TNF receptor superfamily

Last updated
TNFR/NGFR cysteine-rich region
PDB 1tnr EBI.jpg
Structure of the soluble human 55 kd TNF receptor-human TNF beta complex. [1]
Identifiers
SymbolTNFR_c6
Pfam PF00020
Pfam clan CL0607
ECOD 389.1.3
InterPro IPR011614
PROSITE PDOC00561
SCOP2 1tnr / SCOPe / SUPFAM
Membranome 6
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

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. [2] [3] With the exception of nerve growth factor (NGF), all TNFs are homologous to the archetypal TNF-alpha. [4] 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 (e.g. TNFR1), and some lack a TMD entirely (e.g. DcR3). 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. [4]

Contents

The term death receptor refers to those members of the TNF receptor superfamily that contain a death domain, such as TNFR1, Fas receptor, DR4 and DR5. [4] They were named after the fact that they seemed to play an important role in apoptosis (programmed cell death), although they are now known to play other roles as well. [5]

In the strict sense, the term TNF receptor is often used to refer to the archetypal members of the superfamily, namely TNFR1 and TNFR2, which recognize TNF-alpha.

Members

In humans, there are 29 known family members of the TNF receptor superfamily. [6] [7] Historically, the family members have been numerically classified as TNFRSF#, where # denotes the member number, sometimes followed a letter. [2] Some newer additions to the TNF family remain unnumbered, however, such as the TNF receptor superfamily member EDAR. [2] [8]

TypeProtein (member #)SynonymsGeneLigand(s)
1 Tumor necrosis factor receptor 1 (1A)CD120a TNFRSF1A TNF (cachectin)
Tumor necrosis factor receptor 2 (1B)CD120b TNFRSF1B
3 Lymphotoxin beta receptor (3)CD18 LTBR Lymphotoxin beta (TNF-C)
4 OX40 (4)CD134 TNFRSF4 OX40L
5 CD40 (5)Bp50 CD40 CD154
6 Fas receptor (6)Apo-1, CD95 FAS FasL
Decoy receptor 3 (6B)TR6, M68 TNFRSF6B FasL, LIGHT, TL1A
7 CD27 (7)S152, Tp55 CD27 CD70, Siva
8 CD30 (8)Ki-1, TNR8 TNFRSF8 CD153
9 4-1BB (9)CD137 TNFRSF9 4-1BB ligand
10 Death receptor 4 (10A)TRAILR1, Apo-2, CD261 TNFRSF10A TRAIL
Death receptor 5 (10B)TRAILR2, CD262 TNFRSF10B
Decoy receptor 1 (10C)TRAILR3, LIT, TRID, CD263 TNFRSF10C
Decoy receptor 2 (10D)TRAILR4, TRUNDD, CD264 TNFRSF10D
11 RANK (11A)CD265 TNFRSF11A RANKL
Osteoprotegerin (11B)OCIF, TR1 TNFRSF11B
12 TWEAK receptor (12A)Fn14, CD266 TNFRSF12A TWEAK
13 TACI (13B)IGAD2, CD267 TNFRSF13B APRIL, BAFF, CAMLG
BAFF receptor (13C)CD268 TNFRSF13C BAFF
14 Herpesvirus entry mediator (14)ATAR, TR2, CD270 TNFRSF14 LIGHT
16 Nerve growth factor receptor (16)p75NTR, CD271 NGFR NGF, BDNF, NT-3, NT-4
17 B-cell maturation antigen (17)TNFRSF13A, CD269, BCMA TNFRSF17 BAFF
18 Glucocorticoid-induced TNFR-related (18)AITR, CD357 TNFRSF18 GITR ligand
19 TROY (19)TAJ, TRADE TNFRSF19 unknown
19L [9] RELT (19L)FLJ14993 RELT
21 Death receptor 6 (21)CD358 TNFRSF21
25 Death receptor 3 (25)Apo-3, TRAMP, LARD, WS-1 TNFRSF25 TL1A
27 Ectodysplasin A2 receptor (27)XEDAR EDA2R EDA-A2
EDAR [10] Ectodysplasin A receptor (EDAR)Downless Homolog EDAR EDA-A1

Related Research Articles

<span class="mw-page-title-main">Tumor necrosis factor</span> Immune system messenger protein which induces inflammation

Tumor necrosis factor (TNF), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation. TNF is produced primarily by activated macrophages, and induces inflammation by binding to its receptors on other cells. It is a member of the tumor necrosis factor superfamily, a family of transmembrane proteins that are cytokines, chemical messengers of the immune system. Excessive production of TNF plays a critical role in several inflammatory diseases, and TNF-blocking drugs are often employed to treat these diseases.

<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">TRAF2</span> Protein-coding gene in humans

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).

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

Tumor necrosis factor receptor type 1-associated DEATH domain protein is a protein that in humans is encoded by the TRADD gene.

<span class="mw-page-title-main">Lymphotoxin beta receptor</span>

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.

<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">Death receptor 4</span> Protein found in humans

Death receptor 4 (DR4), also known as TRAIL receptor 1 (TRAILR1) and tumor necrosis factor receptor superfamily member 10A (TNFRSF10A), is a cell surface receptor of the TNF-receptor superfamily that binds TRAIL and mediates apoptosis.

<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">Lymphotoxin alpha</span> Protein found in humans

Lymphotoxin-alpha (LT-α) formerly known as tumor necrosis factor-beta (TNF-β) is a protein that in humans is encoded by the LTA gene. Belonging to the hematopoietic cell line, LT-α exhibits anti-proliferative activity and causes the cellular destruction of tumor cell lines. As a cytotoxic protein, LT-α performs a variety of important roles in immune regulation depending on the form that it is secreted as. Unlike other members of the TNF superfamily, LT-α is only found as a soluble homotrimer, when found at the cell surface it is found only as a heterotrimer with LTβ.

<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">Decoy receptor 1</span> Protein-coding gene in the species Homo sapiens

Decoy receptor 1 (DCR1), also known as TRAIL receptor 3 (TRAILR3) and tumor necrosis factor receptor superfamily member 10C (TNFRSF10C), is a human cell surface receptor of the TNF-receptor superfamily.

<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">Death receptor 3</span> Protein found in humans

Death receptor 3 (DR3), also known as tumor necrosis factor receptor superfamily member 25 (TNFRSF25), is a cell surface receptor of the tumor necrosis factor receptor superfamily which mediates apoptotic signalling and differentiation. Its only known TNFSF ligand is TNF-like protein 1A (TL1A).

<span class="mw-page-title-main">TNFRSF12A</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">TNFRSF19</span> Protein-coding gene in the species Homo sapiens

Tumor necrosis factor receptor superfamily, member 19, also known as TNFRSF19 and TROY is a human 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">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).

References

  1. ↑ Banner DW, D'Arcy A, Janes W, et al. (May 1993). "Crystal structure of the soluble human 55 kd TNF receptor-human TNF beta complex: implications for TNF receptor activation". Cell. 73 (3): 431–45. doi:10.1016/0092-8674(93)90132-A. PMID   8387891. S2CID   25155518.
  2. 1 2 3 Locksley RM, Killeen N, Lenardo MJ (2001). "The TNF and TNF receptor superfamilies: integrating mammalian biology". Cell. 104 (4): 487–501. doi: 10.1016/S0092-8674(01)00237-9 . PMID   11239407. S2CID   7657797.
  3. ↑ Hehlgans T, Pfeffer K (2005). "The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games". Immunology. 115 (1): 1–20. doi:10.1111/j.1365-2567.2005.02143.x. PMC   1782125 . PMID   15819693.
  4. 1 2 3 Gravestein, LA; Borst, J (December 1998). "Tumor necrosis factor receptor family members in the immune system". Seminars in Immunology. 10 (6): 423–34. doi:10.1006/smim.1998.0144. PMID   9826575.
  5. ↑ Ashkenazi, A.; Dixit, VM (1998). "Death Receptors: Signaling and Modulation". Science. 281 (5381): 1305–8. doi:10.1126/science.281.5381.1305. PMID   9721089.
  6. ↑ Wallach, David (2018-10-01). "The Tumor Necrosis Factor Family: Family Conventions and Private Idiosyncrasies". Cold Spring Harbor Perspectives in Biology. 10 (10): a028431. doi:10.1101/cshperspect.a028431. ISSN   1943-0264. PMC   6169814 . PMID   28847899.
  7. ↑ "Gene group | HUGO Gene Nomenclature Committee". genenames.org. Retrieved 2025-01-13.
  8. ↑ "UniProt". www.uniprot.org. Retrieved 2025-01-13.
  9. ↑ "Gene symbol report | HUGO Gene Nomenclature Committee". genenames.org. Retrieved 2025-01-13.
  10. ↑ "UniProt". www.uniprot.org. Retrieved 2025-01-13.

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