TNF Gene Summary [Human]
This gene encodes a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. It can bind to, and thus functions through its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. This cytokine is involved in the regulation of a wide spectrum of biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. This cytokine has been implicated in a variety of diseases, including autoimmune diseases, insulin resistance, psoriasis, rheumatoid arthritis ankylosing spondylitis, tuberculosis, autosomal dominant polycystic kidney disease, and cancer. Mutations in this gene affect susceptibility to cerebral malaria, septic shock, and Alzheimer disease. Knockout studies in mice also suggested the neuroprotective function of this cytokine. [provided by RefSeq, Aug 2020]
Details
| Type | Protein Coding |
| Official Symbol | TNF |
| Official Name | tumor necrosis factor [Source:HGNC Symbol;Acc:HGNC:11892] |
| Ensembl ID | ENSG00000204490 |
| Bio databases IDs | |
| Aliases | tumor necrosis factor |
| Synonyms | AT-TNF, DIF, IMD127, LOC103694380, RATTNF, TMTNF, TNF-a, TNF-alpha, Tnfsf1a, TNFSF2, TNF-α, TNLG1F, tumor necrosis factor, Tumor Necrosis Factor α, tumor necrosis factor, α, tumour necrosis factor, tumour Necrosis Factor Alpha, tumour necrosis factor, alpha, tumour Necrosis Factor α, tumour necrosis factor, α |
| Species | Human, Homo sapiens |
| Orthologies |
Protein Domains
A protein domain is a distinct structural or functional region within a protein that can evolve, function, and exist independently of the rest of the protein chain. These domains in human TNF often fold into stable, three-dimensional structures and are associated with specific biological functions, such as binding to DNA, other proteins, or small molecules.
- lectin-like domain
- TNF homology domain
- tumor necrosis factor receptor binding
- protease binding
- nucleic acid binding
- TNF
- protein binding
- cytokine
- cleavage site
- sequence-specific DNA binding
- identical protein binding
- double-stranded DNA binding
- receptor agonist activity
- membrane-proximal domain
Pathways
Biological processes and signaling networks where the TNF gene in human plays a role, providing insight into its function and relevance in health or disease.
Top Findings
The most significant associations for this gene, including commonly observed domains, pathway involvement, and functional highlights based on current data.
disease
- cognitive impairment
- hypertension
- depressive disorder
- acute myeloid leukemia
- neoplasia
- cardiac hypertrophy
- psoriasis
- active rheumatoid arthritis
- psoriatic arthritis
- polyarticular juvenile rheumatoid arthritis
role in cell
- lipolysis in
- accumulation in
- expression in
- differentiation
- cellular infiltration by
- activation in
- proliferation
- mitochondrial respiration in
- respiration
- shedding in
Subcellular Expression
Locations within the cell where the protein is known or predicted to be active, providing insight into its function and cellular context.
- Extracellular Space
- Cytoplasm
- cell surface
- intracellular space
- apical compartment
- membrane surface
- cellular membrane
- Nucleus
- Plasma Membrane
- Golgi Apparatus
- granules
- apical cell surfaces
- plasma membrane extracellular face
- microdomains
- Golgi buds
- mast cell secretory granules
- recycling endosomes
- secretory granules
- membrane rafts
- perikaryon
- exosomes
- plasma
- phagocytic cups
Gene Ontology Annotations
Describes the biological processes, cellular components, and molecular functions associated with the human TNF gene, providing context for its role in the cell.
Biological Process
Functions and activities the gene product is involved in
- positive regulation of JUN kinase activity
- positive regulation of programmed cell death
- JNK cascade
- positive regulation of tyrosine phosphorylation of STAT protein
- induction of apoptosis via death domain receptors
- positive regulation of sequence-specific DNA binding transcription factor activity
- positive regulation of NF-kappaB transcription factor activity
- positive regulation of cytokine production involved in inflammatory response
- regulation of insulin secretion
- inflammatory response
- positive regulation of fractalkine production
- response to hypoxia
- positive regulation of chronic inflammatory response to antigenic stimulus
- negative regulation of transcription, DNA-dependent
- positive regulation of transcription, DNA-dependent
- regulation of immunoglobulin production
- positive regulation of interferon-gamma production
- humoral immune response
- response to macrophage colony-stimulating factor stimulus
- positive regulation of chemokine production
- defense response to Gram-positive bacterium
- positive regulation of peptidyl-serine phosphorylation
- negative regulation of branching involved in lung morphogenesis
- positive regulation of protein localization at cell surface
- negative regulation of vascular wound healing
- positive regulation of inflammatory response
- negative regulation of mitotic cell cycle
- DNA damage response, signal transduction resulting in induction of apoptosis
- negative regulation of interleukin-6 production
- leukocyte migration involved in inflammatory response
- negative regulation of myoblast differentiation
- negative regulation of protein complex disassembly
- positive regulation of humoral immune response mediated by circulating immunoglobulin
- detection of mechanical stimulus involved in sensory perception of pain
- endothelial cell apoptotic process
- positive regulation of fever generation
- positive regulation of podosome assembly
- positive regulation of protein kinase B signaling cascade
- positive regulation of MAP kinase activity
- positive regulation of nitric oxide biosynthetic process
- response to salt stress
- extrinsic apoptotic signaling pathway
- positive regulation of I-kappaB kinase/NF-kappaB cascade
- regulation of I-kappaB kinase/NF-kappaB cascade
- positive regulation of protein complex disassembly
- vasodilation
- positive regulation of cell adhesion
- response to xenobiotic stimulus
- epithelial cell proliferation involved in salivary gland morphogenesis
- positive regulation of transcription from RNA polymerase II promoter
- positive regulation of neuron apoptotic process
- negative regulation of osteoblast differentiation
- positive regulation of smooth muscle cell proliferation
- astrocyte activation
- protein kinase B signaling cascade
- positive regulation of osteoclast differentiation
- response to glucocorticoid stimulus
- positive regulation of mononuclear cell migration
- regulation of reactive oxygen species metabolic process
- regulation of metabolic process
- positive regulation of protein complex assembly
- cellular response to nicotine
- negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
- negative regulation of blood vessel endothelial cell migration
- negative regulation of oxidative phosphorylation
- negative regulation of receptor activity
- positive regulation of glial cell proliferation
- positive regulation of MAPK cascade
- microglial cell activation
- cellular response to retinoic acid
- cellular response to toxin
- positive regulation of protein phosphorylation
- extracellular matrix organization
- positive regulation of extrinsic apoptotic signaling pathway
- negative regulation of lipid storage
- negative regulation of endothelial cell proliferation
- leukocyte tethering or rolling
- positive regulation of cytokine production
- positive regulation of hair follicle development
- negative regulation of apoptotic signaling pathway
- response to fructose stimulus
- macrophage activation involved in immune response
- positive regulation of mitosis
- glucose metabolic process
- negative regulation of L-glutamate transport
- cortical actin cytoskeleton organization
- embryonic digestive tract development
- positive regulation of membrane protein ectodomain proteolysis
- skeletal muscle contraction
- chronic inflammatory response to antigenic stimulus
- negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
- positive regulation of calcineurin-NFAT signaling cascade
- negative regulation of heart rate
- negative regulation of cytokine production involved in immune response
- activation of cysteine-type endopeptidase activity involved in apoptotic process
- calcium-mediated signaling
- vascular endothelial growth factor production
- regulation of synaptic transmission, glutamatergic
- negative regulation of lipid catabolic process
- regulation of synapse organization
- positive regulation of synaptic transmission
- positive regulation of calcidiol 1-monooxygenase activity
- negative regulation of beta-amyloid clearance
- positive regulation of protein catabolic process
- circadian rhythm
- positive regulation of JAK-STAT cascade
- positive regulation of vitamin D biosynthetic process
- positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
- negative regulation of gene expression
- positive regulation of interleukin-8 production
- tumor necrosis factor-mediated signaling pathway
- negative regulation of myosin-light-chain-phosphatase activity
- positive regulation of gene expression
- toll-like receptor 3 signaling pathway
- response to isolation stress
- negative regulation of neurogenesis
- response to activity
- sequestering of triglyceride
- positive regulation of interleukin-6 production
- response to nutrient levels
- protein localization in plasma membrane
- response to virus
- negative regulation of transcription from RNA polymerase II promoter
- cellular response to amino acid stimulus
- response to ethanol
- positive regulation of protein transport
- cognition
- cellular response to ionizing radiation
- positive regulation of interleukin-18 production
- negative regulation of viral genome replication
- positive regulation of DNA biosynthetic process
- positive regulation of blood microparticle formation
- regulation of branching involved in salivary gland morphogenesis
- regulation of endothelial cell apoptotic process
- negative regulation of glucose import
- negative regulation of systemic arterial blood pressure
- negative regulation of fat cell differentiation
- positive regulation of translational initiation by iron
- regulation of fat cell differentiation
- osteoclast differentiation
- cellular response to lipopolysaccharide
- positive regulation of action potential
- positive regulation of JNK cascade
- positive regulation of ERK1 and ERK2 cascade
- positive regulation of apoptotic process
- positive regulation of heterotypic cell-cell adhesion
- positive regulation of chemokine (C-X-C motif) ligand 2 production
- cellular response to interferon-gamma
- positive regulation of hepatocyte proliferation
- negative regulation of myelination
- positive regulation of interleukin-1 beta production
Cellular Component
Where in the cell the gene product is active
- extracellular space
- membrane raft
- external side of plasma membrane
- recycling endosome
- neuronal cell body
- extracellular region
- phagocytic cup
- plasma membrane
- cell surface
Molecular Function
What the gene product does at the molecular level
- identical protein binding
- protein binding
- tumor necrosis factor receptor binding
- transcription regulatory region sequence-specific DNA binding
- protease binding
- cytokine activity