TNF
Gene Name
TNF
Summary
TNF, also known as TNF alpha or tumor necrosis factor, is a 26 kDa cytokine primarily expressed by activated macrophages, T cells, and various other immune cells. It is localised to the cell surface and extracellular space, and plays a crucial role in mediating inflammation and immune responses. TNF functions by binding to its receptors, triggering various signalling pathways that regulate cellular processes such as apoptosis, proliferation, and differentiation. It is involved in numerous biological processes, including the antiviral innate immune response, chronic inflammatory responses, and the regulation of endothelial cell function.
Importance
TNF is relevant to: - The pathogenesis of autoimmune diseases and chronic inflammatory conditions, such as rheumatoid arthritis, due to its role in promoting inflammation and immune cell activation. - Cancer biology, as it can influence tumour growth and metastasis through its effects on the tumour microenvironment. - Neuroinflammation and neurodegenerative diseases, given its involvement in microglial activation and neuronal cell death. - Therapeutic targeting in various diseases, with TNF inhibitors being used in clinical settings to manage inflammatory disorders.
Top Products
For researchers investigating TNF, we recommend two excellent primary antibodies. The first is the well-cited polyclonal antibody, Anti-TNF alpha antibody (ab6671), which has garnered 954 citations, highlighting its reliability in Western blotting (WB). Additionally, we offer the recombinant antibody, Anti-TNF alpha antibody [EPR19147] (ab183218). This product has been validated in knockout models and is suitable for a broader range of applications, including WB, immunocytochemistry (ICC), enzyme-linked immunosorbent assay (ELISA), and immunoprecipitation (IP). With 228 citations, it demonstrates a solid presence in the research community, making it an excellent choice for those seeking consistent and versatile TNF detection. The Human TNF alpha Matched Antibody Pair Kit (ab213467), supported by 2 citations, is an excellent option for researchers looking to accurately measure TNF alpha levels in their samples.
Abcam Product Citation Summary
The data indicates a significant focus on the role of TNF in various inflammatory contexts across multiple species, particularly in mouse and rat models. Studies have explored TNF's involvement in conditions such as obesity, diabetes, and cancer, as well as its expression in response to treatments and injuries. The use of Abcam antibodies in both Western blotting and immunohistochemistry highlights the versatility of these methods in studying TNF's role in different biological processes.
Abcam Product Citation Table
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. Up-regulates 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:16829952, PubMed:22517918, PubMed:23396208). Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces GKAP42 protein degradation in adipocytes which is partially responsible for TNF-induced insulin resistance (By similarity). Plays a role in angiogenesis by inducing VEGF production synergistically with IL1B and IL6 (PubMed:12794819). Promotes osteoclastogenesis and therefore mediates bone resorption (By similarity).
The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.
Involvement in disease
Psoriatic arthritis
PSORAS
An inflammatory, seronegative arthritis associated with psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive, erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoid like pattern that can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis).
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Immunodeficiency 127
IMD127
An autosomal recessive immunologic disorder characterized by increased susceptibility to pulmonary infection with Mycobacterium tuberculosis. Affected individuals develop recurrent pulmonary tuberculosis, but have no adverse reaction to live BCG vaccination.
None
The disease may be caused by variants affecting the gene represented in this entry.
Post-translational modifications
The soluble form derives from the membrane form by proteolytic processing. The membrane-bound form is further proteolytically processed by SPPL2A or SPPL2B through regulated intramembrane proteolysis producing TNF intracellular domains (ICD1 and ICD2) released in the cytosol and TNF C-domain 1 and C-domain 2 secreted into the extracellular space.
The membrane form, but not the soluble form, is phosphorylated on serine residues. Dephosphorylation of the membrane form occurs by binding to soluble TNFRSF1A/TNFR1.
O-glycosylated; glycans contain galactose, N-acetylgalactosamine and N-acetylneuraminic acid.
Tumor necrosis factor, soluble form
The soluble form is demyristoylated at Lys-19 and Lys-20 by SIRT6, promoting its secretion.
Sequence Similarities
Belongs to the tumor necrosis factor family.
Cellular localization
- Cell membrane
- Single-pass type II membrane protein
- Tumor necrosis factor, membrane form
- Membrane
- Single-pass type II membrane protein
- Tumor necrosis factor, soluble form
- Secreted
- C-domain 1
- Secreted
- C-domain 2
- Secreted
Alternative names
TNFA, TNFSF2, TNF, Tumor necrosis factor, Cachectin, TNF-alpha, Tumor necrosis factor ligand superfamily member 2, TNF-a
Database links
swissprot:P01375 omim:191160 entrezGene:7124
Other research areas
- Cardiovascular
- Immuno-oncology
- Neuroscience
- Oncology