Tumor necrosis factor superfamily | |||||||||
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Identifiers | |||||||||
Symbol | TNF | ||||||||
Pfam | PF00229 | ||||||||
InterPro | IPR006052 | ||||||||
PROSITE | PDOC00224 | ||||||||
SCOP2 | 1tnf / SCOPe / SUPFAM | ||||||||
OPM superfamily | 292 | ||||||||
OPM protein | 2hew | ||||||||
Membranome | 80 | ||||||||
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TNF | |||||||||
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Identifiers | |||||||||
Symbol | TNF | ||||||||
Pfam | PF00229 | ||||||||
Pfam clan | CL0100 | ||||||||
ECOD | 10.3.1 | ||||||||
InterPro | IPR006052 | ||||||||
PROSITE | PDOC00561 | ||||||||
SCOP2 | 1tnr / SCOPe / SUPFAM | ||||||||
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The tumor necrosis factor (TNF) superfamily is a protein superfamily of type II transmembrane proteins containing TNF homology domain and forming trimers. Members of this superfamily can be released from the cell membrane by extracellular proteolytic cleavage and function as a cytokine. These proteins are expressed predominantly by immune cells and they regulate diverse cell functions, including immune response and inflammation, but also proliferation, differentiation, apoptosis and embryogenesis. [2] [3]
The superfamily contains 19 members that bind to 29 members of TNF receptor superfamily. [4] An occurrence of orthologs in invertebrates hints at ancient origin of this superfamily in evolution. [2]
The PROSITE pattern of this superfamily is located in a beta sheet in the central section of the protein that is conserved across all members.
There are 19 family members, numerically classified as TNFSF#, where # denotes the member number, sometimes followed by a letter. [4] [2]
TNFSF# | Name | Synonyms | Gene | Function |
---|---|---|---|---|
1 | Lymphotoxin alpha | TNFβ, TNFSF1B | LTA | Induction of inflammation and antiviral response, development of secondary lymphoid organs, role in tumorigenesis |
2 | Tumor necrosis factor | TNFα, Dif, Necrosin, TNFSF1A, ... | TNF | Regulation of immune cells, induction of fever, cachexia, inflammation and apoptosis, inhibition of tumorigenesis and viral replication and response to sepsis |
3 | Lymphotoxin beta | TNFγ | LTB | Induction of inflammation and antiviral response, development of secondary lymphoid organs, role in tumorigenesis |
4 | OX40 ligand | CD252, Gp34, CD134L | TNFSF4 | Activation of T cell immune response by T cell costimulation |
5 | CD40 ligand | CD154, TRAP, Gp39, T-BAM | CD40LG | Regulation of adaptive immune response by activating antigen-presenting cell |
6 | Fas ligand | CD178, APTL, CD95L | FASLG | Regulation of T cell homeostasis by induction of apoptosis |
7 | CD27 ligand | CD70 | CD70 | Regulation of B cell activation and T cell homeostasis |
8 | CD30 ligand | CD153 | TNFSF8 | Induction of apoptosis of T cells and B cells, prevention of autoimmunity |
9 | CD137 ligand | 4-1 BBL | TNFSF9 | |
10 | TNF-related apoptosis-inducing ligand | CD253, APO-2L | TNFSF10 | Inhibition of tumorigenesis, induction of apoptosis |
11 | Receptor activator of nuclear factor kappa-Β ligand | CD254, OPGL, TRANCE, ODF | TNFSF11 | Tissue growth (particularly bone regeneration and remodeling), dendritic cell maturation |
12 | TNF-related weak inducer of apoptosis | APO-3L, DR3L | TNFSF12 | Regulation of angiogenesis, induction of apoptosis |
13 | A proliferation-inducing ligand | CD256, TALL-2, TRDL1 | TNFSF13 | Regulation of B cell development and plasma cell survival |
13B | B-cell activating factor | CD257, BLyS, TALL-1, TNFSF20, ... | TNFSF13B | Stimulation of B cell proliferation and differentiation |
14 | LIGHT | CD258, HVEML | TNFSF14 | Stimulation of T cell proliferation, apoptosis regulation |
15 | Vascular endothelial growth inhibitor | TL1, TL-1A | TNFSF15 | Inhibition of angiogenesis |
18 | TNF superfamily member 18 | GITRL, AITRL, TL-6 | TNFSF18 | Regulation of T cell survival |
19 | Ectodysplasin A | ED1-A1, ED1-A2 | EDA | Development of ectodermal tissues |
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.
Fas ligand is a type-II transmembrane protein expressed on various types of cells, including cytotoxic T lymphocytes, monocytes, neutrophils, breast epithelial cells, vascular endothelial cells and natural killer (NK) cells. It binds with its receptor, called FAS receptor and plays a crucial role in the regulation of the immune system and in induction of apoptosis, a programmed cell death.
In the field of cell biology, TNF-related apoptosis-inducing ligand (TRAIL), is a protein functioning as a ligand that induces the process of cell death called apoptosis.
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 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 (TRAF3) is a protein that in humans is encoded by the TRAF3 gene.
A proliferation-inducing ligand (APRIL), also known as tumor necrosis factor ligand superfamily member 13 (TNFSF13), is a protein of the TNF superfamily recognized by the cell surface receptor TACI. It is encoded by the TNFSF13 gene.
LIGHT, also known as tumor necrosis factor superfamily member 14 (TNFSF14), is a secreted protein of the TNF superfamily. It is recognized by herpesvirus entry mediator (HVEM), as well as decoy receptor 3.
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.
Transmembrane activator and CAML interactor (TACI), also known as tumor necrosis factor receptor superfamily member 13B (TNFRSF13B) is a protein that in humans is encoded by the TNFRSF13B gene.
Decoy receptor 2 (DCR2), also known as TRAIL receptor 4 (TRAILR4) and tumor necrosis factor receptor superfamily member 10D (TNFRSF10D), is a human cell surface receptor of the TNF-receptor superfamily.
B-cell maturation antigen, also known as tumor necrosis factor receptor superfamily member 17 (TNFRSF17), is a protein that in humans is encoded by the TNFRSF17 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.
Death receptor 6 (DR6), also known as tumor necrosis factor receptor superfamily member 21 (TNFRSF21), is a cell surface receptor of the tumor necrosis factor receptor superfamily which activates the JNK and NF-κB pathways. It is mostly expressed in the thymus, spleen and white blood cells. The Gene for DR6 is 78,450 bases long and is found on the 6th chromosome. This is transcribed into a 655 amino acid chain weighing 71.8 kDa. Post transcriptional modifications of this protein include glycosylation on the asparagines at the 82, 141, 252, 257, 278, and 289 amino acid locations.
Tumor necrosis factor (ligand) superfamily, member 12-member 13, also known as TNFSF12-TNFSF13, is a human gene.
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).
Tumor necrosis factor receptor superfamily member 19L is a protein that in humans is encoded by the RELT gene.
In molecular biology, TACI-CRD2 represents the second cysteine-rich protein domain found in the TACI family of proteins. Members of this family are predominantly found in tumour necrosis factor receptor superfamily, member 13b (TACI), and are required for binding to the ligands APRIL and BAFF. TACI-CRD2 stands for Transmembrane Activator and CAML Interactor- Cysteine Rich Domain 2.
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