Tumor necrosis factor

TNF
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1A8M, 1TNF, 2AZ5, 2E7A, 2TUN, 2ZJC, 2ZPX, 3ALQ, 3IT8, 3L9J, 3WD5, 4G3Y, 4TSV, 4TWT, 5TSW
Identifiers
Aliases	TNF, DIF, TNF-alpha, TNFA, TNFSF2, Tumour necrosis factor, TNF-α, tumor necrosis factor, TNLG1F, Tumor necrosis factor alpha
External IDs	OMIM: 191160; MGI: 104798; HomoloGene: 496; GeneCards: TNF; OMA:TNF - orthologs
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6p21.33 Start 31,575,565 bp[1] End 31,578,336 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17 B1|17 18.59 cM Start 35,418,357 bp[2] End 35,420,983 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte testicle bone marrow monocyte bone marrow cells blood lymph node spleen appendix duodenum Top expressed in granulocyte stroma of bone marrow embryo wall of uterus endometrium spleen blood subcutaneous adipose tissue thymus mesenteric lymph nodes More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding protease binding tumor necrosis factor receptor binding cytokine activity identical protein binding Cellular component membrane cell surface integral component of membrane recycling endosome intracellular anatomical structure integral component of plasma membrane phagocytic cup external side of plasma membrane extracellular region plasma membrane membrane raft extracellular space Biological process regulation of protein phosphorylation positive regulation of protein phosphorylation positive regulation of MAP kinase activity response to salt stress positive regulation of calcidiol 1-monooxygenase activity positive regulation of programmed cell death positive regulation of JNK cascade response to organic substance negative regulation of osteoblast differentiation positive regulation of cysteine-type endopeptidase activity involved in apoptotic process negative regulation of viral genome replication humoral immune response positive regulation of interleukin-8 production intrinsic apoptotic signaling pathway in response to DNA damage positive regulation of protein localization to cell surface positive regulation of ERK1 and ERK2 cascade glucose metabolic process animal organ morphogenesis apoptotic signaling pathway negative regulation of alkaline phosphatase activity regulation of I-kappaB kinase/NF-kappaB signaling defense response to Gram-positive bacterium regulation of branching involved in salivary gland morphogenesis positive regulation of phagocytosis negative regulation of fat cell differentiation negative regulation of myoblast differentiation positive regulation of protein kinase B signaling regulation of insulin secretion osteoclast differentiation regulation of tumor necrosis factor-mediated signaling pathway response to virus positive regulation of osteoclast differentiation negative regulation of cytokine production involved in immune response positive regulation of peptidyl-serine phosphorylation negative regulation of branching involved in lung morphogenesis JNK cascade death-inducing signaling complex assembly regulation of osteoclast differentiation defense response to bacterium positive regulation of interleukin-6 production I-kappaB kinase/NF-kappaB signaling positive regulation of translational initiation by iron sequestering of triglyceride positive regulation of chronic inflammatory response to antigenic stimulus positive regulation of chemokine (C-X-C motif) ligand 2 production positive regulation of JUN kinase activity positive regulation of hair follicle development chronic inflammatory response to antigenic stimulus cellular response to organic cyclic compound positive regulation of fever generation extracellular matrix organization positive regulation of DNA-binding transcription factor activity cellular response to nicotine positive regulation of podosome assembly regulation of reactive oxygen species metabolic process positive regulation of protein transport negative regulation of glucose import immune response leukocyte tethering or rolling positive regulation of chemokine production cellular extravasation negative regulation of lipid storage negative regulation of myosin-light-chain-phosphatase activity negative regulation of transcription, DNA-templated cortical actin cytoskeleton organization embryonic digestive tract development leukocyte migration lipopolysaccharide-mediated signaling pathway positive regulation of smooth muscle cell proliferation positive regulation of protein kinase activity positive regulation of superoxide dismutase activity defense response positive regulation of ceramide biosynthetic process positive regulation of protein-containing complex assembly protein kinase B signaling positive regulation of cytokine production epithelial cell proliferation involved in salivary gland morphogenesis positive regulation of nitric oxide biosynthetic process negative regulation of interleukin-6 production positive regulation of membrane protein ectodomain proteolysis positive regulation of humoral immune response mediated by circulating immunoglobulin positive regulation of interferon-gamma production response to glucocorticoid positive regulation of vitamin D biosynthetic process positive regulation of mononuclear cell migration MAPK cascade negative regulation of protein-containing complex disassembly multicellular organism development negative regulation of bicellular tight junction assembly positive regulation of protein-containing complex disassembly regulation of cell population proliferation cellular response to amino acid stimulus negative regulation of extrinsic apoptotic signaling pathway in absence of ligand cellular response to lipopolysaccharide negative regulation of lipid catabolic process regulation of establishment of endothelial barrier positive regulation of cell adhesion regulation of protein secretion positive regulation of apoptotic process inflammatory response activation of cysteine-type endopeptidase activity involved in apoptotic process tumor necrosis factor-mediated signaling pathway positive regulation of I-kappaB kinase/NF-kappaB signaling necroptotic signaling pathway positive regulation of gene expression extrinsic apoptotic signaling pathway extrinsic apoptotic signaling pathway via death domain receptors negative regulation of transcription by RNA polymerase II positive regulation of NF-kappaB transcription factor activity positive regulation of transcription, DNA-templated positive regulation of transcription by RNA polymerase II positive regulation of leukocyte adhesion to arterial endothelial cell positive regulation of leukocyte adhesion to vascular endothelial cell positive regulation of blood microparticle formation negative regulation of endothelial cell proliferation positive regulation of heterotypic cell-cell adhesion negative regulation of mitotic cell cycle endothelial cell apoptotic process positive regulation of vascular associated smooth muscle cell proliferation negative regulation of gene expression protein localization to plasma membrane positive regulation of protein catabolic process regulation of signaling receptor activity regulation of inflammatory response cytokine-mediated signaling pathway positive regulation of calcineurin-NFAT signaling cascade positive regulation of NIK/NF-kappaB signaling Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7124 21926 Ensembl ENSG00000228978 ENSG00000230108 ENSG00000223952 ENSG00000204490 ENSG00000228321 ENSG00000232810 ENSG00000228849 ENSG00000206439 ENSMUSG00000024401 UniProt P01375 P06804 RefSeq (mRNA) NM_000594 NM_001278601 NM_013693 RefSeq (protein) NP_000585 NP_001265530 NP_038721 Location (UCSC) Chr 6: 31.58 – 31.58 Mb Chr 17: 35.42 – 35.42 Mb PubMed search [3] [4]
Wikidata
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Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α^[5][6]) is a cytokine and member of the TNF superfamily, which consists of various transmembrane proteins with a homologous TNF domain. It is the first cytokine to be described as an adipokine as secreted by adipose tissue.^[7]

TNF signaling occurs through two receptors: TNFR1 and TNFR2.^[8][9] TNFR1 is constitutively expressed on most cell types, whereas TNFR2 is restricted primarily to endothelial, epithelial, and subsets of immune cells.^[8][9] TNFR1 signaling tends to be pro-inflammatory and apoptotic, whereas TNFR2 signaling is anti-inflammatory and promotes cell proliferation.^[8][9] Suppression of TNFR1 signaling has been important for treatment of autoimmune diseases,^[10] whereas TNFR2 signaling promotes wound healing.^[9]

TNF-α exists as a transmembrane form (mTNF-α) and as a soluble form (sTNF-α). sTNF-α results from enzymatic cleavage of mTNF-α,^[11] by a process called substrate presentation. mTNF-α is mainly found on monocytes/macrophages where it interacts with tissue receptors by cell-to-cell contact.^[11] sTNF-α selectively binds to TNFR1, whereas mTNF-α binds to both TNFR1 and TNFR2.^[12] TNF-α binding to TNFR1 is irreversible, whereas binding to TNFR2 is reversible.^[13]

The primary role of TNF is in the regulation of immune cells. TNF, as an endogenous pyrogen, is able to induce fever, apoptotic cell death, cachexia, and inflammation, inhibit tumorigenesis and viral replication, and respond to sepsis via IL-1 and IL-6-producing cells. Dysregulation of TNF production has been implicated in a variety of human diseases including Alzheimer's disease,^[14] cancer,^[15] major depression,^[16] psoriasis^[17] and inflammatory bowel disease (IBD).^[18] Though controversial, some studies have linked depression and IBD to increased levels of TNF.^[19][20]

As an adipokine, TNF promotes insulin resistance, and is associated with obesity-induced type 2 diabetes.^[7] As a cytokine, TNF is used by the immune system for cell signaling. If macrophages (certain white blood cells) detect an infection, they release TNF to alert other immune system cells as part of an inflammatory response.^[7] Certain cancers can cause overproduction of TNF. TNF parallels parathyroid hormone both in causing secondary hypercalcemia and in the cancers with which excessive production is associated. Under the name tasonermin, TNF is used as an immunostimulant drug in the treatment of certain cancers. Drugs that counter the action of TNF are used in the treatment of various inflammatory diseases such as rheumatoid arthritis.