KEGG   PATHWAY: pcad04621
Entry
pcad04621                   Pathway                                
Name
NOD-like receptor signaling pathway - Physeter catodon (sperm whale)
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
pcad04621  NOD-like receptor signaling pathway
pcad04621

Organism
Physeter catodon (sperm whale) [GN:pcad]
Gene
102982535  NOD1; nucleotide-binding oligomerization domain-containing protein 1 isoform X3 [KO:K08727]
102989713  RIPK2; receptor-interacting serine/threonine-protein kinase 2 isoform X1 [KO:K08846] [EC:2.7.11.1]
114485485  NF-kappa-B essential modulator-like isoform X1 [KO:K07210]
102980964  IKBKG; NF-kappa-B essential modulator [KO:K07210]
102977668  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X2 [KO:K04467] [EC:2.7.11.10]
102976706  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
102995931  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
102973672  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
102981135  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
102974198  RELA; transcription factor p65 isoform X1 [KO:K04735]
102994188  IL1B; interleukin-1 beta [KO:K04519]
102976313  IL18; interleukin-18 [KO:K05482]
102980126  IL6; interleukin-6 [KO:K05405]
102983069  TNF; tumor necrosis factor [KO:K03156]
102979960  CXCL8; interleukin-8 [KO:K10030]
102981375  growth-regulated protein homolog gamma-like isoform X1 [KO:K05505]
112062060  growth-regulated protein homolog beta [KO:K05505]
102982314  growth-regulated protein homolog beta [KO:K05505]
102990067  monocyte chemotactic protein 1B [KO:K14624]
102975625  CCL5; C-C motif chemokine 5 [KO:K12499]
102992994  cathelicidin-5-like [KO:K13916]
102973809  LOW QUALITY PROTEIN: cathelicidin-1-like [KO:K13916]
112064927  antibacterial protein PR-39-like [KO:K13916]
102993821  LOW QUALITY PROTEIN: uncharacterized protein LOC102993821 [KO:K13916]
102973523  protegrin-5-like [KO:K13916]
112062148  beta-defensin 103A-like [KO:K23126]
102992305  NOD2; LOW QUALITY PROTEIN: nucleotide-binding oligomerization domain-containing protein 2 [KO:K10165]
102995727  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
102983590  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X3 [KO:K04403]
102996495  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
102995606  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793]
102984305  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102989074  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102996353  MAPK8; mitogen-activated protein kinase 8 isoform X3 [KO:K04440] [EC:2.7.11.24]
102977417  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
102984741  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
102977531  MAPK12; mitogen-activated protein kinase 12 isoform X3 [KO:K04441] [EC:2.7.11.24]
102989111  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
102990302  MAPK13; mitogen-activated protein kinase 13 isoform X3 [KO:K04441] [EC:2.7.11.24]
102977994  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
102975458  JUN; transcription factor Jun [KO:K04448]
102992920  ATG16L1; autophagy-related protein 16-1 [KO:K17890]
114485325  autophagy-related protein 16-1-like [KO:K17890]
102991253  ATG5; autophagy protein 5 isoform X1 [KO:K08339]
102980295  ATG12; ubiquitin-like protein ATG12 [KO:K08336]
102996693  GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
102994264  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 isoform X1 [KO:K08341]
102973481  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 isoform X1 [KO:K08341]
102979044  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
102984592  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
102984613  SUGT1; protein SGT1 homolog [KO:K12795]
102988834  SHARPIN; sharpin isoform X2 [KO:K20894]
102977045  RBCK1; ranBP-type and C3HC4-type zinc finger-containing protein 1 isoform X3 [KO:K10630] [EC:2.3.2.31]
102993320  RNF31; E3 ubiquitin-protein ligase RNF31 isoform X3 [KO:K11974] [EC:2.3.2.31]
102978378  XIAP; E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
102974119  TRIP6; thyroid receptor-interacting protein 6 isoform X1 [KO:K12792]
102995507  ERBIN; erbin isoform X2 [KO:K12796]
102981700  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
102981991  BIRC2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
102996185  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
102986959  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
102993207  TRAF6; TNF receptor-associated factor 6 isoform X2 [KO:K03175] [EC:2.3.2.27]
102983532  CARD9; caspase recruitment domain-containing protein 9 isoform X3 [KO:K12794]
102991611  TNFAIP3; tumor necrosis factor alpha-induced protein 3 isoform X1 [KO:K11859] [EC:3.4.19.12]
102978512  AP5S1; AP-5 complex subunit sigma-1 isoform X2 [KO:K12648]
102974816  TRAF3; TNF receptor-associated factor 3 [KO:K03174]
102994775  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
102994478  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
102975438  TANK; TRAF family member-associated NF-kappa-B activator isoform X2 [KO:K12650]
102986279  IRF3; interferon regulatory factor 3 isoform X1 [KO:K05411]
102996452  IRF7; interferon regulatory factor 7 isoform X1 [KO:K09447]
112065747  interferon alpha-1-like [KO:K05414]
102980314  interferon alpha-1-like [KO:K05414]
102990155  IFNB1; interferon beta [KO:K05415]
102992829  NLRX1; NLR family member X1 isoform X1 [KO:K12653]
102987673  ANTXR1; anthrax toxin receptor 1 isoform X1 [KO:K20909]
102996122  ANTXR2; anthrax toxin receptor 2 isoform X1 [KO:K20909]
102996987  NLRP1; LOW QUALITY PROTEIN: NACHT, LRR and PYD domains-containing protein 1 [KO:K12798]
102986634  apoptosis-associated speck-like protein containing a CARD [KO:K12799]
102995954  LOW QUALITY PROTEIN: apoptosis-associated speck-like protein containing a CARD [KO:K12799]
102982110  CASP1; caspase-1 [KO:K01370] [EC:3.4.22.36]
102987942  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
102980439  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
102983822  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
102976103  NLRP3; NACHT, LRR and PYD domains-containing protein 3 [KO:K12800]
102993007  PANX1; pannexin-1 [KO:K03443]
102974552  P2RX7; P2X purinoceptor 7 [KO:K05220]
114486690  TRPM2; transient receptor potential cation channel subfamily M member 2 isoform X2 [KO:K04977] [EC:3.6.1.13]
102976422  transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13]
102981704  TRPM7; transient receptor potential cation channel subfamily M member 7 isoform X1 [KO:K04982] [EC:2.7.11.1]
102983226  TRPV2; transient receptor potential cation channel subfamily V member 2 [KO:K04971]
102978777  CASR; extracellular calcium-sensing receptor [KO:K04612]
102979846  GPRC6A; LOW QUALITY PROTEIN: G-protein coupled receptor family C group 6 member A [KO:K04622]
102995357  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X2 [KO:K05858] [EC:3.1.4.11]
102985636  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
102974165  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
102983015  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
102984842  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
102992034  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
102991951  VDAC1; voltage-dependent anion-selective channel protein 1 isoform X2 [KO:K05862]
102974857  LOW QUALITY PROTEIN: voltage-dependent anion-selective channel protein 1-like [KO:K05862]
102992414  voltage-dependent anion-selective channel protein 1-like [KO:K05862]
102995871  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
102975937  VDAC3; voltage-dependent anion-selective channel protein 3 [KO:K15041]
112066461  voltage-dependent anion-selective channel protein 3-like [KO:K15041]
102979639  MCU; calcium uniporter protein, mitochondrial [KO:K20858]
102995339  OAS2; 2'-5'-oligoadenylate synthase 2 isoform X1 [KO:K14216] [EC:2.7.7.84]
102995791  OAS1; 2'-5'-oligoadenylate synthase 1 isoform X1 [KO:K14216] [EC:2.7.7.84]
102996067  2'-5'-oligoadenylate synthase 1-like [KO:K14216] [EC:2.7.7.84]
102982973  RNASEL; 2-5A-dependent ribonuclease isoform X1 [KO:K01165]
102991159  DHX33; ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
102989898  MFN1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
102977637  LOW QUALITY PROTEIN: mitofusin-1-like [KO:K21356] [EC:3.6.5.-]
102984012  MFN2; mitofusin-2 isoform X1 [KO:K06030] [EC:3.6.5.-]
102985812  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
102976899  RIPK3; LOW QUALITY PROTEIN: receptor-interacting serine/threonine-protein kinase 3 [KO:K08847] [EC:2.7.11.1]
102994647  DNM1L; dynamin-1-like protein isoform X3 [KO:K17065] [EC:3.6.5.5]
102990644  NAMPT; nicotinamide phosphoribosyltransferase isoform X2 [KO:K03462] [EC:2.4.2.12]
102993493  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
102973615  cytochrome b-245 light chain [KO:K08009]
102980847  TXNIP; thioredoxin-interacting protein [KO:K20910]
102981731  TXN2; thioredoxin, mitochondrial isoform X2 [KO:K03671]
102984303  thioredoxin [KO:K03671]
102985965  TXN; thioredoxin [KO:K03671]
114487348  thioredoxin-like [KO:K03671]
102975020  NEK7; serine/threonine-protein kinase Nek7 isoform X1 [KO:K20876] [EC:2.7.11.34]
102982818  BRCC3; lys-63-specific deubiquitinase BRCC36 isoform X1 [KO:K11864] [EC:3.4.19.-]
102980083  LOW QUALITY PROTEIN: heat shock protein HSP 90-alpha-like [KO:K04079]
102988570  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
102985047  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
102978403  LOW QUALITY PROTEIN: heat shock protein HSP 90-beta-like [KO:K04079]
102975580  GPSM3; G-protein-signaling modulator 3 [KO:K15838]
102994486  MEFV; LOW QUALITY PROTEIN: pyrin [KO:K12803]
102988731  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 [KO:K12804]
102988082  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
102973514  FAS-associated death domain protein isoform X1 [KO:K02373]
112067437  FAS-associated death domain protein isoform X1 [KO:K02373]
102995215  NLRP6; LOW QUALITY PROTEIN: NACHT, LRR and PYD domains-containing protein 6 [KO:K20863]
102993187  NACHT, LRR and PYD domains-containing protein 2 [KO:K20864]
102980423  NLRC4; NLR family CARD domain-containing protein 4 [KO:K12805]
102984279  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
102983740  guanylate-binding protein 5 [KO:K20898]
102990974  gamma-interferon-inducible protein 16-like isoform X1 [KO:K20914]
102974426  TP53BP1; TP53-binding protein 1 isoform X1 [KO:K20915]
102983639  RHOA; transforming protein RhoA [KO:K04513]
102973643  PKN1; serine/threonine-protein kinase N1 isoform X1 [KO:K06071] [EC:2.7.11.13]
102982332  PKN2; serine/threonine-protein kinase N2 isoform X2 [KO:K23691] [EC:2.7.11.13]
102982286  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
102983445  guanylate-binding protein 1-like [KO:K20899]
102987795  caspase-13 isoform X1 [KO:K04394] [EC:3.4.22.57 3.4.22.64]
102995659  GSDMD; gasdermin-D isoform X1 [KO:K20917]
102991034  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
102989482  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
102988182  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
102985137  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
102977655  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
102981574  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
102992486  IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]
102983076  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
102975837  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
102974002  MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
102982312  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
114483846  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
pcad04010  MAPK signaling pathway
pcad04064  NF-kappa B signaling pathway
pcad04140  Autophagy - animal
pcad04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
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