KEGG   PATHWAY: bom04668
Entry
bom04668                    Pathway                                
Name
TNF signaling pathway - Bos mutus (wild yak)
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
bom04668  TNF signaling pathway
bom04668

Other DBs
GO: 0033209
Organism
Bos mutus (wild yak) [GN:bom]
Gene
102264358  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
102264450  CCL20; C-C motif chemokine 20 isoform X2 [KO:K14625]
102264680  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X2 [KO:K09048]
102264816  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
102264909  DAB2IP; disabled homolog 2-interacting protein isoform X1 [KO:K19901]
102264969  CCL5; C-C motif chemokine 5 [KO:K12499]
102265057  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
102265067  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:3.4.19.12]
102265200  TNFRSF1B; tumor necrosis factor receptor superfamily member 1B [KO:K05141]
102265346  NOD2; nucleotide-binding oligomerization domain-containing protein 2 [KO:K10165]
102265427  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102266053  TRAF5; TNF receptor-associated factor 5 [KO:K09849]
102266581  ITCH; E3 ubiquitin-protein ligase Itchy homolog isoform X1 [KO:K05632] [EC:2.3.2.26]
102266726  TNFAIP3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
102266863  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
102266922  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
102266960  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
102267423  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
102267773  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
102267895  JUN; transcription factor Jun [KO:K04448]
102268154  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
102268339  MAP3K14; mitogen-activated protein kinase kinase kinase 14 isoform X1 [KO:K04466] [EC:2.7.11.25]
102268417  RELA; transcription factor p65 [KO:K04735]
102268620  DNM1L; dynamin-1-like protein isoform X1 [KO:K17065] [EC:3.6.5.5]
102268679  [KO:K05506]
102269246  [KO:K05505]
102269257  MLKL; mixed lineage kinase domain-like protein isoform X1 [KO:K08849] [EC:2.7.11.1]
102269530  CXCL2; C-X-C motif chemokine 2 [KO:K05505]
102269710  CSF1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453]
102269726  BAG4; BAG family molecular chaperone regulator 4 [KO:K09558]
102269769  RHBDF1; inactive rhomboid protein 1 isoform X1 [KO:K27588]
102269806  BIRC3; baculoviral IAP repeat-containing protein 3 [KO:K16060]
102270401  CX3CL1; fractalkine isoform X1 [KO:K05508]
102271030  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
102271174  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
102271320  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
102271384  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
102271576  LIF; leukemia inhibitory factor [KO:K05419]
102271913  [KO:K14624]
102271962  FADD; FAS-associated death domain protein [KO:K02373]
102271974  [KO:K05505]
102271999  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
102272368  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102272413  VCAM1; LOW QUALITY PROTEIN: vascular cell adhesion protein 1 [KO:K06527]
102272421  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
102272602  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
102272638  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
102272886  SELE; E-selectin [KO:K06494]
102272962  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X3 [KO:K04433] [EC:2.7.12.2]
102272965  JUNB; transcription factor JunB [KO:K09028]
102272983  EDN1; endothelin-1 [KO:K16366]
102273017  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
102273045  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
102273141  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
102273190  IRF1; interferon regulatory factor 1 [KO:K09444]
102273906  FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
102274085  RPS6KA4; ribosomal protein S6 kinase alpha-4 [KO:K16510] [EC:2.7.11.1]
102274461  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
102274553  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102274878  BCL3; B-cell lymphoma 3 protein [KO:K09258]
102275053  FOS; protein c-Fos [KO:K04379]
102275096  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
102275204  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
102275265  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
102275402  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
102275474  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
102276010  VEGFD; vascular endothelial growth factor D isoform X1 [KO:K05449]
102276392  TRAF3; TNF receptor-associated factor 3 [KO:K03174]
102276455  IL15; interleukin-15 [KO:K05433]
102276849  MAP3K5; LOW QUALITY PROTEIN: mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
102277321  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
102277548  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102277623  LTA; lymphotoxin-alpha [KO:K05468]
102277911  TNF; tumor necrosis factor isoform X1 [KO:K03156]
102277976  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
102278516  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
102278856  MAP3K8; mitogen-activated protein kinase kinase kinase 8 [KO:K04415] [EC:2.7.11.25]
102279111  ADAM17; LOW QUALITY PROTEIN: disintegrin and metalloproteinase domain-containing protein 17 [KO:K06059] [EC:3.4.24.86]
102279581  IL18R1; interleukin-18 receptor 1 isoform X1 [KO:K05173]
102279783  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
102279814  PGAM5; serine/threonine-protein phosphatase PGAM5, mitochondrial isoform X1 [KO:K15637] [EC:3.1.3.16]
102280073  RHBDF2; inactive rhomboid protein 2 isoform X1 [KO:K27588]
102280296  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
102280497  [KO:K05415]
102280670  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
102280772  FRMD8; FERM domain-containing protein 8 isoform X1 [KO:K23972]
102280941  VEGFC; vascular endothelial growth factor C [KO:K05449]
102281065  [KO:K05415]
102281443  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
102281505  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
102281756  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
102281886  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
102281987  MMP14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
102282466  [KO:K05415]
102282890  IL1B; interleukin-1 beta [KO:K04519]
102283212  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102283650  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
102283727  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
102283891  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
102284581  [KO:K05415]
102284931  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102285848  MAPK12; LOW QUALITY PROTEIN: mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
102285873  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
102285892  RIPK3; receptor-interacting serine/threonine-protein kinase 3 isoform X1 [KO:K08847] [EC:2.7.11.1]
102286351  [KO:K17072]
102286771  BIRC2; baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060]
102286868  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102286969  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
102287080  JAG1; protein jagged-1 [KO:K06052]
102287278  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
102287348  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
102287586  TRAF1; TNF receptor-associated factor 1 isoform X1 [KO:K03172]
102287919  IL6; interleukin-6 [KO:K05405]
102287968  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
102288212  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X4 [KO:K09049]
102288330  [KO:K01394] [EC:3.4.24.17]
102288402  [KO:K06490]
106701244  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
138990391  CEBPB; CCAAT/enhancer-binding protein beta [KO:K10048]
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
bom04010  MAPK signaling pathway
bom04064  NF-kappa B signaling pathway
bom04120  Ubiquitin mediated proteolysis
bom04151  PI3K-Akt signaling pathway
bom04210  Apoptosis
KO pathway
ko04668   

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