KEGG   PATHWAY: hai04621
Entry
hai04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Hipposideros armiger (great roundleaf 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
hai04621  NOD-like receptor signaling pathway
hai04621

Organism
Hipposideros armiger (great roundleaf bat) [GN:hai]
Gene
109381372  NOD1; nucleotide-binding oligomerization domain-containing protein 1 isoform X1 [KO:K08727]
109387588  RIPK2; receptor-interacting serine/threonine-protein kinase 2 [KO:K08846] [EC:2.7.11.1]
109377344  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
109379632  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
109386279  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
109395326  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
109383860  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
109372541  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
109384322  RELA; transcription factor p65 isoform X1 [KO:K04735]
109393524  IL1B; interleukin-1 beta isoform X1 [KO:K04519]
109388707  IL18; interleukin-18 [KO:K05482]
109387871  IL6; interleukin-6 [KO:K05405]
109373073  TNF; tumor necrosis factor isoform X1 [KO:K03156]
109394819  CXCL8; interleukin-8 [KO:K10030]
109371836  growth-regulated protein homolog gamma-like [KO:K05505]
109394813  growth-regulated protein homolog gamma-like [KO:K05505]
109371834  growth-regulated protein homolog gamma-like [KO:K05505]
109373168  CCL5; C-C motif chemokine 5 [KO:K12499]
109375616  CAMP; cathelicidin antimicrobial peptide [KO:K13916]
109386808  defensin-5-like isoform X1 [KO:K05230]
109378345  neutrophil defensin 4-like [KO:K05230]
109386810  beta-defensin 103-like [KO:K23126]
109383342  NOD2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165]
109389465  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
109392251  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
109380888  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
109374428  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
109385803  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
109394900  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
109392215  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
109377948  mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
109392748  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
109395979  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
109395980  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
109396629  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
109396630  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
109371251  JUN; transcription factor AP-1 [KO:K04448]
109371257  transcription factor AP-1 [KO:K04448]
109374494  ATG16L1; autophagy-related protein 16-1 isoform X1 [KO:K17890]
109395096  ATG5; autophagy protein 5 [KO:K08339]
109387405  ATG12; ubiquitin-like protein ATG12 [KO:K08336]
109394622  GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
109384803  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
109375276  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 isoform X1 [KO:K08341]
109378793  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B isoform X1 [KO:K10435]
109389617  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
109385347  microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
109385358  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
109386829  SUGT1; protein SGT1 homolog [KO:K12795]
109375087  SHARPIN; sharpin isoform X1 [KO:K20894]
109384455  RBCK1; ranBP-type and C3HC4-type zinc finger-containing protein 1 isoform X1 [KO:K10630] [EC:2.3.2.31]
109393686  RNF31; E3 ubiquitin-protein ligase RNF31 isoform X1 [KO:K11974] [EC:2.3.2.31]
109390892  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
109376165  CARD6; caspase recruitment domain-containing protein 6 [KO:K12797]
109374922  TRIP6; thyroid receptor-interacting protein 6 [KO:K12792]
109388059  ERBIN; erbin isoform X1 [KO:K12796]
109375115  baculoviral IAP repeat-containing protein 2-like [KO:K16060]
109375125  BIRC3; baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060]
109376360  LOW QUALITY PROTEIN: putative inhibitor of apoptosis [KO:K16060]
109381672  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
109379157  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
109381153  TRAF6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
109381408  CARD9; caspase recruitment domain-containing protein 9 [KO:K12794]
109385645  TNFAIP3; tumor necrosis factor alpha-induced protein 3 isoform X1 [KO:K11859] [EC:3.4.19.12]
109383826  MAVS; mitochondrial antiviral-signaling protein [KO:K12648]
109381072  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
109381695  TBK1; LOW QUALITY PROTEIN: serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
109386512  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
109379875  TANK; TRAF family member-associated NF-kappa-B activator isoform X1 [KO:K12650]
109391076  IRF3; interferon regulatory factor 3 [KO:K05411]
109375630  IRF7; interferon regulatory factor 7 isoform X1 [KO:K09447]
109374670  interferon alpha-4-like [KO:K05414]
109396418  IFNB1; interferon beta [KO:K05415]
109393900  NLRX1; NLR family member X1 isoform X1 [KO:K12653]
109385418  ANTXR1; anthrax toxin receptor 1 [KO:K20909]
109373531  ANTXR2; anthrax toxin receptor 2 [KO:K20909]
109394604  NLRP1; NACHT, LRR and PYD domains-containing protein 1 [KO:K12798]
109374176  PYCARD; apoptosis-associated speck-like protein containing a CARD [KO:K12799]
109377701  CASP1; caspase-1 [KO:K01370] [EC:3.4.22.36]
109390784  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
109384429  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
109373362  bcl-2-like protein 1 isoform X1 [KO:K04570]
109379548  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
109377395  NLRP3; NACHT, LRR and PYD domains-containing protein 3 [KO:K12800]
109390556  PANX1; pannexin-1 [KO:K03443]
109386041  P2RX7; P2X purinoceptor 7 [KO:K05220]
109372111  TRPM2; transient receptor potential cation channel subfamily M member 2 isoform X1 [KO:K04977] [EC:3.6.1.13]
109394179  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
109382203  TRPV2; transient receptor potential cation channel subfamily V member 2 [KO:K04971]
109386938  CASR; extracellular calcium-sensing receptor [KO:K04612]
109396449  GPRC6A; LOW QUALITY PROTEIN: G-protein coupled receptor family C group 6 member A [KO:K04622]
109378976  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
109378977  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
109384329  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
109383976  PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
109395800  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
109372316  inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
109392407  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
109382625  VDAC1; voltage-dependent anion-selective channel protein 1 isoform X1 [KO:K05862]
109372707  VDAC2; voltage-dependent anion-selective channel protein 2 isoform X1 [KO:K15040]
109392355  voltage-dependent anion-selective channel protein 2-like isoform X1 [KO:K15040]
109386288  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
109372784  MCU; calcium uniporter protein, mitochondrial [KO:K20858]
109382229  LOW QUALITY PROTEIN: 2'-5'-oligoadenylate synthase 3-like [KO:K14216] [EC:2.7.7.84]
109382257  2'-5'-oligoadenylate synthase 1-like [KO:K14216] [EC:2.7.7.84]
109379163  RNASEL; 2-5A-dependent ribonuclease [KO:K01165]
109394667  DHX33; putative ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:3.6.4.13]
109372685  MFN1; mitofusin-1 isoform X1 [KO:K21356] [EC:3.6.5.-]
109381283  MFN2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
109396595  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
109393623  RIPK3; receptor-interacting serine/threonine-protein kinase 3 isoform X1 [KO:K08847] [EC:2.7.11.1]
109372452  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
109392065  NAMPT; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
109376547  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
109389148  cytochrome b-245 light chain [KO:K08009]
109373709  TXNIP; thioredoxin-interacting protein [KO:K20910]
109379344  TXN; thioredoxin [KO:K03671]
109372399  TXN2; thioredoxin, mitochondrial [KO:K03671]
109380507  NEK7; serine/threonine-protein kinase Nek7 isoform X1 [KO:K20876] [EC:2.7.11.34]
109373622  BRCC3; lys-63-specific deubiquitinase BRCC36 isoform X1 [KO:K11864] [EC:3.4.19.-]
109381021  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
109382930  HSP90AB1; LOW QUALITY PROTEIN: heat shock protein HSP 90-beta [KO:K04079]
109373116  GPSM3; G-protein-signaling modulator 3 [KO:K15838]
109374170  PYDC1; pyrin domain-containing protein 1 [KO:K12802]
109376759  MEFV; pyrin isoform X1 [KO:K12803]
109375337  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 [KO:K12804]
109379228  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
109389315  FADD; FAS-associated death domain protein [KO:K02373]
109377699  caspase-12-like isoform X1 [KO:K04741] [EC:3.4.22.-]
109378077  NLRP6; NACHT, LRR and PYD domains-containing protein 6 isoform X1 [KO:K20863]
109373753  NACHT, LRR and PYD domains-containing protein 7-like [KO:K20864]
109372461  NLRP12; NACHT, LRR and PYD domains-containing protein 12 isoform X1 [KO:K20865]
109375674  NAIP; baculoviral IAP repeat-containing protein 1 isoform X1 [KO:K12807]
109388792  NLRC4; NLR family CARD domain-containing protein 4 isoform X1 [KO:K12805]
109395953  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
109378099  guanylate-binding protein 2-like [KO:K20897]
109377796  LOW QUALITY PROTEIN: guanylate-binding protein 2-like [KO:K20897]
109392987  GBP5; guanylate-binding protein 5 [KO:K20898]
109383996  TP53BP1; tumor suppressor p53-binding protein 1 [KO:K20915]
109376114  RHOA; transforming protein RhoA isoform X1 [KO:K04513]
109394244  PKN1; serine/threonine-protein kinase N1 [KO:K06071] [EC:2.7.11.13]
109376724  PKN2; serine/threonine-protein kinase N2 isoform X1 [KO:K23691] [EC:2.7.11.13]
109386914  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
109378100  guanylate-binding protein 4-like isoform X1 [KO:K20899]
109377797  guanylate-binding protein 4-like [KO:K20899]
109377696  caspase-1-like [KO:K04394] [EC:3.4.22.57 3.4.22.64]
109377700  caspase-13-like [KO:K04394] [EC:3.4.22.57 3.4.22.64]
109390835  GSDMD; gasdermin-D [KO:K20917]
109373231  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
109373246  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
109384938  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
109391605  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
109393276  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
109396910  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
109393688  IRF9; interferon regulatory factor 9 [KO:K04693]
109385740  TLR4; toll-like receptor 4 [KO:K10160]
109388568  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
109393491  MYD88; myeloid differentiation primary response protein MyD88 [KO:K04729]
109388403  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
109393185  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
  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
  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
  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
  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
  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
  Authors
Murray PJ
  Title
Beyond peptidoglycan for Nod2.
  Journal
Nat Immunol 10:1053-4 (2009)
DOI:10.1038/ni1009-1053
Reference
  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
  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
  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
  Authors
Man SM, Kanneganti TD
  Title
Regulation of inflammasome activation.
  Journal
Immunol Rev 265:6-21 (2015)
DOI:10.1111/imr.12296
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
hai04010  MAPK signaling pathway
hai04064  NF-kappa B signaling pathway
hai04140  Autophagy - animal
hai04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
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