KEGG   PATHWAY: llv04668
Entry
llv04668                    Pathway                                
Name
TNF signaling pathway - Lutra lutra (Eurasian river otter)
Description
Tumor necrosis factor (TNF), as a critical cytokine, can induce a wide range of intracellular signal pathways including apoptosis and cell survival as well as inflammation and immunity. Activated TNF is assembled to a homotrimer and binds to its receptors (TNFR1, TNFR2) resulting in the trimerization of TNFR1 or TNFR2. TNFR1 is expressed by nearly all cells and is the major receptor for TNF (also called TNF-alpha). In contrast, TNFR2 is expressed in limited cells such as CD4 and CD8 T lymphocytes, endothelial cells, microglia, oligodendrocytes, neuron subtypes, cardiac myocytes, thymocytes and human mesenchymal stem cells. It is the receptor for both TNF and LTA (also called TNF-beta). Upon binding of the ligand, TNFR mediates the association of some adaptor proteins such as TRADD or TRAF2, which in turn initiate recruitment of signal transducers. TNFR1 signaling induces activation of many genes, primarily controlled by two distinct pathways, NF-kappa B pathway and the MAPK cascade, or apoptosis and necroptosis. TNFR2 signaling activates NF-kappa B pathway including PI3K-dependent NF-kappa B pathway and JNK pathway leading to survival.
Class
Environmental Information Processing; Signal transduction
Pathway map
llv04668  TNF signaling pathway
llv04668

Other DBs
GO: 0033209
Organism
Lutra lutra (Eurasian river otter) [GN:llv]
Gene
125103142  tumor necrosis factor isoform X1 [KO:K03156]
125107758  tumor necrosis factor receptor superfamily member 1A-like isoform X1 [KO:K03158]
125092752  BAG family molecular chaperone regulator 4 [KO:K09558]
125108380  disintegrin and metalloproteinase domain-containing protein 17 isoform X1 [KO:K06059] [EC:3.4.24.86]
125090930  inactive rhomboid protein 1 isoform X1 [KO:K27588]
125087594  inactive rhomboid protein 2 [KO:K27588]
125079435  FERM domain-containing protein 8 isoform X1 [KO:K23972]
125088780  tumor necrosis factor receptor type 1-associated DEATH domain protein-like [KO:K03171]
125083298  TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
125085695  TNF receptor-associated factor 5 isoform X1 [KO:K09849]
125103136  receptor-interacting serine/threonine-protein kinase 1-like [KO:K02861] [EC:2.7.11.1]
125079331  LOW QUALITY PROTEIN: baculoviral IAP repeat-containing protein 2-like [KO:K16060]
125079332  baculoviral IAP repeat-containing protein 3-like [KO:K16060]
125102400  LOW QUALITY PROTEIN: mitogen-activated protein kinase kinase kinase 7-like [KO:K04427] [EC:2.7.11.25]
125106336  TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
125101867  TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
125091696  TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
125087109  LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 4-like [KO:K04430] [EC:2.7.12.2]
125085818  dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
125099732  mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
125084526  mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
125093137  mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
125098159  transcription factor Jun [KO:K04448]
125105343  protein c-Fos [KO:K04379]
125108541  E3 ubiquitin-protein ligase Itchy homolog isoform X1 [KO:K05632] [EC:2.3.2.26]
125095000  CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
125087473  dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
125087142  dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
125101777  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
125103018  mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
125096321  mitogen-activated protein kinase 13-like [KO:K04441] [EC:2.7.11.24]
125106184  mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
125106185  mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
125109637  CCAAT/enhancer-binding protein beta [KO:K10048]
125103005  mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
125086838  mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
125091312  NF-kappa-B essential modulator isoform X1 [KO:K07210]
125094028  inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
125084339  LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit alpha-like [KO:K04467] [EC:2.7.11.10]
125105211  NF-kappa-B inhibitor alpha [KO:K04734]
125078405  transcription factor p65 isoform X1 [KO:K04735]
125093224  nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
125107123  mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
125105594  dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
125081690  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
125090203  mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
125104128  ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
125079379  ribosomal protein S6 kinase alpha-4 [KO:K16510] [EC:2.7.11.1]
125095039  cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
125083953  cyclic AMP-responsive element-binding protein 3-like [KO:K09048]
125085653  cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
125086626  cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
125079521  cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
125080714  cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
125095761  cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
125106338  cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
125080867  cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
125101524  cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
125104721  receptor-interacting serine/threonine-protein kinase 3-like isoform X1 [KO:K08847] [EC:2.7.11.1]
125079328  FAS-associated death domain protein-like [KO:K02373]
125094998  caspase-8-like isoform X1 [KO:K04398] [EC:3.4.22.61]
125094997  LOW QUALITY PROTEIN: caspase-10-like [KO:K04400] [EC:3.4.22.63]
125084583  caspase-7 [KO:K04397] [EC:3.4.22.60]
125091274  caspase-3 [KO:K02187] [EC:3.4.22.56]
125081929  serine/threonine-protein phosphatase PGAM5, mitochondrial isoform X1 [KO:K15637] [EC:3.1.3.16]
125106039  dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
125088964  ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:3.4.19.12]
125091577  E3 ubiquitin-protein ligase XIAP isoform X1 [KO:K04725] [EC:2.3.2.27]
125088018  C-C motif chemokine 2 [KO:K14624]
125087970  C-C motif chemokine 5 [KO:K12499]
125096303  C-C motif chemokine 20 isoform X1 [KO:K14625]
125093820  growth-regulated protein homolog gamma-like isoform X1 [KO:K05505]
125093821  LOW QUALITY PROTEIN: growth-regulated alpha protein-like [KO:K05505]
125093822  growth-regulated alpha protein-like [KO:K05505]
125093818  C-X-C motif chemokine 6-like [KO:K05506]
125093857  C-X-C motif chemokine 10-like [KO:K12671]
125089709  fractalkine-like [KO:K05508]
125098134  macrophage colony-stimulating factor 1-like isoform X1 [KO:K05453]
125100468  granulocyte-macrophage colony-stimulating factor-like isoform X1 [KO:K05427]
125084890  tumor necrosis factor receptor superfamily member 6-like [KO:K04390]
125108961  interleukin-18 receptor 1-like [KO:K05173]
125109281  protein jagged-1 [KO:K06052]
125109148  interleukin-1 beta [KO:K04519]
125081177  interleukin-6 [KO:K05405]
125093427  interleukin-15-like [KO:K05433]
125082466  leukemia inhibitory factor [KO:K05419]
125103143  lymphotoxin-alpha [KO:K05468]
125089647  LOW QUALITY PROTEIN: B-cell lymphoma 3 protein-like [KO:K09258]
125086889  suppressor of cytokine signaling 3 [KO:K04696]
125102704  tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
125083470  TNF receptor-associated factor 1 [KO:K03172]
125100150  T-cell-specific guanine nucleotide triphosphate-binding protein 2-like isoform X1 [KO:K17072]
125100151  T-cell-specific guanine nucleotide triphosphate-binding protein 2-like [KO:K17072]
125084267  transcription factor JunB [KO:K09028]
125078732  stromelysin-1 [KO:K01394] [EC:3.4.24.17]
125078733  stromelysin-2-like [KO:K01394] [EC:3.4.24.17]
125109962  matrix metalloproteinase-9 isoform X1 [KO:K01403] [EC:3.4.24.35]
125104089  matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
125103180  endothelin-1 [KO:K16366]
125090950  vascular endothelial growth factor C [KO:K05449]
125091711  vascular endothelial growth factor D-like [KO:K05449]
125089231  nucleotide-binding oligomerization domain-containing protein 2-like isoform X1 [KO:K10165]
125084958  intercellular adhesion molecule 1-like isoform X1 [KO:K06490]
125086398  E-selectin-like [KO:K06494]
125098555  vascular cell adhesion protein 1 isoform X1 [KO:K06527]
125086360  prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
125098107  tumor necrosis factor receptor superfamily member 1B-like isoform X1 [KO:K05141]
125103668  TNF receptor-associated factor 3 isoform X1 [KO:K03174]
125100627  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
125103868  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
125096824  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
125099801  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
125082268  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
125097558  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
125086439  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
125104283  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
125089561  RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
125083234  disabled homolog 2-interacting protein isoform X1 [KO:K19901]
125099754  interferon regulatory factor 1 [KO:K09444]
125083789  interferon beta-like [KO:K05415]
Reference
  Authors
Chu WM
  Title
Tumor necrosis factor.
  Journal
Cancer Lett 328:222-5 (2013)
DOI:10.1016/j.canlet.2012.10.014
Reference
  Authors
Shuh M, Bohorquez H, Loss GE Jr, Cohen AJ
  Title
Tumor Necrosis Factor-alpha: Life and Death of Hepatocytes During Liver Ischemia/Reperfusion Injury.
  Journal
Ochsner J 13:119-30 (2013)
Reference
  Authors
MacEwan DJ
  Title
TNF receptor subtype signalling: differences and cellular consequences.
  Journal
Cell Signal 14:477-92 (2002)
DOI:10.1016/S0898-6568(01)00262-5
Reference
  Authors
Newton K, Dixit VM
  Title
Signaling in innate immunity and inflammation.
  Journal
Cold Spring Harb Perspect Biol 4:a006049 (2012)
DOI:10.1101/cshperspect.a006049
Reference
  Authors
Pomerantz JL, Baltimore D
  Title
NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase.
  Journal
EMBO J 18:6694-704 (1999)
DOI:10.1093/emboj/18.23.6694
Reference
  Authors
Naude PJ, den Boer JA, Luiten PG, Eisel UL
  Title
Tumor necrosis factor receptor cross-talk.
  Journal
FEBS J 278:888-98 (2011)
DOI:10.1111/j.1742-4658.2011.08017.x
Reference
  Authors
Faustman D, Davis M
  Title
TNF receptor 2 pathway: drug target for autoimmune diseases.
  Journal
Nat Rev Drug Discov 9:482-93 (2010)
DOI:10.1038/nrd3030
Reference
  Authors
Chan FK, Shisler J, Bixby JG, Felices M, Zheng L, Appel M, Orenstein J, Moss B, Lenardo MJ
  Title
A role for tumor necrosis factor receptor-2 and receptor-interacting protein in programmed necrosis and antiviral responses.
  Journal
J Biol Chem 278:51613-21 (2003)
DOI:10.1074/jbc.M305633200
Reference
  Authors
Lee MY, Nam KH, Choi KC
  Title
iRhoms; Its Functions and Essential Roles.
  Journal
Biomol Ther (Seoul) 24:109-14 (2016)
DOI:10.4062/biomolther.2015.149
Related
pathway
llv04010  MAPK signaling pathway
llv04064  NF-kappa B signaling pathway
llv04120  Ubiquitin mediated proteolysis
llv04151  PI3K-Akt signaling pathway
llv04210  Apoptosis
KO pathway
ko04668   
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