TNF, Tumor necrosis factor
Also Known as
TNFA_HUMAN, TNF, TNFA, TNFSF2
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)., The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells. Homotrimer. Interacts with SPPL2B.
Isoforms / Transcripts (Protein Coding)
TNF is targeted by Approved Drugs canSAR86, canSAR775510, canSAR13, canSAR1, canSAR775509. (see details)
UniProt: TNF is active in the following subcellular-locations: Cell membrane, Membrane, Secreted.
GO terms: TNF is active in the following subcellular-locations: cell surface, external side of plasma membrane, extracellular region, extracellular space, integral component of plasma membrane, membrane raft, phagocytic cup, plasma membrane, recycling endosome.
Gene Copy Number Variation
In COSMIC - Cell Lines Project TNF has gain in 0 cell-lines, loss in 0 cell-lines and no signal in 0 cell-lines. (see details)
In NCI60, the highest expressing cell lines are: SR, CCRF_CEM, HL_60
In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: HCC366, SU-DHL-16, RC-K8
In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: GM12878, CD20-positive B cell, SK-N-SH(see details)
TNF was reported in the following RNAI studies:
AACR Journals - Results of primary druggable genome v2 (DG2) Achilles heel siRNA screen in KMS11 multiple myeloma cells, the highest RNAi cell lines are: KMS11. (see details)
Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: . (see details)
Screening and Chemistry
TNF has been screened with 508 compounds (897 bioactivities), 308 compounds have bioactivities that show binding affinity of <= 500nM (458 bioactivities). (see details)