Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Cellline Data Matrix
Gene Expression
Gene Copy Number Variation
RNA Interference
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)., The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells. Homotrimer. Interacts with SPPL2B.

4TWT deposition date (2014-07-01)
HUMAN TNFA DIMER IN COMPLEX WITH THE SEMI-SYNTHETIC BICYCLIC PEPTIDE M21
RCSB/PDB
Inspect Structure
See all 3D Structures for TNF

Isoforms / Transcripts (Protein Coding)


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

Sequences


>ENSG00000232810,ENST00000449264,ENSP00000398698,P01375

MSTESMIRDV ELAEEALPKK TGGPQGSRRC LFLSLFSFLI VAGATTLFCL 
LHFGVIGPQR EEFPRDLSLI SPLAQAVRSS SRTPSDKPVA HVVANPQAEG
QLQWLNRRAN ALLANGVELR DNQLVVPSEG LYLIYSQVLF KGQGCPSTHV
LLTHTISRIA VSYQTKVNLL SAIKSPCQRE TPEGAEAKPW YEPIYLGGVF
QLEKGDRLSA EINRPDYLDF AESGQVYFGI IAL

Drugs


TNF is targeted by Approved Drugs Etanercept, Null, Infliximab, Adalimumab, Null. (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

Mutations in Cancer


Please click the link to see mutations reported in COSMIC - Cell Lines Project
Please click the link to see mutations reported in COSMIC
Please click the link to see mutations reported in Cancer Gene Census
Please click the link to see mutations reported in ICGC
(see details)

Gene Expression


In the NCI - NCI 60 Reference panel, the highest expressing cell lines are: SR, CCRFCEM. (see details)

RNA Interference


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)

3D Structures


There are 15 structures (51 chains) solved for TNF
1 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 199 compounds (284 bioactivities), 26 compounds have bioactivities that show binding affinity of <= 500nM (27 bioactivities). (see details)