KEGG   PATHWAY: emac04621
Entry
emac04621                   Pathway                                
Name
NOD-like receptor signaling pathway - Eleginops maclovinus (Patagonian blennie)
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
emac04621  NOD-like receptor signaling pathway
emac04621

Organism
Eleginops maclovinus (Patagonian blennie) [GN:emac]
Gene
134861044  nod1; nucleotide-binding oligomerization domain-containing protein 1 isoform X1 [KO:K08727]
134865454  ripk2; receptor-interacting serine/threonine-protein kinase 2 [KO:K08846] [EC:2.7.11.1]
134870957  ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
134858473  inhibitor of nuclear factor kappa-B kinase subunit alpha-like isoform X1 [KO:K04467] [EC:2.7.11.10]
134870895  inhibitor of nuclear factor kappa-B kinase subunit alpha-like [KO:K04467] [EC:2.7.11.10]
134873220  ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
134881798  nfkbiab; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha b [KO:K04734]
134877093  nfkbiaa; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha a [KO:K04734]
134859597  nfkb1; LOW QUALITY PROTEIN: nuclear factor NF-kappa-B p105 subunit [KO:K02580]
134875789  rela; transcription factor p65 isoform X1 [KO:K04735]
134874249  interleukin-1 beta-like [KO:K04519]
134875426  interleukin-6-like [KO:K05405]
134875099  tnfa; tumor necrosis factor a (TNF superfamily, member 2) [KO:K03156]
134864240  interleukin-8-like [KO:K10030]
134871569  cxcl19; C-X-C motif chemokine 19 [KO:K10030]
134863850  nod2; nucleotide-binding oligomerization domain-containing protein 2 [KO:K10165]
134881884  mitogen-activated protein kinase kinase kinase 7-like [KO:K04427] [EC:2.7.11.25]
134876825  map3k7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
134862741  tab1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
134876983  tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
134869624  tab3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793]
134877926  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
134873272  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
134868533  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
134859047  mapk8a; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
134859865  mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
134870548  mapk8b; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
134865324  mapk14a; mitogen-activated protein kinase 14A isoform X1 [KO:K04441] [EC:2.7.11.24]
134869950  zgc:171775; STKc_p38 domain-containing protein isoform X1 [KO:K04441] [EC:2.7.11.24]
134866220  mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
134879050  mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
134879385  mapk12b; mitogen-activated protein kinase 12b [KO:K04441] [EC:2.7.11.24]
134875755  mapk12a; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
134882213  mapk14b; mitogen-activated protein kinase 14B isoform X1 [KO:K04441] [EC:2.7.11.24]
134868643  june; junE proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
134866042  transcription factor Jun-like [KO:K04448]
134869936  jun; transcription factor AP-1 [KO:K04448]
134880153  atg16l1; autophagy-related protein 16-1 isoform X1 [KO:K17890]
134862296  atg5; autophagy protein 5 [KO:K08339]
134861793  atg12; ubiquitin-like protein ATG12 [KO:K08336]
134863473  gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
134861792  zgc:92606; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
134875439  gabarapl2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
134875655  gabarapa; GABA(A) receptor-associated protein a [KO:K08341]
134864895  map1lc3c; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
134859808  map1lc3cl; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
134875190  map1lc3b; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
134882541  map1lc3a; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
134866263  sugt1; protein SGT1 homolog isoform X1 [KO:K12795]
134866599  ranBP-type and C3HC4-type zinc finger-containing protein 1-like isoform X1 [KO:K20894]
134884207  shrprbck1r; ranBP-type and C3HC4-type zinc finger-containing protein 1 [KO:K10630] [EC:2.3.2.31]
134882566  rbck1; ranBP-type and C3HC4-type zinc finger-containing protein 1 [KO:K10630] [EC:2.3.2.31]
134858125  LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase RNF31-like [KO:K11974] [EC:2.3.2.31]
134866247  rnf31; E3 ubiquitin-protein ligase RNF31 [KO:K11974] [EC:2.3.2.31]
134859884  xiap; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
134875999  trip6; thyroid receptor-interacting protein 6 isoform X1 [KO:K12792]
134868204  erbin; erbin isoform X1 [KO:K12796]
134871736  birc2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
134868188  traf2b; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
134873839  TNF receptor-associated factor 2-like [KO:K03173] [EC:2.3.2.27]
134864101  traf5; TNF receptor-associated factor 5 [KO:K09849]
134863706  traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
134873417  card9; LOW QUALITY PROTEIN: caspase recruitment domain-containing protein 9 [KO:K12794]
134881248  mavs; mitochondrial antiviral-signaling protein [KO:K12648]
134863192  traf3; TNF receptor-associated factor 3 [KO:K03174]
134879216  tbk1; LOW QUALITY PROTEIN: serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
134882420  ikbke; inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
134867507  tank; TRAF family member-associated NF-kappa-B activator [KO:K12650]
134870924  irf3; interferon regulatory factor 3 isoform X1 [KO:K05411]
134878443  irf7; interferon regulatory factor 7 isoform X1 [KO:K09447]
134870800  interferon a3-like [KO:K05414]
134871102  uncharacterized protein LOC134871102 [KO:K05414]
134878662  ifnphi1; interferon phi 1 [KO:K05414]
134879701  nlrx1; NLR family member X1 [KO:K12653]
134868913  antxr1b; anthrax toxin receptor 1 isoform X1 [KO:K20909]
134858727  antxr1d; anthrax toxin receptor 1 [KO:K20909]
134871145  antxr1c; LOW QUALITY PROTEIN: anthrax toxin receptor 1 [KO:K20909]
134868330  anthrax toxin receptor 2-like [KO:K20909]
134873173  antxr1a; anthrax toxin receptor 1 isoform X1 [KO:K20909]
134874129  antxr2a; ANTXR cell adhesion molecule 2a isoform X1 [KO:K20909]
134879956  caspase a-like isoform X1 [KO:K01370] [EC:3.4.22.36]
134865945  bcl2b; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
134861746  bcl2l1; bcl-2-like protein 1 [KO:K04570]
134883569  bcl-2-like protein 1 [KO:K04570]
134863141  ctsba; cathepsin B [KO:K01363] [EC:3.4.22.1]
134864997  pannexin-1-like [KO:K03443]
134880090  pannexin-1-like [KO:K03443]
134874250  p2rx7; P2X purinoceptor 7 isoform X1 [KO:K05220]
134866992  trpm2; transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13]
134862894  trpm7; transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
134872226  casr; extracellular calcium-sensing receptor [KO:K04612]
134861363  gprc6a; G-protein coupled receptor family C group 6 member A [KO:K04622]
134881298  G-protein coupled receptor family C group 6 member A-like [KO:K04622]
134877365  G-protein coupled receptor family C group 6 member A [KO:K04622]
134859199  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1-like isoform X1 [KO:K05858] [EC:3.1.4.11]
134875837  plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
134881970  plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
134876796  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4-like isoform X1 [KO:K05858] [EC:3.1.4.11]
134877086  plcb1l; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
134883603  inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
134882989  inositol 1,4,5-trisphosphate receptor type 1-like isoform X1 [KO:K04958]
134876492  itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
134865125  itpr3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
134872110  vdac1; LOW QUALITY PROTEIN: voltage-dependent anion-selective channel protein 1 [KO:K05862]
134858720  vdac2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
134871239  voltage-dependent anion-selective channel protein 2-like [KO:K15040]
134868313  zgc:56235; voltage-dependent anion-selective channel protein 2-like [KO:K15041]
134873221  vdac3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
134858826  mcu; calcium uniporter protein, mitochondrial isoform X1 [KO:K20858]
134871844  dhx33; ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
134865579  mfn1a; mitofusin-1 isoform X1 [KO:K21356] [EC:3.6.5.-]
134869642  mfn1b; mitofusin-1b [KO:K21356] [EC:3.6.5.-]
134866586  mfn2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
134866131  ripk1l; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
134876137  ripk3; receptor-interacting serine/threonine-protein kinase 3 isoform X1 [KO:K08847] [EC:2.7.11.1]
134882996  ankyrin repeat and protein kinase domain-containing protein 1-like isoform X1 [KO:K08847] [EC:2.7.11.1]
134879179  dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
134873861  si:dkey-32e23.4; LOW QUALITY PROTEIN: dynamin-1-like protein [KO:K17065] [EC:3.6.5.5]
134882661  dnm1l; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
134878942  nampt1; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
134882706  nampt2; nicotinamide phosphoribosyltransferase 2 [KO:K03462] [EC:2.4.2.12]
134860878  cytochrome b-245 heavy chain isoform X1 [KO:K21421] [EC:1.-.-.-]
134863513  cytochrome b-245 light chain [KO:K08009]
134874685  txnipa; thioredoxin interacting protein a [KO:K20910]
134871763  thioredoxin-like [KO:K03671]
134871764  thioredoxin-like [KO:K03671]
134878495  txn2; thioredoxin, mitochondrial [KO:K03671]
134869441  nek7; serine/threonine-protein kinase Nek7 isoform X1 [KO:K20876] [EC:2.7.11.34]
134868245  brcc3; LOW QUALITY PROTEIN: lys-63-specific deubiquitinase [KO:K11864] [EC:3.4.19.-]
134876491  hsp90aa1.2; heat shock protein 90, alpha (cytosolic), class A member 1, tandem duplicate 2 [KO:K04079]
134876789  hsp90aa1.1; heat shock protein HSP 90-alpha 1 [KO:K04079]
134877154  hsp90ab1; heat shock protein HSP 90-beta [KO:K04079]
134863390  proline-serine-threonine phosphatase-interacting protein 1-like isoform X1 [KO:K12804]
134877973  pstpip1a; proline-serine-threonine phosphatase-interacting protein 1a isoform X1 [KO:K12804]
134865670  casp8; caspase-8 [KO:K04398] [EC:3.4.22.61]
134865672  caspase-8-like isoform X1 [KO:K04398] [EC:3.4.22.61]
134866816  casp10; caspase-8 [KO:K04398] [EC:3.4.22.61]
134863816  fadd; protein FADD [KO:K02373]
134882874  protein kinase C delta type-like [KO:K06068] [EC:2.7.11.13]
134882887  prkcda; protein kinase C, delta a [KO:K06068] [EC:2.7.11.13]
134862925  tp53bp1; TP53-binding protein 1 isoform X1 [KO:K20915]
134869584  rho-related GTP-binding protein RhoA-D-like [KO:K04513]
134869593  rho-related GTP-binding protein RhoA-C-like [KO:K04513]
134866513  rho-related GTP-binding protein RhoA-C-like [KO:K04513]
134883347  rhoab; rho-related GTP-binding protein RhoA-B [KO:K04513]
134882594  transforming protein RhoA [KO:K04513]
134864468  pkn1a; serine/threonine-protein kinase N1 isoform X1 [KO:K06071] [EC:2.7.11.13]
134878207  pkn1b; serine/threonine-protein kinase N1b isoform X1 [KO:K06071] [EC:2.7.11.13]
134865785  pkn2a; serine/threonine-protein kinase N2 isoform X1 [KO:K23691] [EC:2.7.11.13]
134871785  14-3-3 protein epsilon [KO:K06630]
134880297  14-3-3 protein epsilon-like [KO:K06630]
134867747  interferon alpha/beta receptor 2-like [KO:K05131]
134869978  jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
134878148  tyk2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
134861047  stat1a; signal transducer and activator of transcription 1a isoform X1 [KO:K11220]
134867158  signal transducer and activator of transcription 1-alpha/beta-like isoform X1 [KO:K11220]
134883587  stat2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
134866425  ticam1; TIR domain-containing adapter molecule 1 [KO:K05842]
134883898  myd88; myeloid differentiation primary response protein MyD88 [KO:K04729]
134876786  irak4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
134860052  sting1; stimulator of interferon genes protein isoform X1 [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
emac04010  MAPK signaling pathway
emac04140  Autophagy - animal
emac04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
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