General Information of Target

Target ID LDTP01860
Target Name Tumor necrosis factor (TNF)
Gene Name TNF
Gene ID 7124
Synonyms
TNFA; TNFSF2; Tumor necrosis factor; Cachectin; TNF-alpha; Tumor necrosis factor ligand superfamily member 2; TNF-a) [Cleaved into: Tumor necrosis factor, membrane form; N-terminal fragment; NTF; Intracellular domain 1; ICD1; Intracellular domain 2; ICD2; C-domain 1; C-domain 2; Tumor necrosis factor, soluble form]
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MSTESMIRDVELAEEALPKKTGGPQGSRRCLFLSLFSFLIVAGATTLFCLLHFGVIGPQR
EEFPRDLSLISPLAQAVRSSSRTPSDKPVAHVVANPQAEGQLQWLNRRANALLANGVELR
DNQLVVPSEGLYLIYSQVLFKGQGCPSTHVLLTHTISRIAVSYQTKVNLLSAIKSPCQRE
TPEGAEAKPWYEPIYLGGVFQLEKGDRLSAEINRPDYLDFAESGQVYFGIIAL
Target Type
Successful
Target Bioclass
Cytokine and receptor
Family
Tumor necrosis factor family
Subcellular location
Secreted; Membrane; Cell membrane
Function
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. Up-regulates 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. 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. 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. Plays a role in angiogenesis by inducing VEGF production synergistically with IL1B and IL6. Promotes osteoclastogenesis and therefore mediates bone resorption.; The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.
TTD ID
T20178
Uniprot ID
P01375
DrugMap ID
TTW86QI
Ensemble ID
ENST00000376122.3
HGNC ID
HGNC:11892
ChEMBL ID
CHEMBL1825

Probe(s) Labeling This Target

PAL-AfBPP Probe
Click To Hide/Show 1 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
STS-1
 Probe Info 
N.A.  LDD0136  [1]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 4 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
rRNA methyltransferase 3, mitochondrial (MRM3) RNA methyltransferase TrmH family Q9HC36
NADH-cytochrome b5 reductase 3 (CYB5R3) Flavoprotein pyridine nucleotide cytochrome reductase family P00387
E3 ubiquitin-protein ligase RNF19B (RNF19B) RBR family Q6ZMZ0
Type 2 phosphatidylinositol 4,5-bisphosphate 4-phosphatase (PIP4P2) . Q8N4L2
Transporter and channel
Click To Hide/Show 8 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Amyloid-beta precursor protein (APP) APP family P05067
Stomatin (STOM) Band 7/mec-2 family P27105
Probable proton-coupled zinc antiporter SLC30A4 (SLC30A4) Cation diffusion facilitator (CDF) transporter (TC 2.A.4) family O14863
Claudin-7 (CLDN7) Claudin family O95471
Aquaporin-3 (AQP3) MIP/aquaporin (TC 1.A.8) family Q92482
Pannexin-1 (PANX1) Pannexin family Q96RD7
Syntaxin-1A (STX1A) Syntaxin family Q16623
Urea transporter 2 (SLC14A2) Urea transporter family Q15849
Transcription factor
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Cyclic AMP-responsive element-binding protein 3-like protein 1 (CREB3L1) BZIP family Q96BA8
GPCR
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Free fatty acid receptor 2 (FFAR2) G-protein coupled receptor 1 family O15552
Immunoglobulin
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
V-type immunoglobulin domain-containing suppressor of T-cell activation (VSIR) . Q9H7M9
Cytokine and receptor
Click To Hide/Show 3 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Tumor necrosis factor (TNF) Tumor necrosis factor family P01375
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) . P19438
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) . P20333
Other
Click To Hide/Show 15 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Bcl-2-like protein 13 (BCL2L13) Bcl-2 family Q9BXK5
Protein FAM209A (FAM209A) FAM209 family Q5JX71
P antigen family member 1 (PAGE1) GAGE family O75459
Leucine-rich repeat transmembrane neuronal protein 2 (LRRTM2) LRRTM family O43300
Beta-sarcoglycan (SGCB) Sarcoglycan beta/delta/gamma/zeta family Q16585
Zinc finger CCHC domain-containing protein 12 (ZCCHC12) ZCCHC12 family Q6PEW1
C-type lectin domain family 10 member A (CLEC10A) . Q8IUN9
Coiled-coil domain-containing protein 107 (CCDC107) . Q8WV48
Coiled-coil domain-containing protein 70 (CCDC70) . Q6NSX1
Fibronectin type III domain-containing protein 9 (FNDC9) . Q8TBE3
Leucine-rich repeat-containing protein 25 (LRRC25) . Q8N386
NF-kappa-B essential modulator (IKBKG) . Q9Y6K9
Pleckstrin homology domain-containing family O member 1 (PLEKHO1) . Q53GL0
Protein KASH5 (KASH5) . Q8N6L0
Serine-rich single-pass membrane protein 1 (SSMEM1) . Q8WWF3

The Drug(s) Related To This Target

Approved
Click To Hide/Show 15 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Adalimumab Antibody DB00051
Golimumab Antibody DB06674
Infliximab Antibody DB00065
Certolizumab Pegol BiotechDrug DB08904
Etanercept Monoclonal antibody DB00005
Amrinone Small molecular drug DB01427
Binimetinib Small molecular drug DB11967
Chloroquine Small molecular drug DB00608
Clenbuterol Small molecular drug DB01407
Epinephrine Small molecular drug DB00668
Pomalidomide Small molecular drug DB08910
Pseudoephedrine Small molecular drug DB00852
Foreskin Fibroblast (Neonatal) . DB10770
Foreskin Keratinocyte (Neonatal) . DB10772
Glycyrrhizic Acid . DB13751
Investigative
Click To Hide/Show 22 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Ame-527 Antibody DB05879
Atiprimod Small molecular drug DB05513
Dexanabinol Small molecular drug DB06444
Dilmapimod Small molecular drug DB12140
Plinabulin Small molecular drug DB05992
Pranlukast Small molecular drug DB01411
Talmapimod Small molecular drug DB05412
Trichostatin A Small molecular drug DB04297
Vx-702 Small molecular drug DB05470
Afelimomab . DB04956
Andrographolide . DB05767
Bryostatin 1 . DB11752
Crx-139 . DB05744
Cyt007-tnfqb . DB05758
Ethyl Pyruvate . DB05869
Oms-103hp . DB05303
Onercept . DB06495
Pn0621 . DB05218
Polaprezinc . DB09221
Pr-104 . DB05968
Sd118 . DB05207
Ysil6 . DB05017
Discontinued
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Isis 104838 Antisense drug D0FX3P
Pnu-282987 Small molecular drug D06LKM

References

1 Design and synthesis of minimalist terminal alkyne-containing diazirine photo-crosslinkers and their incorporation into kinase inhibitors for cell- and tissue-based proteome profiling. Angew Chem Int Ed Engl. 2013 Aug 12;52(33):8551-6. doi: 10.1002/anie.201300683. Epub 2013 Jun 10.