TNF
UniProt ID: P01375
Entrez ID: 7124
Protein name: 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]
External links: UniprotKB HGNC RefSeq COSMIC
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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 cache...
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 (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). {ECO:0000250|UniProtKB:P06804, ECO:0000269|PubMed:12794819, ECO:0000269|PubMed:16829952, ECO:0000269|PubMed:22517918, ECO:0000269|PubMed:23396208}.; FUNCTION: The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells. {ECO:0000269|PubMed:16829952}.
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GO - Biological processes (BP):
activation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0006919]; acute inflammatory response [GO:0002526]; astrocyte activation [GO:0048143]; calcium-mediated signaling [GO:0019722]; cellular response to amino acid stimulus [GO:0071230]; cellular response to amyloid-bet...
activation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0006919]; acute inflammatory response [GO:0002526]; astrocyte activation [GO:0048143]; calcium-mediated signaling [GO:0019722]; cellular response to amino acid stimulus [GO:0071230]; cellular response to amyloid-beta [GO:1904646]; cellular response to interferon-gamma [GO:0071346]; cellular response to nicotine [GO:0071316]; cellular response to organic cyclic compound [GO:0071407]; cellular response to retinoic acid [GO:0071300]; cellular response to toxic substance [GO:0097237]; chronic inflammatory response to antigenic stimulus [GO:0002439]; circadian rhythm [GO:0007623]; cognition [GO:0050890]; cortical actin cytoskeleton organization [GO:0030866]; defense response to Gram-positive bacterium [GO:0050830]; detection of mechanical stimulus involved in sensory perception of pain [GO:0050966]; embryonic digestive tract development [GO:0048566]; endothelial cell apoptotic process [GO:0072577]; epithelial cell proliferation involved in salivary gland morphogenesis [GO:0060664]; extracellular matrix organization [GO:0030198]; extrinsic apoptotic signaling pathway [GO:0097191]; extrinsic apoptotic signaling pathway via death domain receptors [GO:0008625]; glucose metabolic process [GO:0006006]; humoral immune response [GO:0006959]; inflammatory response [GO:0006954]; intrinsic apoptotic signaling pathway in response to DNA damage [GO:0008630]; JNK cascade [GO:0007254]; leukocyte migration involved in inflammatory response [GO:0002523]; leukocyte tethering or rolling [GO:0050901]; lipopolysaccharide-mediated signaling pathway [GO:0031663]; liver regeneration [GO:0097421]; MAPK cascade [GO:0000165]; microglial cell activation [GO:0001774]; necroptotic signaling pathway [GO:0097527]; negative regulation of alkaline phosphatase activity [GO:0010693]; negative regulation of amyloid-beta clearance [GO:1900222]; negative regulation of apoptotic signaling pathway [GO:2001234]; negative regulation of bicellular tight junction assembly [GO:1903347]; negative regulation of bile acid secretion [GO:0120190]; negative regulation of blood vessel endothelial cell migration [GO:0043537]; negative regulation of branching involved in lung morphogenesis [GO:0061048]; negative regulation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0043154]; negative regulation of cytokine production involved in immune response [GO:0002719]; negative regulation of endothelial cell proliferation [GO:0001937]; negative regulation of extrinsic apoptotic signaling pathway in absence of ligand [GO:2001240]; negative regulation of fat cell differentiation [GO:0045599]; negative regulation of gene expression [GO:0010629]; negative regulation of glucose import [GO:0046325]; negative regulation of heart rate [GO:0010459]; negative regulation of interleukin-6 production [GO:0032715]; negative regulation of L-glutamate import across plasma membrane [GO:0002037]; negative regulation of lipid catabolic process [GO:0050995]; negative regulation of lipid storage [GO:0010888]; negative regulation of mitotic cell cycle [GO:0045930]; negative regulation of myelination [GO:0031642]; negative regulation of myoblast differentiation [GO:0045662]; negative regulation of myosin-light-chain-phosphatase activity [GO:0035509]; negative regulation of neurogenesis [GO:0050768]; negative regulation of osteoblast differentiation [GO:0045668]; negative regulation of oxidative phosphorylation [GO:0090324]; negative regulation of production of miRNAs involved in gene silencing by miRNA [GO:1903799]; negative regulation of protein-containing complex disassembly [GO:0043242]; negative regulation of signaling receptor activity [GO:2000272]; negative regulation of systemic arterial blood pressure [GO:0003085]; negative regulation of transcription, DNA-templated [GO:0045892]; negative regulation of transcription by RNA polymerase II [GO:0000122]; negative regulation of vascular wound healing [GO:0061044]; negative regulation of viral genome replication [GO:0045071]; osteoclast differentiation [GO:0030316]; positive regulation of action potential [GO:0045760]; positive regulation of amyloid-beta formation [GO:1902004]; positive regulation of apoptotic process [GO:0043065]; positive regulation of blood microparticle formation [GO:2000334]; positive regulation of calcidiol 1-monooxygenase activity [GO:0060559]; positive regulation of calcineurin-NFAT signaling cascade [GO:0070886]; positive regulation of cell adhesion [GO:0045785]; positive regulation of chemokine (C-X-C motif) ligand 2 production [GO:2000343]; positive regulation of chemokine production [GO:0032722]; positive regulation of chronic inflammatory response to antigenic stimulus [GO:0002876]; positive regulation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0043280]; positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis [GO:2001272]; positive regulation of cytokine production [GO:0001819]; positive regulation of cytokine production involved in inflammatory response [GO:1900017]; positive regulation of DNA-binding transcription factor activity [GO:0051091]; positive regulation of DNA biosynthetic process [GO:2000573]; positive regulation of ERK1 and ERK2 cascade [GO:0070374]; positive regulation of extrinsic apoptotic signaling pathway [GO:2001238]; positive regulation of fever generation [GO:0031622]; positive regulation of fractalkine production [GO:0032724]; positive regulation of gene expression [GO:0010628]; positive regulation of glial cell proliferation [GO:0060252]; positive regulation of hair follicle development [GO:0051798]; positive regulation of hepatocyte proliferation [GO:2000347]; positive regulation of heterotypic cell-cell adhesion [GO:0034116]; positive regulation of humoral immune response mediated by circulating immunoglobulin [GO:0002925]; positive regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043123]; positive regulation of I-kappaB phosphorylation [GO:1903721]; positive regulation of inflammatory response [GO:0050729]; positive regulation of interferon-gamma production [GO:0032729]; positive regulation of interleukin-18 production [GO:0032741]; positive regulation of interleukin-1 beta production [GO:0032731]; positive regulation of interleukin-33 production [GO:0150129]; positive regulation of interleukin-6 production [GO:0032755]; positive regulation of interleukin-8 production [GO:0032757]; positive regulation of JNK cascade [GO:0046330]; positive regulation of JUN kinase activity [GO:0043507]; positive regulation of leukocyte adhesion to arterial endothelial cell [GO:1904999]; positive regulation of leukocyte adhesion to vascular endothelial cell [GO:1904996]; positive regulation of MAPK cascade [GO:0043410]; positive regulation of MAP kinase activity [GO:0043406]; positive regulation of membrane protein ectodomain proteolysis [GO:0051044]; positive regulation of miRNA transcription [GO:1902895]; positive regulation of mitotic nuclear division [GO:0045840]; positive regulation of mononuclear cell migration [GO:0071677]; positive regulation of neuroinflammatory response [GO:0150078]; positive regulation of neuron apoptotic process [GO:0043525]; positive regulation of neutrophil activation [GO:1902565]; positive regulation of NF-kappaB transcription factor activity [GO:0051092]; positive regulation of NIK/NF-kappaB signaling [GO:1901224]; positive regulation of nitric oxide biosynthetic process [GO:0045429]; positive regulation of nitric-oxide synthase activity [GO:0051000]; positive regulation of nitrogen compound metabolic process [GO:0051173]; positive regulation of osteoclast differentiation [GO:0045672]; positive regulation of oxidative stress-induced neuron death [GO:1903223]; positive regulation of peptidyl-serine phosphorylation [GO:0033138]; positive regulation of phagocytosis [GO:0050766]; positive regulation of phosphatidylinositol 3-kinase signaling [GO:0014068]; positive regulation of podosome assembly [GO:0071803]; positive regulation of programmed cell death [GO:0043068]; positive regulation of protein catabolic process [GO:0045732]; positive regulation of protein-containing complex assembly [GO:0031334]; positive regulation of protein-containing complex disassembly [GO:0043243]; positive regulation of protein kinase activity [GO:0045860]; positive regulation of protein kinase B signaling [GO:0051897]; positive regulation of protein localization to cell surface [GO:2000010]; positive regulation of protein localization to plasma membrane [GO:1903078]; positive regulation of protein phosphorylation [GO:0001934]; positive regulation of protein transport [GO:0051222]; positive regulation of receptor signaling pathway via JAK-STAT [GO:0046427]; positive regulation of smooth muscle cell proliferation [GO:0048661]; positive regulation of superoxide dismutase activity [GO:1901671]; positive regulation of synaptic transmission [GO:0050806]; positive regulation of synoviocyte proliferation [GO:1901647]; positive regulation of transcription, DNA-templated [GO:0045893]; positive regulation of transcription by RNA polymerase II [GO:0045944]; positive regulation of translational initiation by iron [GO:0045994]; positive regulation of tyrosine phosphorylation of STAT protein [GO:0042531]; positive regulation of vascular associated smooth muscle cell proliferation [GO:1904707]; positive regulation of vitamin D biosynthetic process [GO:0060557]; protein kinase B signaling [GO:0043491]; protein localization to plasma membrane [GO:0072659]; regulation of branching involved in salivary gland morphogenesis [GO:0060693]; regulation of endothelial cell apoptotic process [GO:2000351]; regulation of establishment of endothelial barrier [GO:1903140]; regulation of fat cell differentiation [GO:0045598]; regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043122]; regulation of immunoglobulin production [GO:0002637]; regulation of insulin secretion [GO:0050796]; regulation of reactive oxygen species metabolic process [GO:2000377]; regulation of synapse organization [GO:0050807]; regulation of synaptic transmission, glutamatergic [GO:0051966]; regulation of transcription by RNA polymerase II [GO:0006357]; response to 3,3',5-triiodo-L-thyronine [GO:1905242]; response to activity [GO:0014823]; response to ethanol [GO:0045471]; response to glucocorticoid [GO:0051384]; response to gold nanoparticle [GO:1990268]; response to Gram-negative bacterium [GO:0140460]; response to hypoxia [GO:0001666]; response to nutrient levels [GO:0031667]; response to paracetamol [GO:1901554]; response to radiation [GO:0009314]; response to salt stress [GO:0009651]; response to virus [GO:0009615]; response to xenobiotic stimulus [GO:0009410]; sequestering of triglyceride [GO:0030730]; skeletal muscle contraction [GO:0003009]; toll-like receptor 3 signaling pathway [GO:0034138]; tumor necrosis factor-mediated signaling pathway [GO:0033209]; vascular endothelial growth factor production [GO:0010573]; vasodilation [GO:0042311]
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GO - Molecular function (MF):
cytokine activity [GO:0005125]; identical protein binding [GO:0042802]; protease binding [GO:0002020]; transcription cis-regulatory region binding [GO:0000976]; tumor necrosis factor receptor binding [GO:0005164]...
cytokine activity [GO:0005125]; identical protein binding [GO:0042802]; protease binding [GO:0002020]; transcription cis-regulatory region binding [GO:0000976]; tumor necrosis factor receptor binding [GO:0005164]
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GO - Cellular component (CC):
cell surface [GO:0009986]; external side of plasma membrane [GO:0009897]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; integral component of plasma membrane [GO:0005887]; membrane [GO:0016020]; membrane raft [GO:0045121]; neuronal cell body [GO:0043025]; phagocytic cup [GO:00...
cell surface [GO:0009986]; external side of plasma membrane [GO:0009897]; extracellular region [GO:0005576]; extracellular space [GO:0005615]; integral component of plasma membrane [GO:0005887]; membrane [GO:0016020]; membrane raft [GO:0045121]; neuronal cell body [GO:0043025]; phagocytic cup [GO:0001891]; plasma membrane [GO:0005886]; protein-containing complex [GO:0032991]; recycling endosome [GO:0055037]
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TNF
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Kaplan plot for TNF in
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*NOTE: the Kaplan plots were collected from OncoLnc