Entry Name TNF signaling pathway - Dasypus novemcinctus (nine-banded armadillo)
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 Dasypus novemcinctus (nine-banded armadillo) [GN:
dnm ]
Gene 101431862 TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158 ]
101413730 RHBDF2; LOW QUALITY PROTEIN: inactive rhomboid protein 2 [KO:K27588 ]
101414836 FRMD8; LOW QUALITY PROTEIN: FERM domain-containing protein 8 [KO:K23972 ]
101428737 TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171 ]
101434084 TRAF5; LOW QUALITY PROTEIN: TNF receptor-associated factor 5 [KO:K09849 ]
101428234 baculoviral IAP repeat-containing protein 2 isoform X1 [KO:K16060 ]
101412966 TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403 ]
101447376 TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404 ]
101414179 TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X2 [KO:K12793 ]
101434584 CFLAR; CASP8 and FADD-like apoptosis regulator isoform X2 [KO:K04724 ]
101412730 NFKBIA; LOW QUALITY PROTEIN: NF-kappa-B inhibitor alpha [KO:K04734 ]
101437556 NFKB1; LOW QUALITY PROTEIN: nuclear factor NF-kappa-B p105 subunit [KO:K02580 ]
101434860 CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870 ]
101414637 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048 ]
101424631 CREB3L3; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048 ]
101411890 CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
101435604 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048 ]
101442310 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048 ]
101414225 ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450 ]
101410933 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
101426399 CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047 ]
101425452 ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049 ]
101433349 CSF1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453 ]
101424799 CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427 ]
101413233 FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390 ]
101435388 T-cell-specific guanine nucleotide triphosphate-binding protein 1-like [KO:K17072 ]
101426900 VEGFD; vascular endothelial growth factor D isoform X1 [KO:K05449 ]
101420406 VEGFC; vascular endothelial growth factor C isoform X1 [KO:K05449 ]
101444788 NOD2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165 ]
101440631 TNFRSF1B; tumor necrosis factor receptor superfamily member 1B isoform X1 [KO:K05141 ]
101444276 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
101443761 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
101426945 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
101423744 phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
101435351 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
101433347 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
101423041 DAB2IP; disabled homolog 2-interacting protein isoform X1 [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
