KEGG   PATHWAY: hoc04621
Entry
hoc04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Hemiscyllium ocellatum (epaulette shark)
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
hoc04621  NOD-like receptor signaling pathway
hoc04621

Organism
Hemiscyllium ocellatum (epaulette shark) [GN:hoc]
Gene
132832207  nucleotide-binding oligomerization domain-containing protein 1-like isoform X1 [KO:K08727]
132832250  nod1; nucleotide-binding oligomerization domain-containing protein 1 [KO:K08727]
132815016  ripk2; receptor-interacting serine/threonine-protein kinase 2 [KO:K08846] [EC:2.7.11.1]
132809022  ikbkg; NF-kappa-B essential modulator [KO:K07210]
132835109  chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
132836867  ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
132836598  NF-kappa-B inhibitor beta-like [KO:K02581]
132817881  nfkbiab; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha b [KO:K04734]
132836599  NF-kappa-B inhibitor alpha-like [KO:K04734]
132833410  nuclear factor NF-kappa-B p105 subunit-like [KO:K02580]
132823388  nuclear factor NF-kappa-B p105 subunit-like isoform X1 [KO:K02580]
132809349  il1b; interleukin-1 beta [KO:K04519]
132829672  interleukin-18-like [KO:K05482]
132829623  uncharacterized protein LOC132829623 isoform X1 [KO:K05482]
132815932  il6; interleukin-6 [KO:K05405]
132832937  lymphotoxin-alpha-like [KO:K03156]
132832938  tumor necrosis factor-like [KO:K03156]
132832939  tumor necrosis factor-like [KO:K03156]
132832940  tumor necrosis factor-like [KO:K03156]
132832724  tumor necrosis factor-like [KO:K03156]
132832738  tumor necrosis factor-like [KO:K03156]
132832745  tumor necrosis factor-like [KO:K03156]
132832823  tumor necrosis factor-like [KO:K03156]
132833321  interleukin-8-like [KO:K10030]
132833328  interleukin-8-like [KO:K10030]
132833369  interleukin-8-like [KO:K10030]
132823202  permeability factor 2-like [KO:K10030]
132820242  interleukin-8-like [KO:K10030]
132820251  interleukin-8-like [KO:K10030]
132820261  interleukin-8-like [KO:K10030]
132820268  interleukin-8-like [KO:K10030]
132820272  interleukin-8-like [KO:K10030]
132820281  interleukin-8-like [KO:K10030]
132832413  map3k7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
132831144  tab1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
132819859  tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
132821030  tab3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
132827194  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
132835028  mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
132823401  mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
132820108  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
132822275  zgc:171775; STKc_p38 domain-containing protein isoform X1 [KO:K04441] [EC:2.7.11.24]
132828395  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
132828396  mitogen-activated protein kinase 13-like [KO:K04441] [EC:2.7.11.24]
132826727  mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
132826728  mitogen-activated protein kinase 12-like [KO:K04441] [EC:2.7.11.24]
132818750  jun; transcription factor AP-1 [KO:K04448]
132821941  autophagy-related protein 16-1-like isoform X1 [KO:K17890]
132816570  autophagy-related protein 16-1-like isoform X1 [KO:K17890]
132831379  atg5; autophagy protein 5 isoform X1 [KO:K08339]
132813073  atg12; ubiquitin-like protein ATG12 [KO:K08336]
132835142  gamma-aminobutyric acid receptor-associated protein [KO:K08341]
132823672  gabarapl2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
132836144  microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
132822794  microtubule-associated proteins 1A/1B light chain 3A isoform X1 [KO:K10435]
132823931  map1lc3b; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
132819280  microtubule-associated proteins 1A/1B light chain 3C-like [KO:K10435]
132816354  sugt1; protein SGT1 homolog isoform X1 [KO:K12795]
132823000  rbck1; ranBP-type and C3HC4-type zinc finger-containing protein 1 [KO:K10630] [EC:2.3.2.31]
132815896  shrprbck1r; ranBP-type and C3HC4-type zinc finger-containing protein 1 [KO:K10630] [EC:2.3.2.31]
132807016  E3 ubiquitin-protein ligase RNF31-like isoform X1 [KO:K11974] [EC:2.3.2.31]
132815444  si:dkey-181m9.8; uncharacterized protein si:dkey-181m9.8 isoform X1 [KO:K11974] [EC:2.3.2.31]
132820159  E3 ubiquitin-protein ligase XIAP-like isoform X1 [KO:K04725] [EC:2.3.2.27]
132835310  trip6; thyroid receptor-interacting protein 6 [KO:K12792]
132822278  erbin; erbin isoform X1 [KO:K12796]
132816336  birc2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
132832429  TNF receptor-associated factor 2-like isoform X1 [KO:K03173] [EC:2.3.2.27]
132832533  TNF receptor-associated factor 2-like [KO:K03173] [EC:2.3.2.27]
132826005  traf2b; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
132819400  TNF receptor-associated factor 5-like [KO:K09849]
132824362  traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
132825953  card9; caspase recruitment domain-containing protein 9 isoform X1 [KO:K12794]
132805532  tnfaip3; tumor necrosis factor alpha-induced protein 3 isoform X1 [KO:K11859] [EC:3.4.19.12]
132829959  tumor necrosis factor alpha-induced protein 3-like isoform X1 [KO:K11859] [EC:3.4.19.12]
132836696  TNF receptor-associated factor 3-like [KO:K03174]
132817941  traf3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
132824857  tbk1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
132828292  serine/threonine-protein kinase TBK1-like isoform X1 [KO:K07211] [EC:2.7.11.10]
132817445  TRAF family member-associated NF-kappa-B activator-like isoform X1 [KO:K12650]
132831443  interferon regulatory factor 3-like [KO:K05411]
132824457  irf7; interferon regulatory factor 7 [KO:K09447]
132830747  ifnphi4; interferon phi 4 [KO:K05414]
132830748  interferon alpha-13-like [KO:K05414]
132829639  nlrx1; NLR family member X1 [KO:K12653]
132834906  anthrax toxin receptor 1-like [KO:K20909]
132837029  anthrax toxin receptor 1-like [KO:K20909]
132816505  antxr2a; ANTXR cell adhesion molecule 2a [KO:K20909]
132830292  caspase-1-like [KO:K01370] [EC:3.4.22.36]
132815631  apoptosis regulator Bcl-2-like [KO:K02161]
132822688  bcl2l1; bcl-2-like protein 1 isoform X1 [KO:K04570]
132819288  cathepsin B-like [KO:K01363] [EC:3.4.22.1]
132816688  panx1a; pannexin-1a isoform X1 [KO:K03443]
132817675  trpm2; LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13]
132834324  trpm7; transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
132820790  casr; extracellular calcium-sensing receptor [KO:K04612]
132832211  G-protein coupled receptor family C group 6 member A-like isoform X1 [KO:K04622]
132835428  G-protein coupled receptor family C group 6 member A-like [KO:K04622]
132835444  G-protein coupled receptor family C group 6 member A-like [KO:K04622]
132805786  gprc6a; G-protein coupled receptor family C group 6 member A [KO:K04622]
132817808  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2-like [KO:K05858] [EC:3.1.4.11]
132836104  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3-like isoform X1 [KO:K05858] [EC:3.1.4.11]
132819522  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
132819886  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
132822387  itpr1b; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
132826793  itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
132828404  itpr3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
132823437  vdac1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
132835111  vdac2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
132837033  vdac3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
132835015  mcu; calcium uniporter protein, mitochondrial [KO:K20858]
132827453  uncharacterized protein LOC132827453 [KO:K14216] [EC:2.7.7.84]
132818933  2-5A-dependent ribonuclease-like [KO:K01165]
132830450  dhx33; ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
132821885  mitofusin-1-like [KO:K21356] [EC:3.6.5.-]
132833518  mfn2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
132832326  ripk1l; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
132809025  si:dkey-32e23.4; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
132824970  dynamin-1-like protein [KO:K17065] [EC:3.6.5.5]
132822481  nampt2; LOW QUALITY PROTEIN: nicotinamide phosphoribosyltransferase 2 [KO:K03462] [EC:2.4.2.12]
132824988  nampt1; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
132820484  cytochrome b-245 heavy chain-like [KO:K21421] [EC:1.-.-.-]
132820754  cytochrome b-245 heavy chain-like [KO:K21421] [EC:1.-.-.-]
132823683  cytochrome b-245 light chain [KO:K08009]
132811103  thioredoxin-interacting protein-like [KO:K20910]
132836633  thioredoxin-like [KO:K03671]
132836634  thioredoxin-like [KO:K03671]
132836635  thioredoxin-like [KO:K03671]
132831323  txn2; thioredoxin, mitochondrial [KO:K03671]
132824735  thioredoxin-like [KO:K03671]
132828753  thioredoxin-like isoform X1 [KO:K03671]
132818989  nek7; serine/threonine-protein kinase Nek7 [KO:K20876] [EC:2.7.11.34]
132820485  brcc3; lys-63-specific deubiquitinase isoform X1 [KO:K11864] [EC:3.4.19.-]
132830173  heat shock protein HSP 90-beta [KO:K04079]
132818344  heat shock protein HSP 90-alpha [KO:K04079]
132834760  proline-serine-threonine phosphatase-interacting protein 1-like isoform X1 [KO:K12804]
132824517  fadd; protein FADD [KO:K02373]
132835212  baculoviral IAP repeat-containing protein 1-like [KO:K12807]
132835225  baculoviral IAP repeat-containing protein 1-like [KO:K12807]
132819694  NLR family CARD domain-containing protein 4-like [KO:K12805]
132822200  protein kinase C delta type-like [KO:K06068] [EC:2.7.11.13]
132834863  tp53bp1; TP53-binding protein 1 isoform X1 [KO:K20915]
132822248  transforming protein RhoA [KO:K04513]
132829929  rho-related GTP-binding protein RhoB-like [KO:K04513]
132836063  pkn1a; serine/threonine-protein kinase N2 isoform X1 [KO:K06071] [EC:2.7.11.13]
132819182  serine/threonine-protein kinase N2-like [KO:K23691] [EC:2.7.11.13]
132830513  ywhae1; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide 1 [KO:K06630]
132832374  guanylate-binding protein 1-like [KO:K20899]
132834016  guanylate-binding protein 1-like [KO:K20899]
132834027  guanylate-binding protein 1-like isoform X1 [KO:K20899]
132819061  jak1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
132836005  tyk2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
132805837  signal transducer and activator of transcription 1-like [KO:K11220]
132817161  signal transducer and activator of transcription 1-alpha/beta-like [KO:K11220]
132807017  interferon regulatory factor 8-like [KO:K04693]
132828975  ticam1; TIR domain-containing adapter molecule 1 [KO:K05842]
132815068  myd88; myeloid differentiation primary response protein MyD88 [KO:K04729]
132824917  interleukin-1 receptor-associated kinase 4-like [KO:K04733] [EC:2.7.11.1]
132823069  sting1; 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
hoc04010  MAPK signaling pathway
hoc04140  Autophagy - animal
hoc04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
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