KEGG   PATHWAY: cdk04621
Entry
cdk04621                    Pathway                                
Name
NOD-like receptor signaling pathway - Camelus dromedarius (Arabian camel)
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
cdk04621  NOD-like receptor signaling pathway
cdk04621

Organism
Camelus dromedarius (Arabian camel) [GN:cdk]
Gene
105095844  NOD1; nucleotide-binding oligomerization domain-containing protein 1 isoform X1 [KO:K08727]
105087544  RIPK2; receptor-interacting serine/threonine-protein kinase 2 [KO:K08846] [EC:2.7.11.1]
105106603  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
105084316  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
105086448  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
105093305  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
105092140  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
105089560  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
105102595  RELA; transcription factor p65 isoform X1 [KO:K04735]
105093155  IL1B; interleukin-1 beta [KO:K04519]
105094167  IL18; interleukin-18 isoform X1 [KO:K05482]
105095065  IL6; interleukin-6 [KO:K05405]
105087473  TNF; tumor necrosis factor [KO:K03156]
105091344  CXCL8; interleukin-8 [KO:K10030]
105091368  permeability factor 2 [KO:K05505]
116158243  growth-regulated alpha protein-like [KO:K05505]
116158247  growth-regulated alpha protein-like [KO:K05505]
105088228  C-C motif chemokine 2 [KO:K14624]
105097869  CCL5; C-C motif chemokine 5 [KO:K12499]
116158223  uncharacterized protein LOC116158223 [KO:K13916]
105105181  antibacterial peptide PMAP-23-like [KO:K13916]
116158224  LOW QUALITY PROTEIN: antibacterial peptide PMAP-23-like [KO:K13916]
105106592  antibacterial peptide PMAP-23-like [KO:K13916]
116158346  LOW QUALITY PROTEIN: cathelin-like [KO:K13916]
116158347  antibacterial peptide PMAP-37-like [KO:K13916]
116149219  beta-defensin 103A-like [KO:K23126]
105097522  NOD2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165]
105095522  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
105091931  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
105100906  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
105089299  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793]
105095214  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105102769  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
105091591  MAPK10; mitogen-activated protein kinase 10 isoform X4 [KO:K04440] [EC:2.7.11.24]
105094659  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
105100625  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
105101337  MAPK13; mitogen-activated protein kinase 13 isoform X2 [KO:K04441] [EC:2.7.11.24]
105101338  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
105090355  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
105090356  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
105092850  JUN; LOW QUALITY PROTEIN: transcription factor AP-1 [KO:K04448]
105105240  ATG16L1; autophagy-related protein 16-1 isoform X1 [KO:K17890]
105097135  ATG5; autophagy protein 5 isoform X1 [KO:K08339]
105095367  ATG12; ubiquitin-like protein ATG12 isoform X1 [KO:K08336]
105084211  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 isoform X1 [KO:K08341]
105103045  GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
105094216  gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
105084948  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
105104671  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
105098492  SUGT1; protein SGT1 homolog [KO:K12795]
105105007  SHARPIN; sharpin isoform X1 [KO:K20894]
105100807  RBCK1; ranBP-type and C3HC4-type zinc finger-containing protein 1 isoform X2 [KO:K10630] [EC:2.3.2.31]
105102415  RNF31; E3 ubiquitin-protein ligase RNF31 [KO:K11974] [EC:2.3.2.31]
105098886  XIAP; E3 ubiquitin-protein ligase XIAP isoform X2 [KO:K04725] [EC:2.3.2.27]
105084323  CARD6; LOW QUALITY PROTEIN: caspase recruitment domain-containing protein 6 [KO:K12797]
105088567  TRIP6; thyroid receptor-interacting protein 6 [KO:K12792]
105084754  ERBIN; erbin isoform X1 [KO:K12796]
105087177  BIRC2; baculoviral IAP repeat-containing protein 2 [KO:K16060]
105087178  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
105106196  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
105099319  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
105106823  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
105106036  CARD9; caspase recruitment domain-containing protein 9 [KO:K12794]
105092086  TNFAIP3; tumor necrosis factor alpha-induced protein 3 isoform X2 [KO:K11859] [EC:3.4.19.12]
105096015  MAVS; mitochondrial antiviral-signaling protein isoform X1 [KO:K12648]
105103454  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
105089261  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
105098613  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
105093693  TANK; TRAF family member-associated NF-kappa-B activator isoform X1 [KO:K12650]
105100198  IRF3; interferon regulatory factor 3 isoform X1 [KO:K05411]
105105431  IRF7; interferon regulatory factor 7 [KO:K09447]
105105541  interferon alpha-1-like [KO:K05414]
105105457  LOW QUALITY PROTEIN: interferon alpha-1-like [KO:K05414]
105105461  LOW QUALITY PROTEIN: interferon alpha-14-like [KO:K05414]
105095932  interferon alpha-14-like [KO:K05414]
116152603  interferon alpha-14-like [KO:K05414]
116152604  interferon alpha-14-like [KO:K05414]
105095933  IFNB1; interferon beta [KO:K05415]
105090145  NLRX1; NLR family member X1 [KO:K12653]
105088916  ANTXR1; anthrax toxin receptor 1 [KO:K20909]
105091771  ANTXR2; anthrax toxin receptor 2 isoform X3 [KO:K20909]
105104784  NLRP1; NACHT, LRR and PYD domains-containing protein 1 isoform X5 [KO:K12798]
105089723  apoptosis-associated speck-like protein containing a CARD isoform X1 [KO:K12799]
105100418  CASP1; caspase-1 [KO:K01370] [EC:3.4.22.36]
105088999  BCL2; LOW QUALITY PROTEIN: apoptosis regulator Bcl-2 [KO:K02161]
105100821  BCL2L1; bcl-2-like protein 1 isoform X2 [KO:K04570]
105101888  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
105104203  NLRP3; NACHT, LRR and PYD domains-containing protein 3 isoform X1 [KO:K12800]
105096544  PANX1; pannexin-1 [KO:K03443]
105102501  P2RX7; P2X purinoceptor 7 [KO:K05220]
105103997  TRPM2; transient receptor potential cation channel subfamily M member 2 isoform X1 [KO:K04977] [EC:3.6.1.13]
105102459  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
105085080  TRPV2; transient receptor potential cation channel subfamily V member 2 isoform X1 [KO:K04971]
105090302  CASR; extracellular calcium-sensing receptor [KO:K04612]
105088336  GPRC6A; G-protein coupled receptor family C group 6 member A [KO:K04622]
105101292  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
105101500  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
105101545  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X4 [KO:K05858] [EC:3.1.4.11]
105096910  PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
105093156  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X2 [KO:K04958]
105102013  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
105101373  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
105090242  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
105092440  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
105086434  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
105092475  MCU; calcium uniporter protein, mitochondrial isoform X1 [KO:K20858]
105101979  OAS1; 2'-5'-oligoadenylate synthase 1 [KO:K14216] [EC:2.7.7.84]
105096236  RNASEL; 2-5A-dependent ribonuclease isoform X1 [KO:K01165]
105104780  DHX33; ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
105085925  MFN1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
105107041  MFN2; mitofusin-2 isoform X1 [KO:K06030] [EC:3.6.5.-]
105087344  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
105102433  RIPK3; receptor-interacting serine/threonine-protein kinase 3 isoform X1 [KO:K08847] [EC:2.7.11.1]
105084508  DNM1L; dynamin-1-like protein isoform X6 [KO:K17065] [EC:3.6.5.5]
105093030  NAMPT; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
105101594  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
105104683  cytochrome b-245 light chain isoform X3 [KO:K08009]
105105888  TXNIP; thioredoxin-interacting protein [KO:K20910]
105087938  TXN; thioredoxin [KO:K03671]
105105211  TXN2; thioredoxin, mitochondrial [KO:K03671]
105090827  NEK7; serine/threonine-protein kinase Nek7 isoform X1 [KO:K20876] [EC:2.7.11.34]
105096837  BRCC3; lys-63-specific deubiquitinase BRCC36 isoform X3 [KO:K11864] [EC:3.4.19.-]
105088639  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
105103462  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
105090859  GPSM3; G-protein-signaling modulator 3 [KO:K15838]
105099760  MEFV; pyrin [KO:K12803]
105087228  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 [KO:K12804]
105099181  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
105104389  FADD; LOW QUALITY PROTEIN: FAS-associated death domain protein [KO:K02373]
105105740  NLRP6; NACHT, LRR and PYD domains-containing protein 6 isoform X2 [KO:K20863]
105106335  NLRP7; LOW QUALITY PROTEIN: NACHT, LRR and PYD domains-containing protein 7 [KO:K20864]
105091262  NLRP12; NACHT, LRR and PYD domains-containing protein 12 [KO:K20865]
105084774  NAIP; baculoviral IAP repeat-containing protein 1 isoform X1 [KO:K12807]
105095602  NLRC4; NLR family CARD domain-containing protein 4 isoform X1 [KO:K12805]
105093214  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
105085616  guanylate-binding protein 5-like isoform X1 [KO:K20898]
105086559  AIM2; LOW QUALITY PROTEIN: interferon-inducible protein AIM2 [KO:K12966]
105086558  IFI16; gamma-interferon-inducible protein 16 [KO:K20914]
105101725  TP53BP1; TP53-binding protein 1 isoform X1 [KO:K20915]
105087723  RHOA; transforming protein RhoA [KO:K04513]
105105969  PKN1; serine/threonine-protein kinase N1 [KO:K06071] [EC:2.7.11.13]
105084522  PKN2; serine/threonine-protein kinase N2 isoform X1 [KO:K23691] [EC:2.7.11.13]
105088124  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
105084527  guanylate-binding protein 1-like [KO:K20899]
105084533  guanylate-binding protein 7-like [KO:K20899]
105102711  guanylate-binding protein 4-like [KO:K20899]
105102014  guanylate-binding protein 6-like [KO:K20899]
116156951  guanylate-binding protein 1-like [KO:K20899]
105100419  caspase-13 [KO:K04394] [EC:3.4.22.57 3.4.22.64]
105105691  GSDMD; gasdermin-D isoform X1 [KO:K20917]
105089868  IFNAR1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
105089871  IFNAR2; interferon alpha/beta receptor 2 [KO:K05131]
105107124  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
105087637  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
105088783  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X2 [KO:K11220]
105086362  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
105102416  IRF9; interferon regulatory factor 9 [KO:K04693]
105104576  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
105091750  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
105090692  MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
105097094  IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
105098117  STING1; stimulator of interferon response cGAMP interactor 1 [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
cdk04010  MAPK signaling pathway
cdk04064  NF-kappa B signaling pathway
cdk04140  Autophagy - animal
cdk04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
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