Transient receptor potential cation channel subfamily V member 5 is a
calcium channel protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''TRPV5''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
Function
The ''TRPV5'' gene is a member of the
transient receptor family and the
TRPV
TRPV is a family of transient receptor potential cation channels (TRP channels) in animals. All TRPVs are highly calcium selective.
TRP channels are a large group of ion channels consisting of six protein families, located mostly on the plasm ...
subfamily. The calcium-selective
channel, TRPV5, encoded by this gene has 6 transmembrane-spanning domains, multiple potential
phosphorylation sites, an N-linked
glycosylation site, and 5 ANK repeats. This protein forms homotetramers or heterotetramers and is activated by a low internal calcium level.
Both TRPV5 and
TRPV6 are expressed in
kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...
and
intestinal
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
epithelial
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercell ...
cells.
TRPV5 is mainly expressed in
kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...
epithelial cells, where it plays an important role in the reabsorption of Ca
2+,
whereas TRPV6 is mainly expressed in the intestine.
The enzyme
α-klotho increases kidney calcium reabsorption by stabilizing TPRV5.
Klotho is a
beta-glucuronidase-like enzyme that activates TRPV5 by removal of
sialic acid.
Clinical significance
Normally, about 95% to 98% of Ca
2+ filtered from the blood by the kidney is reabsorbed by the kidney's
renal tubule
The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structure ...
, mediated by TRPV5.
Genetic deletion of TRPV5 in mice leads to Ca
2+ loss in the urine, and consequential
hyperparathyroidism
Hyperparathyroidism is an increase in parathyroid hormone (PTH) levels in the blood. This occurs from a disorder either within the parathyroid glands (primary hyperparathyroidism) or as response to external stimuli (secondary hyperparathyroidism). ...
, and bone loss.
Inhibitors
*
Econazole is a weak inhibitor of both TRPV5 and
TRPV6, with an IC
50 in the micromolar range
*
ZINC17988990 is a potent and selective inhibitor of TRPV5, with an IC
50 of 177nM and good selectivity over TRPV6 and the other TRPV channel subtypes.
Interactions
TRPV5 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
S100A10
S100 calcium-binding protein A10 (S100A10), also known as p11, is a protein that is encoded by the ''S100A10'' gene in humans and the ''S100a10'' gene in other species. S100A10 is a member of the S100 family of proteins containing two EF-hand cal ...
.
See also
*
TRPV
TRPV is a family of transient receptor potential cation channels (TRP channels) in animals. All TRPVs are highly calcium selective.
TRP channels are a large group of ion channels consisting of six protein families, located mostly on the plasm ...
References
Further reading
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External links
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Ion channels
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