The tumor necrosis factor receptor superfamily (TNFRSF) is a

protein superfamily A protein superfamily is the largest grouping (clade) of proteins for which common ancestry can be inferred (see homology (biology), homology). Usually this common ancestry is inferred from structural alignment and mechanistic similarity, even if n ...

cytokine receptor Cytokine receptors are receptors that bind to cytokines. In recent years, the cytokine receptors have come to demand the attention of more investigators than cytokines themselves, partly because of their remarkable characteristics, and partly be ...

s characterized by the ability to bind

tumor necrosis factors The tumor necrosis factor (TNF) superfamily is a protein superfamily of transmembrane protein#Classification by topology, type II transmembrane proteins containing TNF homology domain and forming Protein trimer, trimers. Members of this superfa ...

(TNFs) via an extracellular

cysteine Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...

-rich domain. With the exception of

nerve growth factor Nerve growth factor (NGF) is a neurotrophic factor and neuropeptide primarily involved in the regulation of growth, maintenance, proliferation, and survival of certain target neurons. It is perhaps the prototypical growth factor, in that it was ...

(NGF), all TNFs are homologous to the archetypal

TNF-alpha 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 o ...

. In their active form, the majority of TNF receptors form trimeric complexes in the plasma membrane. Accordingly, most TNF receptors contain

transmembrane domain A transmembrane domain (TMD, TM domain) is a membrane-spanning protein domain. TMDs may consist of one or several alpha-helices or a transmembrane beta barrel. Because the interior of the lipid bilayer is hydrophobic, the amino acid residues in ...

s (TMDs), although some can be cleaved into soluble forms (e.g.

TNFR1 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). Function The protein encoded ...

), and some lack a TMD entirely (e.g. DcR3). In addition, most TNF receptors require specific adaptor protein such as

TRADD Tumor necrosis factor receptor type 1-associated DEATH domain protein is a protein that in humans is encoded by the ''TRADD'' gene. TRADD is an adaptor protein. Function The protein encoded by this gene is a death domain containing adaptor ...

TRAF TNF receptor associated factors (TRAFs) are a family of proteins primarily involved in the regulation of inflammation, antiviral responses and apoptosis. Currently, seven TRAF proteins have been characterized in mammals: TRAF1, TRAF2, TRAF3, TRAF4 ...

, RIP and

FADD FAS-associated death domain protein, also called MORT1, is encoded by the ''FADD'' gene on the 11q13.3 region of chromosome 11 in humans. FADD is an Signal transducing adaptor protein, adaptor protein that bridges members of the Tumor necrosi ...

for downstream signalling. TNF receptors are primarily involved in

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

and

inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...

, but they can also take part in other

signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a biochemical cascade, series of molecular events. Proteins responsible for detecting stimuli are generally termed receptor (biology), rece ...

pathways, such as proliferation, survival, and differentiation. TNF receptors are expressed in a wide variety of tissues in mammals, especially in

leukocytes White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...

. The term death receptor refers to those members of the TNF receptor superfamily that contain a

death domain The death domain (DD) is a protein interaction module composed of a bundle of six alpha helix, alpha-helices. DD is a subclass of protein structural motif , motif known as the death fold and is related in sequence and structure to the death effecto ...

, such as TNFR1,

Fas receptor The Fas receptor, also known as Fas, FasR, apoptosis antigen 1 (APO-1 or APT), cluster of differentiation 95 (CD95) or tumor necrosis factor receptor superfamily member 6 (TNFRSF6), is a protein that in humans is encoded by the ''FAS'' gene. Fas ...

, DR4 and DR5. 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. In the strict sense, the term TNF receptor is often used to refer to the archetypal members of the superfamily, namely TNFR1 and

TNFR2 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 necr ...

, which recognize TNF-alpha.

Members

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

References

External links

* {{TNF receptor superfamily modulators TNF receptor family Apoptosis Protein superfamilies Single-pass transmembrane proteins

Members

References

Further reading

External links