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TRPV5

From Wikipedia, the free encyclopedia

TRPV5
Identifiers
AliasesTRPV5, CAT2, ECAC1, OTRPC3, transient receptor potential cation channel subfamily V member 5
External IDsOMIM: 606679; MGI: 2429764; HomoloGene: 10520; GeneCards: TRPV5; OMA:TRPV5 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

56302

194352

Ensembl

ENSG00000274348
ENSG00000127412

ENSMUSG00000036899

UniProt

Q9NQA5

P69744

RefSeq (mRNA)

NM_019841

NM_001007572

RefSeq (protein)

NP_062815

NP_001007573

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

Function

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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

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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

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  • 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.[15]

Interactions

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

See also

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References

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  1. ^ a b c ENSG00000127412 GRCh38: Ensembl release 89: ENSG00000274348, ENSG00000127412 – Ensembl, May 2017
  2. ^ a b c 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. ^ a b c 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

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  • Vennekens R, Droogmans G, Nilius B (September 2001). "Functional properties of the epithelial Ca2+ channel, ECaC". General Physiology and Biophysics. 20 (3): 239–53. PMID 11765215.
  • Heiner I, Eisfeld J, Lückhoff A (2004). "Role and regulation of TRP channels in neutrophil granulocytes". Cell Calcium. 33 (5–6): 533–40. doi:10.1016/S0143-4160(03)00058-7. PMID 12765698.
  • Nijenhuis T, Hoenderop JG, Bindels RJ (October 2005). "TRPV5 and TRPV6 in Ca(2+) (re)absorption: regulating Ca(2+) entry at the gate". Pflügers Archiv. 451 (1): 181–92. doi:10.1007/s00424-005-1430-6. PMID 16044309. S2CID 41267019.
  • Mensenkamp AR, Hoenderop JG, Bindels RJ (2007). "TRPV5, the gateway to Ca2+ homeostasis". Transient Receptor Potential (TRP) Channels. Handbook of Experimental Pharmacology. Vol. 179. pp. 207–20. doi:10.1007/978-3-540-34891-7_12. ISBN 978-3-540-34889-4. PMID 17217059.
  • Schoeber JP, Hoenderop JG, Bindels RJ (February 2007). "Concerted action of associated proteins in the regulation of TRPV5 and TRPV6". Biochemical Society Transactions. 35 (Pt 1): 115–9. doi:10.1042/BST0350115. PMID 17233615.
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.


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