Transient receptor potential cation channel subfamily V member 5 is a
calcium channel
A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel, which are a type of calcium channel regulated by changes in membrane potential. Some calcium chan ...
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''TRPV5''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
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
In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols:
:
This equation can be writ ...
sites, an N-linked
glycosylation
Glycosylation is the reaction in which a carbohydrate (or ' glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not ...
site, and 5 ANK repeats. This protein forms homotetramers or heterotetramers and is activated by a low internal calcium level.
Both TRPV5 and
TRPV6
TRPV6 is a membrane calcium (Ca2+) channel protein which is particularly involved in the first step in Ca2+absorption in the intestine.
Classification
Transient Receptor Potential Vanilloid subfamily member 6 (TRPV6) is an epithelial Ca2+ ...
are expressed in
kidney
In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...
and
intestinal epithelial
Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...
cells.
TRPV5 is mainly expressed in
kidney
In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...
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, 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 hyperparathyroi ...
, and bone loss.
Autosomal recessive
hypercalciuria has been described in a family with a missense, inactivating genetic variant in TRPV5. This variant, known as p.(Val598Met), affects the TRP helix region of TRPV5, which is thought to control channel pore gating, assembly and protein folding.
Inhibitors
*
Econazole is a weak inhibitor of both TRPV5 and
TRPV6
TRPV6 is a membrane calcium (Ca2+) channel protein which is particularly involved in the first step in Ca2+absorption in the intestine.
Classification
Transient Receptor Potential Vanilloid subfamily member 6 (TRPV6) is an epithelial Ca2+ ...
, 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 with
S100A10.
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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