Entry Name TNF signaling pathway - Bubalus bubalis (water buffalo)
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 transductionBRITE hierarchy
Pathway map Ortholog table Other DBs Organism Bubalus bubalis (water buffalo) [GN:
bbub ]
Gene 102398200 TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158 ]
102416185 TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171 ]
102394110 BIRC3; baculoviral IAP repeat-containing protein 3 isoform X1 [KO:K16060 ]
102394850 baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060 ]
102395598 TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X2 [KO:K04403 ]
102413796 TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404 ]
102395643 TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X2 [KO:K12793 ]
102412372 CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724 ]
102403930 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X2 [KO:K02580 ]
102401906 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
102406078 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048 ]
102395032 CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
102400784 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048 ]
102416630 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
102398301 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X2 [KO:K09048 ]
102410577 ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450 ]
102393344 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
102400864 CREB5; cyclic AMP-responsive element-binding protein 5 isoform X4 [KO:K09047 ]
102392963 ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X3 [KO:K09049 ]
102395229 CSF1; macrophage colony-stimulating factor 1 isoform X3 [KO:K05453 ]
102413568 CSF2; granulocyte-macrophage colony-stimulating factor precursor [KO:K05427 ]
102408756 FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390 ]
102404604 T-cell-specific guanine nucleotide triphosphate-binding protein 2 [KO:K17072 ]
102408631 VEGFC; vascular endothelial growth factor C isoform X1 [KO:K05449 ]
102413303 VEGFD; vascular endothelial growth factor D isoform X2 [KO:K05449 ]
102390227 NOD2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165 ]
102404165 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
102400519 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
102404610 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
102415109 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
102404517 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649 ]
102395384 phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
Reference Authors Chu WM
Title Tumor necrosis factor.
Journal 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 Reference Authors Newton K, Dixit VM
Title Signaling in innate immunity and inflammation.
Journal 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 Reference Authors Naude PJ, den Boer JA, Luiten PG, Eisel UL
Title Tumor necrosis factor receptor cross-talk.
Journal Reference Authors Faustman D, Davis M
Title TNF receptor 2 pathway: drug target for autoimmune diseases.
Journal 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 Reference Authors Lee MY, Nam KH, Choi KC
Title iRhoms; Its Functions and Essential Roles.
Journal Related KO pathway LinkDB All DBs
