KEGG   PATHWAY: tup04621
Entry
tup04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Tupaia chinensis (Chinese tree shrew)
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
tup04621  NOD-like receptor signaling pathway
tup04621

Organism
Tupaia chinensis (Chinese tree shrew) [GN:tup]
Gene
102496936  NOD1; nucleotide binding oligomerization domain containing 1 [KO:K08727]
102473610  RIPK2; receptor interacting serine/threonine kinase 2 [KO:K08846] [EC:2.7.11.1]
102476758  IKBKG; inhibitor of nuclear factor kappa B kinase subunit gamma [KO:K07210]
102501308  CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
102467954  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
102496652  NFKBIB; NFKB inhibitor beta [KO:K02581]
102494635  NFKBIA; NFKB inhibitor alpha [KO:K04734]
102487413  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
102490451  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
102475138  IL1B; interleukin 1 beta [KO:K04519]
102488248  IL18; interleukin 18 [KO:K05482]
102490996  interleukin-6 [KO:K05405]
106733357  interleukin-6-like [KO:K05405]
106733358  interleukin-6-like [KO:K05405]
106733575  interleukin-6-like [KO:K05405]
106734037  interleukin-6-like [KO:K05405]
106734038  interleukin-6-like [KO:K05405]
106734039  interleukin-6-like [KO:K05405]
102496137  IL6; interleukin-6 [KO:K05405]
106733746  interleukin-6-like [KO:K05405]
102497973  TNF; tumor necrosis factor [KO:K03156]
102471344  CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030]
102472622  growth-regulated alpha protein-like [KO:K05505]
102467686  uncharacterized LOC102467686 [KO:K05505]
102481282  CCL5; C-C motif chemokine ligand 5 [KO:K12499]
102481956  CAMP; cathelin [KO:K13916]
102494573  defensin-5 [KO:K05230]
102498707  Defensin-5; uncharacterized LOC102498707 [KO:K05230]
102499971  Defensin-7; uncharacterized LOC102499971 [KO:K05230]
102494162  defensin-5 [KO:K05230]
102491530  beta-defensin 103-like [KO:K23126]
102497846  NOD2; nucleotide binding oligomerization domain containing 2 [KO:K10165]
102500527  nucleotide-binding oligomerization domain-containing protein 2-like [KO:K10165]
102477331  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
102479566  TAB1; TGF-beta activated kinase 1 (MAP3K7) binding protein 1 [KO:K04403]
102478674  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
102491788  TAB3; TGF-beta activated kinase 1/MAP3K7 binding protein 3 [KO:K12793]
102496453  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102483057  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102475730  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
102472233  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
102497095  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
102487603  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
102501733  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
102495693  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
102481241  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
102496870  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
102472744  ATG16L1; autophagy related 16 like 1 [KO:K17890]
102473456  ATG5; autophagy related 5 [KO:K08339]
102481748  ATG12; autophagy related 12 [KO:K08336]
102485377  GABARAPL1; GABA type A receptor associated protein like 1 [KO:K08341]
102485172  GABARAP; GABA type A receptor-associated protein [KO:K08341]
102502678  GABARAPL2; GABA type A receptor associated protein like 2 [KO:K08341]
102501394  autophagy-related protein 8-like [KO:K08341]
102480495  MAP1LC3A; microtubule associated protein 1 light chain 3 alpha [KO:K10435]
102467810  MAP1LC3C; microtubule associated protein 1 light chain 3 gamma [KO:K10435]
102475394  MAP1LC3B; microtubule associated protein 1 light chain 3 beta [KO:K10435]
102501289  SUGT1; SGT1 homolog, MIS12 kinetochore complex assembly cochaperone [KO:K12795]
102471523  SHARPIN; SHANK associated RH domain interactor [KO:K20894]
102473168  RBCK1; RANBP2-type and C3HC4-type zinc finger containing 1 [KO:K10630] [EC:2.3.2.31]
102496915  RNF31; ring finger protein 31 [KO:K11974] [EC:2.3.2.31]
102500839  XIAP; X-linked inhibitor of apoptosis [KO:K04725] [EC:2.3.2.27]
102480983  CARD6; caspase recruitment domain family member 6 [KO:K12797]
102480155  TRIP6; thyroid hormone receptor interactor 6 [KO:K12792]
102469606  ERBIN; erbb2 interacting protein [KO:K12796]
102493795  BIRC2; baculoviral IAP repeat containing 2 [KO:K16060]
102494213  BIRC3; baculoviral IAP repeat containing 3 [KO:K16060]
102473925  C8G; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
102478124  TRAF5; TNF receptor associated factor 5 [KO:K09849]
102482652  TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]
102480227  CARD9; caspase recruitment domain family member 9 [KO:K12794]
102477224  TNFAIP3; TNF alpha induced protein 3 [KO:K11859] [EC:3.4.19.12]
102475194  MAVS; mitochondrial antiviral signaling protein [KO:K12648]
102471499  TRAF3; TNF receptor associated factor 3 [KO:K03174]
102484078  TBK1; TANK binding kinase 1 [KO:K05410] [EC:2.7.11.10]
102481203  IKBKE; inhibitor of nuclear factor kappa B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
102481347  TANK; TRAF family member associated NFKB activator [KO:K12650]
102489835  IRF3; interferon regulatory factor 3 [KO:K05411]
102487659  IRF7; interferon regulatory factor 7 [KO:K09447]
102498386  interferon alpha-2 [KO:K05414]
102472952  interferon alpha-13 [KO:K05414]
106733346  interferon alpha-13-like [KO:K05414]
102475056  interferon alpha-2 [KO:K05414]
102475482  interferon omega-1 [KO:K05414]
102475884  interferon omega-1 [KO:K05414]
102469574  interferon omega-1 [KO:K05414]
102493858  IFNB1; interferon beta 1 [KO:K05415]
102495601  NLRX1; NLR family member X1 [KO:K12653]
102494227  ANTXR2; anthrax toxin receptor 2 [KO:K20909]
102469015  ANTXR1; anthrax toxin receptor 1 [KO:K20909]
102483486  NLRP1; NLR family pyrin domain containing 1 [KO:K12798]
102485294  PYCARD; PYD and CARD domain containing [KO:K12799]
102490614  CASP1; caspase 1 [KO:K01370] [EC:3.4.22.36]
102474592  BCL2; BCL2, apoptosis regulator [KO:K02161]
102486626  BCL2L1; BCL2 like 1 [KO:K04570]
102483590  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
102492932  NLRP3; NLR family pyrin domain containing 3 [KO:K12800]
102502909  PANX1; pannexin 1 [KO:K03443]
102495976  P2RX7; purinergic receptor P2X 7 [KO:K05220]
102485911  TRPM2; transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13]
106733924  transient receptor potential cation channel subfamily M member 7-like [KO:K04982] [EC:2.7.11.1]
102492170  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
102484491  TRPV2; transient receptor potential cation channel subfamily V member 2 [KO:K04971]
102477960  CASR; calcium sensing receptor [KO:K04612]
102472038  GPRC6A; G protein-coupled receptor class C group 6 member A [KO:K04622]
102477438  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
102476196  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
102472532  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
102492903  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
102473622  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
102482868  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
102475587  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102485453  VDAC1; voltage dependent anion channel 1 [KO:K05862]
102476815  VDAC2; voltage dependent anion channel 2 [KO:K15040]
102503299  VDAC3; voltage dependent anion channel 3 [KO:K15041]
102468332  MCU; mitochondrial calcium uniporter [KO:K20858]
102495865  OAS2; 2'-5'-oligoadenylate synthetase 2 [KO:K14216] [EC:2.7.7.84]
106735200  OAS1; 2'-5'-oligoadenylate synthetase 1 [KO:K14216] [EC:2.7.7.84]
102494136  RNASEL; ribonuclease L [KO:K01165]
102475383  DHX33; DEAH-box helicase 33 [KO:K17820] [EC:5.6.2.6]
102484142  MFN1; mitofusin 1 [KO:K21356] [EC:3.6.5.-]
102474328  MFN2; mitofusin 2 [KO:K06030] [EC:3.6.5.-]
102502622  RIPK1; receptor interacting serine/threonine kinase 1 [KO:K02861] [EC:2.7.11.1]
102503180  RIPK3; receptor interacting serine/threonine kinase 3 [KO:K08847] [EC:2.7.11.1]
102495046  DNM1L; dynamin 1 like [KO:K17065] [EC:3.6.5.5]
102492540  NAMPT; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
102468293  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
102471991  cytochrome b-245 light chain [KO:K08009]
102496166  TXNIP; thioredoxin interacting protein [KO:K20910]
102499666  TXN; thioredoxin [KO:K03671]
102494671  TXN2; thioredoxin 2 [KO:K03671]
102498629  thioredoxin-like [KO:K03671]
102503130  NEK7; NIMA related kinase 7 [KO:K20876] [EC:2.7.11.34]
102499638  BRCC3; BRCA1/BRCA2-containing complex subunit 3 [KO:K11864] [EC:3.4.19.-]
102501383  HSP90AB1; heat shock protein 90 alpha family class B member 1 [KO:K04079]
102468670  HSP90AA1; heat shock protein 90 alpha family class A member 1 [KO:K04079]
102481880  CARD8; caspase recruitment domain family member 8 [KO:K12801]
102486755  GPSM3; G-protein signaling modulator 3 [KO:K15838]
102503323  G-protein-signaling modulator 3-like [KO:K15838]
102484442  PYDC1; pyrin domain containing 1 [KO:K12802]
106734828  pyrin domain-containing protein 1-like [KO:K12802]
102470804  MEFV; MEFV, pyrin innate immunity regulator [KO:K12803]
102479779  PSTPIP1; proline-serine-threonine phosphatase interacting protein 1 [KO:K12804]
102498355  CASP8; caspase 8 [KO:K04398] [EC:3.4.22.61]
102489799  FADD; Fas associated via death domain [KO:K02373]
102489486  caspase-12-like [KO:K04741] [EC:3.4.22.-]
102478852  NLRP6; NLR family pyrin domain containing 6 [KO:K20863]
102496349  NLRP12; NLR family pyrin domain containing 12 [KO:K20865]
102476225  NAIP; NLR family apoptosis inhibitory protein [KO:K12807]
102469158  NLRC4; NLR family CARD domain containing 4 [KO:K12805]
102487574  PRKCD; protein kinase C delta [KO:K06068] [EC:2.7.11.13]
102502568  guanylate-binding protein 2-like [KO:K20897]
102503283  GBP2; guanylate-binding protein 2 [KO:K20897]
102500480  GBP5; guanylate binding protein 5 [KO:K20898]
102470019  AIM2; absent in melanoma 2 [KO:K12966]
102472196  gamma-interferon-inducible protein 16 [KO:K20914]
102502633  TP53BP1; tumor protein p53 binding protein 1 [KO:K20915]
102487039  RHOA; ras homolog family member A [KO:K04513]
102498026  PKN1; protein kinase N1 [KO:K06071] [EC:2.7.11.13]
102486479  PKN2; protein kinase N2 [KO:K23691] [EC:2.7.11.13]
102488678  YWHAE; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon [KO:K06630]
102495198  guanylate-binding protein 1 [KO:K20899]
102501296  GBP4; guanylate-binding protein 4 [KO:K20899]
102500892  GBP7; guanylate-binding protein 7 [KO:K20899]
102489894  CASP4; caspase 4 [KO:K04394] [EC:3.4.22.57 3.4.22.64]
102468460  caspase-13-like [KO:K04394] [EC:3.4.22.57 3.4.22.64]
102498766  GSDMD; gasdermin D [KO:K20917]
102480854  IFNAR1; interferon alpha and beta receptor subunit 1 [KO:K05130]
102477904  IFNAR2; interferon alpha and beta receptor subunit 2 [KO:K05131]
102471806  JAK1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]
102493753  TYK2; tyrosine kinase 2 [KO:K11219] [EC:2.7.10.2]
102476590  STAT1; signal transducer and activator of transcription 1 [KO:K11220]
102477989  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
102495534  IRF9; interferon regulatory factor 9 [KO:K04693]
102501464  TLR4; toll like receptor 4 [KO:K10160]
102480594  TICAM1; toll like receptor adaptor molecule 1 [KO:K05842]
102499350  MYD88; myeloid differentiation primary response 88 [KO:K04729]
102490347  IRAK4; interleukin 1 receptor associated kinase 4 [KO:K04733] [EC:2.7.11.1]
102488712  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
tup04010  MAPK signaling pathway
tup04064  NF-kappa B signaling pathway
tup04140  Autophagy - animal
tup04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
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