Tumor necrosis factor (P01375)

Uniprot ID P01375
Protein Name Tumor necrosis factor
Gene Name TNF
Species Homo sapiens (Human)
Signal peptide(a) N Secretome P(b) 0.894
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). .The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells. {ECO:0000269|PubMed:16829952}.
GO - Molecular function
  • cytokine activity : IDA:BHF-UCL
  • identical protein binding : IDA:BHF-UCL
  • protease binding : IPI:BHF-UCL
  • transcription regulatory region DNA binding : IDA:UniProtKB
  • tumor necrosis factor receptor binding : IDA:BHF-UCL
GO - Biological process
  • activation of cysteine-type endopeptidase activity involved in apoptotic process : IDA:UniProtKB
  • activation of MAPK activity : IDA:BHF-UCL
  • activation of MAPKKK activity : IDA:BHF-UCL
  • astrocyte activation : NAS:ARUK-UCL
  • cellular response to amino acid stimulus : IEA:Ensembl
  • cellular response to nicotine : IDA:UniProtKB
  • cellular response to organic cyclic compound : IDA:UniProtKB
  • chronic inflammatory response to antigenic stimulus : IMP:BHF-UCL
  • cognition : TAS:ARUK-UCL
  • cortical actin cytoskeleton organization : IDA:UniProtKB
  • cytokine-mediated signaling pathway : TAS:Reactome
  • death-inducing signaling complex assembly : TAS:Reactome
  • defense response to Gram-positive bacterium : IEA:Ensembl
  • embryonic digestive tract development : IEP:DFLAT
  • endothelial cell apoptotic process : IEA:Ensembl
  • epithelial cell proliferation involved in salivary gland morphogenesis : IEA:Ensembl
  • extracellular matrix organization : IEA:Ensembl
  • extrinsic apoptotic signaling pathway : IDA:UniProtKB
  • extrinsic apoptotic signaling pathway via death domain receptors : IDA:UniProtKB
  • glucose metabolic process : IEA:Ensembl
  • humoral immune response : IEA:Ensembl
  • I-kappaB kinase/NF-kappaB signaling : TAS:Reactome
  • inflammatory response : IDA:UniProtKB
  • intrinsic apoptotic signaling pathway in response to DNA damage : IEA:Ensembl
  • JNK cascade : IEA:Ensembl
  • leukocyte tethering or rolling : IDA:BHF-UCL
  • lipopolysaccharide-mediated signaling pathway : IDA:UniProtKB
  • MAPK cascade : IMP:UniProtKB
  • microglial cell activation : ISS:ARUK-UCL
  • necroptotic signaling pathway : IDA:UniProtKB
  • negative regulation of alkaline phosphatase activity : IEA:Ensembl
  • negative regulation of amyloid-beta clearance : ISS:ARUK-UCL
  • negative regulation of bicellular tight junction assembly : IDA:UniProtKB
  • negative regulation of branching involved in lung morphogenesis : IDA:UniProtKB
  • negative regulation of cytokine secretion involved in immune response : IDA:BHF-UCL
  • negative regulation of endothelial cell proliferation : IEA:Ensembl
  • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand : IDA:BHF-UCL
  • negative regulation of fat cell differentiation : NAS:BHF-UCL
  • negative regulation of gene expression : IDA:UniProtKB
  • negative regulation of glucose import : IEA:Ensembl
  • negative regulation of interleukin-6 production : IDA:BHF-UCL
  • negative regulation of lipid catabolic process : IDA:BHF-UCL
  • negative regulation of lipid storage : NAS:BHF-UCL
  • negative regulation of mitotic cell cycle : IEA:Ensembl
  • negative regulation of myoblast differentiation : IEA:Ensembl
  • negative regulation of myosin-light-chain-phosphatase activity : IDA:UniProtKB
  • negative regulation of neurogenesis : TAS:ARUK-UCL
  • negative regulation of osteoblast differentiation : IEA:Ensembl
  • negative regulation of protein complex disassembly : IDA:UniProtKB
  • negative regulation of transcription by RNA polymerase II : IDA:UniProtKB
  • negative regulation of transcription, DNA-templated : IDA:UniProtKB
  • negative regulation of viral genome replication : IDA:BHF-UCL
  • osteoclast differentiation : IEA:Ensembl
  • positive regulation of amyloid-beta formation : ISS:ARUK-UCL
  • positive regulation of apoptotic process : IDA:UniProtKB
  • positive regulation of blood microparticle formation : IDA:BHF-UCL
  • positive regulation of calcidiol 1-monooxygenase activity : IDA:BHF-UCL
  • positive regulation of calcineurin-NFAT signaling cascade : IDA:MGI
  • positive regulation of cell adhesion : IMP:UniProtKB
  • positive regulation of ceramide biosynthetic process : TAS:Reactome
  • positive regulation of chemokine (C-X-C motif) ligand 2 production : IDA:BHF-UCL
  • positive regulation of chemokine biosynthetic process : IDA:BHF-UCL
  • positive regulation of chemokine production : IDA:BHF-UCL
  • positive regulation of chemokine secretion : ISS:ARUK-UCL
  • positive regulation of chronic inflammatory response to antigenic stimulus : IEA:Ensembl
  • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process : IDA:UniProtKB
  • positive regulation of cytokine production : IDA:BHF-UCL
  • positive regulation of cytokine secretion : IDA:BHF-UCL
  • positive regulation of DNA-binding transcription factor activity : IDA:BHF-UCL
  • positive regulation of ERK1 and ERK2 cascade : NAS:BHF-UCL
  • positive regulation of fever generation : ISS:BHF-UCL
  • positive regulation of fractalkine biosynthetic process : ISS:ARUK-UCL
  • positive regulation of gene expression : IDA:UniProtKB
  • positive regulation of glial cell proliferation : IDA:ARUK-UCL
  • positive regulation of hair follicle development : IEA:Ensembl
  • positive regulation of heterotypic cell-cell adhesion : IDA:BHF-UCL
  • positive regulation of humoral immune response mediated by circulating immunoglobulin : IEA:Ensembl
  • positive regulation of I-kappaB kinase/NF-kappaB signaling : IDA:BHF-UCL
  • positive regulation of inflammatory response : TAS:ARUK-UCL
  • positive regulation of interferon-gamma production : IEA:Ensembl
  • positive regulation of interleukin-6 biosynthetic process : ISS:ARUK-UCL
  • positive regulation of interleukin-6 production : IDA:ARUK-UCL
  • positive regulation of interleukin-6 secretion : ISS:ARUK-UCL
  • positive regulation of interleukin-8 biosynthetic process : IDA:BHF-UCL
  • positive regulation of interleukin-8 production : IMP:UniProtKB
  • positive regulation of JUN kinase activity : IDA:UniProtKB
  • positive regulation of leukocyte adhesion to arterial endothelial cell : IDA:BHF-UCL
  • positive regulation of leukocyte adhesion to vascular endothelial cell : IDA:BHF-UCL
  • positive regulation of MAP kinase activity : IDA:UniProtKB
  • positive regulation of membrane protein ectodomain proteolysis : IDA:BHF-UCL
  • positive regulation of mononuclear cell migration : NAS:BHF-UCL
  • positive regulation of neuroinflammatory response : TAS:ARUK-UCL
  • positive regulation of neuron apoptotic process : ISS:ARUK-UCL
  • positive regulation of NF-kappaB transcription factor activity : IDA:UniProtKB
  • positive regulation of NIK/NF-kappaB signaling : IDA:UniProtKB
  • positive regulation of nitric oxide biosynthetic process : IDA:BHF-UCL
  • positive regulation of nitric-oxide synthase activity : IC:ARUK-UCL
  • positive regulation of nitrogen compound metabolic process : ISS:ARUK-UCL
  • positive regulation of osteoclast differentiation : IDA:BHF-UCL
  • positive regulation of peptidyl-serine phosphorylation : IDA:BHF-UCL
  • positive regulation of phagocytosis : IMP:AgBase
  • positive regulation of phosphatidylinositol 3-kinase signaling : ISS:ARUK-UCL
  • positive regulation of podosome assembly : IDA:BHF-UCL
  • positive regulation of programmed cell death : IDA:UniProtKB
  • positive regulation of protein catabolic process : IDA:AgBase
  • positive regulation of protein complex assembly : IDA:BHF-UCL
  • positive regulation of protein complex disassembly : IDA:UniProtKB
  • positive regulation of protein kinase activity : IDA:AgBase
  • positive regulation of protein kinase B signaling : ISS:ARUK-UCL
  • positive regulation of protein localization to cell surface : IDA:BHF-UCL
  • positive regulation of protein localization to plasma membrane : ISS:ARUK-UCL
  • positive regulation of protein phosphorylation : IDA:UniProtKB
  • positive regulation of protein transport : IDA:BHF-UCL
  • positive regulation of receptor signaling pathway via JAK-STAT : ISS:ARUK-UCL
  • positive regulation of smooth muscle cell proliferation : IDA:BHF-UCL
  • positive regulation of superoxide dismutase activity : IDA:BHF-UCL
  • positive regulation of synaptic transmission : ISS:ARUK-UCL
  • positive regulation of transcription by RNA polymerase II : IDA:UniProtKB
  • positive regulation of transcription, DNA-templated : IDA:UniProtKB
  • positive regulation of translational initiation by iron : IEA:Ensembl
  • positive regulation of tyrosine phosphorylation of STAT protein : ISS:ARUK-UCL
  • positive regulation of vascular smooth muscle cell proliferation : IEA:Ensembl
  • positive regulation of vitamin D biosynthetic process : IDA:BHF-UCL
  • protein kinase B signaling : IMP:UniProtKB
  • protein localization to plasma membrane : IDA:UniProtKB
  • receptor biosynthetic process : IDA:BHF-UCL
  • regulation of branching involved in salivary gland morphogenesis : IEA:Ensembl
  • regulation of endothelial cell apoptotic process : IMP:ARUK-UCL
  • regulation of establishment of endothelial barrier : IDA:UniProtKB
  • regulation of fat cell differentiation : ISS:ARUK-UCL
  • regulation of I-kappaB kinase/NF-kappaB signaling : IDA:BHF-UCL
  • regulation of immunoglobulin secretion : IEA:Ensembl
  • regulation of insulin secretion : IDA:BHF-UCL
  • regulation of synapse organization : ISS:ARUK-UCL
  • regulation of synaptic transmission, glutamatergic : TAS:ARUK-UCL
  • regulation of transcription by RNA polymerase II : ISS:ARUK-UCL
  • regulation of tumor necrosis factor-mediated signaling pathway : TAS:Reactome
  • response to glucocorticoid : IDA:BHF-UCL
  • response to salt stress : TAS:BHF-UCL
  • response to virus : IDA:BHF-UCL
  • sequestering of triglyceride : IDA:BHF-UCL
  • tumor necrosis factor-mediated signaling pathway : IMP:BHF-UCL
Back
(a) The Signal peptide D-score cutoff for "YES"(having signal peptide) is 0.45.
(b) Non-classically secreted proteins should obtain an NN-score(Neural Networks score) exceeding the normal threshold of 0.5, but not at the same time be predicted to contain a signal peptide.