Names & Taxonomy

Uniprot ID:
P01375
Entry Name:
TNFA_HUMAN
Status:
reviewed
Protein Names:
Tumor necrosis factor (Cachectin) (TNF-alpha) (Tumor necrosis factor ligand superfamily member 2) (TNF-a) [Cleaved into: Tumor necrosis factor, membrane form (N-terminal fragment) (NTF); Intracellular domain 1 (ICD1); Intracellular domain 2 (ICD2); C-domain 1; C-domain 2; Tumor necrosis factor, soluble form]
Gene Names:
TNF TNFA TNFSF2
Gene Names Primary:
TNF
Organism:
Homo sapiens (Human)

Structure

Length:
233
Sequence:
MSTESMIRDVELAEEALPKKTGGPQGSRRCLFLSLFSFLIVAGATTLFCLLHFGVIGPQREEFPRDLSLISPLAQAVRSSSRTPSDKPVAHVVANPQAEGQLQWLNRRANALLANGVELRDNQLVVPSEGLYLIYSQVLFKGQGCPSTHVLLTHTISRIAVSYQTKVNLLSAIKSPCQRETPEGAEAKPWYEPIYLGGVFQLEKGDRLSAEINRPDYLDFAESGQVYFGIIAL
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cell membrane

Function

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).
Cross Reference Drug Bank:
DB00051 DB01427 DB05676 DB08904 DB00608 DB01407 DB00668 DB00005 DB01296 DB06674 DB00065 DB02325 DB08910 DB01411 DB00852 DB01041
Gene Ontology Go:
cell surface
external side of plasma membrane
extracellular region
extracellular space
integral component of plasma membrane
membrane raft
phagocytic cup
plasma membrane
recycling endosome
cytokine activity
identical protein binding
protease binding
transcription regulatory region DNA binding
tumor necrosis factor receptor binding
activation of cysteine-type endopeptidase activity involved in apoptotic process
activation of MAPK activity
activation of MAPKKK activity
cell surface receptor signaling pathway
cellular response to amino acid stimulus
cellular response to nicotine
cellular response to organic cyclic compound
chronic inflammatory response to antigenic stimulus
cortical actin cytoskeleton organization
death-inducing signaling complex assembly
defense response to Gram-positive bacterium
embryonic digestive tract development
epithelial cell proliferation involved in salivary gland morphogenesis
establishment of protein localization to plasma membrane
extracellular matrix organization
extrinsic apoptotic signaling pathway
extrinsic apoptotic signaling pathway via death domain receptors
glucose metabolic process
humoral immune response
I-kappaB kinase/NF-kappaB signaling
inflammatory response
intrinsic apoptotic signaling pathway in response to DNA damage
JNK cascade
leukocyte tethering or rolling
lipopolysaccharide-mediated signaling pathway
MAPK cascade
necroptotic signaling pathway
negative regulation of alkaline phosphatase activity
negative regulation of bicellular tight junction assembly
negative regulation of branching involved in lung morphogenesis
negative regulation of cytokine secretion involved in immune response
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
negative regulation of fat cell differentiation
negative regulation of gene expression
negative regulation of glucose import
negative regulation of growth of symbiont in host
negative regulation of interleukin-6 production
negative regulation of lipid catabolic process
negative regulation of lipid storage
negative regulation of myoblast differentiation
negative regulation of myosin-light-chain-phosphatase activity
negative regulation of osteoblast differentiation
negative regulation of protein complex disassembly
negative regulation of transcription from RNA polymerase II promoter
negative regulation of transcription, DNA-templated
negative regulation of viral genome replication
osteoclast differentiation
positive regulation of apoptotic process
positive regulation of calcidiol 1-monooxygenase activity
positive regulation of cell adhesion
positive regulation of ceramide biosynthetic process
positive regulation of chemokine (C-X-C motif) ligand 2 production
positive regulation of chemokine biosynthetic process
positive regulation of chemokine production
positive regulation of chronic inflammatory response to antigenic stimulus
positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
positive regulation of cytokine production
positive regulation of cytokine secretion
positive regulation of ERK1 and ERK2 cascade
positive regulation of fever generation
positive regulation of gene expression
positive regulation of hair follicle development
positive regulation of heterotypic cell-cell adhesion
positive regulation of humoral immune response mediated by circulating immunoglobulin
positive regulation of I-kappaB kinase/NF-kappaB signaling
positive regulation of interferon-gamma production
positive regulation of interleukin-6 production
positive regulation of interleukin-8 biosynthetic process
positive regulation of interleukin-8 production
positive regulation of JUN kinase activity
positive regulation of leukocyte adhesion to arterial endothelial cell
positive regulation of MAP kinase activity
positive regulation of membrane protein ectodomain proteolysis
positive regulation of mononuclear cell migration
positive regulation of NF-kappaB import into nucleus
positive regulation of NF-kappaB transcription factor activity
positive regulation of NFAT protein import into nucleus
positive regulation of NIK/NF-kappaB signaling
positive regulation of nitric oxide biosynthetic process
positive regulation of osteoclast differentiation
positive regulation of peptidyl-serine phosphorylation
positive regulation of phagocytosis
positive regulation of podosome assembly
positive regulation of programmed cell death
positive regulation of protein complex assembly
positive regulation of protein complex disassembly
positive regulation of protein kinase activity
positive regulation of protein kinase B signaling
positive regulation of protein localization to cell surface
positive regulation of protein phosphorylation
positive regulation of protein transport
positive regulation of sequence-specific DNA binding transcription factor activity
positive regulation of smooth muscle cell proliferation
positive regulation of superoxide dismutase activity
positive regulation of transcription from RNA polymerase II promoter
positive regulation of transcription, DNA-templated
positive regulation of translational initiation by iron
positive regulation of vitamin D biosynthetic process
protein import into nucleus, translocation
protein kinase B signaling
receptor biosynthetic process
regulation of branching involved in salivary gland morphogenesis
regulation of establishment of endothelial barrier
regulation of I-kappaB kinase/NF-kappaB signaling
regulation of immunoglobulin secretion
regulation of insulin secretion
regulation of tumor necrosis factor-mediated signaling pathway
response to glucocorticoid
response to salt stress
response to virus
sequestering of triglyceride
transformed cell apoptotic process
tumor necrosis factor-mediated signaling pathway
Gene Ontology Biological Process:
activation of cysteine-type endopeptidase activity involved in apoptotic process
activation of MAPK activity
activation of MAPKKK activity
cell surface receptor signaling pathway
cellular response to amino acid stimulus
cellular response to nicotine
cellular response to organic cyclic compound
chronic inflammatory response to antigenic stimulus
cortical actin cytoskeleton organization
death-inducing signaling complex assembly
defense response to Gram-positive bacterium
embryonic digestive tract development
epithelial cell proliferation involved in salivary gland morphogenesis
establishment of protein localization to plasma membrane
extracellular matrix organization
extrinsic apoptotic signaling pathway
extrinsic apoptotic signaling pathway via death domain receptors
glucose metabolic process
humoral immune response
I-kappaB kinase/NF-kappaB signaling
inflammatory response
intrinsic apoptotic signaling pathway in response to DNA damage
JNK cascade
leukocyte tethering or rolling
lipopolysaccharide-mediated signaling pathway
MAPK cascade
necroptotic signaling pathway
negative regulation of alkaline phosphatase activity
negative regulation of bicellular tight junction assembly
negative regulation of branching involved in lung morphogenesis
negative regulation of cytokine secretion involved in immune response
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
negative regulation of fat cell differentiation
negative regulation of gene expression
negative regulation of glucose import
negative regulation of growth of symbiont in host
negative regulation of interleukin-6 production
negative regulation of lipid catabolic process
negative regulation of lipid storage
negative regulation of myoblast differentiation
negative regulation of myosin-light-chain-phosphatase activity
negative regulation of osteoblast differentiation
negative regulation of protein complex disassembly
negative regulation of transcription, DNA-templated
negative regulation of transcription from RNA polymerase II promoter
negative regulation of viral genome replication
osteoclast differentiation
positive regulation of apoptotic process
positive regulation of calcidiol 1-monooxygenase activity
positive regulation of cell adhesion
positive regulation of ceramide biosynthetic process
positive regulation of chemokine (C-X-C motif) ligand 2 production
positive regulation of chemokine biosynthetic process
positive regulation of chemokine production
positive regulation of chronic inflammatory response to antigenic stimulus
positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
positive regulation of cytokine production
positive regulation of cytokine secretion
positive regulation of ERK1 and ERK2 cascade
positive regulation of fever generation
positive regulation of gene expression
positive regulation of hair follicle development
positive regulation of heterotypic cell-cell adhesion
positive regulation of humoral immune response mediated by circulating immunoglobulin
positive regulation of I-kappaB kinase/NF-kappaB signaling
positive regulation of interferon-gamma production
positive regulation of interleukin-6 production
positive regulation of interleukin-8 biosynthetic process
positive regulation of interleukin-8 production
positive regulation of JUN kinase activity
positive regulation of leukocyte adhesion to arterial endothelial cell
positive regulation of MAP kinase activity
positive regulation of membrane protein ectodomain proteolysis
positive regulation of mononuclear cell migration
positive regulation of NFAT protein import into nucleus
positive regulation of NF-kappaB import into nucleus
positive regulation of NF-kappaB transcription factor activity
positive regulation of NIK/NF-kappaB signaling
positive regulation of nitric oxide biosynthetic process
positive regulation of osteoclast differentiation
positive regulation of peptidyl-serine phosphorylation
positive regulation of phagocytosis
positive regulation of podosome assembly
positive regulation of programmed cell death
positive regulation of protein complex assembly
positive regulation of protein complex disassembly
positive regulation of protein kinase activity
positive regulation of protein kinase B signaling
positive regulation of protein localization to cell surface
positive regulation of protein phosphorylation
positive regulation of protein transport
positive regulation of sequence-specific DNA binding transcription factor activity
positive regulation of smooth muscle cell proliferation
positive regulation of superoxide dismutase activity
positive regulation of transcription, DNA-templated
positive regulation of transcription from RNA polymerase II promoter
positive regulation of translational initiation by iron
positive regulation of vitamin D biosynthetic process
protein import into nucleus, translocation
protein kinase B signaling
receptor biosynthetic process
regulation of branching involved in salivary gland morphogenesis
regulation of establishment of endothelial barrier
regulation of I-kappaB kinase/NF-kappaB signaling
regulation of immunoglobulin secretion
regulation of insulin secretion
regulation of tumor necrosis factor-mediated signaling pathway
response to glucocorticoid
response to salt stress
response to virus
sequestering of triglyceride
transformed cell apoptotic process
tumor necrosis factor-mediated signaling pathway
Gene Ontology Molecular Function:
cytokine activity
identical protein binding
protease binding
transcription regulatory region DNA binding
tumor necrosis factor receptor binding
Gene Ontology Cellular Component:
cell surface
external side of plasma membrane
extracellular region
extracellular space
integral component of plasma membrane
membrane raft
phagocytic cup
plasma membrane
recycling endosome
Keywords:
3D-structure
Cell membrane
Complete proteome
Cytokine
Direct protein sequencing
Disulfide bond
Glycoprotein
Lipoprotein
Membrane
Myristate
Phosphoprotein
Polymorphism
Reference proteome
Secreted
Signal-anchor
Transmembrane
Transmembrane helix
Interacts With:
Q8UYL3; Q9Y6K9; P19438; P20333

Publication

PubMed ID:
3555974 6392892 3883195 2995927 3856324 3932069 8499947 10202016 14656967 15489334 8631363 8597870 10205166 2009860 1402651 9034191 10369255 16829952 16829951 22517918 23396208 2922050 1964681 2551905 9488135 9442056 12746914 12915457