Aliases for TNF Gene
External Ids for TNF Gene
Previous HGNC Symbols for TNF Gene
Previous GeneCards Identifiers for TNF Gene
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, and cancer. Knockout studies in mice also suggested the neuroprotective function of this cytokine. [provided by RefSeq, Jul 2008]
GeneCards Summary for TNF Gene
TNF (Tumor Necrosis Factor) is a Protein Coding gene. Diseases associated with TNF include mycobacterium chelonae and aphthous stomatitis. Among its related pathways are MAPK signaling pathway and Proteoglycans in cancer. GO annotations related to this gene include identical protein binding and cytokine activity. An important paralog of this gene is TNFSF15.
UniProtKB/Swiss-Prot for TNF Gene
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).
The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.
NF-kappaB (nuclear factor-kappa B) is a rapidly acting primary transcription factor found in all cell types. It is involved in cellular responses to stimuli such as cytokines and stress and plays a key role in regulating the immune response to infection. In unstimulated cells NF-kappaB dimers are sequestered inactively in the cytoplasm by a protein complex called inhibitor of kappa B (IkappaB). IkappaB inactivates NF-kappaB by masking the nuclear localization signals (NLS). Activation of NF-kappaB occurs via degradation of IkappaB, a process that is initiated by its phosphorylation by IkappaB kinase (IKK). Phosphorylated IkappaB becomes dissociated from NF-kappaB, unmasking the NLS. Phosphorylation also results in IkappaB ubiquitination and targeting to the proteasome. NF-kappaB can now enter the nucleus and regulate gene expression. NF-kappaB turns on expression of IkappaB forming a negative feedback loop.