Gene Summary: Tumor necrosis factor (TNF) is a multifunctional proinflammatory cytokine secreted predominantly by monocytes/macrophages that has effects on lipid metabolism, coagulation, insulin resistance, and endothelial function. TNF was originally identified in mouse serum after injection with Mycobacterium bovis strain bacillus Calmette-Guerin (BCG) and endotoxin. Serum from such animals was cytotoxic or cytostatic to a number of mouse and human transformed cell lines and produced hemorrhagic necrosis and in some instances complete regression of certain transplanted tumors in miceGeneral information above from NCBI
Subunit structure: Homotrimer. Interacts with SPPL2B.
Subcellular location: 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.
Post-translational: 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.
Involvement in disease: Psoriatic arthritis (PSORAS) [MIM:607507]: 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). Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
Sequence similarity: Belongs to the tumor necrosis factor family.
General information above from UniProt