KEGG   PATHWAY: dord04621
Entry
dord04621                   Pathway                                
Name
NOD-like receptor signaling pathway - Dipodomys ordii (Ord's kangaroo rat)
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
dord04621  NOD-like receptor signaling pathway
dord04621

Organism
Dipodomys ordii (Ord's kangaroo rat) [GN:dord]
Gene
105999991  Nod1; nucleotide-binding oligomerization domain-containing protein 1 [KO:K08727]
105982876  Ripk2; receptor-interacting serine/threonine-protein kinase 2 isoform X1 [KO:K08846] [EC:2.7.11.1]
106000155  Ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
105986731  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
105991714  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
105993134  Nfkbib; NF-kappa-B inhibitor beta [KO:K02581]
105982592  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
105991225  Nfkb1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
105989242  Rela; transcription factor p65 isoform X1 [KO:K04735]
105988300  Il1b; interleukin-1 beta [KO:K04519]
105980688  Il18; interleukin-18 isoform X1 [KO:K05482]
105991375  Il6; interleukin-6 [KO:K05405]
105997009  Tnf; tumor necrosis factor isoform X1 [KO:K03156]
105988541  Cxcl8; interleukin-8 [KO:K10030]
105988528  permeability factor 2-like [KO:K05505]
105988529  growth-regulated alpha protein-like [KO:K05505]
105985754  C-C motif chemokine 2-like [KO:K14624]
105983400  Ccl5; C-C motif chemokine 5 [KO:K12499]
105994613  Camp; cathelicidin antimicrobial peptide [KO:K13916]
105991559  alpha-defensin 15-like [KO:K05230]
105991560  defensin-5-like [KO:K05230]
105991583  defensin-5-like [KO:K05230]
106001835  neutrophil defensin 8-like [KO:K05230]
105991558  beta-defensin 3-like [KO:K21100]
105991556  beta-defensin 103-like [KO:K23126]
105994470  Nod2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165]
105985880  Map3k7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
106001529  LOW QUALITY PROTEIN: mitogen-activated protein kinase kinase kinase 7-like [KO:K04427] [EC:2.7.11.25]
105991989  Tab1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
105993663  Tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
105993309  Tab3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793]
105981830  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
105997225  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105996777  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
105988509  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
105998906  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
105995746  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
105995771  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
105992729  mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
105981288  Atg16l1; autophagy-related protein 16-1 isoform X1 [KO:K17890]
105990120  Atg5; autophagy protein 5 isoform X1 [KO:K08339]
105985463  Atg12; ubiquitin-like protein ATG12 [KO:K08336]
105983158  Gabarapl2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
106002322  Gabarap; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
105982991  Map1lc3b; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
105981643  Sugt1; suppressor of G2 allele of SKP1 homolog [KO:K12795]
106002166  sharpin [KO:K20894]
105981716  Rbck1; ranBP-type and C3HC4-type zinc finger-containing protein 1 [KO:K10630] [EC:2.3.2.31]
105992527  Rnf31; E3 ubiquitin-protein ligase RNF31 isoform X1 [KO:K11974] [EC:2.3.2.31]
105986903  Xiap; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
105987403  Card6; caspase recruitment domain-containing protein 6 [KO:K12797]
105997300  Trip6; thyroid receptor-interacting protein 6 isoform X1 [KO:K12792]
105985359  Erbb2ip; protein LAP2 isoform X1 [KO:K12796]
105980764  Birc2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
105995582  Traf2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
105984909  Traf5; TNF receptor-associated factor 5 [KO:K09849]
105988129  Traf6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
105995655  Card9; caspase recruitment domain-containing protein 9 isoform X1 [KO:K12794]
105993591  Tnfaip3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
105981763  Mavs; mitochondrial antiviral-signaling protein [KO:K12648]
105983154  Traf3; TNF receptor-associated factor 3 [KO:K03174]
105989073  Tbk1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
105986544  Ikbke; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
105995873  Tank; TRAF family member-associated NF-kappa-B activator isoform X1 [KO:K12650]
105994272  Irf3; interferon regulatory factor 3 [KO:K05411]
105998598  Irf7; interferon regulatory factor 7 isoform X1 [KO:K09447]
105988955  interferon alpha-3-like [KO:K05414]
105988956  interferon alpha-3-like [KO:K05414]
105988976  interferon alpha-2-like [KO:K05414]
105988979  interferon alpha-2-like [KO:K05414]
105988997  interferon alpha-3-like [KO:K05414]
105988998  interferon alpha-3-like [KO:K05414]
105989000  interferon alpha-3-like [KO:K05414]
105988975  Ifnb1; interferon beta [KO:K05415]
105980806  Nlrx1; NLR family member X1 [KO:K12653]
105990210  Antxr1; anthrax toxin receptor 1 [KO:K20909]
105988576  Antxr2; anthrax toxin receptor 2 [KO:K20909]
105983308  NACHT, LRR and PYD domains-containing protein 1-like [KO:K12798]
105983310  NACHT, LRR and PYD domains-containing protein 1-like [KO:K12798]
105983311  NACHT, LRR and PYD domains-containing protein 1-like [KO:K12798]
105983489  LOW QUALITY PROTEIN: NACHT, LRR and PYD domains-containing protein 1-like [KO:K12798]
105981993  apoptosis-associated speck-like protein containing a CARD [KO:K12799]
105980798  caspase-1-like isoform X1 [KO:K01370] [EC:3.4.22.36]
105987599  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
105981697  Bcl2l1; bcl-2-like protein 1 isoform X1 [KO:K04570]
105991593  Ctsb; cathepsin B [KO:K01363] [EC:3.4.22.1]
105985010  Nlrp3; NACHT, LRR and PYD domains-containing protein 3 [KO:K12800]
105995140  Panx1; pannexin-1 [KO:K03443]
105990637  P2rx7; P2X purinoceptor 7 [KO:K05220]
105993972  Trpm2; LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13]
105981106  Trpm7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
105997516  Trpv2; transient receptor potential cation channel subfamily V member 2 [KO:K04971]
105987931  Casr; extracellular calcium-sensing receptor isoform X1 [KO:K04612]
105998164  Gprc6a; G-protein coupled receptor family C group 6 member A isoform X1 [KO:K04622]
105981148  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
105981715  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
105981749  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
105989246  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
105981338  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
106001099  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
105999871  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
105996772  Vdac1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
105992684  Vdac2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
105993234  Vdac3; voltage-dependent anion-selective channel protein 3 [KO:K15041]
105992633  Mcu; calcium uniporter protein, mitochondrial [KO:K20858]
105990722  Oas1; 2'-5'-oligoadenylate synthase 1 [KO:K14216] [EC:2.7.7.84]
105985004  Rnasel; 2-5A-dependent ribonuclease isoform X1 [KO:K01165]
105983304  Dhx33; putative ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
105998865  Mfn1; mitofusin-1 isoform X1 [KO:K21356] [EC:3.6.5.-]
105997460  Mfn2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
105985992  Ripk1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
105992443  Ripk3; receptor-interacting serine/threonine-protein kinase 3 isoform X1 [KO:K08847] [EC:2.7.11.1]
105998625  Dnm1l; dynamin-1-like protein [KO:K17065] [EC:3.6.5.5]
105999663  Nampt; nicotinamide phosphoribosyltransferase isoform X1 [KO:K03462] [EC:2.4.2.12]
105993486  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
105983000  cytochrome b-245 light chain [KO:K08009]
105987141  Txnip; thioredoxin-interacting protein [KO:K20910]
105990827  Txn; thioredoxin [KO:K03671]
105992127  Txn2; thioredoxin, mitochondrial [KO:K03671]
105986505  Nek7; serine/threonine-protein kinase Nek7 [KO:K20876] [EC:2.7.11.34]
105987308  lys-63-specific deubiquitinase BRCC36-like [KO:K11864] [EC:3.4.19.-]
106000139  Brcc3; lys-63-specific deubiquitinase BRCC36 isoform X1 [KO:K11864] [EC:3.4.19.-]
105984907  Hsp90aa1; heat shock protein HSP 90-alpha [KO:K04079]
105987770  Hsp90ab1; heat shock protein HSP 90-beta [KO:K04079]
105999833  Gpsm3; G-protein-signaling modulator 3 [KO:K15838]
105996765  immunity-related GTPase family M protein-like [KO:K14139] [EC:3.6.5.-]
105981967  Mefv; pyrin [KO:K12803]
105982498  Pstpip1; proline-serine-threonine phosphatase-interacting protein 1 [KO:K12804]
105981481  Casp8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
105989060  Fadd; FAS-associated death domain protein [KO:K02373]
106002598  FAS-associated death domain protein-like [KO:K02373]
105994231  NACHT, LRR and PYD domains-containing protein 7-like [KO:K20864]
105994225  Nlrp12; NACHT, LRR and PYD domains-containing protein 12 [KO:K20865]
105985331  Naip; LOW QUALITY PROTEIN: baculoviral IAP repeat-containing protein 1 [KO:K12807]
105983561  Nlrc4; NLR family CARD domain-containing protein 4 isoform X1 [KO:K12805]
105996605  Prkcd; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
105991906  Gbp5; guanylate-binding protein 5 [KO:K20898]
105996423  Aim2; interferon-inducible protein AIM2 [KO:K12966]
105996520  Ifi16; gamma-interferon-inducible protein 16 isoform X1 [KO:K20914]
105981104  Tp53bp1; tumor suppressor p53-binding protein 1 isoform X1 [KO:K20915]
105994567  Rhoa; transforming protein RhoA [KO:K04513]
105999270  Pkn1; serine/threonine-protein kinase N1 isoform X1 [KO:K06071] [EC:2.7.11.13]
105991940  Pkn2; serine/threonine-protein kinase N2 isoform X1 [KO:K23691] [EC:2.7.11.13]
105985830  Ywhae; 14-3-3 protein epsilon [KO:K06630]
105991866  guanylate-binding protein 7-like [KO:K20899]
105991868  LOW QUALITY PROTEIN: guanylate-binding protein 4-like [KO:K20899]
105991871  interferon-induced guanylate-binding protein 1-like [KO:K20899]
105991901  LOW QUALITY PROTEIN: guanylate-binding protein 4-like [KO:K20899]
105991902  LOW QUALITY PROTEIN: guanylate-binding protein 4-like [KO:K20899]
105991903  guanylate-binding protein 4-like [KO:K20899]
105991904  guanylate-binding protein 7-like [KO:K20899]
105991905  guanylate-binding protein 4-like [KO:K20899]
105991907  guanylate-binding protein 4-like [KO:K20899]
105991908  guanylate-binding protein 4-like [KO:K20899]
105980799  Casp5; caspase-5 isoform X1 [KO:K04394] [EC:3.4.22.57 3.4.22.64]
105999020  Gsdmd; gasdermin-D isoform X1 [KO:K20917]
105994024  Ifnar1; interferon alpha/beta receptor 1 [KO:K05130]
105994025  Ifnar2; interferon alpha/beta receptor 2 [KO:K05131]
105988847  Jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
105999053  Tyk2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
105995197  Stat1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
105990116  Stat2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
105992528  Irf9; LOW QUALITY PROTEIN: interferon regulatory factor 9 [KO:K04693]
105996175  Tlr4; toll-like receptor 4 isoform X1 [KO:K10160]
105990289  Ticam1; TIR domain-containing adapter molecule 1 [KO:K05842]
105996289  Myd88; myeloid differentiation primary response protein MyD88 [KO:K04729]
105987554  Irak4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
105988598  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
dord04010  MAPK signaling pathway
dord04064  NF-kappa B signaling pathway
dord04140  Autophagy - animal
dord04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
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