Tclin TNF Tumor necrosis factor

Protein Classes

PANTHER Classes

Protein / Signaling Molecule / Cytokine / Tumor Necrosis Factor Family Member / Tumor Necrosis Factor

DTO Classes

Protein / Signaling / Cytokine / Tumor Necrosis Factor Family Member / Tumor Necrosis Factor

Protein Summary

Description

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 (By similarity). The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells. This gene encodes a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. It can bind to, and thus functions through its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. This cytokine is involved in the regulation of a wide spectrum of biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. This cytokine has been implicated in a variety of diseases, including autoimmune diseases, insulin resistance, and cancer. Knockout studies in mice also suggested the neuroprotective function of this cytokine. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P01375
• O43647
• Q9P1Q2
• Q9UIV3

Gene Name

• TNF

Ensembl ID

• ENST00000376122
• ENSP00000365290
• ENSG00000204490
• ENST00000383496
• ENSP00000372988
• ENSG00000206439
• ENST00000412275
• ENSP00000392858
• ENSG00000228321
• ENST00000420425
• ENSP00000410668
• ENSG00000228849
• ENST00000443707
• ENSP00000389492
• ENSG00000230108
• ENST00000448781
• ENSP00000389490
• ENSG00000223952
• ENST00000449264
• ENSP00000398698
• ENSG00000232810

Symbol

• TNFA
• TNFSF2
• DIF
• TNFA
• TNFSF2
• TNLG1F
• TNF-alpha

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
biological term	1
chemical	1
virus perturbation	1
drug	0.93

Related Tools

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 68208.44   (req: < 5)

Gene RIFs: 4125   (req: <= 3)

Antibodies: 4430   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 68208.44   (req: >= 5)

Gene RIFs: 4125   (req: > 3)

Antibodies: 4430   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 145

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 351

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 5

Approved Drugs (5)

Explore Approved Drugs

1 – 5 of 5

adalimumab

TNFTclin

ANTIBODY BINDING :

golimumab

TNFTclin

ANTIBODY BINDING :

certolizumab pegol

TNFTclin

ANTIBODY BINDING Kd : 10.04575729

etanercept

TNFTclin

INHIBITOR :

infliximab

TNFTclin

ANTIBODY BINDING :

Active Ligands (351)

Explore Active Ligands

1 – 10 of 351

CHEMBL3644500

TNFTclin

IC50 : 8.7

CHEMBL3644498

TNFTclin

IC50 : 7.52

CHEMBL3644504

TNFTclin

IC50 : 7.54

CHEMBL3644499

TNFTclin

IC50 : 8.22

CHEMBL3644501

TNFTclin

IC50 : 8.62

CHEMBL3945875

TNFTclin

IC50 : 8.22

CHEMBL3938524

TNFTclin

IC50 : 9

CHEMBL1287882

TNFTclin

Ki : 9.21

CHEMBL1287908

TNFTclin

Ki : 9.33

CHEMBL1288211

TNFTclin

Ki : 9.38

Orthologs (8)

1 – 5 of 8

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	tumor necrosis factor		494186
Mouse	tumor necrosis factor	MGI:104798	21926
Rat	tumor necrosis factor	RGD:3876	24835
Dog	tumor necrosis factor	VGNC:47647	403922
Horse	tumor necrosis factor	VGNC:24357	100033834

Species	Name	OMA	EggNOG	Inparanoid
Chimp	tumor necrosis factor
Mouse	tumor necrosis factor
Rat	tumor necrosis factor
Dog	tumor necrosis factor
Horse	tumor necrosis factor

Protein Structure (23 Structures, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-P01375-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 5 of 23

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (154)

Reactome (15)

KEGG (59)

PathwayCommons (25)

WikiPathways (55)

Cytokine Signaling in Immune system (R-HSA-1280215)

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Find Similar Targets

Items per page:

5

1 – 5 of 15

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Cytokine Signaling in Immune system	922 targets	R-HSA-1280215
Reactome	Death Receptor Signalling	141 targets	R-HSA-73887
Reactome	Developmental Biology	1055 targets	R-HSA-1266738
Reactome	Immune System	2246 targets	R-HSA-168256
Reactome	Interleukin-10 signaling	45 targets	R-HSA-6783783

Name	Explore in Pharos	Explore in Source
Cytokine Signaling in Immune system	922 targets	R-HSA-1280215
Death Receptor Signalling	141 targets	R-HSA-73887
Developmental Biology	1055 targets	R-HSA-1266738
Immune System	2246 targets	R-HSA-168256
Interleukin-10 signaling	45 targets	R-HSA-6783783

Gene Ontology Terms (156)

Functions (6)

Components (11)

Processes (139)

Find Similar Targets

Items per page:

10

1 – 6 of 6

GO Term	Evidence	Assigned by
cytokine activity	Inferred from Direct Assay (IDA)	BHF-UCL
identical protein binding	Inferred from Direct Assay (IDA)	BHF-UCL
transcription regulatory region DNA binding	Inferred from Direct Assay (IDA)	UniProtKB
tumor necrosis factor receptor binding	Inferred from Direct Assay (IDA)	BHF-UCL
protease binding	Inferred from Physical Interaction (IPI)	BHF-UCL
RNA polymerase II regulatory region sequence-specific DNA binding	Inferred from Sequence or structural Similarity (ISS)	ARUK-UCL

Protein-Protein Interactions (1287)

Explore Interacting Targets

1 – 10 of 1287

• See Interactions on String-DB

TNFRSF1A

Tchem

Novelty: 0.00037847

p_int: 0.999996794

p_ni: 0.000002275

p_wrong: 9.3e-7

Score: 0.999

Data Source: BioPlex,Reactome,STRINGDB

DAG1

Tbio

Family: Enzyme

Novelty: 0.00149278

p_int: 0.997018043

p_ni: 0.002981832

p_wrong: 1.25e-7

Score: 0.205

Data Source: BioPlex,STRINGDB

HSPA13

Tbio

Novelty: 0.03895652

p_int: 0.988975416

p_ni: 0.011024584

Score: 0.603

Data Source: BioPlex,STRINGDB

GUF1

Tbio

Novelty: 0.00422028

p_int: 0.979527956

p_ni: 0.019640972

p_wrong: 0.000831072

Score: 0.2

Data Source: BioPlex,STRINGDB

SFXN5

Tdark

Novelty: 0.30379915

p_int: 0.974090509

p_ni: 0.024865901

p_wrong: 0.00104359

Data Source: BioPlex

NEK7

Tchem

Family: Kinase

Novelty: 0.02675561

p_int: 0.973352473

p_ni: 0.02658634

p_wrong: 0.000061187

Score: 0.161

Data Source: BioPlex,STRINGDB

PLXNA2

Tbio

Novelty: 0.01765957

p_int: 0.963544518

p_ni: 0.036404988

p_wrong: 0.000050495

Score: 0.153

Data Source: BioPlex,STRINGDB

GK

Tbio

Family: Kinase

Novelty: 0.00617547

p_int: 0.961262842

p_ni: 0.038737158

Score: 0.202

Data Source: BioPlex,STRINGDB

CAPNS1

Tbio

Novelty: 0.00954566

p_int: 0.960139914

p_ni: 0.039860086

Score: 0.328

Data Source: BioPlex,STRINGDB

HSPA12A

Tbio

Novelty: 0.11999085

p_int: 0.956488665

p_ni: 0.043511328

p_wrong: 7e-9

Data Source: BioPlex

Publication Statistics

PubMed Score  68208.44

PubMed score by year

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PubTator Score  45431.67

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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Myristate

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