Biology:TRPV5
 Generic protein structure example |
Transient receptor potential cation channel subfamily V member 5 is a calcium channel protein that in humans is encoded by the TRPV5 gene.[1][2][3]
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.[4]
Both TRPV5 and TRPV6 are expressed in kidney and intestinal epithelial cells.[5] TRPV5 is mainly expressed in kidney epithelial cells, where it plays an important role in the reabsorption of Ca2+,[6] whereas TRPV6 is mainly expressed in the intestine.[5] The enzyme α-klotho increases kidney calcium reabsorption by stabilizing TPRV5.[5] Klotho is a beta-glucuronidase-like enzyme that activates TRPV5 by removal of sialic acid.[7]
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.[8] Genetic deletion of TRPV5 in mice leads to Ca2+ loss in the urine, and consequential hyperparathyroidism, and bone loss.[9]
Inhibitors
- Econazole is a weak inhibitor of both TRPV5 and TRPV6, with an IC50 in the micromolar range
- ZINC17988990 is a potent and selective inhibitor of TRPV5, with an IC50 of 177nM and good selectivity over TRPV6 and the other TRPV channel subtypes.[10]
Interactions
TRPV5 has been shown to interact with S100A10.[11]
See also
References
- ↑ "Gene structure and chromosomal mapping of human epithelial calcium channel". Biochemical and Biophysical Research Communications 275 (1): 47–52. August 2000. doi:10.1006/bbrc.2000.3227. PMID 10944439.
- ↑ "Molecular cloning, tissue distribution, and chromosomal mapping of the human epithelial Ca2+ channel (ECAC1)". Genomics 67 (1): 48–53. July 2000. doi:10.1006/geno.2000.6203. PMID 10945469.
- ↑ "International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels". Pharmacological Reviews 57 (4): 427–50. December 2005. doi:10.1124/pr.57.4.6. PMID 16382100.
- ↑ "Entrez Gene: TRPV5 transient receptor potential cation channel, subfamily V, member 5". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=56302.
- ↑ 5.0 5.1 5.2 "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. June 2017. doi:10.1016/j.bbamcr.2016.11.027. PMID 27913205.
- ↑ "Molecular mechanism of active Ca2+ reabsorption in the distal nephron". Annual Review of Physiology 64: 529–49. 2002. doi:10.1146/annurev.physiol.64.081501.155921. PMID 11826278.
- ↑ "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. July 2008. doi:10.1073/pnas.0803223105. PMID 18606998. Bibcode: 2008PNAS..105.9805C.
- ↑ "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. December 2014. doi:10.1074/jbc.M114.616649. PMID 25378396.
- ↑ "Renal Ca2+ wasting, hyperabsorption, and reduced bone thickness in mice lacking TRPV5". The Journal of Clinical Investigation 112 (12): 1906–14. December 2003. doi:10.1172/JCI19826. PMID 14679186.
- ↑ "Structure-based characterization of novel TRPV5 inhibitors". eLife 8. October 2019. doi:10.7554/eLife.49572. PMID 31647410.
- ↑ "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. April 2003. doi:10.1093/emboj/cdg162. PMID 12660155.
Further reading
- "Functional properties of the epithelial Ca2+ channel, ECaC". General Physiology and Biophysics 20 (3): 239–53. September 2001. PMID 11765215.
- "Role and regulation of TRP channels in neutrophil granulocytes". Cell Calcium 33 (5–6): 533–40. 2004. doi:10.1016/S0143-4160(03)00058-7. PMID 12765698.
- "TRPV5 and TRPV6 in Ca(2+) (re)absorption: regulating Ca(2+) entry at the gate". Pflügers Archiv 451 (1): 181–92. October 2005. doi:10.1007/s00424-005-1430-6. PMID 16044309.
- "TRPV5, the gateway to Ca2+ homeostasis". Transient Receptor Potential (TRP) Channels. Handbook of Experimental Pharmacology. 179. 2007. pp. 207–20. doi:10.1007/978-3-540-34891-7_12. ISBN 978-3-540-34889-4.
- "Concerted action of associated proteins in the regulation of TRPV5 and TRPV6". Biochemical Society Transactions 35 (Pt 1): 115–9. February 2007. doi:10.1042/BST0350115. PMID 17233615.
External links
- TRPV5+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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