Molecular Target Synopsis
Domains and Structures
Drugs and Clinical Candidates
Ligand Efficiency Plot
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
Germline Genetics

TNF (P01375) - Overview - Molecular Target Synopsis


TNF, Tumor necrosis factor
UniProt P01375


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., The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells. Homotrimer. Interacts with SPPL2B.

Isoforms / Transcripts (Protein Coding)

Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform


TNF is targeted by Approved Drugs Adalimumab, Infliximab, Golimumab, Etanercept, Certolizumab Pegol. (see details)
Certolizumab Pegol

Sub-cellular localization

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, membrane raft, phagocytic cup, plasma membrane, protein-containing complex, recycling endosome.

GO terms

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)

Gene Expression

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)

3D Structures

For TNF there are:
23 structures (97 chains) solved
4 are solved in complex with at least one small molecule ligand

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry

TNF has been screened with 574 compounds (1086 bioactivities), 320 compounds have bioactivities that show binding affinity of <= 500nM (467 bioactivities). (see details)