Tumor necrosis factor superfamily

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Tumor necrosis factor superfamily
Mouse Tumor Necrosis Factor Alpha.png
Trimeric structure of TNF alpha, produced by Mus musculus , based on PDB structure 2TNF (1.4 Å Resolution). Different colors represent different monomers. Baeyens, KJ et al. (1999). [1] Figure rendered using FirstGlance Jmol.
Identifiers
SymbolTNF
Pfam PF00229
InterPro IPR006052
PROSITE PDOC00224
SCOP2 1tnf / SCOPe / SUPFAM
OPM superfamily 292
OPM protein 2hew
Membranome 80
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
TNF
PDB 1du3 EBI.jpg
crystal structure of trail-sdr5
Identifiers
SymbolTNF
Pfam PF00229
Pfam clan CL0100
ECOD 10.3.1
InterPro IPR006052
PROSITE PDOC00561
SCOP2 1tnr / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

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]

Contents

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.

Members

There are 19 family members, numerically classified as TNFSF#, where # denotes the member number, sometimes followed by a letter. [4] [2]

TNFSF#NameSynonymsGeneFunction
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

Related Research Articles

<span class="mw-page-title-main">Tumor necrosis factor</span> Protein

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.

<span class="mw-page-title-main">Fas ligand</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">TRAIL</span> Mammalian protein

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.

<span class="mw-page-title-main">TNF receptor superfamily</span> Protein superfamily of cytokine receptors

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.

<span class="mw-page-title-main">Tumor necrosis factor receptor 1</span> Membrane receptor protein found in humans

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).

<span class="mw-page-title-main">TRAF1</span> Protein-coding gene in the species Homo sapiens

TNF receptor-associated factor 1 is a protein that in humans is encoded by the TRAF1 gene.

<span class="mw-page-title-main">TRAF3</span> Protein-coding gene in the species Homo sapiens

TNF receptor-associated factor (TRAF3) is a protein that in humans is encoded by the TRAF3 gene.

<span class="mw-page-title-main">APRIL (protein)</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">LIGHT (protein)</span> Secreted protein of the TNF superfamily

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.

<span class="mw-page-title-main">Herpesvirus entry mediator</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">Transmembrane activator and CAML interactor</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">Decoy receptor 2</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">B-cell maturation antigen</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">TNFRSF18</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">Death receptor 6</span> Protein found in humans

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.

<span class="mw-page-title-main">TNFSF12-TNFSF13</span> Protein-coding gene in the species Homo sapiens

Tumor necrosis factor (ligand) superfamily, member 12-member 13, also known as TNFSF12-TNFSF13, is a human gene.

<span class="mw-page-title-main">Tumor necrosis factor receptor 2</span> Membrane receptor protein found in humans

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).

<span class="mw-page-title-main">RELT</span> Protein-coding gene in the species Homo sapiens

Tumor necrosis factor receptor superfamily member 19L is a protein that in humans is encoded by the RELT gene.

<span class="mw-page-title-main">TACI-CRD2 protein domain</span>

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.

References

  1. Baeyens KJ, De Bondt HL, Raeymaekers A, Fiers W, De Ranter CJ (April 1999). "The structure of mouse tumour-necrosis factor at 1.4 A resolution: towards modulation of its selectivity and trimerization". Acta Crystallographica Section D. 55 (Pt 4): 772–8. Bibcode:1999AcCrD..55..772B. doi:10.1107/s0907444998018435. PMID   10089307.
  2. 1 2 3 The evolution of the immune system: conservation and diversification. Amsterdam: Elsevier. 2016. ISBN   978-0-12-801975-7. OCLC   950694824.
  3. Abbas AK, Lichtman AH, Pillai S (May 2017). Cellular and molecular immunology (Ninth ed.). Philadelphia, PA. ISBN   978-0-323-47978-3. OCLC   973917896.{{cite book}}: CS1 maint: location missing publisher (link)
  4. 1 2 Aggarwal BB, Gupta SC, Kim JH (January 2012). "Historical perspectives on tumor necrosis factor and its superfamily: 25 years later, a golden journey". Blood. 119 (3): 651–65. doi:10.1182/blood-2011-04-325225. PMC   3265196 . PMID   22053109.
This article incorporates text from the public domain Pfam and InterPro: IPR006052