KEGG   PATHWAY: nsu04621
Entry
nsu04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Neomonachus schauinslandi (Hawaiian monk seal)
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
nsu04621  NOD-like receptor signaling pathway
nsu04621

Organism
Neomonachus schauinslandi (Hawaiian monk seal) [GN:nsu]
Gene
110569660  MYD88; myeloid differentiation primary response protein MyD88 isoform X2 [KO:K04729]
110570024  IFNAR1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
110570027  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
110570099  [KO:K03671]
110570585  TBK1; serine/threonine-protein kinase TBK1 isoform X2 [KO:K05410] [EC:2.7.11.10]
110570945  ATG16L1; autophagy-related protein 16-1 isoform X2 [KO:K17890]
110570981  PANX1; pannexin-1 [KO:K03443]
110571076  TRPM2; LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13]
110571294  [KO:K04513]
110571680  HSP90AA1; heat shock protein HSP 90-alpha isoform X2 [KO:K04079]
110571685  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
110571840  JAK1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
110571869  TRIP6; thyroid receptor-interacting protein 6 [KO:K12792]
110572155  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
110572826  CARD8; caspase recruitment domain-containing protein 8 [KO:K12801]
110572882  IRF3; interferon regulatory factor 3 isoform X1 [KO:K05411]
110573114  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X2 [KO:K15041]
110573165  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
110573186  [KO:K21421] [EC:1.-.-.-]
110573345  AIM2; LOW QUALITY PROTEIN: interferon-inducible protein AIM2 [KO:K12966]
110573532  IFI16; LOW QUALITY PROTEIN: gamma-interferon-inducible protein 16 [KO:K20914]
110573630  NLRP12; LOW QUALITY PROTEIN: NACHT, LRR and PYD domains-containing protein 12 [KO:K20865]
110573694  NLRP7; LOW QUALITY PROTEIN: NACHT, LRR and PYD domains-containing protein 7 [KO:K20864]
110573917  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
110574060  BRCC3; lys-63-specific deubiquitinase BRCC36 isoform X1 [KO:K11864] [EC:3.4.19.-]
110574091  NEK7; serine/threonine-protein kinase Nek7 [KO:K20876] [EC:2.7.11.34]
110574194  IKBKG; NF-kappa-B essential modulator [KO:K07210]
110574199  RNASEL; LOW QUALITY PROTEIN: 2-5A-dependent ribonuclease [KO:K01165]
110574234  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
110574280  NAMPT; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
110574722  [KO:K03671]
110575086  JUN; transcription factor AP-1 isoform X1 [KO:K04448]
110575133  MFN2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
110575614  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
110575641  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
110575674  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
110575943  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
110575986  RELA; transcription factor p65 [KO:K04735]
110576065  FADD; FAS-associated death domain protein [KO:K02373]
110576276  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
110577152  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
110577285  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
110577355  [KO:K04725] [EC:2.3.2.27]
110577553  RHOA; transforming protein RhoA [KO:K04513]
110577659  [KO:K13916]
110577818  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
110577941  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
110577984  [KO:K15040]
110578100  TXN2; thioredoxin, mitochondrial [KO:K03671]
110578302  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
110578303  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
110578336  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
110578603  [KO:K20910]
110578653  [KO:K04079]
110578687  RIPK2; receptor-interacting serine/threonine-protein kinase 2 isoform X1 [KO:K08846] [EC:2.7.11.1]
110578998  SHARPIN; sharpin isoform X2 [KO:K20894]
110579193  GSDMD; gasdermin-D [KO:K20917]
110579316  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
110579349  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
110579399  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
110579411  MAVS; mitochondrial antiviral-signaling protein isoform X1 [KO:K12648]
110579449  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
110579506  RBCK1; ranBP-type and C3HC4-type zinc finger-containing protein 1 isoform X1 [KO:K10630] [EC:2.3.2.31]
110580018  IL6; interleukin-6 isoform X1 [KO:K05405]
110580034  NOD1; nucleotide-binding oligomerization domain-containing protein 1 isoform X1 [KO:K08727]
110580236  NLRP3; NACHT, LRR and PYD domains-containing protein 3 [KO:K12800]
110580274  [KO:K14139] [EC:3.6.5.-]
110580283  MAPK9; LOW QUALITY PROTEIN: mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
110580296  PKN2; serine/threonine-protein kinase N2 [KO:K23691]
110580324  [KO:K20899]
110580957  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
110581070  DNM1L; dynamin-1-like protein isoform X2 [KO:K17065] [EC:3.6.5.5]
110581097  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
110581233  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
110581279  CARD9; caspase recruitment domain-containing protein 9 [KO:K12794]
110581360  TXN; thioredoxin isoform X1 [KO:K03671]
110581529  TLR4; toll-like receptor 4 [KO:K10160]
110581943  HSP90AB1; heat shock protein HSP 90-beta isoform X1 [KO:K04079]
110582214  IRF7; interferon regulatory factor 7 [KO:K09447]
110582229  NLRP6; NACHT, LRR and PYD domains-containing protein 6 isoform X1 [KO:K20863]
110582413  MFN1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
110582450  CASR; extracellular calcium-sensing receptor isoform X1 [KO:K04612]
110583100  TNFAIP3; tumor necrosis factor alpha-induced protein 3 isoform X1 [KO:K11859] [EC:3.4.19.12]
110583336  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
110583518  GPRC6A; G-protein coupled receptor family C group 6 member A isoform X1 [KO:K04622]
110583654  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X2 [KO:K04427] [EC:2.7.11.25]
110583684  ATG5; autophagy protein 5 isoform X1 [KO:K08339]
110583774  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
110583942  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 [KO:K12804]
110584252  [KO:K23126]
110584589  TRPV2; transient receptor potential cation channel subfamily V member 2 isoform X1 [KO:K04971]
110584666  DHX33; ATP-dependent RNA helicase DHX33 isoform X1 [KO:K17820] [EC:5.6.2.6]
110584690  [KO:K08341]
110584785  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
110584934  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
110585142  NFKBIA; NF-kappa-B inhibitor alpha isoform X2 [KO:K04734]
110585213  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
110585228  RIPK3; receptor-interacting serine/threonine-protein kinase 3 isoform X1 [KO:K08847] [EC:2.7.11.1]
110585585  TP53BP1; TP53-binding protein 1 isoform X2 [KO:K20915]
110585591  IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]
110585592  RNF31; E3 ubiquitin-protein ligase RNF31 isoform X3 [KO:K11974] [EC:2.3.2.31]
110586127  NLRX1; NLR family member X1 isoform X1 [KO:K12653]
110586195  [KO:K04394] [EC:3.4.22.57 3.4.22.64]
110586231  [KO:K04741] [EC:3.4.22.-]
110586282  CARD6; caspase recruitment domain-containing protein 6 [KO:K12797]
110586349  BIRC3; baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060]
110586350  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
110586386  IL18; interleukin-18 isoform X1 [KO:K05482]
110586632  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
110586644  [KO:K03671]
110586713  TNF; tumor necrosis factor [KO:K03156]
110586751  GPSM3; G-protein-signaling modulator 3 isoform X1 [KO:K15838]
110587126  [KO:K05414]
110587130  IFNB1; interferon beta [KO:K05415]
110587131  [KO:K05414]
110587160  IL1B; interleukin-1 beta [KO:K04519]
110587476  NLRC4; LOW QUALITY PROTEIN: NLR family CARD domain-containing protein 4 [KO:K12805]
110587689  SUGT1; protein SGT1 homolog isoform X1 [KO:K12795]
110588052  MEFV; pyrin isoform X1 [KO:K12803]
110588238  OAS1; 2'-5'-oligoadenylate synthase 1 [KO:K14216] [EC:2.7.7.84]
110588261  OAS3; LOW QUALITY PROTEIN: 2'-5'-oligoadenylate synthase 3 [KO:K14216] [EC:2.7.7.84]
110588294  P2RX7; P2X purinoceptor 7 [KO:K05220]
110588305  OAS2; LOW QUALITY PROTEIN: 2'-5'-oligoadenylate synthase 2 [KO:K14216] [EC:2.7.7.84]
110588455  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
110588877  ANTXR1; anthrax toxin receptor 1 [KO:K20909]
110589216  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
110589404  MCU; calcium uniporter protein, mitochondrial [KO:K20858]
110589660  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
110589690  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
110589825  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
110589905  [KO:K12799]
110590011  [KO:K10435]
110590277  NFKBIB; NF-kappa-B inhibitor beta isoform X2 [KO:K02581]
110591049  STING1; stimulator of interferon genes protein [KO:K12654]
110591072  ERBIN; erbin isoform X1 [KO:K12796]
110591098  [KO:K12795]
110591274  ATG12; ubiquitin-like protein ATG12 isoform X1 [KO:K08336]
110591289  VDAC1; voltage-dependent anion-selective channel protein 1 isoform X1 [KO:K05862]
110591323  ANTXR2; anthrax toxin receptor 2 [KO:K20909]
110591342  CXCL8; interleukin-8 [KO:K10030]
110591392  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
110591461  [KO:K05505]
110591463  [KO:K05505]
110591473  [KO:K05505]
110591514  [KO:K08009]
110592138  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
110592166  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
110592370  TANK; TRAF family member-associated NF-kappa-B activator isoform X1 [KO:K12650]
110592805  YWHAE; 14-3-3 protein epsilon [KO:K06630]
110592974  [KO:K14624]
110593073  CCL5; C-C motif chemokine 5 [KO:K12499]
110593479  NOD2; nucleotide-binding oligomerization domain-containing protein 2 [KO:K10165]
110593539  IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
110593674  PKN1; serine/threonine-protein kinase N1 isoform X1 [KO:K06071] [EC:2.7.11.13]
110593684  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X3 [KO:K11219] [EC:2.7.10.2]
110593848  TICAM1; TIR domain-containing adapter molecule 1 isoform X1 [KO:K05842]
110593898  [KO:K03462] [EC:2.4.2.12]
110594190  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B isoform X1 [KO:K10435]
110594214  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
110594300  [KO:K05862]
110594320  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793]
123326492  [KO:K05414]
123326498  [KO:K05414]
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
nsu04010  MAPK signaling pathway
nsu04064  NF-kappa B signaling pathway
nsu04140  Autophagy - animal
nsu04620  Toll-like receptor signaling pathway
KO pathway
ko04621   

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