Summary

Name TNF
Full Name Tumor necrosis factor
Synonyms Cachectin, TNF-alpha, Tumor necrosis factor ligand superfamily member 2, TNF-a | TNFA, TNFSF2
Primary ID P01375
Links - -
Type protein
Relations 100
Pathways Alzheimer, COVID-19 Causal Network, Death Receptor Signaling, EBV infection, FAP: Glucocorticoids, FAP: miRNA and adipogensis, Inflammosome Activation, Inhibition of Apoptosis, Macrophage: Polarization and myogenesis, Macrophage: TNF alpha, Mitochondrial Control of Apoptosis, Multiple sclerosis, NF-KB Canonical, P38 Signaling, P38 Signaling and Myogenesis, SARS-COV APOPTOSIS, SARS-CoV CYTOKINE STORM, SARS-CoV INFLAMMATORY RESPONSE, Satellite: TNFA, TNF-alpha Signaling, Thyroid Hormone Metabolism, Tnfa_Notch_crosstalk
Inhibitors doramapimod
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. 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). Plays a role in angiogenesis by inducing VEGF production synergistically with IL1B and IL6 (PubMed:12794819).

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Modifications Tables

Relations

Regulator Mechanism target score
+ up-regulates img/direct-activation.png deacetylation TNF 0.323
Publications: 2 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png post transcriptional regulation TNF 0.2
Publications: 1
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation SCN4A 0.262
Publications: 1 Organism: Mus Musculus
+ down-regulates img/indirect_inhibition.png Adipogenesis 0.7
Publications: 1 Organism: Homo Sapiens
Pathways:MTOR Signaling, Thyroid Hormone Metabolism
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation TNF 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation SCN1A 0.262
Publications: 1 Organism: Mus Musculus
+ up-regulates img/indirect-activation.png Demyelination 0.7
Publications: 1 Organism: Homo Sapiens
Pathways:Multiple sclerosis
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation NOTCH1 0.495
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png Inflammation 0.7
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, EBV infection, Inflammosome Activation, Multiple sclerosis, NF-KB Canonical, SARS-CoV CYTOKINE STORM, SARS-CoV INFLAMMATORY RESPONSE, TNF-alpha Signaling
+ up-regulates img/indirect-activation.png PIK3CB 0.258
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation BMP4 0.324
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity img/indirect-activation.png TNF 0.7
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation IL6 0.528
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, Multiple sclerosis, SARS-CoV CYTOKINE STORM
+ up-regulates img/indirect-activation.png AKT2 0.327
Publications: 1 Organism: Homo Sapiens
Pathways:P38 Signaling and Myogenesis
+ up-regulates activity img/direct-activation.png binding TNFRSF1A 0.923
Publications: 6 Organism: Homo Sapiens
Pathways:Alzheimer, COVID-19 Causal Network, Death Receptor Signaling, Inhibition of Apoptosis, Mitochondrial Control of Apoptosis, Multiple sclerosis, NF-KB Canonical, P38 Signaling, P38 Signaling and Myogenesis, SARS-COV APOPTOSIS, TNF-alpha Signaling
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation SNAI2 0.316
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/indirect_inhibition.png LZTR1 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity img/indirect_inhibition.png TNF 0.7
Publications: 1
+ up-regulates img/indirect-activation.png MPO-ANCA 0.2
Publications: 1 Organism: Mus Musculus
Tissue: Blood Serum
+ down-regulates activity img/direct_inhibition.png binding TNF 0.4
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation SCN10A 0.282
Publications: 1 Organism: Mus Musculus
+ down-regulates img/direct_inhibition.png chemical inhibition TNF 0.8
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation TNF 0.468
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation NOTCH4 0.319
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation DIO 0.262
Publications: 2 Organism: Rattus Norvegicus
+ up-regulates activity img/direct-activation.png binding TNFRSF1B 0.928
Publications: 3 Organism: , Homo Sapiens
+ up-regulates img/indirect-activation.png AKT1 0.502
Publications: 1 Organism: Homo Sapiens
Pathways:P38 Signaling and Myogenesis
+ up-regulates img/indirect-activation.png TNF 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding PIK3CG 0.303
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation NOD2 0.433
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation SCN8A 0.2
Publications: 1 Organism: Mus Musculus
+ down-regulates activity img/indirect_inhibition.png transcriptional regulation MC1R 0.296
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation TNF 0.514
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png TNF 0.342
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/indirect-activation.png SCN1A 0.262
Publications: 1 Organism: Mus Musculus
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation JAG2 0.325
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation TNF 0.32
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/indirect_inhibition.png IRS1 0.411
Publications: 1 Organism: Homo Sapiens
Pathways:MTOR Signaling
+ up-regulates img/indirect-activation.png ARDS 0.7
Publications: 1 Organism: Homo Sapiens
Pathways:SARS-CoV CYTOKINE STORM
+ up-regulates activity img/indirect-activation.png SCN11A 0.2
Publications: 1 Organism: Mus Musculus
+ down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation SCNN1A 0.314
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png AKT 0.502
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, EBV infection, Inflammosome Activation, Inhibition of Apoptosis, MTOR Signaling, SARS-COV APOPTOSIS, SARS-CoV INFLAMMATORY RESPONSE, Thyroid Hormone Metabolism
+ up-regulates img/indirect-activation.png TNF 0.7
Publications: 1 Organism: Homo Sapiens
Pathways:Multiple sclerosis
+ up-regulates activity img/indirect-activation.png PIK3CA 0.278
Publications: 1 Organism: Mus Musculus
Pathways:MTOR Signaling
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation RIPK2 0.365
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/indirect-activation.png SCN10A 0.282
Publications: 1 Organism: Mus Musculus
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation TNF 0.666
Publications: 1 Organism: Homo Sapiens
Tissue: Skeletal Muscle
Pathways:COVID-19 Causal Network, EBV infection, Inflammosome Activation, Inhibition of Apoptosis, Multiple sclerosis, NF-KB Canonical, SARS-CoV CYTOKINE STORM, SARS-CoV INFLAMMATORY RESPONSE, TNF-alpha Signaling
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation CTSK 0.371
Publications: 1
+ down-regulates activity img/direct_inhibition.png binding TNF 0.4
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation SCN11A 0.2
Publications: 1 Organism: Mus Musculus
+ up-regulates img/indirect-activation.png REL 0.43
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/indirect-activation.png PI3K 0.327
Publications: 1 Organism: Mus Musculus
Pathways:COVID-19 Causal Network, EBV infection, Inflammosome Activation, SARS-CoV INFLAMMATORY RESPONSE, Thyroid Hormone Metabolism
+ up-regulates activity img/indirect-activation.png MAPK14 0.632
Publications: 1 Organism: Homo Sapiens
Pathways:P38 Signaling, P38 Signaling and Myogenesis, TNF-alpha Signaling
+ down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation TNF 0.296
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation SCN5A 0.2
Publications: 1 Organism: Mus Musculus
+ up-regulates activity img/indirect-activation.png Inflammation 0.7
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, EBV infection, Inflammosome Activation, Multiple sclerosis, NF-KB Canonical, SARS-CoV CYTOKINE STORM, SARS-CoV INFLAMMATORY RESPONSE, TNF-alpha Signaling
+ up-regulates img/indirect-activation.png PIK3CD 0.269
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation LPL 0.406
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/indirect-activation.png SCN5A 0.2
Publications: 1 Organism: Mus Musculus
+ up-regulates activity img/indirect-activation.png SCN3A 0.2
Publications: 1 Organism: Mus Musculus
+ down-regulates activity img/direct_inhibition.png binding TNF 0.4
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png binding TNF 0.4
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation SCN2A 0.262
Publications: 1 Organism: Mus Musculus
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation HES1 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png TNF 0.7
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/indirect-activation.png SCN2A 0.262
Publications: 1 Organism: Mus Musculus
+ up-regulates activity img/indirect-activation.png NfKb-p65/p50 0.666
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, EBV infection, Inflammosome Activation, Inhibition of Apoptosis, Multiple sclerosis, NF-KB Canonical, SARS-CoV CYTOKINE STORM, SARS-CoV INFLAMMATORY RESPONSE, TNF-alpha Signaling
+ down-regulates quantity img/indirect_inhibition.png TNF 0.8
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, SARS-CoV CYTOKINE STORM
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation SCN9A 0.256
Publications: 1 Organism: Mus Musculus
+ up-regulates img/direct-activation.png binding TNFRSF21 0.348
Publications: 1 Organism: Homo Sapiens
Tissue: Brain
Pathways:Multiple sclerosis
+ down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation COMT 0.297
Publications: 1 Organism: Rattus Norvegicus
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation TNF 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation TNF 0.343
Publications: 1 Organism: Mus Musculus
+ up-regulates quantity img/indirect-activation.png TNF 0.2
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, SARS-COV APOPTOSIS, SARS-CoV CYTOKINE STORM, SARS-CoV INFLAMMATORY RESPONSE
+ up-regulates quantity img/indirect-activation.png TNF 0.467
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity img/direct-activation.png cleavage TNF 0.692
Publications: 1 Organism: Homo Sapiens
Pathways:P38 Signaling and Myogenesis
+ down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation DIO1 0.2
Publications: 1 Organism: Rattus Norvegicus
Pathways:Thyroid Hormone Metabolism
+ up-regulates activity img/indirect-activation.png SCN9A 0.256
Publications: 1 Organism: Mus Musculus
+ down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation TNF 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/indirect-activation.png GCH1 0.251
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation DNAH10 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png Angiogenesis 0.7
Publications: 1
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation SCN3A 0.2
Publications: 1 Organism: Mus Musculus
+ down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation TNF 0.319
Publications: 1 Organism: Mus Musculus
+ up-regulates activity img/indirect-activation.png SCN4A 0.262
Publications: 1 Organism: Mus Musculus
+ down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation TNF 0.341
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation SERPINA3 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/indirect-activation.png SCN8A 0.2
Publications: 1 Organism: Mus Musculus
+ down-regulates activity img/direct_inhibition.png binding TNF 0.8
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation TNF 0.308
Publications: 1 Organism: Homo Sapiens