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Tumor necrosis factor (TNF), formerly known as TNF-α, is an inflammatory protein and a principal mediator of the innate immune response. TNF is produced primarily by macrophages in response to antigens, and activates inflammatory pathways through its two receptors, TNFR1 and TNFR2. It is a member of the tumor necrosis factor superfamily, a family of type II transmembrane proteins that function as cytokines. Excess production of TNF plays a critical role in the pathology of several inflammatory diseases, and anti-TNF therapies are often employed to treat these diseases.
CD30, also known as TNFRSF8, is a cell membrane protein of the tumor necrosis factor receptor family and a tumor marker.
Receptor activator of nuclear factor κ B (RANK), also known as TRANCE receptor or TNFRSF11A, is a member of the tumor necrosis factor receptor (TNFR) molecular sub-family. RANK is the receptor for RANK-Ligand (RANKL) and part of the RANK/RANKL/OPG signaling pathway that regulates osteoclast differentiation and activation. It is associated with bone remodeling and repair, immune cell function, lymph node development, thermal regulation, and mammary gland development. Osteoprotegerin (OPG) is a decoy receptor for RANKL, and regulates the stimulation of the RANK signaling pathway by competing for RANKL. The cytoplasmic domain of RANK binds TRAFs 1, 2, 3, 5, and 6 which transmit signals to downstream targets such as NF-κB and JNK.
The tumor necrosis factor receptor superfamily (TNFRSF) is a protein superfamily of cytokine receptors characterized by the ability to bind tumor necrosis factors (TNFs) via an extracellular cysteine-rich domain. With the exception of nerve growth factor (NGF), all TNFs are homologous to the archetypal TNF-alpha. In their active form, the majority of TNF receptors form trimeric complexes in the plasma membrane. Accordingly, most TNF receptors contain transmembrane domains (TMDs), although some can be cleaved into soluble forms, and some lack a TMD entirely. In addition, most TNF receptors require specific adaptor protein such as TRADD, TRAF, RIP and FADD for downstream signalling. TNF receptors are primarily involved in apoptosis and inflammation, but they can also take part in other signal transduction pathways, such as proliferation, survival, and differentiation. TNF receptors are expressed in a wide variety of tissues in mammals, especially in leukocytes.
Lymphotoxin is a member of the tumor necrosis factor (TNF) superfamily of cytokines, whose members are responsible for regulating the growth and function of lymphocytes and are expressed by a wide variety of cells in the body.
Tumor necrosis factor receptor superfamily, member 4 (TNFRSF4), also known as CD134 and OX40 receptor, is a member of the TNFR-superfamily of receptors which is not constitutively expressed on resting naïve T cells, unlike CD28. OX40 is a secondary co-stimulatory immune checkpoint molecule, expressed after 24 to 72 hours following activation; its ligand, OX40L, is also not expressed on resting antigen presenting cells, but is following their activation. Expression of OX40 is dependent on full activation of the T cell; without CD28, expression of OX40 is delayed and of fourfold lower levels.
A disintegrin and metalloprotease 17 (ADAM17), also called TACE, is a 70-kDa enzyme that belongs to the ADAM protein family of disintegrins and metalloproteases, activated by substrate presentation.
TNF receptor-associated factor 2 is a protein that in humans is encoded by the TRAF2 gene.
CD120 can refer to two members of the tumor necrosis factor receptor superfamily: tumor necrosis factor receptor 1 (TNFR1) and tumor necrosis factor receptor 2 (TNFR2).
Tumor necrosis factor receptor type 1-associated DEATH domain protein is a protein that in humans is encoded by the TRADD gene.
Lymphotoxin beta receptor (LTBR), also known as tumor necrosis factor receptor superfamily member 3 (TNFRSF3), is a cell surface receptor for lymphotoxin involved in apoptosis and cytokine release. It is a member of the tumor necrosis factor receptor superfamily.
Tumor necrosis factor receptor 1 (TNFR1), also known as tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) and CD120a, is a ubiquitous membrane receptor that binds tumor necrosis factor-alpha (TNFα).
TNF receptor-associated factor 1 is a protein that in humans is encoded by the TRAF1 gene.
TNF receptor-associated factor 5 is a protein that in humans is encoded by the TRAF5 gene.
TNF receptor-associated factor (TRAF3) is a protein that in humans is encoded by the TRAF3 gene.
Herpesvirus entry mediator (HVEM), also known as tumor necrosis factor receptor superfamily member 14 (TNFRSF14), is a human cell surface receptor of the TNF-receptor superfamily encoded by the TNFRSF14 gene.
Decoy receptor 3 (Dcr3), also known as tumor necrosis factor receptor superfamily member 6B (TNFRSF6B), TR6 and M68, is a soluble protein of the tumor necrosis factor receptor superfamily which inhibits Fas ligand-induced apoptosis.
Tumor necrosis factor receptor superfamily member 12A also known as the TWEAK receptor (TWEAKR) is a protein that in humans is encoded by the TNFRSF12A gene.
Tumor necrosis factor receptor superfamily member 18 (TNFRSF18), also known as glucocorticoid-induced TNFR-related protein (GITR) or CD357. GITR is encoded and tnfrsf18 gene at chromosome 4 in mice. GITR is type I transmembrane protein and is described in 4 different isoforms. GITR human orthologue, also called activation-inducible TNFR family receptor (AITR), is encoded by the TNFRSF18 gene at chromosome 1.
Tumor necrosis factor receptor 2 (TNFR2), also known as tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) and CD120b, is one of two membrane receptors that binds tumor necrosis factor-alpha (TNFα). Like its counterpart, tumor necrosis factor receptor 1 (TNFR1), the extracellular region of TNFR2 consists of four cysteine-rich domains which allow for binding to TNFα. TNFR1 and TNFR2 possess different functions when bound to TNFα due to differences in their intracellular structures, such as TNFR2 lacking a death domain (DD).
References
- ↑ Waetzig, Georg H.; Rosenstiel, Philip; Arlt, Alexander; Till, Andreas; Bräutigam, Karen; Schäfer, Heiner; Rose-John, Stefan; Seegert, Dirk; Schreiber, Stefan (2005). "Soluble tumor necrosis factor (TNF) receptor-1 induces apoptosis via reverse TNF signaling and autocrine transforming growth factor-β1". The FASEB Journal. 19 (1): 91–93. doi: 10.1096/fj.04-2073fje . PMID 15514103. S2CID 86190513 . Retrieved 4 February 2015.