KEGG   PATHWAY: bbis04621
Entry
bbis04621                   Pathway                                
Name
NOD-like receptor signaling pathway - Bison bison bison (American bison)
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
bbis04621  NOD-like receptor signaling pathway
bbis04621

Organism
Bison bison bison (American bison) [GN:bbis]
Gene
104980508  NOD1; nucleotide-binding oligomerization domain-containing protein 1 isoform X1 [KO:K08727]
105004581  RIPK2; receptor-interacting serine/threonine-protein kinase 2 [KO:K08846] [EC:2.7.11.1]
105002719  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
104993223  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
104995325  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
104985237  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
104994637  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
104987029  RELA; transcription factor p65 [KO:K04735]
104984411  IL1B; interleukin-1 beta [KO:K04519]
104981315  IL18; interleukin-18 isoform X1 [KO:K05482]
104987936  IL6; interleukin-6 [KO:K05405]
104983770  TNF; tumor necrosis factor isoform X1 [KO:K03156]
104987314  C-X-C motif chemokine 15-like [KO:K10030]
104987320  interleukin-8 [KO:K10030]
104987311  growth-regulated protein homolog gamma [KO:K05505]
104987339  growth-regulated alpha protein-like [KO:K05505]
105003994  C-C motif chemokine 2 [KO:K14624]
105004018  CCL5; C-C motif chemokine 5 [KO:K12499]
105004670  cathelicidin-3 [KO:K13916]
105004671  cathelicidin-2 [KO:K13916]
105004672  cathelicidin-6 [KO:K13916]
105004674  cathelicidin-5 [KO:K13916]
105004762  cathelicidin-4-like [KO:K13916]
104997252  cathelicidin-7 [KO:K13916]
104981038  beta-defensin 103A-like [KO:K23126]
104999593  NOD2; LOW QUALITY PROTEIN: nucleotide-binding oligomerization domain-containing protein 2 [KO:K10165]
104984790  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
104992373  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
105004816  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
104987008  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793]
104986748  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
104995620  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
104998999  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
104992939  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
104981526  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
104981967  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
104981977  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
104994938  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
104994939  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
105000175  JUN; transcription factor AP-1 [KO:K04448]
104989529  ATG16L1; autophagy-related protein 16-1 isoform X1 [KO:K17890]
105000685  ATG5; autophagy protein 5 isoform X1 [KO:K08339]
105004469  ATG12; ubiquitin-like protein ATG12 [KO:K08336]
104993929  GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
105002133  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
104996574  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
104986209  MAP1LC3C; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
104999438  MAP1LC3A; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
104996554  MAP1LC3B; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
104997113  microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
104993064  SUGT1; suppressor of G2 allele of SKP1 homolog isoform X1 [KO:K12795]
104991562  sharpin [KO:K20894]
104990011  RBCK1; ranBP-type and C3HC4-type zinc finger-containing protein 1 [KO:K10630] [EC:2.3.2.31]
104982029  RNF31; E3 ubiquitin-protein ligase RNF31 [KO:K11974] [EC:2.3.2.31]
104984445  E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
104998525  CARD6; caspase recruitment domain-containing protein 6 [KO:K12797]
104987138  TRIP6; LOW QUALITY PROTEIN: thyroid receptor-interacting protein 6 [KO:K12792]
104992602  ERBB2IP; protein LAP2 isoform X1 [KO:K12796]
104984863  baculoviral IAP repeat-containing protein 2-like [KO:K16060]
104991056  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
104982944  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
104984231  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
104982477  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
104991664  TNFAIP3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
104986050  MAVS; mitochondrial antiviral-signaling protein isoform X1 [KO:K12648]
104996935  TRAF3; TNF receptor-associated factor 3 [KO:K03174]
104989798  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
104998823  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
105002394  TANK; TRAF family member-associated NF-kappa-B activator isoform X1 [KO:K12650]
104995732  IRF3; interferon regulatory factor 3 [KO:K05411]
104985722  IRF7; interferon regulatory factor 7 [KO:K09447]
104992606  interferon alpha-A [KO:K05414]
104999951  interferon alpha-H-like [KO:K05414]
104994732  interferon alpha-G [KO:K05414]
104989082  interferon alpha-B-like [KO:K05414]
104995056  interferon alpha-H-like [KO:K05414]
105000964  interferon alpha-2-like [KO:K05414]
104996675  interferon alpha-C [KO:K05414]
104984810  interferon alpha-H-like [KO:K05414]
105003125  interferon alpha-1 [KO:K05414]
104985507  interferon alpha-F [KO:K05414]
104997583  interferon alpha-H [KO:K05414]
105000961  IFNB1; interferon beta [KO:K05415]
105000962  interferon beta-2 [KO:K05415]
105000963  interferon beta-2-like [KO:K05415]
104983695  interferon beta-1 [KO:K05415]
104996149  interferon beta-2-like [KO:K05415]
104981391  NLRX1; NLR family member X1 [KO:K12653]
104992432  ANTXR1; LOW QUALITY PROTEIN: anthrax toxin receptor 1 [KO:K20909]
104992904  ANTXR2; anthrax toxin receptor 2 [KO:K20909]
104993983  NLRP1; NACHT, LRR and PYD domains-containing protein 1 isoform X1 [KO:K12798]
104986686  apoptosis-associated speck-like protein containing a CARD [KO:K12799]
104982832  caspase-1-like [KO:K01370] [EC:3.4.22.36]
104999231  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
104980990  bcl-2-like protein 1 [KO:K04570]
104989915  BCL2L1; bcl-2-like protein 1 [KO:K04570]
104988812  CTSB; cathepsin B isoform X1 [KO:K01363] [EC:3.4.22.1]
104993291  NLRP3; NACHT, LRR and PYD domains-containing protein 3 isoform X1 [KO:K12800]
104999615  PANX1; pannexin-1 [KO:K03443]
104989624  P2RX7; P2X purinoceptor 7 isoform X1 [KO:K05220]
104985012  TRPM2; transient receptor potential cation channel subfamily M member 2 [KO:K04977] [EC:3.6.1.13]
104988247  TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982] [EC:2.7.11.1]
104990693  TRPV2; transient receptor potential cation channel subfamily V member 2 [KO:K04971]
104984500  CASR; LOW QUALITY PROTEIN: extracellular calcium-sensing receptor [KO:K04612]
105004259  GPRC6A; LOW QUALITY PROTEIN: G-protein coupled receptor family C group 6 member A [KO:K04622]
104987189  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
104994462  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
104984484  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
104984486  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
104991589  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
105000232  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
104995001  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
104991863  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
104997530  VDAC2; voltage-dependent anion-selective channel protein 2 isoform X1 [KO:K15040]
104993226  VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041]
104997490  MCU; calcium uniporter protein, mitochondrial [KO:K20858]
104980026  OAS2; 2'-5'-oligoadenylate synthase 2 isoform X1 [KO:K14216] [EC:2.7.7.84]
104980028  2'-5'-oligoadenylate synthase 1-like [KO:K14216] [EC:2.7.7.84]
104980029  2'-5'-oligoadenylate synthase 1-like [KO:K14216] [EC:2.7.7.84]
104993780  2'-5'-oligoadenylate synthase 1-like [KO:K14216] [EC:2.7.7.84]
104998092  RNASEL; 2-5A-dependent ribonuclease [KO:K01165]
104993978  DHX33; putative ATP-dependent RNA helicase DHX33 [KO:K17820] [EC:5.6.2.6]
104999982  MFN1; mitofusin-1 [KO:K21356] [EC:3.6.5.-]
104995829  MFN2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
105001321  LOW QUALITY PROTEIN: receptor-interacting serine/threonine-protein kinase 1-like [KO:K02861] [EC:2.7.11.1]
104982049  RIPK3; receptor-interacting serine/threonine-protein kinase 3 isoform X1 [KO:K08847] [EC:2.7.11.1]
105003424  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
104989728  NAMPT; nicotinamide phosphoribosyltransferase [KO:K03462] [EC:2.4.2.12]
104979895  cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
104991474  cytochrome b-245 light chain [KO:K08009]
104983336  TXNIP; thioredoxin-interacting protein [KO:K20910]
104991168  TXN; thioredoxin [KO:K03671]
105003400  TXN2; thioredoxin, mitochondrial [KO:K03671]
104981843  NEK7; serine/threonine-protein kinase Nek7 isoform X1 [KO:K20876] [EC:2.7.11.34]
105005197  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
104996944  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
104983964  GPSM3; G-protein-signaling modulator 3 [KO:K15838]
104988893  MEFV; LOW QUALITY PROTEIN: pyrin [KO:K12803]
104990959  PSTPIP1; proline-serine-threonine phosphatase-interacting protein 1 isoform X1 [KO:K12804]
105003655  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
104986928  FADD; LOW QUALITY PROTEIN: FAS-associated death domain protein [KO:K02373]
105004176  NACHT, LRR and PYD domains-containing protein 7-like [KO:K20864]
104984172  NLRP12; NACHT, LRR and PYD domains-containing protein 12 [KO:K20865]
104998427  NAIP; baculoviral IAP repeat-containing protein 1 [KO:K12807]
104980943  NLRC4; NLR family CARD domain-containing protein 4 [KO:K12805]
104997117  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
105003307  interferon-induced guanylate-binding protein 2-like [KO:K20897]
105003309  GBP5; guanylate-binding protein 5 isoform X1 [KO:K20898]
104993617  AIM2; LOW QUALITY PROTEIN: interferon-inducible protein AIM2 [KO:K12966]
104993535  IFI16; gamma-interferon-inducible protein 16 [KO:K20914]
104985789  TP53BP1; tumor suppressor p53-binding protein 1 isoform X1 [KO:K20915]
104997209  RHOA; transforming protein RhoA [KO:K04513]
104999818  PKN1; serine/threonine-protein kinase N1 [KO:K06071] [EC:2.7.11.13]
105003295  PKN2; serine/threonine-protein kinase N2 isoform X1 [KO:K23691] [EC:2.7.11.13]
105003907  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
104994563  14-3-3 protein 3-like [KO:K06630]
105003297  guanylate-binding protein 4-like [KO:K20899]
105003298  interferon-induced guanylate-binding protein 1-like [KO:K20899]
105003303  guanylate-binding protein 6-like isoform X1 [KO:K20899]
105003304  guanylate-binding protein 4-like isoform X1 [KO:K20899]
105003308  interferon-induced guanylate-binding protein 1-like [KO:K20899]
104983676  caspase-13 [KO:K04394] [EC:3.4.22.57 3.4.22.64]
104999074  GSDMD; gasdermin-D [KO:K20917]
105004621  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
105004624  IFNAR2; interferon alpha/beta receptor 2 [KO:K05131]
104988726  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
104979826  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
105003595  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
104988072  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
104982030  IRF9; interferon regulatory factor 9 [KO:K04693]
104994776  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
104979701  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
104985366  MYD88; myeloid differentiation primary response protein MyD88 isoform X1 [KO:K04729]
105003529  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
104996188  TMEM173; stimulator of interferon genes protein [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
bbis04010  MAPK signaling pathway
bbis04064  NF-kappa B signaling pathway
bbis04140  Autophagy - animal
bbis04620  Toll-like receptor signaling pathway
KO pathway
ko04621   
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