KEGG   PATHWAY: btax04668
Entry
btax04668                   Pathway                                
Name
TNF signaling pathway - Budorcas taxicolor (takin)
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
btax04668  TNF signaling pathway
btax04668

Other DBs
GO: 0033209
Organism
Budorcas taxicolor (takin) [GN:btax]
Gene
128043869  CCL20; C-C motif chemokine 20 [KO:K14625]
128043958  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
128044434  [KO:K06527]
128044435  [KO:K06527]
128044447  JUN; transcription factor Jun [KO:K04448]
128044474  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
128044745  CSF1; macrophage colony-stimulating factor 1 [KO:K05453]
128044759  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
128045803  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
128046532  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
128046584  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
128046952  IL6; interleukin-6 [KO:K05405]
128047244  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
128047426  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
128047668  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X1 [KO:K03158]
128047885  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
128048350  [KO:K04374]
128048391  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
128048763  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
128049014  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
128049417  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
128049546  [KO:K05505]
128049610  [KO:K05505]
128049611  [KO:K05505]
128049619  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
128049973  [KO:K05506]
128050033  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
128050540  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
128050697  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
128050788  JUNB; transcription factor JunB [KO:K09028]
128050853  [KO:K17072]
128050854  [KO:K17072]
128050857  [KO:K17072]
128050882  IRF1; interferon regulatory factor 1 [KO:K09444]
128050899  [KO:K06490]
128051495  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
128051508  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
128051541  [KO:K06490]
128051607  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
128051762  [KO:K03174]
128052214  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
128052448  TRAF1; TNF receptor-associated factor 1 [KO:K03172]
128052625  [KO:K05415]
128052626  [KO:K05415]
128052627  [KO:K05415]
128052628  [KO:K05415]
128052635  [KO:K05415]
128052636  [KO:K05415]
128052637  [KO:K05415]
128052638  [KO:K05415]
128052639  [KO:K05415]
128052640  [KO:K05415]
128052652  [KO:K05415]
128053126  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
128053214  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
128053252  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
128053331  TNFAIP3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
128053747  MMP14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
128053951  FOS; protein c-Fos [KO:K04379]
128054045  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
128054462  RIPK3; receptor-interacting serine/threonine-protein kinase 3 [KO:K08847] [EC:2.7.11.1]
128054614  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
128055230  DAB2IP; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
128055238  ADAM17; disintegrin and metalloproteinase domain-containing protein 17 [KO:K06059] [EC:3.4.24.86]
128055294  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
128055475  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
128055801  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
128055992  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
128056360  EDN1; endothelin-1 isoform X1 [KO:K16366]
128056429  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
128056569  IL1B; interleukin-1 beta [KO:K04519]
128056589  IL18R1; interleukin-18 receptor 1 [KO:K05173]
128056772  TNF; tumor necrosis factor [KO:K03156]
128056921  LTA; lymphotoxin-alpha [KO:K05468]
128058122  JAG1; protein jagged-1 [KO:K06052]
128058313  CEBPB; CCAAT/enhancer-binding protein beta [KO:K10048]
128058597  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
128058726  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
128058832  ITCH; E3 ubiquitin-protein ligase Itchy homolog isoform X1 [KO:K05632] [EC:2.3.2.26]
128060118  BIRC2; LOW QUALITY PROTEIN: baculoviral IAP repeat-containing protein 2 [KO:K16060]
128060385  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
128060491  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
128060536  [KO:K01394] [EC:3.4.24.17]
128060900  CASP10; caspase-10 [KO:K04400] [EC:3.4.22.63]
128061416  TNFRSF1B; tumor necrosis factor receptor superfamily member 1B [KO:K05141]
128061475  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
128061491  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
128061601  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
128061711  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
128061758  SELE; E-selectin [KO:K06494]
128061813  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
128062119  LIF; leukemia inhibitory factor [KO:K05419]
128062160  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
128062532  IL15; interleukin-15 [KO:K05433]
128062655  PGAM5; serine/threonine-protein phosphatase PGAM5, mitochondrial isoform X1 [KO:K15637] [EC:3.1.3.16]
128062951  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:3.4.19.12]
128063092  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
128063251  CX3CL1; fractalkine isoform X1 [KO:K05508]
128063292  BCL3; B-cell lymphoma 3 protein [KO:K09258]
128063305  NOD2; nucleotide-binding oligomerization domain-containing protein 2 [KO:K10165]
128063711  MLKL; mixed lineage kinase domain-like protein [KO:K08849] [EC:2.7.11.1]
128063870  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
128064467  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
128064641  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
128064680  RHBDF2; inactive rhomboid protein 2 [KO:K27588]
128064715  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
128064775  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
128064805  [KO:K12499]
128065013  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
128065178  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
128065365  [KO:K14624]
128065610  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
128065635  RHBDF1; inactive rhomboid protein 1 isoform X1 [KO:K27588]
128066235  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
128066643  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
128066664  TRAF3; TNF receptor-associated factor 3 [KO:K03174]
128066790  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
128067048  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
128067677  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
128067718  CASP7; caspase-7 isoform X1 [KO:K04397] [EC:3.4.22.60]
128067871  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
128068238  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
128068298  BAG4; BAG family molecular chaperone regulator 4 [KO:K09558]
128068325  VEGFC; vascular endothelial growth factor C [KO:K05449]
128068336  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
128068508  RPS6KA4; ribosomal protein S6 kinase alpha-4 [KO:K16510] [EC:2.7.11.1]
128068546  RELA; transcription factor p65 [KO:K04735]
128068641  FADD; FAS-associated death domain protein [KO:K02373]
128068699  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
128068735  FRMD8; FERM domain-containing protein 8 [KO:K23972]
128069947  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
128070186  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
128070203  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
128070311  VEGFD; vascular endothelial growth factor D [KO:K05449]
128071103  [KO:K05870]
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
btax04010  MAPK signaling pathway
btax04064  NF-kappa B signaling pathway
btax04120  Ubiquitin mediated proteolysis
btax04151  PI3K-Akt signaling pathway
btax04210  Apoptosis
KO pathway
ko04668   

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