Tumor necrosis factor

Name	Tumor necrosis factor
Synonyms	Cachectin TNF-a TNF-alpha TNFA TNFSF2 Tumor necrosis factor ligand superfamily member 2
Gene Name	TNF
Organism	Human
Amino acid sequence	>lcl\|BSEQ0001404\|Tumor necrosis factor MSTESMIRDVELAEEALPKKTGGPQGSRRCLFLSLFSFLIVAGATTLFCLLHFGVIGPQR EEFPRDLSLISPLAQAVRSSSRTPSDKPVAHVVANPQAEGQLQWLNRRANALLANGVELR DNQLVVPSEGLYLIYSQVLFKGQGCPSTHVLLTHTISRIAVSYQTKVNLLSAIKSPCQRE TPEGAEAKPWYEPIYLGGVFQLEKGDRLSAEINRPDYLDFAESGQVYFGIIAL
Number of residues	233
Molecular Weight	25644.15
Theoretical pI	6.92
GO Classification	Functions cytokine activity identical protein binding transcription regulatory region DNA binding tumor necrosis factor receptor binding protease binding Processes positive regulation of sequence-specific DNA binding transcription factor activity positive regulation of nitric oxide biosynthetic process cortical actin cytoskeleton organization humoral immune response positive regulation of interleukin-8 production negative regulation of glucose import extracellular matrix organization response to virus negative regulation of branching involved in lung morphogenesis defense response to Gram-positive bacterium negative regulation of osteoblast differentiation response to glucocorticoid positive regulation of programmed cell death cellular response to organic cyclic compound establishment of protein localization to plasma membrane inflammatory response activation of MAPK activity necroptotic signaling pathway positive regulation of transcription, DNA-templated negative regulation of lipid catabolic process negative regulation of protein complex disassembly negative regulation of interleukin-6 production response to salt stress negative regulation of transcription from RNA polymerase II promoter chronic inflammatory response to antigenic stimulus positive regulation of I-kappaB kinase/NF-kappaB signaling negative regulation of bicellular tight junction assembly JNK cascade positive regulation of protein complex assembly death-inducing signaling complex assembly positive regulation of fever generation regulation of branching involved in salivary gland morphogenesis negative regulation of viral genome replication transformed cell apoptotic process protein kinase B signaling positive regulation of NF-kappaB import into nucleus cellular response to nicotine negative regulation of myosin-light-chain-phosphatase activity glucose metabolic process positive regulation of chemokine production positive regulation of mononuclear cell migration MAPK cascade negative regulation of transcription, DNA-templated extrinsic apoptotic signaling pathway negative regulation of lipid storage positive regulation of translational initiation by iron regulation of establishment of endothelial barrier negative regulation of myoblast differentiation epithelial cell proliferation involved in salivary gland morphogenesis regulation of tumor necrosis factor-mediated signaling pathway intrinsic apoptotic signaling pathway in response to DNA damage positive regulation of gene expression positive regulation of peptidyl-serine phosphorylation positive regulation of protein kinase B signaling positive regulation of calcidiol 1-monooxygenase activity negative regulation of fat cell differentiation regulation of I-kappaB kinase/NF-kappaB signaling positive regulation of MAP kinase activity protein import into nucleus, translocation regulation of immunoglobulin secretion positive regulation of NF-kappaB transcription factor activity positive regulation of cytokine secretion positive regulation of apoptotic process negative regulation of gene expression positive regulation of transcription from RNA polymerase II promoter negative regulation of growth of symbiont in host positive regulation of chemokine biosynthetic process sequestering of triglyceride lipopolysaccharide-mediated signaling pathway positive regulation of interferon-gamma production negative regulation of alkaline phosphatase activity negative regulation of extrinsic apoptotic signaling pathway in absence of ligand activation of MAPKKK activity positive regulation of protein phosphorylation regulation of insulin secretion positive regulation of interleukin-8 biosynthetic process positive regulation of membrane protein ectodomain proteolysis positive regulation of hair follicle development positive regulation of ERK1 and ERK2 cascade tumor necrosis factor-mediated signaling pathway I-kappaB kinase/NF-kappaB signaling negative regulation of cytokine secretion involved in immune response osteoclast differentiation positive regulation of ceramide biosynthetic process cell surface receptor signaling pathway positive regulation of vitamin D biosynthetic process positive regulation of chronic inflammatory response to antigenic stimulus positive regulation of smooth muscle cell proliferation positive regulation of cell adhesion positive regulation of heterotypic cell-cell adhesion positive regulation of protein transport positive regulation of osteoclast differentiation positive regulation of podosome assembly positive regulation of interleukin-6 production receptor biosynthetic process positive regulation of cysteine-type endopeptidase activity involved in apoptotic process positive regulation of humoral immune response mediated by circulating immunoglobulin embryonic digestive tract development activation of cysteine-type endopeptidase activity involved in apoptotic process positive regulation of protein complex disassembly positive regulation of JUN kinase activity positive regulation of chemokine (C-X-C motif) ligand 2 production positive regulation of phagocytosis leukocyte tethering or rolling positive regulation of cytokine production positive regulation of NIK/NF-kappaB signaling cellular response to amino acid stimulus positive regulation of NFAT protein import into nucleus positive regulation of protein localization to cell surface positive regulation of protein kinase activity extrinsic apoptotic signaling pathway via death domain receptors Components membrane raft cell surface recycling endosome extracellular region phagocytic cup external side of plasma membrane plasma membrane integral component of plasma membrane extracellular space
General Function	Tumor necrosis factor receptor binding
Specific 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).The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.
Transmembrane Regions	36-56
GenBank Protein ID	339741
UniProtKB ID	P01375
UniProtKB Entry Name	TNFA_HUMAN
Cellular Location	Cell membrane
Gene sequence	>lcl\|BSEQ0021837\|Tumor necrosis factor (TNF) ATGAGCACTGAAAGCATGATCCGGGACGTGGAGCTGGCCGAGGAGGCGCTCCCCAAGAAG ACAGGGGGGCCCCAGGGCTCCAGGCGGTGCTTGTTCCTCAGCCTCTTCTCCTTCCTGATC GTGGCAGGCGCCACCACGCTCTTCTGCCTGCTGCACTTTGGAGTGATCGGCCCCCAGAGG GAAGAGTTCCCCAGGGACCTCTCTCTAATCAGCCCTCTGGCCCAGGCAGTCAGATCATCT TCTCGAACCCCGAGTGACAAGCCTGTAGCCCATGTTGTAGCAAACCCTCAAGCTGAGGGG CAGCTCCAGTGGCTGAACCGCCGGGCCAATGCCCTCCTGGCCAATGGCGTGGAGCTGAGA GATAACCAGCTGGTGGTGCCATCAGAGGGCCTGTACCTCATCTACTCCCAGGTCCTCTTC AAGGGCCAAGGCTGCCCCTCCACCCATGTGCTCCTCACCCACACCATCAGCCGCATCGCC GTCTCCTACCAGACCAAGGTCAACCTCCTCTCTGCCATCAAGAGCCCCTGCCAGAGGGAG ACCCCAGAGGGGGCTGAGGCCAAGCCCTGGTATGAGCCCATCTATCTGGGAGGGGTCTTC CAGCTGGAGAAGGGTGACCGACTCAGCGCTGAGATCAATCGGCCCGACTATCTCGACTTT GCCGAGTCTGGGCAGGTCTACTTTGGGATCATTGCCCTGTGA
GenBank Gene ID	M16441
GeneCard ID	None
GenAtlas ID	TNF
HGNC ID	HGNC:11892
Chromosome Location	6
Locus	6p21.3
References	Nedospasov SA, Shakhov AN, Turetskaya RL, Mett VA, Azizov MM, Georgiev GP, Korobko VG, Dobrynin VN, Filippov SA, Bystrov NS, et al.: Tandem arrangement of genes coding for tumor necrosis factor (TNF-alpha) and lymphotoxin (TNF-beta) in the human genome. Cold Spring Harb Symp Quant Biol. 1986;51 Pt 1:611-24.[3555974 ] Pennica D, Nedwin GE, Hayflick JS, Seeburg PH, Derynck R, Palladino MA, Kohr WJ, Aggarwal BB, Goeddel DV: Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature. 1984 Dec 20-1985 Jan 2;312(5996):724-9.[6392892 ] Shirai T, Yamaguchi H, Ito H, Todd CW, Wallace RB: Cloning and expression in Escherichia coli of the gene for human tumour necrosis factor. Nature. 1985 Feb 28-Mar 6;313(6005):803-6.[3883195 ] Nedwin GE, Naylor SL, Sakaguchi AY, Smith D, Jarrett-Nedwin J, Pennica D, Goeddel DV, Gray PW: Human lymphotoxin and tumor necrosis factor genes: structure, homology and chromosomal localization. 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