TRPV5

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.{{cite web | title = Entrez Gene: TRPV5 transient receptor potential cation channel, subfamily V, member 5| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=56302}}

Both TRPV5 and TRPV6 are expressed in kidney and intestinal epithelial cells.{{cite journal | vauthors = van Goor MK, Hoenderop JG, van der Wijst J | title = TRP channels in calcium homeostasis: from hormonal control to structure-function relationship of TRPV5 and TRPV6 | journal = Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | volume = 1864 | issue = 6 | pages = 883–893 | date = June 2017 | pmid = 27913205 | doi = 10.1016/j.bbamcr.2016.11.027 | doi-access = }} TRPV5 is mainly expressed in kidney epithelial cells, where it plays an important role in the reabsorption of Ca²⁺,{{cite journal | vauthors = Hoenderop JG, Nilius B, Bindels RJ | title = Molecular mechanism of active Ca2+ reabsorption in the distal nephron | journal = Annual Review of Physiology | volume = 64 | pages = 529–49 | year = 2002 | pmid = 11826278 | doi = 10.1146/annurev.physiol.64.081501.155921 }} 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.{{cite journal | vauthors = Cha SK, Ortega B, Kurosu H, Rosenblatt KP, Kuro-O M, Huang CL | title = Removal of sialic acid involving Klotho causes cell-surface retention of TRPV5 channel via binding to galectin-1 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 28 | pages = 9805–10 | date = July 2008 | pmid = 18606998 | pmc = 2474477 | doi = 10.1073/pnas.0803223105 | bibcode = 2008PNAS..105.9805C | doi-access = free }}

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.{{cite journal | vauthors = Wolf MT, An SW, Nie M, Bal MS, Huang CL | title = Klotho up-regulates renal calcium channel transient receptor potential vanilloid 5 (TRPV5) by intra- and extracellular N-glycosylation-dependent mechanisms | journal = The Journal of Biological Chemistry | volume = 289 | issue = 52 | pages = 35849–57 | date = December 2014 | pmid = 25378396 | pmc = 4276853 | doi = 10.1074/jbc.M114.616649 | doi-access = free }} Genetic deletion of TRPV5 in mice leads to Ca²⁺ loss in the urine, and consequential hyperparathyroidism, and bone loss.{{cite journal | vauthors = Hoenderop JG, van Leeuwen JP, van der Eerden BC, Kersten FF, van der Kemp AW, Mérillat AM, Waarsing JH, Rossier BC, Vallon V, Hummler E, Bindels RJ | display-authors = 6 | title = Renal Ca2+ wasting, hyperabsorption, and reduced bone thickness in mice lacking TRPV5 | journal = The Journal of Clinical Investigation | volume = 112 | issue = 12 | pages = 1906–14 | date = December 2003 | pmid = 14679186 | pmc = 297001 | doi = 10.1172/JCI19826 }}

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.{{cite journal | vauthors = Gorvin CM | title = A successful conclusion to the long search for TRPV5 pathogenic variants in monogenic hypercalciuria | journal = European Journal of Human Genetics | volume = 32| issue = 11| pages = 1345–46| date = June 2024 | pmid = 38839989 | doi = 10.1038/s41431-024-01613-y | pmc = 11576729 | url = }}

• 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.{{cite journal | vauthors = Hughes TE, Del Rosario JS, Kapoor A, Yazici AT, Yudin Y, Fluck EC, Filizola M, Rohacs T, Moiseenkova-Bell VY | display-authors = 6 | title = Structure-based characterization of novel TRPV5 inhibitors | journal = eLife | volume = 8 | date = October 2019 | pmid = 31647410 | doi = 10.7554/eLife.49572 | pmc = 6834369 | doi-access = free }}

TRPV5 has been shown to interact with S100A10.{{cite journal | vauthors = van de Graaf SF, Hoenderop JG, Gkika D, Lamers D, Prenen J, Rescher U, Gerke V, Staub O, Nilius B, Bindels RJ | display-authors = 6 | title = Functional expression of the epithelial Ca(2+) channels (TRPV5 and TRPV6) requires association of the S100A10-annexin 2 complex | journal = The EMBO Journal | volume = 22 | issue = 7 | pages = 1478–87 | date = April 2003 | pmid = 12660155 | pmc = 152906 | doi = 10.1093/emboj/cdg162 }}

• TRPV

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• {{cite journal | vauthors = Vennekens R, Droogmans G, Nilius B | title = Functional properties of the epithelial Ca2+ channel, ECaC | journal = General Physiology and Biophysics | volume = 20 | issue = 3 | pages = 239–53 | date = September 2001 | pmid = 11765215 }}
• {{cite journal | vauthors = Heiner I, Eisfeld J, Lückhoff A | title = Role and regulation of TRP channels in neutrophil granulocytes | journal = Cell Calcium | volume = 33 | issue = 5–6 | pages = 533–40 | year = 2004 | pmid = 12765698 | doi = 10.1016/S0143-4160(03)00058-7 }}
• {{cite journal | vauthors = Nijenhuis T, Hoenderop JG, Bindels RJ | title = TRPV5 and TRPV6 in Ca(2+) (re)absorption: regulating Ca(2+) entry at the gate | journal = Pflügers Archiv | volume = 451 | issue = 1 | pages = 181–92 | date = October 2005 | pmid = 16044309 | doi = 10.1007/s00424-005-1430-6 | s2cid = 41267019 }}
• {{cite book | vauthors = Mensenkamp AR, Hoenderop JG, Bindels RJ | title = Transient Receptor Potential (TRP) Channels | chapter = TRPV5, the gateway to Ca2+ homeostasis | volume = 179 | issue = 179 | pages = 207–20 | year = 2007 | pmid = 17217059 | doi = 10.1007/978-3-540-34891-7_12 | isbn = 978-3-540-34889-4 | series = Handbook of Experimental Pharmacology }}
• {{cite journal | vauthors = Schoeber JP, Hoenderop JG, Bindels RJ | title = Concerted action of associated proteins in the regulation of TRPV5 and TRPV6 | journal = Biochemical Society Transactions | volume = 35 | issue = Pt 1 | pages = 115–9 | date = February 2007 | pmid = 17233615 | doi = 10.1042/BST0350115 }}

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• {{MeshName|TRPV5+protein,+human}}

{{NLM content}}

{{Ion channels|g4}}

{{Transient receptor potential channel modulators}}

Category:Ion channels

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