPSM3; G-protein-signaling modulator 3 [KO:K15838]
123631934  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
123632226  GPRC6A; G-protein coupled receptor family C group 6 member A isoform X1 [KO:K04622]
123632301  MEFV; pyrin isoform X1 [KO:K12803]
123632689  PYCARD; apoptosis-associated speck-like protein containing a CARD [KO:K12799]
123632778  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
123632820  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
123632869  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
123632871  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
123633076  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
123633115  ATG5; autophagy protein 5 isoform X1 [KO:K08339]
123633309  TNFAIP3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
123633357  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
123633883  [KO:K20910]
123634210  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
123634464  MFN2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
123634646  AIM2; LOW QUALITY PROTEIN: interferon-inducible protein AIM2 [KO:K12966]
123635156  [KO:K20914]
123635159  IFI16; gamma-interferon-inducible protein 16 isoform X1 [KO:K20914]
123635425  GBP4; guanylate-binding protein 4 isoform X1 [KO:K20899]
123635426  [KO:K20899]
123635427  GBP2; guanylate-binding protein 2 [KO:K20897]
123635428  GBP5; guanylate-binding protein 5 [KO:K20898]
123635434  PKN2; serine/threonine-protein kinase N2 [KO:K23691]
123635562  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
123635592  JUN; transcription factor AP-1 [KO:K04448]
123636728  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
123637002  ANTXR1; anthrax toxin receptor 1 [KO:K20909]
123637166  IL1B; interleukin-1 beta [KO:K04519]
123637772  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
123637810  PKN1; serine/threonine-protein kinase N1 isoform X1 [KO:K06071] [EC:2.7.11.13]
123637842  STING1; stimulator of interferon genes protein [KO:K12654]
123638176  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
123638837  [KO:K11864] [EC:3.4.19.-]
123638892  IRGM; immunity-related GTPase family M protein [KO:K14139] [EC:3.6.5.-]
123639308  TXN2; thioredoxin, mitochondrial [KO:K03671]
123639558  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
123639648  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
123639836  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
123639867  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
123639915  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
123640016  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
123640344  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
123640770  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
123640771  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
123641353  RELA; transcription factor p65 isoform X1 [KO:K04735]
123641430  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
123641480  NLRX1; NLR family member X1 [KO:K12653]
123641690  IL18; interleukin-18 [KO:K05482]
123641767  CASP1; caspase-1 isoform X1 [KO:K01370] [EC:3.4.22.36]
123641788  [KO:K04741] [EC:3.4.22.-]
123641867  [KO:K04394] [EC:3.4.22.57 3.4.22.64]
123641896  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
123641897  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
123641985  [KO:K12806]
123641986  [KO:K12806]
123641987  [KO:K04394] [EC:3.4.22.57 3.4.22.64]
123641988  CASR; extracellular calcium-sensing receptor [KO:K04612]
123641989  [KO:K12806]
123642209  PANX1; pannexin-1 isoform X1 [KO:K03443]
123642600  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
123642797  FADD; FAS-associated death domain protein [KO:K02373]
123642940  IRF7; interferon regulatory factor 7 isoform X1 [KO:K09447]
123643616  [KO:K04513]
123643619  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
123643826  ATG16L1; autophagy-related protein 16-1 isoform X1 [KO:K17890]
123643895  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
123643931  TANK; LOW QUALITY PROTEIN: TRAF family member-associated NF-kappa-B activator [KO:K12650]
123644162  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
123644872  SHARPIN; sharpin isoform X1 [KO:K20894]
123644911  GSDMD; gasdermin-D [KO:K20917]
123645000  RIPK2; receptor-interacting serine/threonine-protein kinase 2 [KO:K08846] [EC:2.7.11.1]
123645603  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
123645632  [KO:K05414]
123645638  [KO:K05414]
123645752  [KO:K05414]
123645754  [KO:K05414]
123645755  [KO:K05414]
123645758  [KO:K05414]
123645793  CARD9; caspase recruitment domain-containing protein 9 isoform X1 [KO:K12794]
123646094  TLR4; toll-like receptor 4 [KO:K10160]
123646249  IFNB1; interferon beta [KO:K05415]
123646605  TXN; thioredoxin [KO:K03671]
123646712  [KO:K05414]
123646908  IL6; interleukin-6 [KO:K05405]
123647039  NOD1; nucleotide-binding oligomerization domain-containing protein 1 isoform X1 [KO:K08727]
123647729  NAMPT; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
123648000  CARD6; caspase recruitment domain-containing protein 6 [KO:K12797]
123648499  ERBIN; erbin isoform X1 [KO:K12796]
123648608  ATG12; ubiquitin-like protein ATG12 isoform X1 [KO:K08336]
123648884  SUGT1; protein SGT1 homolog [KO:K12795]
123649353  NLRP3; NACHT, LRR and PYD domains-containing protein 3 isoform X1 [KO:K12800]
123650127  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
123650134  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
123650270  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
123650367  MCU; calcium uniporter protein, mitochondrial [KO:K20858]
123650465  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
123650662  NLRP1; NACHT, LRR and PYD domains-containing protein 1 isoform X1 [KO:K12798]
123650691  RIPK3; receptor-interacting serine/threonine-protein kinase 3 [KO:K08847] [EC:2.7.11.1]
123650767  RNF31; E3 ubiquitin-protein ligase RNF31 isoform X1 [KO:K11974] [EC:2.3.2.31]
123650803  IRF9; interferon regulatory factor 9 [KO:K04693]
123650831  DHX33; ATP-dependent RNA helicase DHX33 isoform X1 [KO:K17820] [EC:5.6.2.6]
123650859  [KO:K08341]
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
lcat04010  MAPK signaling pathway
lcat04064  NF-kappa B signaling pathway
lcat04140  Autophagy - animal
lcat04620  Toll-like receptor signaling pathway
KO pathway
ko04621   

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