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 ...
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 bec ...
s characterized by the ability to bind
tumor necrosis factors (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, sometime ...
-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 on ...
(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 (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 b ...
), 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 m ...
,
TRAF,
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
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 adaptor protein that bridges members of the tumor necrosis factor receptor superfamily, such a ...
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 incl ...
and
inflammation
Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
, 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 mult ...
.
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.
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, 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