KEGG   PATHWAY: sund04621
Entry
sund04621                   Pathway                                
Name
NOD-like receptor signaling pathway - Sceloporus undulatus (fence lizard)
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
sund04621  NOD-like receptor signaling pathway
sund04621

Organism
Sceloporus undulatus (fence lizard) [GN:sund]
Gene
121933480  NOD1; nucleotide-binding oligomerization domain-containing protein 1 isoform X1 [KO:K08727]
121928539  RIPK2; receptor-interacting serine/threonine-protein kinase 2 isoform X1 [KO:K08846] [EC:2.7.11.1]
121914514  receptor-interacting serine/threonine-protein kinase 2-like [KO:K08846] [EC:2.7.11.1]
121922695  IKBKG; NF-kappa-B essential modulator [KO:K07210]
121925441  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
121933447  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
121915161  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
121919325  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
121931415  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
121915610  RELA; transcription factor p65 isoform X1 [KO:K04735]
121932679  IL1B; interleukin-1 beta [KO:K04519]
121934420  interleukin-18-like [KO:K05482]
121935009  IL6; interleukin-6 isoform X1 [KO:K05405]
121922683  tumor necrosis factor-like [KO:K03156]
121922772  tumor necrosis factor-like [KO:K03156]
121932474  interleukin-8-like [KO:K10030]
121934343  interleukin-8-like [KO:K10030]
121930577  growth-regulated alpha protein-like [KO:K10030]
121916773  C-C motif chemokine 5-like [KO:K12499]
121916905  C-C motif chemokine 5-like [KO:K12499]
121932841  cathelicidin-related peptide Oh-Cath-like [KO:K13916]
121934434  cathelicidin-2-like [KO:K13916]
121929396  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
121930589  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
121916815  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
121925281  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
121932739  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
121916521  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
121923830  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
121931541  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
121928200  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
121929971  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
121930696  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
121930697  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
121928905  JUN; transcription factor AP-1 [KO:K04448]
121925482  ATG16L1; autophagy-related protein 16-1 isoform X1 [KO:K17890]
121918936  ATG5; autophagy protein 5 [KO:K08339]
121922091  ATG12; ubiquitin-like protein ATG12 [KO:K08336]
121933122  gamma-aminobutyric acid receptor-associated protein [KO:K08341]
121920610  gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
121914764  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
121929874  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A isoform X1 [KO:K10435]
121920478  microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
121914565  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
121915303  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
121926543  SUGT1; protein SGT1 homolog [KO:K12795]
121928055  SHARPIN; sharpin isoform X1 [KO:K10630] [EC:2.3.2.31]
121929852  RBCK1; ranBP-type and C3HC4-type zinc finger-containing protein 1 [KO:K10630] [EC:2.3.2.31]
121932883  RNF31; E3 ubiquitin-protein ligase RNF31 [KO:K11974] [EC:2.3.2.31]
121936807  E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
121932552  TRIP6; thyroid receptor-interacting protein 6 isoform X1 [KO:K12792]
121921408  ERBIN; LOW QUALITY PROTEIN: erbin [KO:K12796]
121927176  BIRC2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
121936587  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
121929536  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
121936811  CARD9; caspase recruitment domain-containing protein 9 [KO:K12794]
121918866  TNFAIP3; tumor necrosis factor alpha-induced protein 3 isoform X1 [KO:K11859] [EC:3.4.19.12]
121930466  MAVS; mitochondrial antiviral-signaling protein isoform X1 [KO:K12648]
121927129  TRAF3; TNF receptor-associated factor 3 [KO:K03174]
121931127  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
121928472  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
121937060  TANK; TRAF family member-associated NF-kappa-B activator isoform X1 [KO:K12650]
121932898  IRF3; interferon regulatory factor 3 isoform X1 [KO:K05411]
121920016  IRF7; interferon regulatory factor 7 isoform X1 [KO:K09447]
121923586  interferon beta-like [KO:K05414]
121924215  interferon beta-like [KO:K05414]
121920523  interferon alpha-13-like [KO:K05414]
121920524  interferon alpha-13-like [KO:K05414]
121920526  interferon beta-like [KO:K05414]
121920528  interferon beta-like [KO:K05414]
121920529  interferon alpha-11-like [KO:K05414]
121934502  NLRX1; NLR family member X1 [KO:K12653]
121930457  ANTXR2; anthrax toxin receptor 2 isoform X1 [KO:K20909]
121935697  ANTXR1; anthrax toxin receptor 1 [KO:K20909]
121932453  NACHT, LRR and PYD domains-containing protein 1-like isoform X1 [KO:K12798]
121935506  apoptosis-associated speck-like protein containing a CARD [KO:K12799]
121916819  caspase-1-like [KO:K01370] [EC:3.4.22.36]
121929439  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
121929893  BCL2L1; bcl-2-like protein 1 [KO:K04570]
121931257  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
121926656  PANX1; LOW QUALITY PROTEIN: pannexin-1 [KO:K03443]
121916733  P2RX7; P2X purinoceptor 7 isoform X1 [KO:K05220]
121926477  TRPM2; transient receptor potential cation channel subfamily M member 2 isoform X1 [KO:K04977] [EC:3.6.1.13]
121933020  TRPM7; LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
121916842  transient receptor potential cation channel subfamily V member 2-like [KO:K04971]
121920483  CASR; extracellular calcium-sensing receptor isoform X1 [KO:K04612]
121919581  GPRC6A; G-protein coupled receptor family C group 6 member A [KO:K04622]
121933158  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
121918973  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
121918974  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
121915711  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
121921093  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
121932190  ITPR2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
121928090  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
121922438  VDAC1; voltage-dependent anion-selective channel protein 1 isoform X1 [KO:K05862]
121926063  VDAC2; voltage-dependent anion-selective channel protein 2 isoform X1 [KO:K15040]
121933450  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
121926196  MCU; calcium uniporter protein, mitochondrial isoform X1 [KO:K20858]
121923507  2'-5'-oligoadenylate synthase-like protein 2 isoform X1 [KO:K14216] [EC:2.7.7.84]
121928772  2-5A-dependent ribonuclease-like [KO:K01165]
121928906  2-5A-dependent ribonuclease-like [KO:K01165]
121917147  DHX33; ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
121925598  MFN1; mitofusin-1 isoform X1 [KO:K21356] [EC:3.6.5.-]
121936124  MFN2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
121929823  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
121932626  RIPK3; receptor-interacting serine/threonine-protein kinase 3 isoform X1 [KO:K08847] [EC:2.7.11.1]
121922691  dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
121930492  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
121931650  NAMPT; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
121927171  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
121914709  cytochrome b-245 light chain [KO:K08009]
121915580  thioredoxin-interacting protein [KO:K20910]
121920539  TXN; thioredoxin [KO:K03671]
121921622  thioredoxin-like [KO:K03671]
121931321  TXN2; thioredoxin, mitochondrial [KO:K03671]
121928849  NEK7; serine/threonine-protein kinase Nek7 isoform X1 [KO:K20876] [EC:2.7.11.34]
121937152  BRCC3; lys-63-specific deubiquitinase BRCC36 [KO:K11864] [EC:3.4.19.-]
121927409  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
121925519  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
121922020  GPSM3; G-protein-signaling modulator 3 [KO:K15838]
121932401  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 isoform X1 [KO:K12804]
121919902  NLRP12; NACHT, LRR and PYD domains-containing protein 12 isoform X1 [KO:K20865]
121922655  baculoviral IAP repeat-containing protein 1 isoform X1 [KO:K12807]
121919552  NLRC4; NLR family CARD domain-containing protein 4 [KO:K12805]
121922638  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
121932993  TP53BP1; TP53-binding protein 1 isoform X1 [KO:K20915]
121922392  transforming protein RhoA-like isoform X1 [KO:K04513]
121921506  RHOA; transforming protein RhoA [KO:K04513]
121921345  PKN1; serine/threonine-protein kinase N1 isoform X1 [KO:K06071] [EC:2.7.11.13]
121928417  PKN2; serine/threonine-protein kinase N2 [KO:K23691] [EC:2.7.11.13]
121917041  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
121917810  guanylate-binding protein 1-like [KO:K20899]
121916022  guanylate-binding protein 1-like isoform X1 [KO:K20899]
121916024  guanylate-binding protein 1-like isoform X1 [KO:K20899]
121925451  IFNAR1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
121925518  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
121928485  JAK1; LOW QUALITY PROTEIN: tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
121921615  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
121935257  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
121921484  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
121932884  IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]
121936774  TLR4; toll-like receptor 4 [KO:K10160]
121936822  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
121935209  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
121931563  IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
121928901  STING1; 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
sund04010  MAPK signaling pathway
sund04140  Autophagy - animal
sund04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
LinkDB

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