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: BHF-UCL <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-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ
  • "A phosphatidylinositol 3-kinase/Akt pathway, activated by tumor necrosis factor or interleukin-1, inhibits apoptosis but does not activate NFkappaB in human endothelial cells."
    Madge L.A., Pober J.S.
    J. Biol. Chem. 275:15458-15465(2000) [PubMed] [Europe PMC] [Abstract]
• identical protein binding Source: BHF-UCLInferred from direct assayⁱ
  • "Inactivation of TNF signaling by rationally designed dominant-negative TNF variants."
    Steed P.M., Tansey M.G., Zalevsky J., Zhukovsky E.A., Desjarlais J.R., Szymkowski D.E., Abbott C., Carmichael D., Chan C., Cherry L., Cheung P., Chirino A.J., Chung H.H., Doberstein S.K., Eivazi A., Filikov A.V., Gao S.X., Hubert R.S.

    , Hwang M., Hyun L., Kashi S., Kim A., Kim E., Kung J., Martinez S.P., Muchhal U.S., Nguyen D.H., O'Brien C., O'Keefe D., Singer K., Vafa O., Vielmetter J., Yoder S.C., Dahiyat B.I.
    Science 301:1895-1898(2003) [PubMed] [Europe PMC] [Abstract]
• protease binding Source: BHF-UCL <p>Inferred from Physical Interaction</p> <p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ipi">GO evidence code guide</a></p> Inferred from physical interactionⁱ
  • "Catalytic activity of ADAM8, ADAM15, and MDC-L (ADAM28) on synthetic peptide substrates and in ectodomain cleavage of CD23."
    Fourie A.M., Coles F., Moreno V., Karlsson L.
    J. Biol. Chem. 278:30469-30477(2003) [PubMed] [Europe PMC] [Abstract]
• transcription regulatory region DNA binding Source: UniProtKBInferred from direct assayⁱ
  • "TNF-alpha represses transcription of human Bone Morphogenetic Protein-4 in lung epithelial cells."
    Zhu N.L., Li C., Huang H.H., Sebald M., Londhe V.A., Heisterkamp N., Warburton D., Bellusci S., Minoo P.
    Gene 393:70-80(2007) [PubMed] [Europe PMC] [Abstract]
• tumor necrosis factor receptor binding Source: BHF-UCLInferred from direct assayⁱ
  • "Inactivation of TNF signaling by rationally designed dominant-negative TNF variants."
    Steed P.M., Tansey M.G., Zalevsky J., Zhukovsky E.A., Desjarlais J.R., Szymkowski D.E., Abbott C., Carmichael D., Chan C., Cherry L., Cheung P., Chirino A.J., Chung H.H., Doberstein S.K., Eivazi A., Filikov A.V., Gao S.X., Hubert R.S.

    , Hwang M., Hyun L., Kashi S., Kim A., Kim E., Kung J., Martinez S.P., Muchhal U.S., Nguyen D.H., O'Brien C., O'Keefe D., Singer K., Vafa O., Vielmetter J., Yoder S.C., Dahiyat B.I.
    Science 301:1895-1898(2003) [PubMed] [Europe PMC] [Abstract]

GO - Biological processⁱ

• activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKBInferred from direct assayⁱ
  • "Gas6/Axl signaling activates the phosphatidylinositol 3-kinase/Akt1 survival pathway to protect oligodendrocytes from tumor necrosis factor alpha-induced apoptosis."
    Shankar S.L., O'Guin K., Kim M., Varnum B., Lemke G., Brosnan C.F., Shafit-Zagardo B.
    J. Neurosci. 26:5638-5648(2006) [PubMed] [Europe PMC] [Abstract]
• activation of MAPK activity Source: BHF-UCLInferred from direct assayⁱ
  • "A phosphatidylinositol 3-kinase/Akt pathway, activated by tumor necrosis factor or interleukin-1, inhibits apoptosis but does not activate NFkappaB in human endothelial cells."
    Madge L.A., Pober J.S.
    J. Biol. Chem. 275:15458-15465(2000) [PubMed] [Europe PMC] [Abstract]
• activation of MAPKKK activity Source: BHF-UCLInferred from direct assayⁱ
  • "AIP1/DAB2IP, a novel member of the Ras-GAP family, transduces TRAF2-induced ASK1-JNK activation."
    Zhang H., Zhang R., Luo Y., D'Alessio A., Pober J.S., Min W.
    J. Biol. Chem. 279:44955-44965(2004) [PubMed] [Europe PMC] [Abstract]
• astrocyte activation Source: ARUK-UCL <p>Non-traceable Author Statement</p> <p>Used for statements in the abstract, introduction or discussion of a paper that cannot be traced back to another publication.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#nas">GO evidence code guide</a></p> Non-traceable author statementⁱ
  • "Role of TNF in mast cell neuroinflammation and pain."
    Gu Y., Yang D.K., Spinas E., Kritas S.K., Saggini A., Caraffa A., Antinolfi P., Saggini R., Conti P.
    J. Biol. Regul. Homeost. Agents 29:787-791(2015) [PubMed] [Europe PMC] [Abstract]
• cellular response to amino acid stimulus Source: Ensembl
• cellular response to nicotine Source: UniProtKBInferred from direct assayⁱ
  • "Nicotine induces resistance to chemotherapy by modulating mitochondrial signaling in lung cancer."
    Zhang J., Kamdar O., Le W., Rosen G.D., Upadhyay D.
    Am. J. Respir. Cell Mol. Biol. 40:135-146(2009) [PubMed] [Europe PMC] [Abstract]
• cellular response to organic cyclic compound Source: UniProtKBInferred from direct assayⁱ
  • "Inhibitory effects of honokiol on lipopolysaccharide-induced cellular responses and signaling events in human renal mesangial cells."
    Wu F., Zhang W., Li L., Zheng F., Shao X., Zhou J., Li H.
    Eur. J. Pharmacol. 654:117-121(2011) [PubMed] [Europe PMC] [Abstract]
• chronic inflammatory response to antigenic stimulus Source: BHF-UCL <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-go-evidence-codes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ
  • "Inactivation of TNF signaling by rationally designed dominant-negative TNF variants."
    Steed P.M., Tansey M.G., Zalevsky J., Zhukovsky E.A., Desjarlais J.R., Szymkowski D.E., Abbott C., Carmichael D., Chan C., Cherry L., Cheung P., Chirino A.J., Chung H.H., Doberstein S.K., Eivazi A., Filikov A.V., Gao S.X., Hubert R.S.

    , Hwang M., Hyun L., Kashi S., Kim A., Kim E., Kung J., Martinez S.P., Muchhal U.S., Nguyen D.H., O'Brien C., O'Keefe D., Singer K., Vafa O., Vielmetter J., Yoder S.C., Dahiyat B.I.
    Science 301:1895-1898(2003) [PubMed] [Europe PMC] [Abstract]
• cognition Source: ARUK-UCL <p>Traceable Author Statement</p> <p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#tas">GO evidence code guide</a></p> Traceable author statementⁱ
  • "TNF-alpha protein synthesis inhibitor restores neuronal function and reverses cognitive deficits induced by chronic neuroinflammation."
    Belarbi K., Jopson T., Tweedie D., Arellano C., Luo W., Greig N.H., Rosi S.
    J Neuroinflammation 9:23-23(2012) [PubMed] [Europe PMC] [Abstract]
• cortical actin cytoskeleton organization Source: UniProtKBInferred from direct assayⁱ
  • "Tumor necrosis factor disrupts claudin-5 endothelial tight junction barriers in two distinct NF-kappaB-dependent phases."
    Clark P.R., Kim R.K., Pober J.S., Kluger M.S.
    PLoS ONE 10:e0120075-e0120075(2015) [PubMed] [Europe PMC] [Abstract]
• cytokine-mediated signaling pathway Source: Reactome
• death-inducing signaling complex assembly Source: Reactome
• defense response to Gram-positive bacterium Source: Ensembl
• embryonic digestive tract development Source: DFLAT <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-go-evidence-codes#iep">GO evidence code guide</a></p> Inferred from expression patternⁱ
  • "TGF-beta2 suppresses macrophage cytokine production and mucosal inflammatory responses in the developing intestine."
    Maheshwari A., Kelly D.R., Nicola T., Ambalavanan N., Jain S.K., Murphy-Ullrich J., Athar M., Shimamura M., Bhandari V., Aprahamian C., Dimmitt R.A., Serra R., Ohls R.K.
    Gastroenterology 140:242-253(2011) [PubMed] [Europe PMC] [Abstract]
• endothelial cell apoptotic process Source: Ensembl
• epithelial cell proliferation involved in salivary gland morphogenesis Source: Ensembl
• extracellular matrix organization Source: Ensembl
• extrinsic apoptotic signaling pathway Source: UniProtKBInferred from direct assayⁱ
  • "Contrasting effects of IG20 and its splice isoforms, MADD and DENN-SV, on tumor necrosis factor alpha-induced apoptosis and activation of caspase-8 and -3."
    Al-Zoubi A.M., Efimova E.V., Kaithamana S., Martinez O., El-Azami El-Idrissi M., Dogan R.E., Prabhakar B.S.
    J. Biol. Chem. 276:47202-47211(2001) [PubMed] [Europe PMC] [Abstract]
  • "Competitive control of independent programs of tumor necrosis factor receptor-induced cell death by TRADD and RIP1."
    Zheng L., Bidere N., Staudt D., Cubre A., Orenstein J., Chan F.K., Lenardo M.
    Mol. Cell. Biol. 26:3505-3513(2006) [PubMed] [Europe PMC] [Abstract]
• extrinsic apoptotic signaling pathway via death domain receptors Source: UniProtKBInferred from direct assayⁱ
  • "Nicotine induces resistance to chemotherapy by modulating mitochondrial signaling in lung cancer."
    Zhang J., Kamdar O., Le W., Rosen G.D., Upadhyay D.
    Am. J. Respir. Cell Mol. Biol. 40:135-146(2009) [PubMed] [Europe PMC] [Abstract]
• glucose metabolic process Source: Ensembl
• humoral immune response Source: Ensembl
• I-kappaB kinase/NF-kappaB signaling Source: Reactome
• inflammatory response Source: UniProtKBInferred from direct assayⁱ
  • "Inhibitory effects of honokiol on lipopolysaccharide-induced cellular responses and signaling events in human renal mesangial cells."
    Wu F., Zhang W., Li L., Zheng F., Shao X., Zhou J., Li H.
    Eur. J. Pharmacol. 654:117-121(2011) [PubMed] [Europe PMC] [Abstract]
• intrinsic apoptotic signaling pathway in response to DNA damage Source: Ensembl
• JNK cascade Source: Ensembl
• leukocyte tethering or rolling Source: BHF-UCLInferred from direct assayⁱ
  • "Differential ability of exogenous chemotactic agents to disrupt transendothelial migration of flowing neutrophils."
    Luu N.T., Rainger G.E., Nash G.B.
    J. Immunol. 164:5961-5969(2000) [PubMed] [Europe PMC] [Abstract]
• lipopolysaccharide-mediated signaling pathway Source: UniProtKBInferred from direct assayⁱ
  • "Inhibitory effects of honokiol on lipopolysaccharide-induced cellular responses and signaling events in human renal mesangial cells."
    Wu F., Zhang W., Li L., Zheng F., Shao X., Zhou J., Li H.
    Eur. J. Pharmacol. 654:117-121(2011) [PubMed] [Europe PMC] [Abstract]
• MAPK cascade Source: UniProtKBInferred from mutant phenotypeⁱ
  • "Inhibitory effects of honokiol on lipopolysaccharide-induced cellular responses and signaling events in human renal mesangial cells."
    Wu F., Zhang W., Li L., Zheng F., Shao X., Zhou J., Li H.
    Eur. J. Pharmacol. 654:117-121(2011) [PubMed] [Europe PMC] [Abstract]
• microglial cell activation Source: ARUK-UCL
• necroptotic signaling pathway Source: UniProtKBInferred from direct assayⁱ
  • "Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase."
    Sun L., Wang H., Wang Z., He S., Chen S., Liao D., Wang L., Yan J., Liu W., Lei X., Wang X.
    Cell 148:213-227(2012) [PubMed] [Europe PMC] [Abstract]
  • "The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways."
    Wang Z., Jiang H., Chen S., Du F., Wang X.
    Cell 148:228-243(2012) [PubMed] [Europe PMC] [Abstract]
  • "The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis."
    Li J., McQuade T., Siemer A.B., Napetschnig J., Moriwaki K., Hsiao Y.S., Damko E., Moquin D., Walz T., McDermott A., Chan F.K., Wu H.
    Cell 150:339-350(2012) [PubMed] [Europe PMC] [Abstract]
• negative regulation of alkaline phosphatase activity Source: Ensembl
• negative regulation of amyloid-beta clearance Source: ARUK-UCL
• negative regulation of bicellular tight junction assembly Source: UniProtKBInferred from direct assayⁱ
  • "Tumor necrosis factor disrupts claudin-5 endothelial tight junction barriers in two distinct NF-kappaB-dependent phases."
    Clark P.R., Kim R.K., Pober J.S., Kluger M.S.
    PLoS ONE 10:e0120075-e0120075(2015) [PubMed] [Europe PMC] [Abstract]
• negative regulation of branching involved in lung morphogenesis Source: UniProtKBInferred from direct assayⁱ
  • "TNF-alpha represses transcription of human Bone Morphogenetic Protein-4 in lung epithelial cells."
    Zhu N.L., Li C., Huang H.H., Sebald M., Londhe V.A., Heisterkamp N., Warburton D., Bellusci S., Minoo P.
    Gene 393:70-80(2007) [PubMed] [Europe PMC] [Abstract]
• negative regulation of cytokine secretion involved in immune response Source: BHF-UCLInferred from direct assayⁱ
  • "Tumor necrosis factor alpha decreases, and interleukin-10 increases, the sensitivity of human monocytes to dexamethasone: potential regulation of the glucocorticoid receptor."
    Franchimont D., Martens H., Hagelstein M.T., Louis E., Dewe W., Chrousos G.P., Belaiche J., Geenen V.
    J. Clin. Endocrinol. Metab. 84:2834-2839(1999) [PubMed] [Europe PMC] [Abstract]
• negative regulation of endothelial cell proliferation Source: Ensembl
• negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: BHF-UCLInferred from direct assayⁱ
  • "The CXC-chemokine platelet factor 4 promotes monocyte survival and induces monocyte differentiation into macrophages."
    Scheuerer B., Ernst M., Durrbaum-Landmann I., Fleischer J., Grage-Griebenow E., Brandt E., Flad H.D., Petersen F.
    Blood 95:1158-1166(2000) [PubMed] [Europe PMC] [Abstract]
  • "A phosphatidylinositol 3-kinase/Akt pathway, activated by tumor necrosis factor or interleukin-1, inhibits apoptosis but does not activate NFkappaB in human endothelial cells."
    Madge L.A., Pober J.S.
    J. Biol. Chem. 275:15458-15465(2000) [PubMed] [Europe PMC] [Abstract]
• negative regulation of fat cell differentiation Source: BHF-UCLNon-traceable author statementⁱ
  • "Cytokines promote Wnt signaling and inflammation and impair the normal differentiation and lipid accumulation in 3T3-L1 preadipocytes."
    Gustafson B., Smith U.
    J. Biol. Chem. 281:9507-9516(2006) [PubMed] [Europe PMC] [Abstract]
• negative regulation of gene expression Source: UniProtKBInferred from direct assayⁱ
  • "Estrogen receptor (ER)-mediated transcriptional regulation of the human corticotropin-releasing hormone-binding protein promoter: differential effects of ERalpha and ERbeta."
    van de Stolpe A., Slycke A.J., Reinders M.O., Zomer A.W., Goodenough S., Behl C., Seasholtz A.F., van der Saag P.T.
    Mol. Endocrinol. 18:2908-2923(2004) [PubMed] [Europe PMC] [Abstract]
• negative regulation of glucose import Source: Ensembl
• negative regulation of interleukin-6 production Source: BHF-UCLInferred from direct assayⁱ
  • "Tumor necrosis factor alpha decreases, and interleukin-10 increases, the sensitivity of human monocytes to dexamethasone: potential regulation of the glucocorticoid receptor."
    Franchimont D., Martens H., Hagelstein M.T., Louis E., Dewe W., Chrousos G.P., Belaiche J., Geenen V.
    J. Clin. Endocrinol. Metab. 84:2834-2839(1999) [PubMed] [Europe PMC] [Abstract]
• negative regulation of lipid catabolic process Source: BHF-UCLInferred from direct assayⁱ
  • "Interleukin-1beta and tumour necrosis factor-alpha impede neutral lipid turnover in macrophage-derived foam cells."
    Persson J., Nilsson J., Lindholm M.W.
    BMC Immunol. 9:70-70(2008) [PubMed] [Europe PMC] [Abstract]
• negative regulation of lipid storage Source: BHF-UCLNon-traceable author statementⁱ
  • "Cytokines promote Wnt signaling and inflammation and impair the normal differentiation and lipid accumulation in 3T3-L1 preadipocytes."
    Gustafson B., Smith U.
    J. Biol. Chem. 281:9507-9516(2006) [PubMed] [Europe PMC] [Abstract]
• negative regulation of mitotic cell cycle Source: Ensembl
• negative regulation of myoblast differentiation Source: Ensembl
• negative regulation of myosin-light-chain-phosphatase activity Source: UniProtKBInferred from direct assayⁱ
  • "Tumor necrosis factor disrupts claudin-5 endothelial tight junction barriers in two distinct NF-kappaB-dependent phases."
    Clark P.R., Kim R.K., Pober J.S., Kluger M.S.
    PLoS ONE 10:e0120075-e0120075(2015) [PubMed] [Europe PMC] [Abstract]
• negative regulation of neurogenesis Source: ARUK-UCLTraceable author statementⁱ
  • "Fractalkine and CX 3 CR1 regulate hippocampal neurogenesis in adult and aged rats."
    Bachstetter A.D., Morganti J.M., Jernberg J., Schlunk A., Mitchell S.H., Brewster K.W., Hudson C.E., Cole M.J., Harrison J.K., Bickford P.C., Gemma C.
    Neurobiol. Aging 32:2030-2044(2011) [PubMed] [Europe PMC] [Abstract]
• negative regulation of osteoblast differentiation Source: Ensembl
• negative regulation of protein complex disassembly Source: UniProtKBInferred from direct assayⁱ
  • "RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site is critical for tumor necrosis factor-induced ASK1-JNK/p38 activation."
    Zhang H., Zhang H., Lin Y., Li J., Pober J.S., Min W.
    J. Biol. Chem. 282:14788-14796(2007) [PubMed] [Europe PMC] [Abstract]
• negative regulation of transcription, DNA-templated Source: UniProtKBInferred from direct assayⁱ
  • "Tumor necrosis factor-alpha down-regulates human Cu/Zn superoxide dismutase 1 promoter via JNK/AP-1 signaling pathway."
    Afonso V., Santos G., Collin P., Khatib A.M., Mitrovic D.R., Lomri N., Leitman D.C., Lomri A.
    Free Radic. Biol. Med. 41:709-721(2006) [PubMed] [Europe PMC] [Abstract]
  • "TNF-alpha represses transcription of human Bone Morphogenetic Protein-4 in lung epithelial cells."
    Zhu N.L., Li C., Huang H.H., Sebald M., Londhe V.A., Heisterkamp N., Warburton D., Bellusci S., Minoo P.
    Gene 393:70-80(2007) [PubMed] [Europe PMC] [Abstract]
• negative regulation of transcription by RNA polymerase II Source: UniProtKBInferred from direct assayⁱ
  • "Estrogen receptor (ER)-mediated transcriptional regulation of the human corticotropin-releasing hormone-binding protein promoter: differential effects of ERalpha and ERbeta."
    van de Stolpe A., Slycke A.J., Reinders M.O., Zomer A.W., Goodenough S., Behl C., Seasholtz A.F., van der Saag P.T.
    Mol. Endocrinol. 18:2908-2923(2004) [PubMed] [Europe PMC] [Abstract]
• negative regulation of viral genome replication Source: BHF-UCLInferred from direct assayⁱ
  • "TNF-alpha inhibits HIV-1 replication in peripheral blood monocytes and alveolar macrophages by inducing the production of RANTES and decreasing C-C chemokine receptor 5 (CCR5) expression."
    Lane B.R., Markovitz D.M., Woodford N.L., Rochford R., Strieter R.M., Coffey M.J.
    J. Immunol. 163:3653-3661(1999) [PubMed] [Europe PMC] [Abstract]
• osteoclast differentiation Source: Ensembl
• positive regulation of amyloid-beta formation Source: ARUK-UCL
• positive regulation of apoptotic process Source: UniProtKBInferred from direct assayⁱ
  • "Gas6/Axl signaling activates the phosphatidylinositol 3-kinase/Akt1 survival pathway to protect oligodendrocytes from tumor necrosis factor alpha-induced apoptosis."
    Shankar S.L., O'Guin K., Kim M., Varnum B., Lemke G., Brosnan C.F., Shafit-Zagardo B.
    J. Neurosci. 26:5638-5648(2006) [PubMed] [Europe PMC] [Abstract]
  • "RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site is critical for tumor necrosis factor-induced ASK1-JNK/p38 activation."
    Zhang H., Zhang H., Lin Y., Li J., Pober J.S., Min W.
    J. Biol. Chem. 282:14788-14796(2007) [PubMed] [Europe PMC] [Abstract]
  • "RIP1 is required for IAP inhibitor-mediated sensitization of childhood acute leukemia cells to chemotherapy-induced apoptosis."
    Loder S., Fakler M., Schoeneberger H., Cristofanon S., Leibacher J., Vanlangenakker N., Bertrand M.J., Vandenabeele P., Jeremias I., Debatin K.M., Fulda S.
    Leukemia 26:1020-1029(2012) [PubMed] [Europe PMC] [Abstract]
• positive regulation of blood microparticle formation Source: BHF-UCLInferred from direct assayⁱ
  • "MicroRNA-19b functions as potential anti-thrombotic protector in patients with unstable angina by targeting tissue factor."
    Li S., Ren J., Xu N., Zhang J., Geng Q., Cao C., Lee C., Song J., Li J., Chen H.
    J. Mol. Cell. Cardiol. 75:49-57(2014) [PubMed] [Europe PMC] [Abstract]
• positive regulation of calcidiol 1-monooxygenase activity Source: BHF-UCLInferred from direct assayⁱ
  • "Tumor necrosis factor-alpha induces vitamin D-1-hydroxylase activity in normal human alveolar macrophages."
    Pryke A.M., Duggan C., White C.P., Posen S., Mason R.S.
    J. Cell. Physiol. 142:652-656(1990) [PubMed] [Europe PMC] [Abstract]
• positive regulation of calcineurin-NFAT signaling cascade Source: MGIInferred from direct assayⁱ
  • "NFAT3 is specifically required for TNF-alpha-induced cyclooxygenase-2 (COX-2) expression and transformation of Cl41 cells."
    Yan Y., Li J., Ouyang W., Ma Q., Hu Y., Zhang D., Ding J., Qu Q., Subbaramaiah K., Huang C.
    J. Cell. Sci. 119:2985-2994(2006) [PubMed] [Europe PMC] [Abstract]
• positive regulation of cell adhesion Source: UniProtKBInferred from mutant phenotypeⁱ
  • "Glucocorticoid-induced tumor necrosis factor receptor family-related ligand triggering upregulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 and promotes leukocyte adhesion."
    Lacal P.M., Petrillo M.G., Ruffini F., Muzi A., Bianchini R., Ronchetti S., Migliorati G., Riccardi C., Graziani G., Nocentini G.
    J. Pharmacol. Exp. Ther. 347:164-172(2013) [PubMed] [Europe PMC] [Abstract]
• positive regulation of ceramide biosynthetic process Source: Reactome
• positive regulation of chemokine (C-X-C motif) ligand 2 production Source: BHF-UCLInferred from direct assayⁱ
  • "Erk5 activation elicits a vasoprotective endothelial phenotype via induction of Kruppel-like factor 4 (KLF4)."
    Ohnesorge N., Viemann D., Schmidt N., Czymai T., Spiering D., Schmolke M., Ludwig S., Roth J., Goebeler M., Schmidt M.
    J. Biol. Chem. 285:26199-26210(2010) [PubMed] [Europe PMC] [Abstract]
• positive regulation of chemokine biosynthetic process Source: BHF-UCLInferred from direct assayⁱ
  • "TNF-alpha inhibits HIV-1 replication in peripheral blood monocytes and alveolar macrophages by inducing the production of RANTES and decreasing C-C chemokine receptor 5 (CCR5) expression."
    Lane B.R., Markovitz D.M., Woodford N.L., Rochford R., Strieter R.M., Coffey M.J.
    J. Immunol. 163:3653-3661(1999) [PubMed] [Europe PMC] [Abstract]
• positive regulation of chemokine production Source: BHF-UCLInferred from direct assayⁱ
  • "TNF-alpha inhibits HIV-1 replication in peripheral blood monocytes and alveolar macrophages by inducing the production of RANTES and decreasing C-C chemokine receptor 5 (CCR5) expression."
    Lane B.R., Markovitz D.M., Woodford N.L., Rochford R., Strieter R.M., Coffey M.J.
    J. Immunol. 163:3653-3661(1999) [PubMed] [Europe PMC] [Abstract]
• positive regulation of chemokine secretion Source: ARUK-UCL
• positive regulation of chronic inflammatory response to antigenic stimulus Source: Ensembl
• positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKBInferred from direct assayⁱ
  • "Contrasting effects of IG20 and its splice isoforms, MADD and DENN-SV, on tumor necrosis factor alpha-induced apoptosis and activation of caspase-8 and -3."
    Al-Zoubi A.M., Efimova E.V., Kaithamana S., Martinez O., El-Azami El-Idrissi M., Dogan R.E., Prabhakar B.S.
    J. Biol. Chem. 276:47202-47211(2001) [PubMed] [Europe PMC] [Abstract]
• positive regulation of cytokine production Source: BHF-UCLInferred from direct assayⁱ
  • "Macrophage colony stimulating factor expression in human cardiac cells is upregulated by tumor necrosis factor-alpha via an NF-kappaB dependent mechanism."
    Hohensinner P.J., Kaun C., Rychli K., Niessner A., Pfaffenberger S., Rega G., de Martin R., Maurer G., Ullrich R., Huber K., Wojta J.
    J. Thromb. Haemost. 5:2520-2528(2007) [PubMed] [Europe PMC] [Abstract]
• positive regulation of cytokine secretion Source: BHF-UCLInferred from direct assayⁱ
  • "Tumor necrosis factor alpha decreases, and interleukin-10 increases, the sensitivity of human monocytes to dexamethasone: potential regulation of the glucocorticoid receptor."
    Franchimont D., Martens H., Hagelstein M.T., Louis E., Dewe W., Chrousos G.P., Belaiche J., Geenen V.
    J. Clin. Endocrinol. Metab. 84:2834-2839(1999) [PubMed] [Europe PMC] [Abstract]
• positive regulation of DNA-binding transcription factor activity Source: BHF-UCLInferred from direct assayⁱ
  • "A phosphatidylinositol 3-kinase/Akt pathway, activated by tumor necrosis factor or interleukin-1, inhibits apoptosis but does not activate NFkappaB in human endothelial cells."
    Madge L.A., Pober J.S.
    J. Biol. Chem. 275:15458-15465(2000) [PubMed] [Europe PMC] [Abstract]
• positive regulation of ERK1 and ERK2 cascade Source: BHF-UCLNon-traceable author statementⁱ
  • "Human osteoclast-poor osteopetrosis with hypogammaglobulinemia due to TNFRSF11A (RANK) mutations."
    Guerrini M.M., Sobacchi C., Cassani B., Abinun M., Kilic S.S., Pangrazio A., Moratto D., Mazzolari E., Clayton-Smith J., Orchard P., Coxon F.P., Helfrich M.H., Crockett J.C., Mellis D., Vellodi A., Tezcan I., Notarangelo L.D., Rogers M.J.

    , Vezzoni P., Villa A., Frattini A.
    Am. J. Hum. Genet. 83:64-76(2008) [PubMed] [Europe PMC] [Abstract]
• positive regulation of fever generation Source: BHF-UCL
• positive regulation of fractalkine biosynthetic process Source: ARUK-UCL
• positive regulation of gene expression Source: UniProtKBInferred from direct assayⁱ
  • "Isolation and characterization of human beta-defensin-3, a novel human inducible peptide antibiotic."
    Harder J., Bartels J., Christophers E., Schroeder J.-M.
    J. Biol. Chem. 276:5707-5713(2001) [PubMed] [Europe PMC] [Abstract]
  • "Proinflammatory stimuli induce galectin-9 in human mesenchymal stromal cells to suppress T-cell proliferation."
    Gieseke F., Kruchen A., Tzaribachev N., Bentzien F., Dominici M., Muller I.
    Eur. J. Immunol. 43:2741-2749(2013) [PubMed] [Europe PMC] [Abstract]
• positive regulation of glial cell proliferation Source: ARUK-UCLInferred from direct assayⁱ
  • "Proliferation of astrocytes in vitro in response to cytokines. A primary role for tumor necrosis factor."
    Selmaj K.W., Farooq M., Norton W.T., Raine C.S., Brosnan C.F.
    J. Immunol. 144:129-135(1990) [PubMed] [Europe PMC] [Abstract]
• positive regulation of hair follicle development Source: Ensembl
• positive regulation of heterotypic cell-cell adhesion Source: BHF-UCLInferred from direct assayⁱ
  • "Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin."
    Ouchi N., Kihara S., Arita Y., Maeda K., Kuriyama H., Okamoto Y., Hotta K., Nishida M., Takahashi M., Nakamura T., Yamashita S., Funahashi T., Matsuzawa Y.
    Circulation 100:2473-2476(1999) [PubMed] [Europe PMC] [Abstract]
  • "Erk5 activation elicits a vasoprotective endothelial phenotype via induction of Kruppel-like factor 4 (KLF4)."
    Ohnesorge N., Viemann D., Schmidt N., Czymai T., Spiering D., Schmolke M., Ludwig S., Roth J., Goebeler M., Schmidt M.
    J. Biol. Chem. 285:26199-26210(2010) [PubMed] [Europe PMC] [Abstract]
• positive regulation of humoral immune response mediated by circulating immunoglobulin Source: Ensembl
• positive regulation of I-kappaB kinase/NF-kappaB signaling Source: BHF-UCLInferred from direct assayⁱ
  • "AIP1/DAB2IP, a novel member of the Ras-GAP family, transduces TRAF2-induced ASK1-JNK activation."
    Zhang H., Zhang R., Luo Y., D'Alessio A., Pober J.S., Min W.
    J. Biol. Chem. 279:44955-44965(2004) [PubMed] [Europe PMC] [Abstract]
  • "Macrophage colony stimulating factor expression in human cardiac cells is upregulated by tumor necrosis factor-alpha via an NF-kappaB dependent mechanism."
    Hohensinner P.J., Kaun C., Rychli K., Niessner A., Pfaffenberger S., Rega G., de Martin R., Maurer G., Ullrich R., Huber K., Wojta J.
    J. Thromb. Haemost. 5:2520-2528(2007) [PubMed] [Europe PMC] [Abstract]
• positive regulation of inflammatory response Source: ARUK-UCLTraceable author statementⁱ
  • "Tumor necrosis factor alpha: a link between neuroinflammation and excitotoxicity."
    Olmos G., Llado J.
    Mediators Inflamm. 2014:861231-861231(2014) [PubMed] [Europe PMC] [Abstract]
• positive regulation of interferon-gamma production Source: Ensembl
• positive regulation of interleukin-6 biosynthetic process Source: ARUK-UCL
• positive regulation of interleukin-6 production Source: ARUK-UCLInferred from direct assayⁱ
  • "TNFalpha induces the expression of genes associated with endothelial dysfunction through p38MAPK-mediated down-regulation of miR-149."
    Palmieri D., Capponi S., Geroldi A., Mura M., Mandich P., Palombo D.
    Biochem. Biophys. Res. Commun. 443:246-251(2014) [PubMed] [Europe PMC] [Abstract]
• positive regulation of interleukin-6 secretion Source: ARUK-UCL
• positive regulation of interleukin-8 biosynthetic process Source: BHF-UCLInferred from direct assayⁱ
  • "Erk5 activation elicits a vasoprotective endothelial phenotype via induction of Kruppel-like factor 4 (KLF4)."
    Ohnesorge N., Viemann D., Schmidt N., Czymai T., Spiering D., Schmolke M., Ludwig S., Roth J., Goebeler M., Schmidt M.
    J. Biol. Chem. 285:26199-26210(2010) [PubMed] [Europe PMC] [Abstract]
• positive regulation of interleukin-8 production Source: UniProtKBInferred from mutant phenotypeⁱ
  • "The molecular chaperone HSP70 binds to and stabilizes NOD2, an important protein involved in Crohn disease."
    Mohanan V., Grimes C.L.
    J. Biol. Chem. 289:18987-18998(2014) [PubMed] [Europe PMC] [Abstract]
• positive regulation of JUN kinase activity Source: UniProtKBInferred from direct assayⁱ
  • "RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site is critical for tumor necrosis factor-induced ASK1-JNK/p38 activation."
    Zhang H., Zhang H., Lin Y., Li J., Pober J.S., Min W.
    J. Biol. Chem. 282:14788-14796(2007) [PubMed] [Europe PMC] [Abstract]
• positive regulation of leukocyte adhesion to arterial endothelial cell Source: BHF-UCLInferred from direct assayⁱ
  • "Site-specific microRNA-92a regulation of Kruppel-like factors 4 and 2 in atherosusceptible endothelium."
    Fang Y., Davies P.F.
    Arterioscler. Thromb. Vasc. Biol. 32:979-987(2012) [PubMed] [Europe PMC] [Abstract]
• positive regulation of leukocyte adhesion to vascular endothelial cell Source: BHF-UCLInferred from direct assayⁱ
  • "MicroRNA-141 regulates the expression level of ICAM-1 on endothelium to decrease myocardial ischemia-reperfusion injury."
    Liu R.R., Li J., Gong J.Y., Kuang F., Liu J.Y., Zhang Y.S., Ma Q.L., Song C.J., Truax A.D., Gao F., Yang K., Jin B.Q., Chen L.H.
    Am. J. Physiol. Heart Circ. Physiol. 309:H1303-13(2015) [PubMed] [Europe PMC] [Abstract]
• positive regulation of MAP kinase activity Source: UniProtKBInferred from direct assayⁱ
  • "RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site is critical for tumor necrosis factor-induced ASK1-JNK/p38 activation."
    Zhang H., Zhang H., Lin Y., Li J., Pober J.S., Min W.
    J. Biol. Chem. 282:14788-14796(2007) [PubMed] [Europe PMC] [Abstract]
• positive regulation of membrane protein ectodomain proteolysis Source: BHF-UCLInferred from direct assayⁱ
  • "The role of CXCL16 and its processing metalloproteinases ADAM10 and ADAM17 in the proliferation and migration of human mesangial cells."
    Schramme A., Abdel-Bakky M.S., Kampfer-Kolb N., Pfeilschifter J., Gutwein P.
    Biochem. Biophys. Res. Commun. 370:311-316(2008) [PubMed] [Europe PMC] [Abstract]
• positive regulation of mononuclear cell migration Source: BHF-UCLNon-traceable author statementⁱ
  • "The role of bone morphogenetic protein-5 (BMP-5) in human nephrosclerosis."
    Bramlage C.P., Muller G.A., Tampe B., Bevanda J., Maatouk I., Koziolek M., Lange K., Ahrens K., Schmid H., Cohen C.D., Bramlage P., Kretzler M., Strutz F.
    J. Nephrol. 24:647-655(2011) [PubMed] [Europe PMC] [Abstract]
• positive regulation of neuroinflammatory response Source: ARUK-UCLTraceable author statementⁱ
  • "TNF-alpha protein synthesis inhibitor restores neuronal function and reverses cognitive deficits induced by chronic neuroinflammation."
    Belarbi K., Jopson T., Tweedie D., Arellano C., Luo W., Greig N.H., Rosi S.
    J Neuroinflammation 9:23-23(2012) [PubMed] [Europe PMC] [Abstract]
  • "Role of TNF in mast cell neuroinflammation and pain."
    Gu Y., Yang D.K., Spinas E., Kritas S.K., Saggini A., Caraffa A., Antinolfi P., Saggini R., Conti P.
    J. Biol. Regul. Homeost. Agents 29:787-791(2015) [PubMed] [Europe PMC] [Abstract]
• positive regulation of neuron apoptotic process Source: ARUK-UCL
• positive regulation of NF-kappaB transcription factor activity Source: UniProtKBInferred from direct assayⁱ
  • "A pathway for tumor necrosis factor-alpha-induced Bcl10 nuclear translocation. Bcl10 is up-regulated by NF-kappaB and phosphorylated by Akt1 and then complexes with Bcl3 to enter the nucleus."
    Yeh P.Y., Kuo S.H., Yeh K.H., Chuang S.E., Hsu C.H., Chang W.C., Lin H.I., Gao M., Cheng A.L.
    J. Biol. Chem. 281:167-175(2006) [PubMed] [Europe PMC] [Abstract]
  • "Competitive control of independent programs of tumor necrosis factor receptor-induced cell death by TRADD and RIP1."
    Zheng L., Bidere N., Staudt D., Cubre A., Orenstein J., Chan F.K., Lenardo M.
    Mol. Cell. Biol. 26:3505-3513(2006) [PubMed] [Europe PMC] [Abstract]
  • "Coiled-coil domain containing 3 (CCDC3) represses tumor necrosis factor-alpha/nuclear factor kappaB-induced endothelial inflammation."
    Azad A.K., Chakrabarti S., Xu Z., Davidge S.T., Fu Y.
    Cell. Signal. 26:2793-2800(2014) [PubMed] [Europe PMC] [Abstract]
• positive regulation of NIK/NF-kappaB signaling Source: UniProtKBInferred from direct assayⁱ
  • "Bacterial effector binding to ribosomal protein s3 subverts NF-kappaB function."
    Gao X., Wan F., Mateo K., Callegari E., Wang D., Deng W., Puente J., Li F., Chaussee M.S., Finlay B.B., Lenardo M.J., Hardwidge P.R.
    PLoS Pathog. 5:E1000708-E1000708(2009) [PubMed] [Europe PMC] [Abstract]
• positive regulation of nitric oxide biosynthetic process Source: BHF-UCLInferred from direct assayⁱ
  • "Nitric oxide mediates cytokine-induced inhibition of insulin secretion by human islets of Langerhans."
    Corbett J.A., Sweetland M.A., Wang J.L., Lancaster J.R. Jr., McDaniel M.L.
    Proc. Natl. Acad. Sci. U.S.A. 90:1731-1735(1993) [PubMed] [Europe PMC] [Abstract]
• positive regulation of nitric-oxide synthase activity Source: ARUK-UCL <p>Inferred by Curator</p> <p>Used for cases where an annotation is not supported by any evidence but can be reasonably inferred by a curator from other GO annotations for which evidence <br />is available.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ic">GO evidence code guide</a></p> Inferred by curatorⁱ
  • "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 nitrogen compound metabolic process Source: ARUK-UCL
• positive regulation of osteoclast differentiation Source: BHF-UCLInferred from direct assayⁱ
  • "IL-23 induces human osteoclastogenesis via IL-17 in vitro, and anti-IL-23 antibody attenuates collagen-induced arthritis in rats."
    Yago T., Nanke Y., Kawamoto M., Furuya T., Kobashigawa T., Kamatani N., Kotake S.
    Arthritis Res. Ther. 9:R96-R96(2007) [PubMed] [Europe PMC] [Abstract]
• positive regulation of peptidyl-serine phosphorylation Source: BHF-UCLInferred from direct assayⁱ
  • "RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site is critical for tumor necrosis factor-induced ASK1-JNK/p38 activation."
    Zhang H., Zhang H., Lin Y., Li J., Pober J.S., Min W.
    J. Biol. Chem. 282:14788-14796(2007) [PubMed] [Europe PMC] [Abstract]
  • "Vascular endothelial growth factor induces heat shock protein (HSP) 27 serine 82 phosphorylation and endothelial tubulogenesis via protein kinase D and independent of p38 kinase."
    Evans I.M., Britton G., Zachary I.C.
    Cell. Signal. 20:1375-1384(2008) [PubMed] [Europe PMC] [Abstract]
• positive regulation of phagocytosis Source: AgBaseInferred from mutant phenotypeⁱ
  • "Internalization of Staphylococcus aureus by bovine endothelial cells is associated with the activity state of NF-kappaB and modulated by the pro-inflammatory cytokines TNF-alpha and IL-1beta."
    Oviedo-Boyso J., Barriga-Rivera J.G., Valdez-Alarcon J.J., Bravo-Patino A., Carabez-Trejo A., Cajero-Juarez M., Baizabal-Aguirre V.M.
    Scand. J. Immunol. 67:169-176(2008) [PubMed] [Europe PMC] [Abstract]
• positive regulation of phosphatidylinositol 3-kinase signaling Source: ARUK-UCL
• positive regulation of podosome assembly Source: BHF-UCLInferred from direct assayⁱ
  • "Eosinophils adhere to vascular cell adhesion molecule-1 via podosomes."
    Johansson M.W., Lye M.H., Barthel S.R., Duffy A.K., Annis D.S., Mosher D.F.
    Am. J. Respir. Cell Mol. Biol. 31:413-422(2004) [PubMed] [Europe PMC] [Abstract]
• positive regulation of programmed cell death Source: UniProtKBInferred from direct assayⁱ
  • "Competitive control of independent programs of tumor necrosis factor receptor-induced cell death by TRADD and RIP1."
    Zheng L., Bidere N., Staudt D., Cubre A., Orenstein J., Chan F.K., Lenardo M.
    Mol. Cell. Biol. 26:3505-3513(2006) [PubMed] [Europe PMC] [Abstract]
• positive regulation of protein catabolic process Source: AgBaseInferred from direct assayⁱ
  • "The Npro product of classical swine fever virus interacts with IkappaBalpha, the NF-kappaB inhibitor."
    Doceul V., Charleston B., Crooke H., Reid E., Powell P.P., Seago J.
    J. Gen. Virol. 89:1881-1889(2008) [PubMed] [Europe PMC] [Abstract]
• positive regulation of protein complex assembly Source: BHF-UCLInferred from direct assayⁱ
  • "AIP1 mediates TNF-alpha-induced ASK1 activation by facilitating dissociation of ASK1 from its inhibitor 14-3-3."
    Zhang R., He X., Liu W., Lu M., Hsieh J.-T., Min W.
    J. Clin. Invest. 111:1933-1943(2003) [PubMed] [Europe PMC] [Abstract]
• positive regulation of protein complex disassembly Source: UniProtKBInferred from direct assayⁱ
  • "RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site is critical for tumor necrosis factor-induced ASK1-JNK/p38 activation."
    Zhang H., Zhang H., Lin Y., Li J., Pober J.S., Min W.
    J. Biol. Chem. 282:14788-14796(2007) [PubMed] [Europe PMC] [Abstract]
• positive regulation of protein kinase activity Source: AgBaseInferred from direct assayⁱ
  • "Nonstructural 5A protein of hepatitis C virus modulates tumor necrosis factor alpha-stimulated nuclear factor kappa B activation."
    Park K.J., Choi S.H., Lee S.Y., Hwang S.B., Lai M.M.
    J. Biol. Chem. 277:13122-13128(2002) [PubMed] [Europe PMC] [Abstract]
• positive regulation of protein kinase B signaling Source: ARUK-UCL
• positive regulation of protein localization to cell surface Source: BHF-UCLInferred from direct assayⁱ
  • "Bone morphogenetic protein (BMP) and activin type II receptors balance BMP9 signals mediated by activin receptor-like kinase-1 in human pulmonary artery endothelial cells."
    Upton P.D., Davies R.J., Trembath R.C., Morrell N.W.
    J. Biol. Chem. 284:15794-15804(2009) [PubMed] [Europe PMC] [Abstract]
• positive regulation of protein localization to plasma membrane Source: ARUK-UCL
• positive regulation of protein phosphorylation Source: UniProtKBInferred from direct assayⁱ
  • "Gas6/Axl signaling activates the phosphatidylinositol 3-kinase/Akt1 survival pathway to protect oligodendrocytes from tumor necrosis factor alpha-induced apoptosis."
    Shankar S.L., O'Guin K., Kim M., Varnum B., Lemke G., Brosnan C.F., Shafit-Zagardo B.
    J. Neurosci. 26:5638-5648(2006) [PubMed] [Europe PMC] [Abstract]
  • "RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site is critical for tumor necrosis factor-induced ASK1-JNK/p38 activation."
    Zhang H., Zhang H., Lin Y., Li J., Pober J.S., Min W.
    J. Biol. Chem. 282:14788-14796(2007) [PubMed] [Europe PMC] [Abstract]
• positive regulation of protein transport Source: BHF-UCLInferred from direct assayⁱ
  • "AIP1/DAB2IP, a novel member of the Ras-GAP family, transduces TRAF2-induced ASK1-JNK activation."
    Zhang H., Zhang R., Luo Y., D'Alessio A., Pober J.S., Min W.
    J. Biol. Chem. 279:44955-44965(2004) [PubMed] [Europe PMC] [Abstract]
• positive regulation of receptor signaling pathway via JAK-STAT Source: ARUK-UCL
• positive regulation of smooth muscle cell proliferation Source: BHF-UCLInferred from direct assayⁱ
  • "Ginsenoside Rg1 inhibits tumor necrosis factor-alpha (TNF-alpha)-induced human arterial smooth muscle cells (HASMCs) proliferation."
    Zhang H.S., Wang S.Q.
    J. Cell. Biochem. 98:1471-1481(2006) [PubMed] [Europe PMC] [Abstract]
• positive regulation of superoxide dismutase activity Source: BHF-UCLInferred from direct assayⁱ
  • "MicroRNA-21 modulates the levels of reactive oxygen species by targeting SOD3 and TNFalpha."
    Zhang X., Ng W.L., Wang P., Tian L., Werner E., Wang H., Doetsch P., Wang Y.
    Cancer Res. 72:4707-4713(2012) [PubMed] [Europe PMC] [Abstract]
• positive regulation of synaptic transmission Source: ARUK-UCL
• positive regulation of transcription, DNA-templated Source: UniProtKBInferred from direct assayⁱ
  • "TNF-alpha represses transcription of human Bone Morphogenetic Protein-4 in lung epithelial cells."
    Zhu N.L., Li C., Huang H.H., Sebald M., Londhe V.A., Heisterkamp N., Warburton D., Bellusci S., Minoo P.
    Gene 393:70-80(2007) [PubMed] [Europe PMC] [Abstract]
• positive regulation of transcription by RNA polymerase II Source: UniProtKBInferred from direct assayⁱ
  • "Estrogen receptor (ER)-mediated transcriptional regulation of the human corticotropin-releasing hormone-binding protein promoter: differential effects of ERalpha and ERbeta."
    van de Stolpe A., Slycke A.J., Reinders M.O., Zomer A.W., Goodenough S., Behl C., Seasholtz A.F., van der Saag P.T.
    Mol. Endocrinol. 18:2908-2923(2004) [PubMed] [Europe PMC] [Abstract]
• positive regulation of translational initiation by iron Source: Ensembl
• positive regulation of tyrosine phosphorylation of STAT protein Source: ARUK-UCL
• positive regulation of vascular smooth muscle cell proliferation Source: Ensembl
• positive regulation of vitamin D biosynthetic process Source: BHF-UCLInferred from direct assayⁱ
  • "Tumor necrosis factor-alpha induces vitamin D-1-hydroxylase activity in normal human alveolar macrophages."
    Pryke A.M., Duggan C., White C.P., Posen S., Mason R.S.
    J. Cell. Physiol. 142:652-656(1990) [PubMed] [Europe PMC] [Abstract]
• protein kinase B signaling Source: UniProtKBInferred from mutant phenotypeⁱ
  • "Inhibitory effects of honokiol on lipopolysaccharide-induced cellular responses and signaling events in human renal mesangial cells."
    Wu F., Zhang W., Li L., Zheng F., Shao X., Zhou J., Li H.
    Eur. J. Pharmacol. 654:117-121(2011) [PubMed] [Europe PMC] [Abstract]
• protein localization to plasma membrane Source: UniProtKBInferred from direct assayⁱ
  • "Tumor necrosis factor disrupts claudin-5 endothelial tight junction barriers in two distinct NF-kappaB-dependent phases."
    Clark P.R., Kim R.K., Pober J.S., Kluger M.S.
    PLoS ONE 10:e0120075-e0120075(2015) [PubMed] [Europe PMC] [Abstract]
• receptor biosynthetic process Source: BHF-UCLInferred from direct assayⁱ
  • "Tumor necrosis factor alpha decreases, and interleukin-10 increases, the sensitivity of human monocytes to dexamethasone: potential regulation of the glucocorticoid receptor."
    Franchimont D., Martens H., Hagelstein M.T., Louis E., Dewe W., Chrousos G.P., Belaiche J., Geenen V.
    J. Clin. Endocrinol. Metab. 84:2834-2839(1999) [PubMed] [Europe PMC] [Abstract]
• regulation of branching involved in salivary gland morphogenesis Source: Ensembl
• regulation of endothelial cell apoptotic process Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "Reverse signaling through transmembrane TNF confers resistance to lipopolysaccharide in human monocytes and macrophages."
    Eissner G., Kirchner S., Lindner H., Kolch W., Janosch P., Grell M., Scheurich P., Andreesen R., Holler E.
    J. Immunol. 164:6193-6198(2000) [PubMed] [Europe PMC] [Abstract]
• regulation of establishment of endothelial barrier Source: UniProtKBInferred from direct assayⁱ
  • "Tumor necrosis factor disrupts claudin-5 endothelial tight junction barriers in two distinct NF-kappaB-dependent phases."
    Clark P.R., Kim R.K., Pober J.S., Kluger M.S.
    PLoS ONE 10:e0120075-e0120075(2015) [PubMed] [Europe PMC] [Abstract]
• regulation of fat cell differentiation Source: ARUK-UCL
• regulation of I-kappaB kinase/NF-kappaB signaling Source: BHF-UCLInferred from direct assayⁱ
  • "A phosphatidylinositol 3-kinase/Akt pathway, activated by tumor necrosis factor or interleukin-1, inhibits apoptosis but does not activate NFkappaB in human endothelial cells."
    Madge L.A., Pober J.S.
    J. Biol. Chem. 275:15458-15465(2000) [PubMed] [Europe PMC] [Abstract]
• regulation of immunoglobulin secretion Source: Ensembl
• regulation of insulin secretion Source: BHF-UCLInferred from direct assayⁱ
  • "Nitric oxide mediates cytokine-induced inhibition of insulin secretion by human islets of Langerhans."
    Corbett J.A., Sweetland M.A., Wang J.L., Lancaster J.R. Jr., McDaniel M.L.
    Proc. Natl. Acad. Sci. U.S.A. 90:1731-1735(1993) [PubMed] [Europe PMC] [Abstract]
• regulation of synapse organization Source: ARUK-UCL
• regulation of synaptic transmission, glutamatergic Source: ARUK-UCLTraceable author statementⁱ
  • "TNF-alpha protein synthesis inhibitor restores neuronal function and reverses cognitive deficits induced by chronic neuroinflammation."
    Belarbi K., Jopson T., Tweedie D., Arellano C., Luo W., Greig N.H., Rosi S.
    J Neuroinflammation 9:23-23(2012) [PubMed] [Europe PMC] [Abstract]
• regulation of transcription by RNA polymerase II Source: ARUK-UCL
• regulation of tumor necrosis factor-mediated signaling pathway Source: Reactome
• response to glucocorticoid Source: BHF-UCLInferred from direct assayⁱ
  • "Tumor necrosis factor alpha decreases, and interleukin-10 increases, the sensitivity of human monocytes to dexamethasone: potential regulation of the glucocorticoid receptor."
    Franchimont D., Martens H., Hagelstein M.T., Louis E., Dewe W., Chrousos G.P., Belaiche J., Geenen V.
    J. Clin. Endocrinol. Metab. 84:2834-2839(1999) [PubMed] [Europe PMC] [Abstract]
• response to salt stress Source: BHF-UCLTraceable author statementⁱ
  • "Ectodomain shedding of TNF-alpha is enhanced by nardilysin via activation of ADAM proteases."
    Hiraoka Y., Yoshida K., Ohno M., Matsuoka T., Kita T., Nishi E.
    Biochem. Biophys. Res. Commun. 370:154-158(2008) [PubMed] [Europe PMC] [Abstract]
• response to virus Source: BHF-UCLInferred from direct assayⁱ
  • "TNF-alpha inhibits HIV-1 replication in peripheral blood monocytes and alveolar macrophages by inducing the production of RANTES and decreasing C-C chemokine receptor 5 (CCR5) expression."
    Lane B.R., Markovitz D.M., Woodford N.L., Rochford R., Strieter R.M., Coffey M.J.
    J. Immunol. 163:3653-3661(1999) [PubMed] [Europe PMC] [Abstract]
• sequestering of triglyceride Source: BHF-UCLInferred from direct assayⁱ
  • "Interleukin-1beta and tumour necrosis factor-alpha impede neutral lipid turnover in macrophage-derived foam cells."
    Persson J., Nilsson J., Lindholm M.W.
    BMC Immunol. 9:70-70(2008) [PubMed] [Europe PMC] [Abstract]
• tumor necrosis factor-mediated signaling pathway Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "A phosphatidylinositol 3-kinase/Akt pathway, activated by tumor necrosis factor or interleukin-1, inhibits apoptosis but does not activate NFkappaB in human endothelial cells."
    Madge L.A., Pober J.S.
    J. Biol. Chem. 275:15458-15465(2000) [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

Topology

Keywords - Cellular componentⁱ

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechⁱ

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseaseⁱ

Mutagenesis

Organism-specific databases

Miscellaneous databases

Chemistry databases

Polymorphism and mutation databases

<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_processing_section">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

Miscellaneous 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_section">'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_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsⁱ

GO - Molecular functionⁱ

• cytokine activity Source: BHF-UCLInferred from direct assayⁱ
  • "A phosphatidylinositol 3-kinase/Akt pathway, activated by tumor necrosis factor or interleukin-1, inhibits apoptosis but does not activate NFkappaB in human endothelial cells."
    Madge L.A., Pober J.S.
    J. Biol. Chem. 275:15458-15465(2000) [PubMed] [Europe PMC] [Abstract]
• identical protein binding Source: BHF-UCLInferred from direct assayⁱ
  • "Inactivation of TNF signaling by rationally designed dominant-negative TNF variants."
    Steed P.M., Tansey M.G., Zalevsky J., Zhukovsky E.A., Desjarlais J.R., Szymkowski D.E., Abbott C., Carmichael D., Chan C., Cherry L., Cheung P., Chirino A.J., Chung H.H., Doberstein S.K., Eivazi A., Filikov A.V., Gao S.X., Hubert R.S.

    , Hwang M., Hyun L., Kashi S., Kim A., Kim E., Kung J., Martinez S.P., Muchhal U.S., Nguyen D.H., O'Brien C., O'Keefe D., Singer K., Vafa O., Vielmetter J., Yoder S.C., Dahiyat B.I.
    Science 301:1895-1898(2003) [PubMed] [Europe PMC] [Abstract]
• protease binding Source: BHF-UCLInferred from physical interactionⁱ
  • "Catalytic activity of ADAM8, ADAM15, and MDC-L (ADAM28) on synthetic peptide substrates and in ectodomain cleavage of CD23."
    Fourie A.M., Coles F., Moreno V., Karlsson L.
    J. Biol. Chem. 278:30469-30477(2003) [PubMed] [Europe PMC] [Abstract]
• tumor necrosis factor receptor binding Source: BHF-UCLInferred from direct assayⁱ
  • "Inactivation of TNF signaling by rationally designed dominant-negative TNF variants."
    Steed P.M., Tansey M.G., Zalevsky J., Zhukovsky E.A., Desjarlais J.R., Szymkowski D.E., Abbott C., Carmichael D., Chan C., Cherry L., Cheung P., Chirino A.J., Chung H.H., Doberstein S.K., Eivazi A., Filikov A.V., Gao S.X., Hubert R.S.

    , Hwang M., Hyun L., Kashi S., Kim A., Kim E., Kung J., Martinez S.P., Muchhal U.S., Nguyen D.H., O'Brien C., O'Keefe D., Singer K., Vafa O., Vielmetter J., Yoder S.C., Dahiyat B.I.
    Science 301:1895-1898(2003) [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

Secondary structure

3D structure databases

Miscellaneous 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_length">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>Sequence (1+)ⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">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_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">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.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

        10         20         30         40         50
MSTESMIRDV ELAEEALPKK TGGPQGSRRC LFLSLFSFLI VAGATTLFCL 
        60         70         80         90        100
LHFGVIGPQR EEFPRDLSLI SPLAQAVRSS SRTPSDKPVA HVVANPQAEG 
       110        120        130        140        150
QLQWLNRRAN ALLANGVELR DNQLVVPSEG LYLIYSQVLF KGQGCPSTHV 
       160        170        180        190        200
LLTHTISRIA VSYQTKVNLL SAIKSPCQRE TPEGAEAKPW YEPIYLGGVF 
       210        220        230 
QLEKGDRLSA EINRPDYLDF AESGQVYFGI IAL                   

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautionⁱ

Experimental Info

<p>This subsection of the ‘Sequence’ section provides information on polymorphic variants. If the variant is associated with a disease state, the description of the latter can be found in the <a href="http://www.uniprot.org/manual/involvement_in_disease">'Involvement in disease'</a> subsection.<p><a href='/help/polymorphism' target='_top'>More...</a></p>Polymorphismⁱ

Natural variant

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityⁱ

<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

• 100% Identity
• 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

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesⁱ

Sequence databases

3D structure databases