Entry Name TNF signaling pathway - Rousettus aegyptiacus (Egyptian rousette)
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 Rousettus aegyptiacus (Egyptian rousette) [GN:
ray ]
Gene 107519788 TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X1 [KO:K03158 ]
107515963 BAG4; BAG family molecular chaperone regulator 4 isoform X1 [KO:K09558 ]
107498263 ADAM17; LOW QUALITY PROTEIN: disintegrin and metalloproteinase domain-containing protein 17 [KO:K06059 ] [EC:3.4.24.86 ]
107520081 TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171 ]
107521637 TRAF5; LOW QUALITY PROTEIN: TNF receptor-associated factor 5 [KO:K09849 ]
107500809 TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403 ]
107518453 TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404 ]
107503638 TAB3; LOW QUALITY PROTEIN: TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 [KO:K12793 ]
107503157 CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724 ]
107517900 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
107505169 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
107509179 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048 ]
107502779 CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
107511864 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048 ]
107510647 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048 ]
107499057 CREB3L2; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
107504977 ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450 ]
107500816 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
107505683 CREB5; cyclic AMP-responsive element-binding protein 5 [KO:K09047 ]
107498439 ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049 ]
107516132 CSF1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453 ]
107497048 CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427 ]
107502212 FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390 ]
107512244 NOD2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165 ]
107513133 TNFRSF1B; tumor necrosis factor receptor superfamily member 1B [KO:K05141 ]
107520152 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
107517828 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
107513958 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
107521668 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649 ]
107517899 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
107498704 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
107516304 DAB2IP; LOW QUALITY PROTEIN: disabled homolog 2-interacting protein [KO:K19901 ]
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
