KEGG   PATHWAY: mna04621
Entry
mna04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Miniopterus natalensis (Natal long-fingered bat)
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
mna04621  NOD-like receptor signaling pathway
mna04621

Organism
Miniopterus natalensis (Natal long-fingered bat) [GN:mna]
Gene
107544418  NOD1; nucleotide-binding oligomerization domain-containing protein 1 [KO:K08727]
107526473  RIPK2; receptor-interacting serine/threonine-protein kinase 2 [KO:K08846] [EC:2.7.11.1]
107544156  IKBKG; NF-kappa-B essential modulator [KO:K07210]
107542599  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
107523913  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
107532199  NFKBIB; NF-kappa-B inhibitor beta isoform X1 [KO:K02581]
107526117  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
107545508  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
107533544  RELA; transcription factor p65 [KO:K04735]
107528631  IL1B; interleukin-1 beta [KO:K04519]
107531295  IL18; interleukin-18 [KO:K05482]
107540295  IL6; interleukin-6 [KO:K05405]
107538974  TNF; tumor necrosis factor [KO:K03156]
107534494  CXCL8; interleukin-8 [KO:K10030]
107534487  permeability factor 2-like [KO:K05505]
107532582  C-C motif chemokine 2-like [KO:K14624]
107528872  CCL5; C-C motif chemokine 5 [KO:K12499]
107529421  CAMP; cathelicidin antimicrobial peptide [KO:K13916]
107541945  beta-defensin 103-like [KO:K23126]
107531027  NOD2; nucleotide-binding oligomerization domain-containing protein 2 [KO:K10165]
107533446  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
107531263  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
107545742  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
107534451  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
107541504  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
107530451  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
107537133  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
107527953  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
107528432  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
107545565  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
107545613  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
107536041  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
107536051  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
107536966  JUN; transcription factor AP-1 [KO:K04448]
107530749  ATG16L1; autophagy-related protein 16-1 isoform X1 [KO:K17890]
107540698  ATG5; autophagy protein 5 isoform X1 [KO:K08339]
107546475  ATG12; LOW QUALITY PROTEIN: ubiquitin-like protein ATG12 [KO:K08336]
107524724  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
107544101  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
107544523  GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
107525472  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
107537212  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
107531368  SUGT1; protein SGT1 homolog [KO:K12795]
107539988  sharpin [KO:K20894]
107527772  RBCK1; ranBP-type and C3HC4-type zinc finger-containing protein 1 isoform X1 [KO:K10630] [EC:2.3.2.31]
107531721  RNF31; E3 ubiquitin-protein ligase RNF31 [KO:K11974] [EC:2.3.2.31]
107524984  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
107545892  CARD6; caspase recruitment domain-containing protein 6 [KO:K12797]
107540915  TRIP6; thyroid receptor-interacting protein 6 [KO:K12792]
107529313  ERBIN; protein LAP2 isoform X1 [KO:K12796]
107532417  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
107532418  baculoviral IAP repeat-containing protein 3-like [KO:K16060]
107536208  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
107538857  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
107531990  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
107535599  CARD9; caspase recruitment domain-containing protein 9 [KO:K12794]
107530982  TNFAIP3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
107536394  MAVS; mitochondrial antiviral-signaling protein [KO:K12648]
107538601  TRAF3; TNF receptor-associated factor 3 [KO:K03174]
107527094  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
107538891  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
107524265  TANK; TRAF family member-associated NF-kappa-B activator isoform X1 [KO:K12650]
107531880  IRF3; interferon regulatory factor 3 [KO:K05411]
107542325  IRF7; interferon regulatory factor 7 [KO:K09447]
107531433  IFNB1; interferon beta [KO:K05415]
107533090  NLRX1; NLR family member X1 [KO:K12653]
107537134  ANTXR2; anthrax toxin receptor 2 [KO:K20909]
107545938  ANTXR1; anthrax toxin receptor 1 [KO:K20909]
107527983  NLRP1; NACHT, LRR and PYD domains-containing protein 1 [KO:K12798]
107540813  PYCARD; apoptosis-associated speck-like protein containing a CARD isoform X1 [KO:K12799]
107532340  caspase-1-like [KO:K01370] [EC:3.4.22.36]
107545431  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
107527777  BCL2L1; bcl-2-like protein 1 [KO:K04570]
107527504  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
107529863  NLRP3; NACHT, LRR and PYD domains-containing protein 3 [KO:K12800]
107532361  PANX1; pannexin-1 [KO:K03443]
107529593  P2RX7; P2X purinoceptor 7 [KO:K05220]
107537463  TRPM2; transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13]
107534881  TRPM7; transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
107524567  TRPV2; transient receptor potential cation channel subfamily V member 2 [KO:K04971]
107527344  CASR; extracellular calcium-sensing receptor [KO:K04612]
107526315  GPRC6A; G-protein coupled receptor family C group 6 member A isoform X1 [KO:K04622]
107542967  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
107536366  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
107536369  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
107539797  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
107529142  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
107525255  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
107541588  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
107525398  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
107545842  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
107523910  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
107545816  MCU; calcium uniporter protein, mitochondrial [KO:K20858]
107529575  2'-5'-oligoadenylate synthase 1-like [KO:K14216] [EC:2.7.7.84]
107529617  2'-5'-oligoadenylate synthase 3-like [KO:K14216] [EC:2.7.7.84]
107545518  2'-5'-oligoadenylate synthase 1-like [KO:K14216] [EC:2.7.7.84]
107546295  RNASEL; 2-5A-dependent ribonuclease [KO:K01165]
107528050  DHX33; putative ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
107541104  MFN1; mitofusin-1 isoform X1 [KO:K21356] [EC:3.6.5.-]
107531559  MFN2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
107542939  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
107531682  RIPK3; receptor-interacting serine/threonine-protein kinase 3 [KO:K08847] [EC:2.7.11.1]
107528369  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
107530827  NAMPT; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
107540071  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
107525738  LOW QUALITY PROTEIN: cytochrome b-245 light chain [KO:K08009]
107529104  TXNIP; thioredoxin-interacting protein [KO:K20910]
107537627  thioredoxin [KO:K03671]
107544767  TXN2; thioredoxin, mitochondrial isoform X1 [KO:K03671]
107540243  NEK7; serine/threonine-protein kinase Nek7 isoform X1 [KO:K20876] [EC:2.7.11.34]
107540220  BRCC3; lys-63-specific deubiquitinase BRCC36 [KO:K11864] [EC:3.4.19.-]
107536915  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
107536502  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
107538972  GPSM3; G-protein-signaling modulator 3 [KO:K15838]
107540798  PYDC1; pyrin domain-containing protein 1 [KO:K12802]
107535793  MEFV; pyrin [KO:K12803]
107538057  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 [KO:K12804]
107533931  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
107542171  FADD; FAS-associated death domain protein [KO:K02373]
107532383  caspase-12-like isoform X1 [KO:K04741] [EC:3.4.22.-]
107532339  caspase recruitment domain-containing protein 18-like [KO:K12806]
107544440  NLRP6; NACHT, LRR and PYD domains-containing protein 6 [KO:K20863]
107540453  NLRP12; NACHT, LRR and PYD domains-containing protein 12 isoform X1 [KO:K20865]
107537803  NAIP; baculoviral IAP repeat-containing protein 1 [KO:K12807]
107541770  NLRC4; NLR family CARD domain-containing protein 4 isoform X1 [KO:K12805]
107534935  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
107535772  GBP5; guanylate-binding protein 5 [KO:K20898]
107535995  TP53BP1; tumor suppressor p53-binding protein 1 isoform X1 [KO:K20915]
107529450  RHOA; transforming protein RhoA [KO:K04513]
107542375  PKN1; serine/threonine-protein kinase N1 isoform X1 [KO:K06071] [EC:2.7.11.13]
107535768  PKN2; serine/threonine-protein kinase N2 [KO:K23691] [EC:2.7.11.13]
107535607  YWHAE; 14-3-3 protein epsilon [KO:K06630]
107535763  guanylate-binding protein 1-like [KO:K20899]
107535765  guanylate-binding protein 4-like [KO:K20899]
107532382  caspase-13-like [KO:K04394] [EC:3.4.22.57 3.4.22.64]
107542742  GSDMD; gasdermin-D [KO:K20917]
107537477  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
107533604  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
107533300  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
107540521  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
107546189  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
107531724  IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]
107537636  TLR4; toll-like receptor 4 [KO:K10160]
107525658  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
107524328  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
107528202  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
107530112  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
mna04010  MAPK signaling pathway
mna04064  NF-kappa B signaling pathway
mna04140  Autophagy - animal
mna04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
LinkDB

DBGET integrated database retrieval system