KEGG   PATHWAY: mlx04621
Entry
mlx04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Mirounga leonina (Southern elephant 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
mlx04621  NOD-like receptor signaling pathway
mlx04621

Organism
Mirounga leonina (Southern elephant seal) [GN:mlx]
Gene
117997460  [KO:K03671]
117997742  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
117997743  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
117997991  NLRP12; LOW QUALITY PROTEIN: NACHT, LRR and PYD domains-containing protein 12 [KO:K20865]
117997999  [KO:K20864]
117998214  CARD8; caspase recruitment domain-containing protein 8 [KO:K12801]
117998287  IRF3; interferon regulatory factor 3 isoform X1 [KO:K05411]
117998660  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
117998734  TXN2; thioredoxin, mitochondrial [KO:K03671]
117998991  [KO:K05414]
117998992  [KO:K05414]
117998993  [KO:K05414]
117998994  IFNB1; interferon beta [KO:K05415]
117999009  [KO:K05414]
117999434  TRIP6; thyroid receptor-interacting protein 6 [KO:K12792]
117999561  [KO:K12799]
117999637  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
117999826  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
117999941  DHX33; ATP-dependent RNA helicase DHX33 isoform X1 [KO:K17820] [EC:5.6.2.6]
117999993  GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
118000105  TRPV2; transient receptor potential cation channel subfamily V member 2 isoform X1 [KO:K04971]
118000148  [KO:K12795]
118000272  TXNIP; thioredoxin-interacting protein [KO:K20910]
118000841  TNFAIP3; tumor necrosis factor alpha-induced protein 3 isoform X1 [KO:K11859] [EC:3.4.19.12]
118001048  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
118001095  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
118001265  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
118001326  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
118001330  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
118001383  GPRC6A; G-protein coupled receptor family C group 6 member A isoform X1 [KO:K04622]
118001551  ATG5; autophagy protein 5 isoform X1 [KO:K08339]
118001625  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
118001922  MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
118002022  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
118002595  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
118002835  [KO:K04734]
118002880  [KO:K04734]
118002967  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 isoform X1 [KO:K12804]
118003092  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
118003249  TP53BP1; TP53-binding protein 1 isoform X1 [KO:K20915]
118003350  TRPM7; transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
118003694  RIPK3; receptor-interacting serine/threonine-protein kinase 3 [KO:K08847] [EC:2.7.11.1]
118003728  RNF31; E3 ubiquitin-protein ligase RNF31 isoform X1 [KO:K11974] [EC:2.3.2.31]
118003729  IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]
118004389  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
118004524  [KO:K05862]
118004956  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
118005110  CAMP; cathelicidin antimicrobial peptide [KO:K13916]
118005176  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
118005236  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
118005289  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
118005670  RHOA; transforming protein RhoA [KO:K04513]
118005930  PKN1; serine/threonine-protein kinase N1 isoform X1 [KO:K06071] [EC:2.7.11.13]
118006360  [KO:K12797]
118006489  [KO:K12797]
118006618  MFN1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
118007038  CASR; extracellular calcium-sensing receptor isoform X1 [KO:K04612]
118007513  NLRC4; LOW QUALITY PROTEIN: NLR family CARD domain-containing protein 4 [KO:K12805]
118007867  IL1B; interleukin-1 beta [KO:K04519]
118007918  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
118008022  ANTXR1; anthrax toxin receptor 1 isoform X1 [KO:K20909]
118008624  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
118008707  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
118008943  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
118009146  [KO:K21421] [EC:1.-.-.-]
118009370  SUGT1; protein SGT1 homolog [KO:K12795]
118009917  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
118009921  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
118010103  [KO:K23126]
118010160  [KO:K14216] [EC:2.7.7.84]
118010368  [KO:K04440] [EC:2.7.11.24]
118010408  ANTXR2; anthrax toxin receptor 2 isoform X1 [KO:K20909]
118010458  CXCL8; interleukin-8 [KO:K10030]
118010849  [KO:K14139] [EC:3.6.5.-]
118011016  [KO:K14216] [EC:2.7.7.84]
118011081  [KO:K10435]
118011244  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
118011247  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
118011281  MAVS; mitochondrial antiviral-signaling protein isoform X1 [KO:K12648]
118011353  BCL2L1; bcl-2-like protein 1 [KO:K04570]
118011363  RBCK1; ranBP-type and C3HC4-type zinc finger-containing protein 1 isoform X1 [KO:K10630] [EC:2.3.2.31]
118011399  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
118011595  IRGM; LOW QUALITY PROTEIN: immunity-related GTPase family M protein [KO:K14139] [EC:3.6.5.-]
118011922  ATG16L1; autophagy-related protein 16-1 isoform X1 [KO:K17890]
118012152  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
118012204  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
118012404  TANK; TRAF family member-associated NF-kappa-B activator isoform X1 [KO:K12650]
118012526  [KO:K15041]
118012582  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
118013143  BIRC3; baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060]
118013146  BIRC2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
118013165  [KO:K04394] [EC:3.4.22.57 3.4.22.64]
118013166  [KO:K04741] [EC:3.4.22.-]
118013235  IL18; interleukin-18 isoform X1 [KO:K05482]
118013310  NLRX1; NLR family member X1 [KO:K12653]
118013440  PANX1; pannexin-1 [KO:K03443]
118013777  AIM2; LOW QUALITY PROTEIN: interferon-inducible protein AIM2 [KO:K12966]
118013952  [KO:K20914]
118014127  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
118014138  [KO:K03671]
118014239  NEK7; serine/threonine-protein kinase Nek7 isoform X1 [KO:K20876] [EC:2.7.11.34]
118014299  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
118014341  BRCC3; lys-63-specific deubiquitinase BRCC36 isoform X1 [KO:K11864] [EC:3.4.19.-]
118014362  RNASEL; LOW QUALITY PROTEIN: 2-5A-dependent ribonuclease [KO:K01165]
118014480  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
118014550  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
118014942  [KO:K04079]
118014994  RIPK2; receptor-interacting serine/threonine-protein kinase 2 [KO:K08846] [EC:2.7.11.1]
118015271  GSDMD; gasdermin-D isoform X1 [KO:K20917]
118015300  SHARPIN; LOW QUALITY PROTEIN: sharpin [KO:K20894]
118015773  TRAF6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
118015997  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
118016059  RELA; transcription factor p65 [KO:K04735]
118016168  FADD; FAS-associated death domain protein [KO:K02373]
118016222  IRF7; interferon regulatory factor 7 [KO:K09447]
118016346  NLRP6; NACHT, LRR and PYD domains-containing protein 6 [KO:K20863]
118016548  ATG12; ubiquitin-like protein ATG12 isoform X1 [KO:K08336]
118016634  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
118016696  STING1; stimulator of interferon genes protein [KO:K12654]
118016850  ERBIN; erbin isoform X1 [KO:K12796]
118017503  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
118017524  CARD9; caspase recruitment domain-containing protein 9 [KO:K12794]
118017761  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
118017830  TXN; thioredoxin isoform X1 [KO:K03671]
118018321  OAS1; 2'-5'-oligoadenylate synthase 1 [KO:K14216] [EC:2.7.7.84]
118018447  P2RX7; P2X purinoceptor 7 [KO:K05220]
118018489  OAS2; LOW QUALITY PROTEIN: 2'-5'-oligoadenylate synthase 2 [KO:K14216] [EC:2.7.7.84]
118018490  OAS3; LOW QUALITY PROTEIN: 2'-5'-oligoadenylate synthase 3 [KO:K14216] [EC:2.7.7.84]
118018829  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
118018831  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
118018938  [KO:K20899]
118019172  [KO:K20899]
118019178  PKN2; serine/threonine-protein kinase N2 [KO:K23691]
118019316  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
118019356  JUN; transcription factor AP-1 [KO:K04448]
118019997  MFN2; mitofusin-2 isoform X1 [KO:K06030] [EC:3.6.5.-]
118020633  NAMPT; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
118020856  IL6; interleukin-6 [KO:K05405]
118020927  NOD1; nucleotide-binding oligomerization domain-containing protein 1 isoform X1 [KO:K08727]
118021446  MCU; calcium uniporter protein, mitochondrial [KO:K20858]
118021749  MEFV; pyrin isoform X1 [KO:K12803]
118021936  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
118022144  CTSB; cathepsin B [KO:K01363] [EC:3.4.22.1]
118022683  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
118022776  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
118023475  [KO:K08009]
118023484  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
118023557  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
118023796  NOD2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165]
118024839  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
118025020  CCL5; C-C motif chemokine 5 [KO:K12499]
118025227  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
118025517  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
118025560  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
118025672  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 isoform X1 [KO:K08341]
118026506  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
118026897  NLRP3; NACHT, LRR and PYD domains-containing protein 3 isoform X1 [KO:K12800]
118026954  TRPM2; transient receptor potential cation channel subfamily M member 2 isoform X1 [KO:K04977] [EC:3.6.1.13]
118027047  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
118027255  TNF; tumor necrosis factor [KO:K03156]
118027301  GPSM3; G-protein-signaling modulator 3 [KO:K15838]
118027395  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
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
mlx04010  MAPK signaling pathway
mlx04064  NF-kappa B signaling pathway
mlx04140  Autophagy - animal
mlx04620  Toll-like receptor signaling pathway
KO pathway
ko04621   

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