Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations

TNF (P01375) - Overview - Molecular Target Synopsis

Protein


TNF, Tumor necrosis factor
UniProt P01375

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)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
233ENSG00000232810ENST00000449264ENSP00000398698P01375-1

Drugs


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

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 raft, phagocytic cup, plasma membrane, recycling endosome.



UniProt
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)

RNA Interference


TNF was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: . (see details)

3D Structures


There are 22 structures (91 chains) solved for TNF
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 508 compounds (897 bioactivities), 308 compounds have bioactivities that show binding affinity of <= 500nM (458 bioactivities). (see details)