Tclin TNF Tumor necrosis factor

Protein Summary

Description

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 (PubMed:23396208). Key mediator of cell death in the anticancer action of BCG-stimulated neutrophils in combination with DIABLO/SMAC mimetic in the RT4v6 bladder cancer cell line (PubMed:22517918, PubMed:16829952, PubMed:23396208). Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces GKAP42 protein degradation in adipocytes which is partially responsible for TNF-induced insulin resistance (By similarity). The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells. This gene encodes a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. It can bind to, and thus functions through its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. This cytokine is involved in the regulation of a wide spectrum of biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. This cytokine has been implicated in a variety of diseases, including autoimmune diseases, insulin resistance, and cancer. Knockout studies in mice also suggested the neuroprotective function of this cytokine. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P01375
• O43647
• Q9P1Q2
• Q9UIV3

Gene Name

• TNF

Ensembl ID

• ENST00000376122
• ENSP00000365290
• ENSG00000204490
• ENST00000383496
• ENSP00000372988
• ENSG00000206439
• ENST00000412275
• ENSP00000392858
• ENSG00000228321
• ENST00000420425
• ENSP00000410668
• ENSG00000228849
• ENST00000443707
• ENSP00000389492
• ENSG00000230108
• ENST00000448781
• ENSP00000389490
• ENSG00000223952
• ENST00000449264
• ENSP00000398698
• ENSG00000232810

Symbol

• TNFA
• TNFSF2
• DIF
• TNFA
• TNFSF2
• TNLG1F
• TNF-alpha

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
biological term	1
chemical	1
virus perturbation	1
drug	0.93

Protein Classes

PANTHER Classes

Protein / Signaling Molecule / Cytokine / Tumor Necrosis Factor Family Member / Tumor Necrosis Factor

DTO Classes

Protein / Signaling / Cytokine / Tumor Necrosis Factor Family Member / Tumor Necrosis Factor

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 78397.92   (req: < 5)

Gene RIFs: 4125   (req: <= 3)

Antibodies: 4430   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 78397.92   (req: >= 5)

Gene RIFs: 4125   (req: > 3)

Antibodies: 4430   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 145

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 449

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 5