Tumor necrosis factor

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functionⁱ

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

• cytokine activity Source: RGD
• identical protein binding Source: RGD
• protease binding Source: RGD
• transcription regulatory region sequence-specific DNA binding Source: RGD
• tumor necrosis factor receptor binding Source: RGD <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ
  • "Effect of endotoxin on expression of TNF receptors and transport of TNF-alpha at the blood-brain barrier of the rat."
    Osburg B., Peiser C., Domling D., Schomburg L., Ko Y.T., Voigt K., Bickel U.
    Am J Physiol Endocrinol Metab 283:E899-908(2002) [PubMed] [Europe PMC] [Abstract]

GO - Biological processⁱ

• activation of cysteine-type endopeptidase activity involved in apoptotic process Source: RGD
• activation of MAPK activity Source: RGD
• activation of MAPKKK activity Source: RGD
• acute inflammatory response Source: RGD <p>Inferred from Expression Pattern</p> <p>Covers cases where the annotation is inferred from the timing or location of expression of a gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iep">GO evidence code guide</a></p> Inferred from expression patternⁱ
  • "Effect of low-level laser therapy on the expression of inflammatory mediators and on neutrophils and macrophages in acute joint inflammation."
    Alves A.C., Vieira R., Leal-Junior E., dos Santos S., Ligeiro A.P., Albertini R., Junior J., de Carvalho P.
    Arthritis Res Ther 15:R116-R116(2013) [PubMed] [Europe PMC] [Abstract]
• animal organ morphogenesis Source: RGD
• apoptotic process Source: RGDInferred from direct assayⁱ
  • "Tumor necrosis factor induces apoptosis in hepatoma cells by increasing Ca(2+) release from the endoplasmic reticulum and suppressing Bcl-2 expression."
    Kim B.C., Kim H.T., Mamura M., Ambudkar I.S., Choi K.S., Kim S.J.
    J Biol Chem 277:31381-31389(2002) [PubMed] [Europe PMC] [Abstract]
• apoptotic signaling pathway Source: RGD
• calcium-mediated signaling Source: RGDInferred from direct assayⁱ
  • "Tumor necrosis factor induces apoptosis in hepatoma cells by increasing Ca(2+) release from the endoplasmic reticulum and suppressing Bcl-2 expression."
    Kim B.C., Kim H.T., Mamura M., Ambudkar I.S., Choi K.S., Kim S.J.
    J Biol Chem 277:31381-31389(2002) [PubMed] [Europe PMC] [Abstract]
• cell activation Source: RGDInferred from direct assayⁱ
  • "Cardiovascular and renal sympathetic activation by blood-borne TNF-alpha in rat: the role of central prostaglandins."
    Zhang Z.H., Wei S.G., Francis J., Felder R.B.
    Am J Physiol Regul Integr Comp Physiol 284:R916-27(2003) [PubMed] [Europe PMC] [Abstract]
• cellular extravasation Source: RGD
• cellular response to amino acid stimulus Source: RGD
• cellular response to amyloid-beta Source: RGDInferred from expression patternⁱ
  • "Triptolide inhibits amyloid-beta1-42-induced TNF-alpha and IL-1beta production in cultured rat microglia."
    Jiao J., Xue B., Zhang L., Gong Y., Li K., Wang H., Jing L., Xie J., Wang X.
    J Neuroimmunol 205:32-36(2008) [PubMed] [Europe PMC] [Abstract]
• cellular response to interferon-gamma Source: RGDInferred from expression patternⁱ
  • "Interferon-gamma down-regulates expression of tumor necrosis factor-alpha converting enzyme/a disintegrin and metalloproteinase 17 in activated hepatic stellate cells of rats."
    Fujita T., Maesawa C., Oikawa K., Nitta H., Wakabayashi G., Masuda T.
    Int J Mol Med 17:605-616(2006) [PubMed] [Europe PMC] [Abstract]
• cellular response to lipopolysaccharide Source: RGD <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ
  • "Inhibition of tumor necrosis factor alpha secretion in rat Kupffer cells by siRNA: in vivo efficacy of siRNA-liposomes."
    Jing Y., Shishkov A., Ponnappa B.C.
    Biochim Biophys Acta 1780:34-40(2008) [PubMed] [Europe PMC] [Abstract]
• cellular response to molecule of bacterial origin Source: RGDInferred from expression patternⁱ
  • "Role of Kupffer cells in developing streptococcal cell wall granulomas. Streptococcal cell wall induction of inflammatory cytokines and mediators."
    Manthey C.L., Kossmann T., Allen J.B., Corcoran M.L., Brandes M.E., Wahl S.M.
    Am J Pathol 140:1205-1214(1992) [PubMed] [Europe PMC] [Abstract]
• cellular response to nicotine Source: RGD
• cellular response to organic cyclic compound Source: RGD
• cellular response to retinoic acid Source: RGDInferred from expression patternⁱ
  • "Retinoic acid inhibits expression of TNF-alpha and iNOS in activated rat microglia."
    Dheen S.T., Jun Y., Yan Z., Tay S.S., Ling E.A.
    Glia 50:21-31(2005) [PubMed] [Europe PMC] [Abstract]
• cellular response to toxic substance Source: RGDInferred from expression patternⁱ
  • "Expression of the tumor necrosis factor alpha gene and early response genes by nodularin, a liver tumor promoter, in primary cultured rat hepatocytes."
    Sueoka E., Sueoka N., Okabe S., Kozu T., Komori A., Ohta T., Suganuma M., Kim S.J., Lim I.K., Fujiki H.
    J Cancer Res Clin Oncol 123:413-419(1997) [PubMed] [Europe PMC] [Abstract]
• chronic inflammatory response to antigenic stimulus Source: RGD
• circadian rhythm Source: RGDInferred from expression patternⁱ
  • "Diurnal variations of tumor necrosis factor alpha mRNA and alpha-tubulin mRNA in rat brain."
    Bredow S., Guha-Thakurta N., Taishi P., Obal F. Jr., Krueger J.M.
    Neuroimmunomodulation 4:84-90(1997) [PubMed] [Europe PMC] [Abstract]
• cortical actin cytoskeleton organization Source: RGD
• defense response Source: RGD
• defense response to bacterium Source: RGD
• defense response to Gram-positive bacterium Source: RGD
• detection of mechanical stimulus involved in sensory perception of pain Source: RGDInferred from mutant phenotypeⁱ
  • "The role of tumor necrosis factor-alpha in the neuropathic pain induced by Lumbar 5 ventral root transection in rat."
    Xu J.T., Xin W.J., Zang Y., Wu C.Y., Liu X.G.
    Pain 123:306-321(2006) [PubMed] [Europe PMC] [Abstract]
• embryonic digestive tract development Source: RGD
• endothelial cell apoptotic process Source: RGD
• epithelial cell proliferation involved in salivary gland morphogenesis Source: RGD
• extracellular matrix organization Source: RGD
• extrinsic apoptotic signaling pathway Source: RGD
• extrinsic apoptotic signaling pathway via death domain receptors Source: RGD
• glucose metabolic process Source: RGD
• humoral immune response Source: RGD
• inflammatory response Source: RGD
• intrinsic apoptotic signaling pathway in response to DNA damage Source: RGD
• JNK cascade Source: RGD
• leukocyte migration Source: RGD
• leukocyte migration involved in inflammatory response Source: RGDInferred from expression patternⁱ
  • "Dihydroartemisinin protects against alcoholic liver injury through alleviating hepatocyte steatosis in a farnesoid X receptor-dependent manner."
    Xu W., Lu C., Yao L., Zhang F., Shao J., Zheng S.
    Toxicol Appl Pharmacol 315:23-34(2017) [PubMed] [Europe PMC] [Abstract]
• leukocyte tethering or rolling Source: RGD
• lipopolysaccharide-mediated signaling pathway Source: RGD
• liver regeneration Source: RGDInferred from expression patternⁱ
  • "Bile ducts and portal and central veins are major producers of tumor necrosis factor alpha in regenerating rat liver."
    Loffreda S., Rai R., Yang S.Q., Lin H.Z., Diehl A.M.
    Gastroenterology 112:2089-2098(1997) [PubMed] [Europe PMC] [Abstract]
• MAPK cascade Source: RGD
• microglial cell activation Source: RGD
• multicellular organism development Source: RGD
• necroptotic signaling pathway Source: UniProtKB
• negative regulation of alkaline phosphatase activity Source: RGD
• negative regulation of amyloid-beta clearance Source: RGD
• negative regulation of apoptotic process Source: RGDInferred from direct assayⁱ
  • "Tumour necrosis factor alpha (TNF alpha) suppresses apoptosis and induces DNA synthesis in rodent hepatocytes: a mediator of the hepatocarcinogenicity of peroxisome proliferators?"
    Rolfe M., James N.H., Roberts R.A.
    Carcinogenesis 18:2277-2280(1997) [PubMed] [Europe PMC] [Abstract]
• negative regulation of apoptotic signaling pathway Source: RGD
• negative regulation of bicellular tight junction assembly Source: RGD
• negative regulation of bile acid secretion Source: RGDInferred from direct assayⁱ
  • "Tumor necrosis factor-alpha and interleukin-6 reduce bile canalicular contractions of rat hepatocytes."
    Ikeda S., Mitaka T., Harada K., Sato F., Mochizuki Y., Hirata K.
    Surgery 133:101-109(2003) [PubMed] [Europe PMC] [Abstract]
• negative regulation of blood vessel endothelial cell migration Source: RGD
• negative regulation of branching involved in lung morphogenesis Source: RGD
• negative regulation of cell population proliferation Source: RGDInferred from direct assayⁱ
  • "Interleukin-1beta and TNF-alpha act in synergy to inhibit longitudinal growth in fetal rat metatarsal bones."
    Martensson K., Chrysis D., Savendahl L.
    J Bone Miner Res 19:1805-1812(2004) [PubMed] [Europe PMC] [Abstract]
• negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: RGD
• negative regulation of cytokine production involved in immune response Source: RGD
• negative regulation of endothelial cell proliferation Source: RGD
• negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: RGD
• negative regulation of fat cell differentiation Source: RGDInferred from direct assayⁱ
  • "Tumor necrosis factor-alpha stimulates cell proliferation in adipose tissue-derived stromal-vascular cell culture: promotion of adipose tissue expansion by paracrine growth factors."
    Kras K.M., Hausman D.B., Martin R.J.
    Obes Res 8:186-193(2000) [PubMed] [Europe PMC] [Abstract]
• negative regulation of gene expression Source: RGD
• negative regulation of glucose import Source: RGDInferred from direct assayⁱ
  • "Tumor necrosis factor alpha produces insulin resistance in skeletal muscle by activation of inhibitor kappaB kinase in a p38 MAPK-dependent manner."
    de Alvaro C., Teruel T., Hernandez R., Lorenzo M.
    J Biol Chem 279:17070-17078(2004) [PubMed] [Europe PMC] [Abstract]
• negative regulation of heart rate Source: RGDInferred from mutant phenotypeⁱ
  • "Tumor necrosis factor alpha: a major contributor to the hyperdynamic circulation in prehepatic portal-hypertensive rats."
    Lopez-Talavera J.C., Merrill W.W., Groszmann R.J.
    Gastroenterology 108:761-767(1995) [PubMed] [Europe PMC] [Abstract]
• negative regulation of interleukin-6 production Source: RGD
• negative regulation of L-glutamate import across plasma membrane Source: RGDInferred from direct assayⁱ
  • "TNF alpha potentiates glutamate neurotoxicity by inhibiting glutamate uptake in organotypic brain slice cultures: neuroprotection by NF kappa B inhibition."
    Zou J.Y., Crews F.T.
    Brain Res 1034:11-24(2005) [PubMed] [Europe PMC] [Abstract]
• negative regulation of lipid catabolic process Source: RGD
• negative regulation of mitotic cell cycle Source: RGD
• negative regulation of myelination Source: RGDInferred from mutant phenotypeⁱ
  • "Rat cerebellar slice cultures exposed to bilirubin evidence reactive gliosis, excitotoxicity and impaired myelinogenesis that is prevented by AMPA and TNF-alpha inhibitors."
    Barateiro A., Domingues H.S., Fernandes A., Relvas J.B., Brites D.
    Mol Neurobiol 49:424-439(2014) [PubMed] [Europe PMC] [Abstract]
• negative regulation of myoblast differentiation Source: RGD
• negative regulation of myosin-light-chain-phosphatase activity Source: RGD
• negative regulation of osteoblast differentiation Source: RGD
• negative regulation of oxidative phosphorylation Source: RGDInferred from direct assayⁱ
  • "Increased nitric oxide synthase activity as a cause of mitochondrial dysfunction in rat hepatocytes: roles for tumor necrosis factor alpha."
    Kurose I., Miura S., Higuchi H., Watanabe N., Kamegaya Y., Takaishi M., Tomita K., Fukumura D., Kato S., Ishii H.
    Hepatology 24:1185-1192(1996) [PubMed] [Europe PMC] [Abstract]
• negative regulation of production of miRNAs involved in gene silencing by miRNA Source: RGD
• negative regulation of protein-containing complex disassembly Source: RGD
• negative regulation of signaling receptor activity Source: RGD
• negative regulation of systemic arterial blood pressure Source: RGDInferred from mutant phenotypeⁱ
  • "Tumor necrosis factor alpha: a major contributor to the hyperdynamic circulation in prehepatic portal-hypertensive rats."
    Lopez-Talavera J.C., Merrill W.W., Groszmann R.J.
    Gastroenterology 108:761-767(1995) [PubMed] [Europe PMC] [Abstract]
• negative regulation of transcription, DNA-templated Source: RGD
• negative regulation of transcription by RNA polymerase II Source: RGD
• negative regulation of vascular wound healing Source: RGD
• negative regulation of viral genome replication Source: RGD
• osteoclast differentiation Source: RGD
• positive regulation of action potential Source: RGDInferred from direct assayⁱ
  • "Increased sensitivity of injured and adjacent uninjured rat primary sensory neurons to exogenous tumor necrosis factor-alpha after spinal nerve ligation."
    Schafers M., Lee D.H., Brors D., Yaksh T.L., Sorkin L.S.
    J Neurosci 23:3028-3038(2003) [PubMed] [Europe PMC] [Abstract]
• positive regulation of amyloid-beta formation Source: RGD
• positive regulation of apoptotic process Source: RGDInferred from mutant phenotypeⁱ
  • "Reduction of experimental necrotizing enterocolitis with anti-TNF-alpha."
    Halpern M.D., Clark J.A., Saunders T.A., Doelle S.M., Hosseini D.M., Stagner A.M., Dvorak B.
    Am J Physiol Gastrointest Liver Physiol 290:G757-64(2006) [PubMed] [Europe PMC] [Abstract]
  • "Short-term TNF-alpha inhibition reduces short-term and long-term inflammatory changes post-ischemia/reperfusion in rat intestinal transplantation."
    Gerlach U.A., Atanasov G., Wallenta L., Polenz D., Reutzel-Selke A., Kloepfel M., Jurisch A., Marksteiner M., Loddenkemper C., Neuhaus P., Sawitzki B., Pascher A.
    Transplantation 97:732-739(2014) [PubMed] [Europe PMC] [Abstract]
• positive regulation of blood microparticle formation Source: RGD
• positive regulation of calcidiol 1-monooxygenase activity Source: RGD
• positive regulation of calcineurin-NFAT signaling cascade Source: RGD
• positive regulation of cell adhesion Source: RGD
• positive regulation of chemokine (C-X-C motif) ligand 2 production Source: RGD
• positive regulation of chemokine production Source: RGD
• positive regulation of chronic inflammatory response to antigenic stimulus Source: RGD
• positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: RGD
• positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis Source: RGDInferred from mutant phenotypeⁱ
  • "Role of anti-tumor necrosis factor-alpha in ischemia/reperfusion injury in isolated rat liver in a blood-free environment."
    Ben-Ari Z., Hochhauser E., Burstein I., Papo O., Kaganovsky E., Krasnov T., Vamichkim A., Vidne B.A.
    Transplantation 73:1875-1880(2002) [PubMed] [Europe PMC] [Abstract]
• positive regulation of cytokine production Source: RGD
• positive regulation of cytokine production involved in inflammatory response Source: RGD
• positive regulation of DNA-binding transcription factor activity Source: RGD
• positive regulation of DNA biosynthetic process Source: RGDInferred from direct assayⁱ
  • "Tumour necrosis factor alpha (TNF alpha) suppresses apoptosis and induces DNA synthesis in rodent hepatocytes: a mediator of the hepatocarcinogenicity of peroxisome proliferators?"
    Rolfe M., James N.H., Roberts R.A.
    Carcinogenesis 18:2277-2280(1997) [PubMed] [Europe PMC] [Abstract]
• positive regulation of extrinsic apoptotic signaling pathway Source: GO_Central <p>Inferred from Biological aspect of Ancestor</p> <p>A type of phylogenetic evidence whereby an aspect of a descendent is inferred through the characterization of an aspect of a ancestral gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iba">GO evidence code guide</a></p> Inferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• positive regulation of fever generation Source: RGD
• positive regulation of fractalkine production Source: ARUK-UCLInferred from direct assayⁱ
  • "Fractalkine (CX3CL1) stimulated by nuclear factor kappaB (NF-kappaB)-dependent inflammatory signals induces aortic smooth muscle cell proliferation through an autocrine pathway."
    Chandrasekar B., Mummidi S., Perla R.P., Bysani S., Dulin N.O., Liu F., Melby P.C.
    Biochem J 373:547-558(2003) [PubMed] [Europe PMC] [Abstract]
• positive regulation of gene expression Source: UniProtKBInferred from direct assayⁱ
  • "Astrocyte galectin-9 potentiates microglial TNF secretion."
    Steelman A.J., Li J.
    J. Neuroinflamm. 11:144-144(2014) [PubMed] [Europe PMC] [Abstract]
• positive regulation of glial cell proliferation Source: RGD
• positive regulation of hair follicle development Source: RGD
• positive regulation of hepatocyte proliferation Source: RGDInferred from direct assayⁱ
  • "Tumor necrosis factor-alpha modulates effects of aryl hydrocarbon receptor ligands on cell proliferation and expression of cytochrome P450 enzymes in rat liver "stem-like" cells."
    Umannova L., Zatloukalova J., Machala M., Krcmar P., Majkova Z., Hennig B., Kozubik A., Vondracek J.
    Toxicol Sci 99:79-89(2007) [PubMed] [Europe PMC] [Abstract]
• positive regulation of heterotypic cell-cell adhesion Source: RGD
• positive regulation of humoral immune response mediated by circulating immunoglobulin Source: RGD
• positive regulation of I-kappaB kinase/NF-kappaB signaling Source: ARUK-UCLInferred from direct assayⁱ
  • "Fractalkine (CX3CL1) stimulated by nuclear factor kappaB (NF-kappaB)-dependent inflammatory signals induces aortic smooth muscle cell proliferation through an autocrine pathway."
    Chandrasekar B., Mummidi S., Perla R.P., Bysani S., Dulin N.O., Liu F., Melby P.C.
    Biochem J 373:547-558(2003) [PubMed] [Europe PMC] [Abstract]
• positive regulation of I-kappaB phosphorylation Source: RGD
• positive regulation of inflammatory response Source: RGDInferred from mutant phenotypeⁱ
  • "Reduction of experimental necrotizing enterocolitis with anti-TNF-alpha."
    Halpern M.D., Clark J.A., Saunders T.A., Doelle S.M., Hosseini D.M., Stagner A.M., Dvorak B.
    Am J Physiol Gastrointest Liver Physiol 290:G757-64(2006) [PubMed] [Europe PMC] [Abstract]
• positive regulation of interferon-gamma production Source: RGD
• positive regulation of interleukin-18 production Source: RGDInferred from mutant phenotypeⁱ
  • "Reduction of experimental necrotizing enterocolitis with anti-TNF-alpha."
    Halpern M.D., Clark J.A., Saunders T.A., Doelle S.M., Hosseini D.M., Stagner A.M., Dvorak B.
    Am J Physiol Gastrointest Liver Physiol 290:G757-64(2006) [PubMed] [Europe PMC] [Abstract]
• positive regulation of interleukin-1 beta production Source: RGD
• positive regulation of interleukin-33 production Source: RGD
• positive regulation of interleukin-6 production Source: ARUK-UCLInferred from direct assayⁱ
  • "TNF-alpha-sensitive brain pericytes activate microglia by releasing IL-6 through cooperation between IkappaB-NFkappaB and JAK-STAT3 pathways."
    Matsumoto J., Dohgu S., Takata F., Machida T., Bolukbasi Hatip F.F., Hatip-Al-Khatib I., Yamauchi A., Kataoka Y.
    Brain Res 1692:34-44(2018) [PubMed] [Europe PMC] [Abstract]
• positive regulation of interleukin-8 production Source: RGD
• positive regulation of JNK cascade Source: RGD
• positive regulation of JUN kinase activity Source: RGD
• positive regulation of leukocyte adhesion to arterial endothelial cell Source: RGD
• positive regulation of leukocyte adhesion to vascular endothelial cell Source: RGD
• positive regulation of MAP kinase activity Source: RGD
• positive regulation of membrane protein ectodomain proteolysis Source: RGD
• positive regulation of mitotic nuclear division Source: RGDInferred from mutant phenotypeⁱ
  • "The mitogenic activity of the liver growth factor is mediated by tumor necrosis factor alpha in rat liver."
    Diaz-Gil J.J., Majano P.L., Lopez-Cabrera M., Sanchez-Lopez V., Rua C., Machin C., Trilla C., Garcia-Canero R., Moreno-Otero R.
    J Hepatol 38:598-604(2003) [PubMed] [Europe PMC] [Abstract]
• positive regulation of neuron apoptotic process Source: RGDInferred from mutant phenotypeⁱ
  • "Macrophage-derived tumor necrosis factor alpha, an early developmental signal for motoneuron death."
    Sedel F., Bechade C., Vyas S., Triller A.
    J Neurosci 24:2236-2246(2004) [PubMed] [Europe PMC] [Abstract]
  • "Microglia-derived proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta induce Purkinje neuronal apoptosis via their receptors in hypoxic neonatal rat brain."
    Kaur C., Sivakumar V., Zou Z., Ling E.A.
    Brain Struct Funct 219:151-170(2014) [PubMed] [Europe PMC] [Abstract]
• positive regulation of neutrophil activation Source: RGDInferred from mutant phenotypeⁱ
  • "Complement and tumor necrosis factor-alpha contribute to Mac-1 (CD11b/CD18) up-regulation and systemic neutrophil activation during endotoxemia in vivo."
    Witthaut R., Farhood A., Smith C.W., Jaeschke H.
    J Leukoc Biol 55:105-111(1994) [PubMed] [Europe PMC] [Abstract]
• positive regulation of NF-kappaB transcription factor activity Source: ARUK-UCLInferred from direct assayⁱ
  • "TNF-alpha-sensitive brain pericytes activate microglia by releasing IL-6 through cooperation between IkappaB-NFkappaB and JAK-STAT3 pathways."
    Matsumoto J., Dohgu S., Takata F., Machida T., Bolukbasi Hatip F.F., Hatip-Al-Khatib I., Yamauchi A., Kataoka Y.
    Brain Res 1692:34-44(2018) [PubMed] [Europe PMC] [Abstract]
• positive regulation of NIK/NF-kappaB signaling Source: RGD
• positive regulation of nitric oxide biosynthetic process Source: RGD
• positive regulation of nitric-oxide synthase activity Source: RGDInferred from mutant phenotypeⁱ
  • "Tumor necrosis factor alpha regulates nitric oxide synthase expression in portal hypertensive gastric mucosa of rats."
    Ohta M., Tarnawski A.S., Itani R., Pai R., Tomikawa M., Sugimachi K., Sarfeh I.J.
    Hepatology 27:906-913(1998) [PubMed] [Europe PMC] [Abstract]
• positive regulation of nitrogen compound metabolic process Source: RGD
• positive regulation of osteoclast differentiation Source: RGD
• positive regulation of oxidative stress-induced neuron death Source: RGDInferred from direct assayⁱ
  • "TNF alpha potentiates glutamate neurotoxicity by inhibiting glutamate uptake in organotypic brain slice cultures: neuroprotection by NF kappa B inhibition."
    Zou J.Y., Crews F.T.
    Brain Res 1034:11-24(2005) [PubMed] [Europe PMC] [Abstract]
• positive regulation of peptidyl-serine phosphorylation Source: ARUK-UCLInferred from direct assayⁱ
  • "TNF-alpha-sensitive brain pericytes activate microglia by releasing IL-6 through cooperation between IkappaB-NFkappaB and JAK-STAT3 pathways."
    Matsumoto J., Dohgu S., Takata F., Machida T., Bolukbasi Hatip F.F., Hatip-Al-Khatib I., Yamauchi A., Kataoka Y.
    Brain Res 1692:34-44(2018) [PubMed] [Europe PMC] [Abstract]
• positive regulation of phagocytosis Source: RGD
• positive regulation of phosphatidylinositol 3-kinase signaling Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "Fractalkine (CX3CL1) stimulated by nuclear factor kappaB (NF-kappaB)-dependent inflammatory signals induces aortic smooth muscle cell proliferation through an autocrine pathway."
    Chandrasekar B., Mummidi S., Perla R.P., Bysani S., Dulin N.O., Liu F., Melby P.C.
    Biochem J 373:547-558(2003) [PubMed] [Europe PMC] [Abstract]
• positive regulation of podosome assembly Source: RGD
• positive regulation of pri-miRNA transcription by RNA polymerase II Source: RGD
• positive regulation of programmed cell death Source: RGD
• positive regulation of protein catabolic process Source: RGD
• positive regulation of protein-containing complex assembly Source: RGD
• positive regulation of protein-containing complex disassembly Source: RGD
• positive regulation of protein kinase activity Source: RGD
• positive regulation of protein kinase B signaling Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "Fractalkine (CX3CL1) stimulated by nuclear factor kappaB (NF-kappaB)-dependent inflammatory signals induces aortic smooth muscle cell proliferation through an autocrine pathway."
    Chandrasekar B., Mummidi S., Perla R.P., Bysani S., Dulin N.O., Liu F., Melby P.C.
    Biochem J 373:547-558(2003) [PubMed] [Europe PMC] [Abstract]
• positive regulation of protein localization to cell surface Source: RGD
• positive regulation of protein localization to plasma membrane Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "Control of synaptic strength by glial TNFalpha."
    Beattie E.C., Stellwagen D., Morishita W., Bresnahan J.C., Ha B.K., Von Zastrow M., Beattie M.S., Malenka R.C.
    Science 295:2282-2285(2002) [PubMed] [Europe PMC] [Abstract]
• positive regulation of protein phosphorylation Source: RGD
• positive regulation of protein transport Source: RGDInferred from direct assayⁱ
  • "Trafficking of ganglioside GD3 to mitochondria by tumor necrosis factor-alpha."
    Garcia-Ruiz C., Colell A., Morales A., Calvo M., Enrich C., Fernandez-Checa J.C.
    J Biol Chem 277:36443-36448(2002) [PubMed] [Europe PMC] [Abstract]
• positive regulation of receptor signaling pathway via JAK-STAT Source: ARUK-UCLInferred from direct assayⁱ
  • "TNF-alpha-sensitive brain pericytes activate microglia by releasing IL-6 through cooperation between IkappaB-NFkappaB and JAK-STAT3 pathways."
    Matsumoto J., Dohgu S., Takata F., Machida T., Bolukbasi Hatip F.F., Hatip-Al-Khatib I., Yamauchi A., Kataoka Y.
    Brain Res 1692:34-44(2018) [PubMed] [Europe PMC] [Abstract]
• positive regulation of smooth muscle cell proliferation Source: RGD
• positive regulation of superoxide dismutase activity Source: RGD
• positive regulation of synaptic transmission Source: RGDInferred from mutant phenotypeⁱ
  • "Control of synaptic strength by glial TNFalpha."
    Beattie E.C., Stellwagen D., Morishita W., Bresnahan J.C., Ha B.K., Von Zastrow M., Beattie M.S., Malenka R.C.
    Science 295:2282-2285(2002) [PubMed] [Europe PMC] [Abstract]
• positive regulation of synoviocyte proliferation Source: RGD
• positive regulation of transcription, DNA-templated Source: RGD
• positive regulation of transcription by RNA polymerase II Source: ARUK-UCLInferred from direct assayⁱ
  • "Fractalkine (CX3CL1) stimulated by nuclear factor kappaB (NF-kappaB)-dependent inflammatory signals induces aortic smooth muscle cell proliferation through an autocrine pathway."
    Chandrasekar B., Mummidi S., Perla R.P., Bysani S., Dulin N.O., Liu F., Melby P.C.
    Biochem J 373:547-558(2003) [PubMed] [Europe PMC] [Abstract]
• positive regulation of translational initiation by iron Source: RGD
• positive regulation of tyrosine phosphorylation of STAT protein Source: ARUK-UCLInferred from direct assayⁱ
  • "TNF-alpha-sensitive brain pericytes activate microglia by releasing IL-6 through cooperation between IkappaB-NFkappaB and JAK-STAT3 pathways."
    Matsumoto J., Dohgu S., Takata F., Machida T., Bolukbasi Hatip F.F., Hatip-Al-Khatib I., Yamauchi A., Kataoka Y.
    Brain Res 1692:34-44(2018) [PubMed] [Europe PMC] [Abstract]
• positive regulation of vascular associated smooth muscle cell proliferation Source: RGD
• positive regulation of vitamin D biosynthetic process Source: RGD
• protein kinase B signaling Source: RGD
• protein localization to plasma membrane Source: RGD
• regulation of branching involved in salivary gland morphogenesis Source: RGD
• regulation of cell population proliferation Source: RGDInferred from direct assayⁱ
  • "Tumor necrosis factor-alpha stimulates cell proliferation in adipose tissue-derived stromal-vascular cell culture: promotion of adipose tissue expansion by paracrine growth factors."
    Kras K.M., Hausman D.B., Martin R.J.
    Obes Res 8:186-193(2000) [PubMed] [Europe PMC] [Abstract]
• regulation of endothelial cell apoptotic process Source: RGD
• regulation of establishment of endothelial barrier Source: RGD
• regulation of I-kappaB kinase/NF-kappaB signaling Source: RGD
• regulation of immunoglobulin production Source: RGD
• regulation of inflammatory response Source: RGD
• regulation of insulin secretion Source: RGD
• regulation of osteoclast differentiation Source: RGD
• regulation of protein phosphorylation Source: RGD
• regulation of protein secretion Source: RGD
• regulation of reactive oxygen species metabolic process Source: RGD
• regulation of synapse organization Source: RGD
• regulation of transcription by RNA polymerase II Source: ARUK-UCLInferred from direct assayⁱ
  • "Fractalkine (CX3CL1) stimulated by nuclear factor kappaB (NF-kappaB)-dependent inflammatory signals induces aortic smooth muscle cell proliferation through an autocrine pathway."
    Chandrasekar B., Mummidi S., Perla R.P., Bysani S., Dulin N.O., Liu F., Melby P.C.
    Biochem J 373:547-558(2003) [PubMed] [Europe PMC] [Abstract]
• response to 3,3',5-triiodo-L-thyronine Source: RGDInferred from expression patternⁱ
  • "Effects of acute lindane intoxication and thyroid hormone administration in relation to nuclear factor-kappaB activation, tumor necrosis factor-alpha expression, and Kupffer cell function in the rat."
    Valencia C., Cornejo P., Romanque P., Tapia G., Varela P., Videla L.A., Fernandez V.
    Toxicol Lett 148:21-28(2004) [PubMed] [Europe PMC] [Abstract]
• response to activity Source: RGDInferred from expression patternⁱ
  • "Eccentric contraction induces inflammatory responses in rat skeletal muscle: role of tumor necrosis factor-alpha."
    Liao P., Zhou J., Ji L.L., Zhang Y.
    Am J Physiol Regul Integr Comp Physiol 298:R599-607(2010) [PubMed] [Europe PMC] [Abstract]
• response to bacterium Source: RGDInferred from expression patternⁱ
  • "Bidirectional effects of hepatic ischemia/reperfusion on E. coli-induced TNF-alpha gene expression."
    Epperly N.A., Lechner A.J., Johanns C.A., Webster R.O., Matuschak G.M.
    Am J Physiol 270:R289-97(1996) [PubMed] [Europe PMC] [Abstract]
• response to drug Source: RGDInferred from expression patternⁱ
  • "Effect of sulfasalazine on renal ischemia/reperfusion injury in rats."
    Camara-Lemarroy C.R., Guzman-de la Garza F.J., Alarcon-Galvan G., Cordero-Perez P., Fernandez-Garza N.E.
    Ren Fail 31:822-828(2009) [PubMed] [Europe PMC] [Abstract]
  • "Protective effect of dioscin against thioacetamide-induced acute liver injury via FXR/AMPK signaling pathway in vivo."
    Zheng L., Yin L., Xu L., Qi Y., Li H., Xu Y., Han X., Liu K., Peng J.
    Biomed Pharmacother 97:481-488(2018) [PubMed] [Europe PMC] [Abstract]
• response to ethanol Source: RGDInferred from expression patternⁱ
  • "Dihydroartemisinin protects against alcoholic liver injury through alleviating hepatocyte steatosis in a farnesoid X receptor-dependent manner."
    Xu W., Lu C., Yao L., Zhang F., Shao J., Zheng S.
    Toxicol Appl Pharmacol 315:23-34(2017) [PubMed] [Europe PMC] [Abstract]
• response to glucocorticoid Source: RGD
• response to gold nanoparticle Source: RGDInferred from expression patternⁱ
  • "Effects of gold nanoparticles on endotoxin-induced uveitis in rats."
    Pereira D.V., Petronilho F., Pereira H.R., Vuolo F., Mina F., Possato J.C., Vitto M.F., de Souza D.R., da Silva L., da Silva Paula M.M., de Souza C.T., Dal-Pizzol F.
    Invest Ophthalmol Vis Sci 53:8036-8041(2012) [PubMed] [Europe PMC] [Abstract]
• response to Gram-negative bacterium Source: RGDInferred from expression patternⁱ
  • "Sequential alterations in tissue lipoprotein lipase, triglyceride secretion rates, and serum tumor necrosis factor alpha during Escherichia coli bacteremic sepsis in relation to the development of hypertriglyceridemia."
    Lanza-Jacoby S., Phetteplace H., Sedkova N., Knee G.
    Shock 9:46-51(1998) [PubMed] [Europe PMC] [Abstract]
• response to hypoxia Source: RGDInferred from expression patternⁱ
  • "Effects of NF-kappaB oligonucleotide "decoys" on gene expression in P7 rat hippocampus after hypoxia/ischemia."
    Qiu J., Hu X., Nesic O., Grafe M.R., Rassin D.K., Wood T.G., Perez-Polo J.R.
    J Neurosci Res 77:108-118(2004) [PubMed] [Europe PMC] [Abstract]
• response to lipopolysaccharide Source: UniProtKBInferred from mutant phenotypeⁱ
  • "Astrocyte galectin-9 potentiates microglial TNF secretion."
    Steelman A.J., Li J.
    J. Neuroinflamm. 11:144-144(2014) [PubMed] [Europe PMC] [Abstract]
• response to mechanical stimulus Source: RGDInferred from expression patternⁱ
  • "Differential expression of TNF-alpha, IL-6, and IGF-1 by graded mechanical stress in normal rat myocardium."
    Palmieri E.A., Benincasa G., Di Rella F., Casaburi C., Monti M.G., De Simone G., Chiariotti L., Palombini L., Bruni C.B., Sacca L., Cittadini A.
    Am J Physiol Heart Circ Physiol 282:H926-34(2002) [PubMed] [Europe PMC] [Abstract]
• response to nutrient levels Source: RGDInferred from expression patternⁱ
  • "High-fat diets promote insulin resistance through cytokine gene expression in growing female rats."
    Flanagan A.M., Brown J.L., Santiago C.A., Aad P.Y., Spicer L.J., Spicer M.T.
    J Nutr Biochem 19:505-513(2008) [PubMed] [Europe PMC] [Abstract]
• response to organic cyclic compound Source: RGDInferred from expression patternⁱ
  • "Dihydroartemisinin protects against alcoholic liver injury through alleviating hepatocyte steatosis in a farnesoid X receptor-dependent manner."
    Xu W., Lu C., Yao L., Zhang F., Shao J., Zheng S.
    Toxicol Appl Pharmacol 315:23-34(2017) [PubMed] [Europe PMC] [Abstract]
• response to organic substance Source: RGD
• response to paracetamol Source: RGDInferred from expression patternⁱ
  • "Impairment of TNF-alpha expression and secretion in primary rat liver cell cultures by acetaminophen treatment."
    Nastevska C., Gerber E., Horbach M., Rohrdanz E., Kahl R.
    Toxicology 133:85-92(1999) [PubMed] [Europe PMC] [Abstract]
• response to radiation Source: RGDInferred from expression patternⁱ
  • "[Effect of electroacupuncture on the expression of spinal glial fibrillary acidic protein, tumor necrosis factor-alpha and interleukin-1beta in chronic neuropathic pain rats]."
    Sun T., Cui C.B., Luo J.G., Zhang L., Fu Z.J., Song W.G.
    Zhen Ci Yan Jiu 35:12-16(2010) [PubMed] [Europe PMC] [Abstract]
• response to virus Source: RGD
• sequestering of triglyceride Source: RGD
• signal transduction Source: RGDInferred from direct assayⁱ
  • "Tumor necrosis factor induces apoptosis in hepatoma cells by increasing Ca(2+) release from the endoplasmic reticulum and suppressing Bcl-2 expression."
    Kim B.C., Kim H.T., Mamura M., Ambudkar I.S., Choi K.S., Kim S.J.
    J Biol Chem 277:31381-31389(2002) [PubMed] [Europe PMC] [Abstract]
• skeletal muscle contraction Source: RGDInferred from expression patternⁱ
  • "Eccentric contraction induces inflammatory responses in rat skeletal muscle: role of tumor necrosis factor-alpha."
    Liao P., Zhou J., Ji L.L., Zhang Y.
    Am J Physiol Regul Integr Comp Physiol 298:R599-607(2010) [PubMed] [Europe PMC] [Abstract]
• toll-like receptor 3 signaling pathway Source: UniProtKBInferred from mutant phenotypeⁱ
  • "Astrocyte galectin-9 potentiates microglial TNF secretion."
    Steelman A.J., Li J.
    J. Neuroinflamm. 11:144-144(2014) [PubMed] [Europe PMC] [Abstract]
• tumor necrosis factor-mediated signaling pathway Source: RGD
• vascular endothelial growth factor production Source: UniProtKB
• vasodilation Source: RGDInferred from mutant phenotypeⁱ
  • "Age-associated impairment in vasorelaxation to fluid shear stress in the female vasculature is improved by TNF-alpha antagonism."
    Arenas I.A., Xu Y., Davidge S.T.
    Am J Physiol Heart Circ Physiol 290:H1259-63(2006) [PubMed] [Europe PMC] [Abstract]

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsⁱ

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationⁱ

• UniProt annotation
• GO - Cellular component

Topology

Keywords - Cellular componentⁱ

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingⁱ

Molecule processing

Amino acid modifications

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationⁱ

Sites

Keywords - PTMⁱ

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressionⁱ

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

GO - Molecular functionⁱ

• cytokine activity Source: RGD
• identical protein binding Source: RGD
• protease binding Source: RGD
• tumor necrosis factor receptor binding Source: RGDInferred from direct assayⁱ
  • "Effect of endotoxin on expression of TNF receptors and transport of TNF-alpha at the blood-brain barrier of the rat."
    Osburg B., Peiser C., Domling D., Schomburg L., Ko Y.T., Voigt K., Bickel U.
    Am J Physiol Endocrinol Metab 283:E899-908(2002) [PubMed] [Europe PMC] [Abstract]

Protein-protein interaction databases

Chemistry databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structureⁱ

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsⁱ

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesⁱ

Keywords - Domainⁱ

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequenceⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingⁱ: The displayed sequence is further processed into a mature form.

        10         20         30         40         50
MSTESMIRDV ELAEEALPKK MGGLQNSRRC LCLSLFSFLL VAGATTLFCL 
        60         70         80         90        100
LNFGVIGPNK EEKFPNGLPL ISSMAQTLTL RSSSQNSSDK PVAHVVANHQ 
       110        120        130        140        150
AEEQLEWLSQ RANALLANGM DLKDNQLVVP ADGLYLIYSQ VLFKGQGCPD 
       160        170        180        190        200
YVLLTHTVSR FAISYQEKVS LLSAIKSPCP KDTPEGAELK PWYEPMYLGG 
       210        220        230 
VFQLEKGDLL SAEVNLPKYL DITESGQVYF GVIAL                 

Experimental Info

Natural variant

Sequence databases

Genome annotation databases

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsⁱ

• 90% Identity
• 50% Identity

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesⁱ

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationⁱ

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousⁱ

Keywords - Technical termⁱ

Documents

1. SIMILARITY comments
   Index of protein domains and families