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). Usually this common ancestry is inferred from structural alignment and mechanistic similarity, even if no sequence similar ...
of
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 type II transmembrane proteins containing TNF homology domain and forming trimers. Members of this superfamily can be released from the cell membrane by extracellular pro ...
(TNFs) via an extracellular
cysteine
Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile.
When present as a deprotonated catalytic residue, some ...
-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, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...
.
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) is a membrane-spanning protein domain. TMDs generally adopt an alpha helix topological conformation, although some TMDs such as those in porins can adopt a different conformation. Because the interior of the lipid bi ...
s (TMDs), although some can be cleaved into soluble forms (e.g.
TNFR1), and some lack a TMD entirely (e.g.
DcR3
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.
Discovery
D ...
). In addition, most TNF receptors require specific
adaptor protein such as
TRADD,
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
Rest in peace (RIP), a phrase from the Latin (), is sometimes used in traditional Christian services and prayers, such as in the Catholic, Lutheran, Anglican, and Methodist denominations, to wish the soul of a decedent eternal rest and peace. ...
and
FADD for downstream signalling. TNF receptors are primarily involved in
apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes ( morphology) and death. These changes in ...
and
inflammation
Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
, 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 series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...
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, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mu ...
.
The term death receptor refers to those members of the TNF receptor superfamily that contain a
death domain
Death is the irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain ...
, 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 necro ...
, which recognize TNF-alpha.
Members
There are 27 family members, numerically classified as TNFRSF#, where # denotes the member number, sometimes followed a letter.
References
Further reading
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External links
*
{{TNF receptor superfamily modulators
TNF receptor family
Apoptosis
Protein superfamilies
Single-pass transmembrane proteins