TRPV5

Last updated

TRPV5
Identifiers
Aliases TRPV5 , CAT2, ECAC1, OTRPC3, transient receptor potential cation channel subfamily V member 5
External IDs OMIM: 606679; MGI: 2429764; HomoloGene: 10520; GeneCards: TRPV5; OMA:TRPV5 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_019841

NM_001007572

RefSeq (protein)

NP_062815

NP_001007573

Location (UCSC) Chr 7: 142.91 – 142.93 Mb Chr 6: 41.63 – 41.66 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Transient receptor potential cation channel subfamily V member 5 is a calcium channel protein that in humans is encoded by the TRPV5 gene. [5] [6] [7]

Contents

Function

The TRPV5 gene is a member of the transient receptor family and the TRPV 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. [8]

Both TRPV5 and TRPV6 are expressed in kidney and intestinal epithelial cells. [9] TRPV5 is mainly expressed in kidney epithelial cells, where it plays an important role in the reabsorption of Ca2+, [10] whereas TRPV6 is mainly expressed in the intestine. [9] The enzyme α-klotho increases kidney calcium reabsorption by stabilizing TPRV5. [9] Klotho is a beta-glucuronidase-like enzyme that activates TRPV5 by removal of sialic acid. [11]

Clinical significance

Normally, about 95% to 98% of Ca2+ filtered from the blood by the kidney is reabsorbed by the kidney's renal tubule, mediated by TRPV5. [12] Genetic deletion of TRPV5 in mice leads to Ca2+ loss in the urine, and consequential hyperparathyroidism, and bone loss. [13]


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. [14]

Inhibitors

Interactions

TRPV5 has been shown to interact with S100A10. [16]

See also

Related Research Articles

<span class="mw-page-title-main">Ion channel</span> Pore-forming membrane protein

Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ions across the cell membrane, controlling the flow of ions across secretory and epithelial cells, and regulating cell volume. Ion channels are present in the membranes of all cells. Ion channels are one of the two classes of ionophoric proteins, the other being ion transporters.

Transient receptor potential channels are a group of ion channels located mostly on the plasma membrane of numerous animal cell types. Most of these are grouped into two broad groups: Group 1 includes TRPC, TRPV, TRPVL, TRPM, TRPS, TRPN, and TRPA. Group 2 consists of TRPP and TRPML. Other less-well categorized TRP channels exist, including yeast channels and a number of Group 1 and Group 2 channels present in non-animals. Many of these channels mediate a variety of sensations such as pain, temperature, different kinds of taste, pressure, and vision. In the body, some TRP channels are thought to behave like microscopic thermometers and used in animals to sense hot or cold. Some TRP channels are activated by molecules found in spices like garlic (allicin), chili pepper (capsaicin), wasabi ; others are activated by menthol, camphor, peppermint, and cooling agents; yet others are activated by molecules found in cannabis or stevia. Some act as sensors of osmotic pressure, volume, stretch, and vibration. Most of the channels are activated or inhibited by signaling lipids and contribute to a family of lipid-gated ion channels.

<span class="mw-page-title-main">Gitelman syndrome</span> Genetic kidney disorder

Gitelman syndrome (GS) is an autosomal recessive kidney tubule disorder characterized by low blood levels of potassium and magnesium, decreased excretion of calcium in the urine, and elevated blood pH. It is the most frequent hereditary salt-losing tubulopathy. Gitelman syndrome is caused by disease-causing variants on both alleles of the SLC12A3 gene. The SLC12A3 gene encodes the thiazide-sensitive sodium-chloride cotransporter, which can be found in the distal convoluted tubule of the kidney.

<span class="mw-page-title-main">Klotho (biology)</span> Human enzyme

Klotho is an enzyme that in humans is encoded by the KL gene. The three subfamilies of klotho are α-klotho, β-klotho, and γ-klotho. α-klotho activates FGF23, and β-klotho activates FGF19 and FGF21. When the subfamily is not specified, the word "klotho" typically refers to the α-klotho subfamily, because α-klotho was discovered before the other members.

<span class="mw-page-title-main">TRPV6</span> Protein-coding gene in the species Homo sapiens

TRPV6 is a membrane calcium (Ca2+) channel protein which is particularly involved in the first step in Ca2+absorption in the intestine.

TRPC is a family of transient receptor potential cation channels in animals.

<span class="mw-page-title-main">TRPV</span> Subgroup of TRP cation channels named after the vanilloid receptor

TRPV is a family of transient receptor potential cation channels in animals. All TRPVs are highly calcium selective.

TRPM is a family of transient receptor potential ion channels (M standing for wikt:melastatin). Functional TRPM channels are believed to form tetramers. The TRPM family consists of eight different channels, TRPM1–TRPM8.

<span class="mw-page-title-main">TRPC1</span> Protein and coding gene in humans

Transient receptor potential canonical 1 (TRPC1) is a protein that in humans is encoded by the TRPC1 gene.

<span class="mw-page-title-main">TRPC5</span> Protein-coding gene in the species Homo sapiens

Short transient receptor potential channel 5 (TrpC5) also known as transient receptor protein 5 (TRP-5) is a protein that in humans is encoded by the TRPC5 gene. TrpC5 is subtype of the TRPC family of mammalian transient receptor potential ion channels.

<span class="mw-page-title-main">TRPM2</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel, subfamily M, member 2, also known as TRPM2, is a protein that in humans is encoded by the TRPM2 gene.

<span class="mw-page-title-main">TRPM5</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily M member 5 (TRPM5), also known as long transient receptor potential channel 5 is a protein that in humans is encoded by the TRPM5 gene.

<span class="mw-page-title-main">TRPV2</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily V member 2 is a protein that in humans is encoded by the TRPV2 gene. TRPV2 is a nonspecific cation channel that is a part of the TRP channel family. This channel allows the cell to communicate with its extracellular environment through the transfer of ions, and responds to noxious temperatures greater than 52 °C. It has a structure similar to that of potassium channels, and has similar functions throughout multiple species; recent research has also shown multiple interactions in the human body.

<span class="mw-page-title-main">TRPM4</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily M member 4 (hTRPM4), also known as melastatin-4, is a protein that in humans is encoded by the TRPM4 gene.

<span class="mw-page-title-main">TRPM3</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily M member 3 is a protein that in humans is encoded by the TRPM3 gene.

<span class="mw-page-title-main">TRPM7</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel, subfamily M, member 7, also known as TRPM7, is a human gene encoding a protein of the same name.

<span class="mw-page-title-main">S100A10</span> Protein-coding gene in the species Homo sapiens

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 calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells. They regulate a number of cellular processes such as cell cycle progression and differentiation. The S100 protein is implicated in exocytosis and endocytosis by reorganization of F-actin.

<span class="mw-page-title-main">ITPR2</span> Protein-coding gene in humans

Inositol 1,4,5-trisphosphate receptor, type 2, also known as ITPR2, is a protein which in humans is encoded by the ITPR2 gene. The protein encoded by this gene is both a receptor for inositol triphosphate and a calcium channel.

The transient receptor potential Ca2+ channel (TRP-CC) family (TC# 1.A.4) is a member of the voltage-gated ion channel (VIC) superfamily and consists of cation channels conserved from worms to humans. The TRP-CC family also consists of seven subfamilies (TRPC, TRPV, TRPM, TRPN, TRPA, TRPP, and TRPML) based on their amino acid sequence homology:

  1. the canonical or classic TRPs,
  2. the vanilloid receptor TRPs,
  3. the melastatin or long TRPs,
  4. ankyrin (whose only member is the transmembrane protein 1 [TRPA1])
  5. TRPN after the nonmechanoreceptor potential C (nonpC), and the more distant cousins,
  6. the polycystins
  7. and mucolipins.
<span class="mw-page-title-main">ZINC17988990</span> Chemical compound

ZINC17988990 is a drug which acts as a potent and selective inhibitor for the TRPV5 calcium channel, with an IC50 of 177 nM and high selectivity for TRPV5 over TRPV6 and the other subtypes of TRPV. It is the first selective inhibitor to be developed for TRPV5, and may be useful for modulating calcium reabsorption in the kidneys.

References

  1. 1 2 3 ENSG00000127412 GRCh38: Ensembl release 89: ENSG00000274348, ENSG00000127412 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000036899 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Müller D, Hoenderop JG, Merkx GF, van Os CH, Bindels RJ (August 2000). "Gene structure and chromosomal mapping of human epithelial calcium channel". Biochemical and Biophysical Research Communications. 275 (1): 47–52. doi:10.1006/bbrc.2000.3227. PMID   10944439.
  6. Müller D, Hoenderop JG, Meij IC, van den Heuvel LP, Knoers NV, den Hollander AI, et al. (July 2000). "Molecular cloning, tissue distribution, and chromosomal mapping of the human epithelial Ca2+ channel (ECAC1)". Genomics. 67 (1): 48–53. doi:10.1006/geno.2000.6203. PMID   10945469.
  7. Clapham DE, Julius D, Montell C, Schultz G (December 2005). "International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels". Pharmacological Reviews. 57 (4): 427–50. doi:10.1124/pr.57.4.6. PMID   16382100. S2CID   17936350.
  8. "Entrez Gene: TRPV5 transient receptor potential cation channel, subfamily V, member 5".
  9. 1 2 3 van Goor MK, Hoenderop JG, van der Wijst J (June 2017). "TRP channels in calcium homeostasis: from hormonal control to structure-function relationship of TRPV5 and TRPV6". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1864 (6): 883–893. doi:10.1016/j.bbamcr.2016.11.027. PMID   27913205.
  10. Hoenderop JG, Nilius B, Bindels RJ (2002). "Molecular mechanism of active Ca2+ reabsorption in the distal nephron". Annual Review of Physiology. 64: 529–49. doi:10.1146/annurev.physiol.64.081501.155921. PMID   11826278.
  11. Cha SK, Ortega B, Kurosu H, Rosenblatt KP, Kuro-O M, Huang CL (July 2008). "Removal of sialic acid involving Klotho causes cell-surface retention of TRPV5 channel via binding to galectin-1". Proceedings of the National Academy of Sciences of the United States of America. 105 (28): 9805–10. Bibcode:2008PNAS..105.9805C. doi: 10.1073/pnas.0803223105 . PMC   2474477 . PMID   18606998.
  12. Wolf MT, An SW, Nie M, Bal MS, Huang CL (December 2014). "Klotho up-regulates renal calcium channel transient receptor potential vanilloid 5 (TRPV5) by intra- and extracellular N-glycosylation-dependent mechanisms". The Journal of Biological Chemistry. 289 (52): 35849–57. doi: 10.1074/jbc.M114.616649 . PMC   4276853 . PMID   25378396.
  13. Hoenderop JG, van Leeuwen JP, van der Eerden BC, Kersten FF, van der Kemp AW, Mérillat AM, et al. (December 2003). "Renal Ca2+ wasting, hyperabsorption, and reduced bone thickness in mice lacking TRPV5". The Journal of Clinical Investigation. 112 (12): 1906–14. doi:10.1172/JCI19826. PMC   297001 . PMID   14679186.
  14. Gorvin CM (June 2024). "A successful conclusion to the long search for TRPV5 pathogenic variants in monogenic hypercalciuria". European Journal of Human Genetics. 32 (11): 1345–46. doi:10.1038/s41431-024-01613-y. PMC   11576729 . PMID   38839989.
  15. Hughes TE, Del Rosario JS, Kapoor A, Yazici AT, Yudin Y, Fluck EC, et al. (October 2019). "Structure-based characterization of novel TRPV5 inhibitors". eLife. 8. doi: 10.7554/eLife.49572 . PMC   6834369 . PMID   31647410.
  16. van de Graaf SF, Hoenderop JG, Gkika D, Lamers D, Prenen J, Rescher U, et al. (April 2003). "Functional expression of the epithelial Ca(2+) channels (TRPV5 and TRPV6) requires association of the S100A10-annexin 2 complex". The EMBO Journal. 22 (7): 1478–87. doi:10.1093/emboj/cdg162. PMC   152906 . PMID   12660155.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.