TNF - Tumor necrosis factor - human protein (Function)
 
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TNF »  Tumor necrosis factor
 
Protein also known as:  Tumor necrosis factor ligand superfamily member 2 (TNF-a). Cleaved into:  C-domain 1; C-domain 2; Intracellular domain 1; Intracellular domain 2; Tumor necrosis factor, membrane form; Tumor necrosis factor, soluble form.
Gene name:  TNF
Family name: Tumor necrosis factor
Entry whose protein(s) existence is based on evidence at protein level
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1 2680 1
GENE REF ISO

Function

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Overview 
The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.  
2
  • UniProtKB
Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T-cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Upregulates the expression of protein phosphatase 1 (PP1), which dephosphorylates the key 'Ser-418' residue of FOXP3, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed23396208).  
3
  • UniProtKB
GO molecular function 
Cytokine activitydefinition[GO:0005125]  
1
  • BHF-UCL
Identical protein bindingdefinition[GO:0042802]  
1
  • BHF-UCL
Protease bindingdefinition[GO:0002020]  
1
  • BHF-UCL
Protein bindingdefinition[GO:0005515]  
12
  • IntAct
  • UniProtKB
Transcription regulatory region DNA bindingdefinition[GO:0044212]  
1
  • UniProtKB
Tumor necrosis factor receptor bindingdefinition[GO:0005164]  
1
  • BHF-UCL
GO biological process 
Activation of cysteine-type endopeptidase activity involved in apoptotic processdefinition[GO:0006919]  
1
  • UniProtKB
Activation of MAPK activitydefinition[GO:0000187]  
1
  • BHF-UCL
Activation of MAPKKK activitydefinition[GO:0000185]  
1
  • BHF-UCL
Calcium-mediated signalingdefinition[GO:0019722] silver  
1
  • Ortholog Compara
Cell activationdefinition[GO:0001775] silver  
1
  • Ortholog Compara
Cellular response to amino acid stimulusdefinition[GO:0071230] silver  
1
  • Ortholog Compara
Cellular response to nicotinedefinition[GO:0071316]  
1
  • UniProtKB
Cellular response to organic cyclic compounddefinition[GO:0071407]  
1
  • UniProtKB
Chronic inflammatory response to antigenic stimulusdefinition[GO:0002439]  
1
  • BHF-UCL
Defense response to Gram-positive bacteriumdefinition[GO:0050830] silver  
1
  • Ortholog Compara
Detection of mechanical stimulus involved in sensory perception of paindefinition[GO:0050966] silver  
1
  • Ortholog Compara
Embryonic digestive tract developmentdefinition[GO:0048566]  
1
  • DFLAT
Epithelial cell proliferation involved in salivary gland morphogenesisdefinition[GO:0060664] silver  
1
  • Ortholog Compara
Extracellular matrix organizationdefinition[GO:0030198] silver  
1
  • Ortholog Compara
Extrinsic apoptotic signaling pathwaydefinition[GO:0097191]  
2
  • UniProtKB
Extrinsic apoptotic signaling pathway via death domain receptorsdefinition[GO:0008625]  
4
  • BHF-UCL
  • UniProtKB
Glucose metabolic processdefinition[GO:0006006] silver  
1
  • Ortholog Compara
Humoral immune responsedefinition[GO:0006959] silver  
1
  • Ortholog Compara
Inflammatory responsedefinition[GO:0006954]  
2
  • UniProtKB
  • BHF-UCL
Intrinsic apoptotic signaling pathway in response to DNA damagedefinition[GO:0008630] silver  
1
  • Ortholog Compara
JNK cascadedefinition[GO:0007254] silver  
1
  • Ortholog Compara
Leukocyte tethering or rollingdefinition[GO:0050901]  
1
  • BHF-UCL
Lipopolysaccharide-mediated signaling pathwaydefinition[GO:0031663]  
1
  • UniProtKB
MAPK cascadedefinition[GO:0000165]  
1
  • UniProtKB
Necroptotic signaling pathwaydefinition[GO:0097527]  
4
  • UniProtKB
  • BHF-UCL
Negative regulation of alkaline phosphatase activitydefinition[GO:0010693] silver  
1
  • Ortholog Compara
Negative regulation of branching involved in lung morphogenesisdefinition[GO:0061048]  
1
  • UniProtKB
Negative regulation of cell proliferationdefinition[GO:0008285] silver  
1
  • Ortholog Compara
Negative regulation of cytokine secretion involved in immune responsedefinition[GO:0002740]  
1
  • BHF-UCL
Negative regulation of extrinsic apoptotic signaling pathway in absence of liganddefinition[GO:2001240]  
2
  • BHF-UCL
Negative regulation of fat cell differentiationdefinition[GO:0045599]  
1
  • BHF-UCL
Negative regulation of gene expressiondefinition[GO:0010629]  
1
  • UniProtKB
Negative regulation of glucose importdefinition[GO:0046325] silver  
1
  • Ortholog Compara
Negative regulation of growth of symbiont in hostdefinition[GO:0044130] silver  
1
  • Ortholog Compara
Negative regulation of interleukin-6 productiondefinition[GO:0032715]  
1
  • BHF-UCL
Negative regulation of L-glutamate transportdefinition[GO:0002037] silver  
1
  • Ortholog Compara
Negative regulation of lipid catabolic processdefinition[GO:0050995]  
1
  • BHF-UCL
Negative regulation of lipid storagedefinition[GO:0010888]  
1
  • BHF-UCL
Negative regulation of myoblast differentiationdefinition[GO:0045662] silver  
1
  • Ortholog Compara
Negative regulation of osteoblast differentiationdefinition[GO:0045668] silver  
1
  • Ortholog Compara
Negative regulation of protein complex disassemblydefinition[GO:0043242]  
1
  • UniProtKB
Negative regulation of transcription from RNA polymerase II promoterdefinition[GO:0000122]  
1
  • UniProtKB
Negative regulation of transcription, DNA-templateddefinition[GO:0045892]  
2
  • UniProtKB
Negative regulation of viral genome replicationdefinition[GO:0045071]  
1
  • BHF-UCL
Osteoclast differentiationdefinition[GO:0030316] silver  
1
  • Ortholog Compara
Positive regulation of action potentialdefinition[GO:0045760] silver  
1
  • Ortholog Compara
Positive regulation of apoptotic processdefinition[GO:0043065]  
3
  • UniProtKB
Positive regulation of calcidiol 1-monooxygenase activitydefinition[GO:0060559]  
1
  • BHF-UCL
Positive regulation of chemokine (C-X-C motif) ligand 2 productiondefinition[GO:2000343]  
1
  • BHF-UCL
Positive regulation of chemokine biosynthetic processdefinition[GO:0045080]  
1
  • BHF-UCL
Positive regulation of chemokine productiondefinition[GO:0032722]  
1
  • BHF-UCL
Positive regulation of chronic inflammatory response to antigenic stimulusdefinition[GO:0002876] silver  
1
  • Ortholog Compara
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic processdefinition[GO:0043280]  
1
  • UniProtKB
Positive regulation of cytokine productiondefinition[GO:0001819]  
1
  • BHF-UCL
Positive regulation of cytokine secretiondefinition[GO:0050715]  
1
  • BHF-UCL
Positive regulation of ERK1 and ERK2 cascadedefinition[GO:0070374]  
1
  • BHF-UCL
Positive regulation of fever generationdefinition[GO:0031622]  
1
  • Ortholog Curator
Positive regulation of gene expressiondefinition[GO:0010628]  
1
  • AgBase
Positive regulation of hair follicle developmentdefinition[GO:0051798] silver  
1
  • Ortholog Compara
Positive regulation of heterotypic cell-cell adhesiondefinition[GO:0034116]  
2
  • BHF-UCL
Positive regulation of humoral immune response mediated by circulating immunoglobulindefinition[GO:0002925] silver  
1
  • Ortholog Compara
Positive regulation of I-kappaB kinase/NF-kappaB signalingdefinition[GO:0043123]  
2
  • BHF-UCL
Positive regulation of interferon-gamma productiondefinition[GO:0032729] silver  
1
  • Ortholog Compara
Positive regulation of interleukin-18 productiondefinition[GO:0032741] silver  
1
  • Ortholog Compara
Positive regulation of interleukin-6 productiondefinition[GO:0032755] silver  
1
  • Ortholog Compara
Positive regulation of interleukin-8 biosynthetic processdefinition[GO:0045416]  
1
  • BHF-UCL
Positive regulation of JUN kinase activitydefinition[GO:0043507]  
1
  • UniProtKB
Positive regulation of MAP kinase activitydefinition[GO:0043406]  
3
  • BHF-UCL
  • UniProtKB
Positive regulation of membrane protein ectodomain proteolysisdefinition[GO:0051044]  
1
  • BHF-UCL
Positive regulation of mitotic nuclear divisiondefinition[GO:0045840] silver  
1
  • Ortholog Compara
Positive regulation of mononuclear cell migrationdefinition[GO:0071677]  
1
  • BHF-UCL
Positive regulation of neuron apoptotic processdefinition[GO:0043525] silver  
1
  • Ortholog Compara
Positive regulation of NF-kappaB import into nucleusdefinition[GO:0042346]  
1
  • BHF-UCL
Positive regulation of NF-kappaB transcription factor activitydefinition[GO:0051092]  
7
  • BHF-UCL
  • UniProtKB
  • MGI
  • AgBase
Positive regulation of NFAT protein import into nucleusdefinition[GO:0051533]  
1
  • MGI
Positive regulation of nitric oxide biosynthetic processdefinition[GO:0045429]  
1
  • BHF-UCL
Positive regulation of osteoclast differentiationdefinition[GO:0045672]  
1
  • BHF-UCL
Positive regulation of peptidyl-serine phosphorylationdefinition[GO:0033138]  
2
  • BHF-UCL
Positive regulation of phagocytosisdefinition[GO:0050766]  
1
  • AgBase
Positive regulation of podosome assemblydefinition[GO:0071803]  
1
  • BHF-UCL
Positive regulation of programmed cell deathdefinition[GO:0043068]  
1
  • UniProtKB
Positive regulation of protein complex assemblydefinition[GO:0031334]  
1
  • BHF-UCL
Positive regulation of protein complex disassemblydefinition[GO:0043243]  
2
  • UniProtKB
  • BHF-UCL
Positive regulation of protein kinase activitydefinition[GO:0045860]  
1
  • AgBase
Positive regulation of protein kinase B signalingdefinition[GO:0051897] silver  
1
  • Ortholog Compara
Positive regulation of protein localization to cell surfacedefinition[GO:2000010]  
1
  • BHF-UCL
Positive regulation of protein phosphorylationdefinition[GO:0001934]  
3
  • UniProtKB
  • BHF-UCL
Positive regulation of protein transportdefinition[GO:0051222]  
1
  • BHF-UCL
Positive regulation of sequence-specific DNA binding transcription factor activitydefinition[GO:0051091]  
1
  • BHF-UCL
Positive regulation of smooth muscle cell proliferationdefinition[GO:0048661]  
1
  • BHF-UCL
Positive regulation of synaptic transmissiondefinition[GO:0050806] silver  
1
  • Ortholog Compara
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944]  
3
  • BHF-UCL
  • MGI
  • UniProtKB
Positive regulation of transcription, DNA-templateddefinition[GO:0045893]  
3
  • UniProtKB
  • BHF-UCL
Positive regulation of translational initiation by irondefinition[GO:0045994] silver  
1
  • Ortholog Compara
Positive regulation of vitamin D biosynthetic processdefinition[GO:0060557]  
1
  • BHF-UCL
Protein import into nucleus, translocationdefinition[GO:0000060]  
1
  • UniProtKB
Protein kinase B signalingdefinition[GO:0043491]  
1
  • UniProtKB
Receptor biosynthetic processdefinition[GO:0032800]  
1
  • BHF-UCL
Regulation of branching involved in salivary gland morphogenesisdefinition[GO:0060693] silver  
1
  • Ortholog Compara
Regulation of I-kappaB kinase/NF-kappaB signalingdefinition[GO:0043122]  
1
  • BHF-UCL
Regulation of immunoglobulin secretiondefinition[GO:0051023] silver  
1
  • Ortholog Compara
Regulation of insulin secretiondefinition[GO:0050796]  
1
  • BHF-UCL
Response to activitydefinition[GO:0014823] silver  
1
  • Ortholog Compara
Response to drugdefinition[GO:0042493] silver