Tumor necrosis factor

NameTumor necrosis factor
SynonymsCachectin TNF-a TNF-alpha TNFA TNFSF2 Tumor necrosis factor ligand superfamily member 2
Gene NameTNF
OrganismHuman
Amino acid sequence
>lcl|BSEQ0001404|Tumor necrosis factor
MSTESMIRDVELAEEALPKKTGGPQGSRRCLFLSLFSFLIVAGATTLFCLLHFGVIGPQR
EEFPRDLSLISPLAQAVRSSSRTPSDKPVAHVVANPQAEGQLQWLNRRANALLANGVELR
DNQLVVPSEGLYLIYSQVLFKGQGCPSTHVLLTHTISRIAVSYQTKVNLLSAIKSPCQRE
TPEGAEAKPWYEPIYLGGVFQLEKGDRLSAEINRPDYLDFAESGQVYFGIIAL
Number of residues233
Molecular Weight25644.15
Theoretical pI6.92
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 FunctionTumor necrosis factor receptor binding
Specific FunctionCytokine 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 Regions36-56
GenBank Protein ID339741
UniProtKB IDP01375
UniProtKB Entry NameTNFA_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0021837|Tumor necrosis factor (TNF)
ATGAGCACTGAAAGCATGATCCGGGACGTGGAGCTGGCCGAGGAGGCGCTCCCCAAGAAG
ACAGGGGGGCCCCAGGGCTCCAGGCGGTGCTTGTTCCTCAGCCTCTTCTCCTTCCTGATC
GTGGCAGGCGCCACCACGCTCTTCTGCCTGCTGCACTTTGGAGTGATCGGCCCCCAGAGG
GAAGAGTTCCCCAGGGACCTCTCTCTAATCAGCCCTCTGGCCCAGGCAGTCAGATCATCT
TCTCGAACCCCGAGTGACAAGCCTGTAGCCCATGTTGTAGCAAACCCTCAAGCTGAGGGG
CAGCTCCAGTGGCTGAACCGCCGGGCCAATGCCCTCCTGGCCAATGGCGTGGAGCTGAGA
GATAACCAGCTGGTGGTGCCATCAGAGGGCCTGTACCTCATCTACTCCCAGGTCCTCTTC
AAGGGCCAAGGCTGCCCCTCCACCCATGTGCTCCTCACCCACACCATCAGCCGCATCGCC
GTCTCCTACCAGACCAAGGTCAACCTCCTCTCTGCCATCAAGAGCCCCTGCCAGAGGGAG
ACCCCAGAGGGGGCTGAGGCCAAGCCCTGGTATGAGCCCATCTATCTGGGAGGGGTCTTC
CAGCTGGAGAAGGGTGACCGACTCAGCGCTGAGATCAATCGGCCCGACTATCTCGACTTT
GCCGAGTCTGGGCAGGTCTACTTTGGGATCATTGCCCTGTGA
GenBank Gene IDM16441
GeneCard IDNone
GenAtlas IDTNF
HGNC IDHGNC:11892
Chromosome Location6
Locus6p21.3
References
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