Tumor necrosis factor

NameTumor necrosis factor
Synonyms
  • Cachectin
  • 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
  • transcription regulatory region DNA binding
  • tumor necrosis factor receptor binding
  • protease binding
  • identical protein binding
  • cytokine activity
Processes
  • positive regulation of smooth muscle cell proliferation
  • cellular response to nicotine
  • negative regulation of myosin-light-chain-phosphatase activity
  • death-inducing signaling complex assembly
  • positive regulation of fever generation
  • receptor biosynthetic process
  • necroptotic signaling pathway
  • embryonic digestive tract development
  • epithelial cell proliferation involved in salivary gland morphogenesis
  • regulation of tumor necrosis factor-mediated signaling pathway
  • MAPK cascade
  • negative regulation of transcription, DNA-templated
  • positive regulation of protein complex assembly
  • positive regulation of NF-kappaB transcription factor activity
  • positive regulation of cytokine secretion
  • positive regulation of peptidyl-serine phosphorylation
  • positive regulation of protein kinase B signaling
  • positive regulation of sequence-specific DNA binding transcription factor activity
  • positive regulation of mononuclear cell migration
  • humoral immune response
  • positive regulation of interleukin-8 production
  • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
  • activation of MAPKKK activity
  • positive regulation of transcription from RNA polymerase II promoter
  • negative regulation of growth of symbiont in host
  • positive regulation of programmed cell death
  • negative regulation of myoblast differentiation
  • regulation of immunoglobulin secretion
  • inflammatory response
  • activation of MAPK activity
  • osteoclast differentiation
  • positive regulation of ceramide biosynthetic process
  • regulation of insulin secretion
  • positive regulation of interleukin-8 biosynthetic process
  • chronic inflammatory response to antigenic stimulus
  • negative regulation of alkaline phosphatase activity
  • JNK cascade
  • positive regulation of osteoclast differentiation
  • positive regulation of podosome assembly
  • cell surface receptor signaling pathway
  • positive regulation of NF-kappaB import into nucleus
  • negative regulation of cytokine secretion involved in immune response
  • glucose metabolic process
  • positive regulation of chemokine production
  • positive regulation of JUN kinase activity
  • positive regulation of chemokine (C-X-C motif) ligand 2 production
  • positive regulation of interleukin-6 production
  • positive regulation of translational initiation by iron
  • regulation of establishment of endothelial barrier
  • regulation of I-kappaB kinase/NF-kappaB signaling
  • positive regulation of protein transport
  • intrinsic apoptotic signaling pathway in response to DNA damage
  • positive regulation of gene expression
  • positive regulation of protein kinase activity
  • extrinsic apoptotic signaling pathway via death domain receptors
  • positive regulation of phagocytosis
  • protein import into nucleus, translocation
  • sequestering of triglyceride
  • positive regulation of protein complex disassembly
  • positive regulation of apoptotic process
  • negative regulation of gene expression
  • defense response to Gram-positive bacterium
  • negative regulation of osteoblast differentiation
  • positive regulation of hair follicle development
  • positive regulation of protein localization to cell surface
  • positive regulation of protein phosphorylation
  • positive regulation of interferon-gamma production
  • negative regulation of interleukin-6 production
  • response to salt stress
  • response to glucocorticoid
  • tumor necrosis factor-mediated signaling pathway
  • positive regulation of cell adhesion
  • positive regulation of chronic inflammatory response to antigenic stimulus
  • negative regulation of branching involved in lung morphogenesis
  • I-kappaB kinase/NF-kappaB signaling
  • negative regulation of viral genome replication
  • transformed cell apoptotic process
  • negative regulation of transcription from RNA polymerase II promoter
  • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
  • positive regulation of humoral immune response mediated by circulating immunoglobulin
  • negative regulation of protein complex disassembly
  • positive regulation of heterotypic cell-cell adhesion
  • extrinsic apoptotic signaling pathway
  • negative regulation of lipid storage
  • protein kinase B signaling
  • leukocyte tethering or rolling
  • positive regulation of cytokine production
  • regulation of branching involved in salivary gland morphogenesis
  • activation of cysteine-type endopeptidase activity involved in apoptotic process
  • positive regulation of calcidiol 1-monooxygenase activity
  • negative regulation of fat cell differentiation
  • positive regulation of nitric oxide biosynthetic process
  • cortical actin cytoskeleton organization
  • cellular response to amino acid stimulus
  • positive regulation of NFAT protein import into nucleus
  • positive regulation of chemokine biosynthetic process
  • positive regulation of MAP kinase activity
  • lipopolysaccharide-mediated signaling pathway
  • cellular response to organic cyclic compound
  • establishment of protein localization to plasma membrane
  • extracellular matrix organization
  • response to virus
  • positive regulation of membrane protein ectodomain proteolysis
  • positive regulation of NIK/NF-kappaB signaling
  • positive regulation of ERK1 and ERK2 cascade
  • positive regulation of I-kappaB kinase/NF-kappaB signaling
  • negative regulation of bicellular tight junction assembly
  • positive regulation of transcription, DNA-templated
  • negative regulation of lipid catabolic process
  • positive regulation of vitamin D biosynthetic process
  • negative regulation of glucose import
Components
  • plasma membrane
  • extracellular space
  • cell surface
  • membrane raft
  • phagocytic cup
  • external side of plasma membrane
  • integral component of plasma membrane
  • recycling endosome
  • extracellular region
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.
Pfam Domain Function
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 IDNot Available
GenAtlas IDTNF
HGNC IDHGNC:11892
Chromosome Location6
Locus6p21.3
References
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