KEGG   PATHWAY: etf04668
Entry
etf04668                    Pathway                                
Name
TNF signaling pathway - Echinops telfairi (small Madagascar hedgehog)
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
etf04668  TNF signaling pathway
etf04668

Other DBs
GO: 0033209
Organism
Echinops telfairi (small Madagascar hedgehog) [GN:etf]
Gene
101654642  TNF; tumor necrosis factor [KO:K03156]
101657422  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
101648400  BAG4; BAG family molecular chaperone regulator 4 [KO:K09558]
101641143  ADAM17; disintegrin and metalloproteinase domain-containing protein 17 [KO:K06059] [EC:3.4.24.86]
101653370  RHBDF2; inactive rhomboid protein 2 [KO:K27588]
101645847  RHBDF1; inactive rhomboid protein 1 [KO:K27588]
101638525  FRMD8; FERM domain-containing protein 8 [KO:K23972]
101643813  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X3 [KO:K03171]
101643556  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
101655200  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
101652750  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
101655890  baculoviral IAP repeat-containing protein 3 [KO:K16060]
101659133  baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
115869468  baculoviral IAP repeat-containing protein 2 [KO:K16060]
101647452  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
101649684  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
101642439  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
101640111  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793]
101647011  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
101663385  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
101654493  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
101653598  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
101645489  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
101656959  JUN; transcription factor AP-1 [KO:K04448]
101656124  FOS; proto-oncogene c-Fos [KO:K04379]
101654665  ITCH; E3 ubiquitin-protein ligase Itchy homolog [KO:K05632] [EC:2.3.2.26]
101664220  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X2 [KO:K04724]
101639675  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
101643832  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X2 [KO:K04433] [EC:2.7.12.2]
101657745  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
101656204  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101653430  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
101653940  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
101645193  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
101650553  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
101648136  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
101657011  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
101649582  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
101656238  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
101663870  RELA; transcription factor p65 [KO:K04735]
101662652  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101649071  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
101650474  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101648971  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101661786  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101645368  RPS6KA5; ribosomal protein S6 kinase alpha-5 [KO:K04445] [EC:2.7.11.1]
101652875  RPS6KA4; ribosomal protein S6 kinase alpha-4 [KO:K16510] [EC:2.7.11.1]
101646557  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
101653565  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
101648900  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
101654666  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X2 [KO:K09048]
101654039  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X3 [KO:K09048]
101639977  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
101656771  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
101650311  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
101648034  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X2 [KO:K09047]
101662802  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X2 [KO:K09049]
101639698  RIPK3; receptor-interacting serine/threonine-protein kinase 3 [KO:K08847] [EC:2.7.11.1]
101638051  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
101664540  CASP10; caspase-10 [KO:K04400] [EC:3.4.22.63]
101657187  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
101643856  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
101651769  MLKL; mixed lineage kinase domain-like protein [KO:K08849] [EC:2.7.11.1]
101654518  PGAM5; serine/threonine-protein phosphatase PGAM5, mitochondrial isoform X1 [KO:K15637] [EC:3.1.3.16]
101650823  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
101660776  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD [KO:K08601] [EC:3.4.19.12]
101662600  E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
101641002  C-C motif chemokine 2-like isoform X1 [KO:K14624]
101662141  monocyte chemotactic protein 1B-like [KO:K14624]
101645531  CCL5; C-C motif chemokine 5 [KO:K12499]
101648039  growth-regulated protein homolog gamma-like [KO:K05505]
101647727  growth-regulated protein homolog gamma-like [KO:K05505]
101638057  alveolar macrophage chemotactic factor [KO:K05506]
101640576  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
101657308  CX3CL1; fractalkine [KO:K05508]
101657479  CSF1; LOW QUALITY PROTEIN: macrophage colony-stimulating factor 1 [KO:K05453]
101659612  IL18R1; interleukin-18 receptor 1 [KO:K05173]
101645683  JAG1; protein jagged-1 [KO:K06052]
101639333  IL1B; interleukin-1 beta [KO:K04519]
123522712  interleukin-6-like [KO:K05405]
101644240  IL6; interleukin-6 [KO:K05405]
101652010  IL15; interleukin-15 isoform X3 [KO:K05433]
101651949  LIF; leukemia inhibitory factor [KO:K05419]
101654325  LTA; lymphotoxin-alpha [KO:K05468]
101641445  BCL3; B-cell lymphoma 3 protein [KO:K09258]
101653170  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
101651870  TNFAIP3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
101663447  TRAF1; LOW QUALITY PROTEIN: TNF receptor-associated factor 1 [KO:K03172]
101640106  T-cell-specific guanine nucleotide triphosphate-binding protein 2-like [KO:K17072]
101653736  JUNB; transcription factor jun-B [KO:K09028]
101656613  stromelysin-1 [KO:K01394] [EC:3.4.24.17]
101657229  stromelysin-2 [KO:K01394] [EC:3.4.24.17]
101662935  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
101656746  MMP14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
101649218  EDN1; endothelin-1 [KO:K16366]
101664676  VEGFD; vascular endothelial growth factor D isoform X1 [KO:K05449]
101649959  VEGFC; vascular endothelial growth factor C [KO:K05449]
101661310  NOD2; nucleotide-binding oligomerization domain-containing protein 2 [KO:K10165]
101651441  ICAM1; intercellular adhesion molecule 1 [KO:K06490]
101647112  SELE; E-selectin [KO:K06494]
101651428  VCAM1; vascular cell adhesion protein 1 [KO:K06527]
101653785  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
101662341  TNFRSF1B; tumor necrosis factor receptor superfamily member 1B [KO:K05141]
101663779  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
101641853  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101654217  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
101640675  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
101655654  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101659995  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101657368  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101643102  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101649881  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101655315  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101640716  disabled homolog 2-interacting protein [KO:K19901]
101653393  IRF1; interferon regulatory factor 1 isoform X1 [KO:K09444]
101650550  IFNB1; interferon beta [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
etf04010  MAPK signaling pathway
etf04064  NF-kappa B signaling pathway
etf04120  Ubiquitin mediated proteolysis
etf04151  PI3K-Akt signaling pathway
etf04210  Apoptosis
KO pathway
ko04668   
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