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
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 ...
(TNFα).
Function
The protein encoded by this gene is a member of the
tumor necrosis factor receptor
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 grow ...
superfamily, which also contains TNFRSF1B. This protein is one of the major receptors for the
tumor necrosis factor-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 ...
. This receptor can activate the
transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...
NF-κB
Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular ...
, mediate
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 function as a regulator of
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 ...
. Antiapoptotic protein BCL2-associated athanogene 4 (BAG4/SODD) and adaptor proteins TRADD and TRAF2 have been shown to interact with this receptor, and thus play regulatory roles in the
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 ...
mediated by the receptor.
Clinical significance
Germline mutations of the extracellular domains of this receptor were found to be associated with the human
genetic disorder
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
called tumor necrosis factor associated periodic syndrome (TRAPS) or
periodic fever syndrome
Periodic fever syndromes are a set of disorders characterized by recurrent episodes of systemic and organ-specific inflammation. Unlike autoimmune disorders such as systemic lupus erythematosus, in which the disease is caused by abnormalities of ...
.
Impaired receptor clearance is thought to be a mechanism of the disease.
Mutations in the TNFRSF1A gene are associated with elevated risk of multiple sclerosis.
Serum levels of TNFRSF1A are elevated in schizophrenia and bipolar disorder,
and high levels are associated with more severe psychotic symptoms.
High serum levels are also associated with cognitive impairment and dementia.
Interactions
TNFRSF1A has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with:
*
BAG4
BAG family molecular chaperone regulator 4 is a protein that in humans is encoded by the ''BAG4'' gene.
Function
The protein encoded by this gene is a member of the BAG1-related protein family. BAG1 is an anti-apoptotic protein that functions ...
,
*
CASP10
Caspase-10 is an enzyme that, in humans, is encoded by the ''CASP10'' gene.
This gene encodes a protein that is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execut ...
,
* 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 ...
,
* IKK2
IKK-β also known as inhibitor of nuclear factor kappa-B kinase subunit beta is a protein that in humans is encoded by the ''IKBKB'' (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta) gene.
Function
IKK-β is an enzy ...
,
* JAK1
JAK1 is a human tyrosine kinase protein essential for signaling for certain type I and type II cytokines. It interacts with the common gamma chain (γc) of type I cytokine receptors, to elicit signals from the IL-2 receptor family (e.g. IL-2R, I ...
,
* JAK2
Janus kinase 2 (commonly called JAK2) is a non-receptor tyrosine kinase. It is a member of the Janus kinase family and has been implicated in signaling by members of the type II cytokine receptor family (e.g. interferon receptors), the GM-CSF rece ...
,
* PIP4K2B
Phosphatidylinositol-5-phosphate 4-kinase type-2 beta is an enzyme that in humans is encoded by the ''PIP4K2B'' gene.
The protein encoded by this gene catalyzes the phosphorylation of phosphatidylinositol 4-phosphate on the fifth hydroxyl of th ...
,
* PSMD2
26S proteasome non-ATPase regulatory subunit 2, also as known as 26S Proteasome Regulatory Subunit Rpn1 (systematic nomenclature), is an enzyme that in humans is encoded by the ''PSMD2'' gene.
Structure
Gene expression
The gene ''PSMD2'' encode ...
,
* RIPK1
Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions in a variety of cellular pathways related to both cell survival and death. In terms of cell death, RIPK1 plays a role in apoptosis and necroptosis. Some of the cell survival ...
,
* SUMO1,
* 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 ...
* TRAF2
TNF receptor-associated factor 2 is a protein that in humans is encoded by the ''TRAF2'' gene.
Function
The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, an ...
,
* TRPC4AP
Trpc4-associated protein is a protein that in humans is encoded by the ''TRPC4AP'' gene.
Model organisms
Model organisms have been used in the study of TRPC4AP function. A conditional knockout mouse line, called ''Trpc4aptm1a(KOMP)Wtsi'' wa ...
,
* TNF
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 ...
, and
* UBE2I
SUMO-conjugating enzyme UBC9 is an enzyme that in humans is encoded by the ''UBE2I'' gene. It is also sometimes referred to as "ubiquitin conjugating enzyme E2I" or "ubiquitin carrier protein 9", even though these names do not accurately describe ...
.
See also
* Cluster of differentiation
The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophen ...
* TNF receptor associated periodic syndrome
TNF receptor associated periodic syndrome (TRAPSsubscription needed) is a periodic fever syndrome associated with mutations in a receptor for the molecule tumor necrosis factor (TNF) that is inheritable in an autosomal dominant manner. Individual ...
References
Further reading
*
*
*
*
*
*
External links
*
*
{{TNF receptor superfamily modulators
Clusters of differentiation
TNF receptor family