KEGG   PATHWAY: mdo04621
Entry
mdo04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Monodelphis domestica (gray short-tailed opossum)
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
mdo04621  NOD-like receptor signaling pathway
mdo04621

Organism
Monodelphis domestica (gray short-tailed opossum) [GN:mdo]
Gene
100032532  NOD1; nucleotide binding oligomerization domain containing 1 [KO:K08727]
100029371  RIPK2; receptor interacting serine/threonine kinase 2 [KO:K08846] [EC:2.7.11.1]
100022918  IKBKG; inhibitor of nuclear factor kappa B kinase subunit gamma [KO:K07210]
100027952  CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
100033031  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
100013691  NFKBIB; NFKB inhibitor beta [KO:K02581]
100011769  NFKBIA; NFKB inhibitor alpha [KO:K04734]
100014446  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
100030053  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
100026024  IL1B; interleukin 1 beta [KO:K04519]
103102395  interleukin-18-like [KO:K05482]
103101367  interleukin-18-like [KO:K05482]
103101192  interleukin-18-like [KO:K05482]
103104339  IL6; interleukin 6 [KO:K05405]
100023069  TNF; tumor necrosis factor [KO:K03156]
100023722  IL8; interleukin-8 [KO:K10030]
100023783  CXCL1; growth-regulated alpha protein [KO:K05505]
103093665  C-C motif chemokine 2-like [KO:K14624]
100021011  CCL5; C-C motif chemokine ligand 5 [KO:K12499]
100023883  protegrin-2-like [KO:K13916]
100620004  cathelicidin-6-like [KO:K13916]
100617650  cathelicidin-6-like [KO:K13916]
103103724  cathelicidin-2-like [KO:K13916]
103104080  cathelicidin-related peptide batroxicidin-like [KO:K13916]
103104254  antimicrobial protein CAP18-like [KO:K13916]
100617165  cathelicidin-4-like [KO:K13916]
103106845  antibacterial peptide PMAP-36-like [KO:K13916]
103092095  antibacterial peptide PMAP-36-like [KO:K13916]
100619794  DEFA6; defensin alpha 6 [KO:K05230]
100032666  beta-defensin 103A-like [KO:K23126]
100018299  NOD2; nucleotide binding oligomerization domain containing 2 [KO:K10165]
100019975  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
100012432  TAB1; TGF-beta activated kinase 1 (MAP3K7) binding protein 1 [KO:K04403]
100026855  TAB2; TGF-beta activated kinase 1/MAP3K7 binding protein 2 [KO:K04404]
100018532  TAB3; TGF-beta activated kinase 1/MAP3K7 binding protein 3 [KO:K12793]
100028096  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100012916  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100028089  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
100618895  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
100010279  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
100010891  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
100026324  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
100028821  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
100018774  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
100021305  ATG16L1; autophagy related 16 like 1 [KO:K17890]
100021270  ATG5; autophagy related 5 [KO:K08339]
100029238  ATG12; autophagy related 12 [KO:K08336]
100029139  GABARAPL2; GABA type A receptor associated protein like 2 [KO:K08341]
100016545  GABARAP; GABA type A receptor-associated protein [KO:K08341]
100010204  gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
100019121  GABARAPL1; GABA type A receptor associated protein like 1 [KO:K08341]
100018370  MAP1LC3B; microtubule associated protein 1 light chain 3 beta [KO:K10435]
100027672  MAP1LC3C; microtubule associated protein 1 light chain 3 gamma [KO:K10435]
100028493  MAP1LC3A; microtubule associated protein 1 light chain 3 alpha [KO:K10435]
100013988  SUGT1; SGT1 homolog, MIS12 kinetochore complex assembly cochaperone [KO:K12795]
100017663  SHARPIN; SHANK associated RH domain interactor [KO:K20894]
100011102  RBCK1; RANBP2-type and C3HC4-type zinc finger containing 1 [KO:K10630] [EC:2.3.2.31]
100030741  RNF31; ring finger protein 31 [KO:K11974] [EC:2.3.2.31]
100016651  XIAP; X-linked inhibitor of apoptosis [KO:K04725] [EC:2.3.2.27]
100018349  CARD6; caspase recruitment domain family member 6 [KO:K12797]
100018084  TRIP6; thyroid hormone receptor interactor 6 [KO:K12792]
100019097  ERBIN; erbb2 interacting protein [KO:K12796]
100010782  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
100010741  baculoviral IAP repeat-containing protein 2-like [KO:K16060]
100017243  TRAF2; TNF receptor associated factor 2 [KO:K03173] [EC:2.3.2.27]
100022268  TRAF5; TNF receptor associated factor 5 [KO:K09849]
100010055  TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]
100020522  CARD9; caspase recruitment domain family member 9 [KO:K12794]
100025842  TNFAIP3; TNF alpha induced protein 3 [KO:K11859] [EC:3.4.19.12]
103094760  MAVS; mitochondrial antiviral signaling protein [KO:K12648]
100017361  TRAF3; TNF receptor associated factor 3 [KO:K03174]
100019578  IKBKE; inhibitor of nuclear factor kappa B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
100022154  TANK; TRAF family member associated NFKB activator [KO:K12650]
100030239  IRF3; interferon regulatory factor 3 [KO:K05411]
100021311  IFN7; type I interferon 7 [KO:K05414]
100021419  interferon tau-2-like [KO:K05414]
100021467  interferon alpha-16-like [KO:K05414]
100021290  IFN3; type I interferon 3 [KO:K05414]
100021340  IFN4; type I interferon 4 [KO:K05414]
100021368  interferon tau-2-like [KO:K05414]
100021487  IFN2; type I interferon 2 [KO:K05414]
100021258  IFNB1; interferon beta [KO:K05415]
100031223  NLRX1; NLR family member X1 [KO:K12653]
100018511  ANTXR2; anthrax toxin receptor 2 [KO:K20909]
100018714  ANTXRL; anthrax toxin receptor-like [KO:K20909]
100032754  ANTXR1; anthrax toxin receptor 1 [KO:K20909]
103095197  NLRP1; NLR family pyrin domain containing 1 [KO:K12798]
100016983  apoptosis-associated speck-like protein containing a CARD [KO:K12799]
100032596  caspase-1-like [KO:K01370] [EC:3.4.22.36]
100032610  caspase-1-like [KO:K01370] [EC:3.4.22.36]
100032592  caspase-1-like [KO:K01370] [EC:3.4.22.36]
100016570  BCL2; BCL2, apoptosis regulator [KO:K02161]
100010654  BCL2L1; BCL2 like 1 [KO:K04570]
100032681  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
100014304  PANX1; pannexin 1 [KO:K03443]
100020874  P2X purinoceptor 7-like [KO:K05220]
100020934  P2RX7; P2X purinoceptor 7 [KO:K05220]
100618566  TRPM2; transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13]
100031256  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
100617606  TRPV2; transient receptor potential cation channel subfamily V member 2 [KO:K04971]
100018274  CASR; calcium sensing receptor [KO:K04612]
100029974  GPRC6A; G protein-coupled receptor class C group 6 member A [KO:K04622]
100033281  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
100031660  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
100031869  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
100031263  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
100013305  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
100010212  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
100025596  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
100014869  VDAC1; voltage dependent anion channel 1 [KO:K05862]
100012461  VDAC2; voltage dependent anion channel 2 [KO:K15040]
100030164  VDAC3; voltage dependent anion channel 3 [KO:K15041]
100010373  MCU; mitochondrial calcium uniporter [KO:K20858]
100028903  OAS1; 2'-5'-oligoadenylate synthase 1 [KO:K14216] [EC:2.7.7.84]
100028774  OAS3; 2'-5'-oligoadenylate synthase 3 [KO:K14216] [EC:2.7.7.84]
100028841  2'-5'-oligoadenylate synthase 1-like [KO:K14216] [EC:2.7.7.84]
100023689  RNASEL; ribonuclease L [KO:K01165]
100022751  DHX33; DEAH-box helicase 33 [KO:K17820] [EC:5.6.2.6]
100013460  MFN1; mitofusin 1 [KO:K21356] [EC:3.6.5.-]
100013425  MFN2; mitofusin 2 [KO:K06030] [EC:3.6.5.-]
100028597  RIPK1; receptor interacting serine/threonine kinase 1 [KO:K02861] [EC:2.7.11.1]
100022725  dynamin-1-like protein [KO:K17065] [EC:3.6.5.5]
100012742  DNM1L; dynamin 1 like [KO:K17065] [EC:3.6.5.5]
100019192  NAMPT; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
100017914  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
100026086  uncharacterized LOC100026086 [KO:K08009]
100013163  TXNIP; thioredoxin interacting protein [KO:K20910]
100024935  TXN2; thioredoxin 2 [KO:K03671]
100026840  NEK7; NIMA related kinase 7 [KO:K20876] [EC:2.7.11.34]
100014766  BRCC3; BRCA1/BRCA2-containing complex subunit 3 [KO:K11864] [EC:3.4.19.-]
100010162  lys-63-specific deubiquitinase BRCC36 [KO:K11864] [EC:3.4.19.-]
100017761  HSP90AA1; heat shock protein 90 alpha family class A member 1 [KO:K04079]
100013102  HSP90AB1; heat shock protein 90 alpha family class B member 1 [KO:K04079]
100024159  GPSM3; G-protein signaling modulator 3 [KO:K15838]
100017024  MEFV; MEFV, pyrin innate immunity regulator [KO:K12803]
100025253  PSTPIP1; proline-serine-threonine phosphatase interacting protein 1 [KO:K12804]
100017025  CASP18; caspase-18 [KO:K04398] [EC:3.4.22.61]
100617599  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
100031941  FADD; Fas associated via death domain [KO:K02373]
100032606  caspase-13-like [KO:K04741] [EC:3.4.22.-]
100032604  caspase-12-like [KO:K04741] [EC:3.4.22.-]
100018825  NLRP12; NLR family pyrin domain containing 12 [KO:K20865]
100030722  PRKCD; protein kinase C delta [KO:K06068] [EC:2.7.11.13]
103096087  IFI16; interferon-inducible protein AIM2 [KO:K12966]
100011435  TP53BP1; tumor protein p53 binding protein 1 [KO:K20915]
100021110  RHOA; ras homolog family member A [KO:K04513]
100026472  PKN1; protein kinase N1 [KO:K06071] [EC:2.7.11.13]
100027775  PKN2; protein kinase N2 [KO:K23691] [EC:2.7.11.13]
100012276  YWHAE; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon [KO:K06630]
100027633  guanylate-binding protein 1-like [KO:K20899]
100027621  guanylate-binding protein 1-like [KO:K20899]
100027544  guanylate-binding protein 1-like [KO:K20899]
100027586  GBP7; guanylate-binding protein 7 [KO:K20899]
100032600  caspase-13-like [KO:K04394] [EC:3.4.22.57 3.4.22.64]
103101815  GSDMD; gasdermin D [KO:K20917]
103092556  IFNAR2; interferon alpha and beta receptor subunit 2 [KO:K05131]
100031307  JAK1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]
100012931  TYK2; tyrosine kinase 2 [KO:K11219] [EC:2.7.10.2]
100028917  STAT1; signal transducer and activator of transcription 1 [KO:K11220]
100030758  IRF9; interferon regulatory factor 9 [KO:K04693]
100014467  TLR4; toll like receptor 4 [KO:K10160]
100023610  TICAM1; toll like receptor adaptor molecule 1 [KO:K05842]
100019202  IRAK4; interleukin 1 receptor associated kinase 4 [KO:K04733] [EC:2.7.11.1]
100025682  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
mdo04010  MAPK signaling pathway
mdo04064  NF-kappa B signaling pathway
mdo04140  Autophagy - animal
mdo04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
LinkDB

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