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TRPV5

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 511

Nomenclature: TRPV5

Family: Transient Receptor Potential channels (TRP)

Contents:

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 729 7q34 TRPV5 transient receptor potential cation channel subfamily V member 5 12
Mouse 6 1 723 6 B2.1 Trpv5 transient receptor potential cation channel, subfamily V, member 5 28
Rat 6 1 723 4q23 Trpv5 transient receptor potential cation channel, subfamily V, member 5 16-17
Previous and Unofficial Names Click here for help
OTRPC3 | ECaC | ECaC1 | epithelial calcium channel 1 | calcium transporter 2 | osm-9-like TRP channel 3 | CAT2 | transient receptor potential cation channel
Database Links Click here for help
Alphafold Q9NQA5 (Hs), P69744 (Mm), Q9JIP0 (Rn)
CATH/Gene3D 1.25.40.20
ChEMBL Target CHEMBL1628474 (Hs)
Ensembl Gene ENSG00000127412 (Hs), ENSMUSG00000036899 (Mm), ENSRNOG00000015394 (Rn)
Entrez Gene 56302 (Hs), 194352 (Mm), 116469 (Rn)
Human Protein Atlas ENSG00000127412 (Hs)
KEGG Gene hsa:56302 (Hs), mmu:194352 (Mm), rno:116469 (Rn)
OMIM 606679 (Hs)
Pharos Q9NQA5 (Hs)
RefSeq Nucleotide NM_019841 (Hs), NM_001007572 (Mm), NM_053787 (Rn)
RefSeq Protein NP_062815 (Hs), NP_001007573 (Mm), NP_446239 (Rn)
UniProtKB Q9NQA5 (Hs), P69744 (Mm), Q9JIP0 (Rn)
Wikipedia TRPV5 (Hs)
Associated Proteins Click here for help
Heteromeric Pore-forming Subunits
Name References
TRPV6 6
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
calmodulin 11
Rab11a 20
BSPRY 23
NHERF4 22
S100A10/annexin 2 21
80K-H 3
calbindin-D (28K) 10
Functional Characteristics Click here for help
γ = 59–78 pS for monovalent ions at negative potentials, conducts mono- and di-valents with high selectivity for divalents (PCa/PNa > 107); voltage- and time- dependent inward rectification; inhibited by intracellular Ca2+ promoting fast inactivation and slow downregulation; feedback inhibition by Ca2+ reduced by calcium binding protein 80-K-H; inhibited by extracellular and intracellular acidosis; upregulated by 1,25-dihydrovitamin D3
Ion Selectivity and Conductance Comments
At present the only ion selectivity data available for TRPV5 is from rabbit studies. Ion selectivity is ordered Na+ > Li+ > K+ > Cs+ > NMDG+ (N-methyl-G-glucamine) [14], and Ca2+ > Ba2+ = Sr2+ > Mn2+ [26].

Overall single channel conductance is 72-82 pS [14]. Subject to Mg2+ block. PCa:PNa ratio > 100 [14,26].
Voltage Dependence Comments
Blocking by intracellular Mg2+ displays voltage dependency [14].
Activators (Human)
constitutively active (with strong buffering of intracellular Ca2+)
Other channel blockers (Human)
Pb2+ = Cu2+ = Gd3+ > Cd2+ > Zn2+ > La3+ > Co2+ > Fe2

Download all structure-activity data for this target as a CSV file go icon to follow link

Activator Comments
TRPV5 is constitutively active [26]. Its function is modulated by extracellular protons [27,29-30]. Parathyroid hormone, 17β-estradiol and 1,25-dihydroxyvitamin D(3) activate TRPV5 by upregulating its expression level as well as directly activating the channel [2,4,7,18]. Klotho increases plasma membrane TRPV5 abundance by hydrolysis of its extracellular N-linked oligosaccharides [1].
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
gentamicin Small molecule or natural product Approved drug Hs Inhibition 6.0 pIC50 - - 25
⤷ pIC50 6.0 (IC50 1x10-6 M) [25]
tetrahydrocannabivarin Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.4 pIC50 - - 9
⤷ pIC50 5.4 (IC50 4x10-6 M) [9]
oxoglaucine Small molecule or natural product Hs Inhibition 4.8 pIC50 - - 31
⤷ pIC50 4.8 (IC50 1.5x10-5 M) [31]
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
ruthenium red Oc Inhibition 6.9 pIC50 - -150.0 – 100.0 13
⤷ pIC50 6.9 (IC50 1.11x10-7 M) [13]
Holding voltage: -150.0 – 100.0 mV
ruthenium red Click here for species-specific activity table Hs - 6.9 pIC50 - -
⤷ pIC50 6.9 (IC50 1.21x10-7 M)
Mg2+ Click here for species-specific activity table Hs - - - - -
⤷
econazole Small molecule or natural product Approved drug Click here for species-specific activity table Hs - - - - -
⤷
miconazole Small molecule or natural product Approved drug Click here for species-specific activity table Hs - - - - -
⤷
View species-specific channel blocker tables
Immunopharmacology Comments
Expressed on human T cells [15].
Tissue Distribution Click here for help
Kidney, prostate, testes, placenta, pancreas, brain.
Species:  Human
Technique:  RT-PCR
References:  12
Kidney.
Species:  Mouse
Technique:  RT-PCR
References:  28
Osteoclasts. Note that human osteoclasts also express TRPV5.
Species:  Mouse
Technique:  RT-PCR and immunocytochemistry.
References:  24
Kidney.
Species:  Rat
Technique:  Northern Blot and RT-PCR.
References:  16
Pancreatic islet cells
Species:  Rat
Technique:  RT-PCR, immunocytochemistry
References:  8
Functional Assays Click here for help
Two-electrode voltage clamp.
Species:  Rat
Tissue:  Xenopus laevis oocytes injected with TRPV5 cDNA.
Response measured:  Ca2+-evoked currents.
References:  16
Patch clamp (whole-cell recordings).
Species:  Rat
Tissue:  Kidney.
Response measured:  Ca2+-evoked currents.
References:  17
Patch clamp (whole-cell recordings), Ca2+ imaging
Species:  Rabbit
Tissue:  transfected HEK293 cells
Response measured:  Ca2+-evoked currents
References:  26
Physiological Functions Click here for help
Ca2+ (re)absorption.
Species:  Mouse
Tissue:  Kidney, intestines, bone.
References:  24
Ca2+ (re)absorption.
Species:  Human
Tissue:  Kidney, intestines, bone.
References:  12
Physiological Consequences of Altering Gene Expression Click here for help
Osteporosis
Species:  Mouse
Tissue:  Bone
Technique:  TRPV5 knockout
References:  5
Hypercalciuria
Species:  Mouse
Tissue:  Kidney
Technique:  Downregulation/knockout mouse
References:  5,19
Diabetes mellitus type 2
Species:  Rat
Tissue:  Pancreatic islet cells
Technique:  Downregulation of TRPV5
References:  8
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Trpv5tm1Bind Trpv5tm1Bind/Trpv5tm1Bind
involves: 129 * C57BL/6		 MGI:2429764  MP:0003795 abnormal bone structure PMID: 14679186 
Trpv5tm1Bind Trpv5tm1Bind/Trpv5tm1Bind
involves: 129 * C57BL/6		 MGI:2429764  MP:0004231 abnormal calcium ion homeostasis PMID: 14679186 
Trpv5tm1Bind Trpv5tm1Bind/Trpv5tm1Bind
involves: 129 * C57BL/6		 MGI:2429764  MP:0004214 abnormal long bone diaphysis morphology PMID: 14679186 
Trpv5tm1Bind Trpv5tm1Bind/Trpv5tm1Bind
involves: 129 * C57BL/6		 MGI:2429764  MP:0010111 abnormal renal calcium reabsorption PMID: 14679186 
Trpv5tm1Bind Trpv5tm1Bind/Trpv5tm1Bind
involves: 129 * C57BL/6		 MGI:2429764  MP:0005400 abnormal vitamin level PMID: 14679186 
Trpv5tm1Bind Trpv5tm1Bind/Trpv5tm1Bind
involves: 129 * C57BL/6		 MGI:2429764  MP:0009346 decreased cancellous bone thickness PMID: 14679186 
Trpv5tm1Bind Trpv5tm1Bind/Trpv5tm1Bind
involves: 129 * C57BL/6		 MGI:2429764  MP:0000135 decreased cortical bone thickness PMID: 14679186 
Trpv5tm1Bind Trpv5tm1Bind/Trpv5tm1Bind
involves: 129 * C57BL/6		 MGI:2429764  MP:0009350 decreased urine pH PMID: 14679186 
Trpv5tm1Bind Trpv5tm1Bind/Trpv5tm1Bind
involves: 129 * C57BL/6		 MGI:2429764  MP:0005441 hypercalciuria PMID: 14679186 
Trpv5tm1Bind Trpv5tm1Bind/Trpv5tm1Bind
involves: 129 * C57BL/6		 MGI:2429764  MP:0002901 hyperphosphaturia PMID: 14679186 
Trpv5tm1Bind Trpv5tm1Bind/Trpv5tm1Bind
involves: 129 * C57BL/6		 MGI:2429764  MP:0004984 increased osteoclast cell number PMID: 14679186 
Trpv5tm1Bind Trpv5tm1Bind/Trpv5tm1Bind
involves: 129 * C57BL/6		 MGI:2429764  MP:0001762 polyuria PMID: 14679186 

References

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1. Chang Q, Hoefs S, van der Kemp AW, Topala CN, Bindels RJ, Hoenderop JG. (2005) The beta-glucuronidase klotho hydrolyzes and activates the TRPV5 channel. Science, 310 (5747): 490-3. [PMID:16239475]

2. de Groot T, Lee K, Langeslag M, Xi Q, Jalink K, Bindels RJ, Hoenderop JG. (2009) Parathyroid hormone activates TRPV5 via PKA-dependent phosphorylation. J Am Soc Nephrol, 20 (8): 1693-704. [PMID:19423690]

3. Gkika D, Mahieu F, Nilius B, Hoenderop JG, Bindels RJ. (2004) 80K-H as a new Ca2+ sensor regulating the activity of the epithelial Ca2+ channel transient receptor potential cation channel V5 (TRPV5). J Biol Chem, 279 (25): 26351-7. [PMID:15100231]

4. Hoenderop JG, Müller D, Van Der Kemp AW, Hartog A, Suzuki M, Ishibashi K, Imai M, Sweep F, Willems PH, Van Os CH et al.. (2001) Calcitriol controls the epithelial calcium channel in kidney. J Am Soc Nephrol, 12 (7): 1342-9. [PMID:11423563]

5. 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. (2003) Renal Ca2+ wasting, hyperabsorption, and reduced bone thickness in mice lacking TRPV5. J Clin Invest, 112 (12): 1906-14. [PMID:14679186]

6. Hoenderop JG, Voets T, Hoefs S, Weidema F, Prenen J, Nilius B, Bindels RJ. (2003) Homo- and heterotetrameric architecture of the epithelial Ca2+ channels TRPV5 and TRPV6. EMBO J, 22 (4): 776-85. [PMID:12574114]

7. Irnaten M, Blanchard-Gutton N, Praetorius J, Harvey BJ. (2009) Rapid effects of 17beta-estradiol on TRPV5 epithelial Ca2+ channels in rat renal cells. Steroids, 74 (8): 642-9. [PMID:19463684]

8. Janssen SW, Hoenderop JG, Hermus AR, Sweep FC, Martens GJ, Bindels RJ. (2002) Expression of the novel epithelial Ca2+ channel ECaC1 in rat pancreatic islets. J Histochem Cytochem, 50 (6): 789-98. [PMID:12019295]

9. Janssens A, Silvestri C, Martella A, Vanoevelen JM, Di Marzo V, Voets T. (2018) Δ9-tetrahydrocannabivarin impairs epithelial calcium transport through inhibition of TRPV5 and TRPV6. Pharmacol Res, 136: 83-89. [PMID:30170189]

10. Lambers TT, Mahieu F, Oancea E, Hoofd L, de Lange F, Mensenkamp AR, Voets T, Nilius B, Clapham DE, Hoenderop JG et al.. (2006) Calbindin-D28K dynamically controls TRPV5-mediated Ca2+ transport. EMBO J, 25 (13): 2978-88. [PMID:16763551]

11. Lambers TT, Weidema AF, Nilius B, Hoenderop JG, Bindels RJ. (2004) Regulation of the mouse epithelial Ca2(+) channel TRPV6 by the Ca(2+)-sensor calmodulin. J Biol Chem, 279 (28): 28855-61. [PMID:15123711]

12. Müller D, Hoenderop JG, Meij IC, van den Heuvel LP, Knoers NV, den Hollander AI, Eggert P, García-Nieto V, Claverie-Martín F, Bindels RJ. (2000) Molecular cloning, tissue distribution, and chromosomal mapping of the human epithelial Ca2+ channel (ECAC1). Genomics, 67 (1): 48-53. [PMID:10945469]

13. Nilius B, Prenen J, Vennekens R, Hoenderop JG, Bindels RJ, Droogmans G. (2001) Pharmacological modulation of monovalent cation currents through the epithelial Ca2+ channel ECaC1. Br J Pharmacol, 134 (3): 453-62. [PMID:11588099]

14. Nilius B, Vennekens R, Prenen J, Hoenderop JG, Bindels RJ, Droogmans G. (2000) Whole-cell and single channel monovalent cation currents through the novel rabbit epithelial Ca2+ channel ECaC. J Physiol (Lond.), 527 Pt 2: 239-48. [PMID:10970426]

15. Parenti A, De Logu F, Geppetti P, Benemei S. (2016) What is the evidence for the role of TRP channels in inflammatory and immune cells?. Br J Pharmacol, 173 (6): 953-69. [PMID:26603538]

16. Peng JB, Chen XZ, Berger UV, Vassilev PM, Brown EM, Hediger MA. (2000) A rat kidney-specific calcium transporter in the distal nephron. J Biol Chem, 275 (36): 28186-94. [PMID:10875938]

17. Suzuki M, Ishibashi K, Ooki G, Tsuruoka S, Imai M. (2000) Electrophysiologic characteristics of the Ca-permeable channels, ECaC and CaT, in the kidney. Biochem Biophys Res Commun, 274 (2): 344-9. [PMID:10913341]

18. Van Abel M, Hoenderop JG, Dardenne O, St Arnaud R, Van Os CH, Van Leeuwen HJ, Bindels RJ. (2002) 1,25-dihydroxyvitamin D(3)-independent stimulatory effect of estrogen on the expression of ECaC1 in the kidney. J Am Soc Nephrol, 13 (8): 2102-9. [PMID:12138142]

19. van Abel M, Hoenderop JG, van der Kemp AW, Friedlaender MM, van Leeuwen JP, Bindels RJ. (2005) Coordinated control of renal Ca(2+) transport proteins by parathyroid hormone. Kidney Int, 68 (4): 1708-21. [PMID:16164647]

20. van de Graaf SF, Chang Q, Mensenkamp AR, Hoenderop JG, Bindels RJ. (2006) Direct interaction with Rab11a targets the epithelial Ca2+ channels TRPV5 and TRPV6 to the plasma membrane. Mol Cell Biol, 26 (1): 303-12. [PMID:16354700]

21. van de Graaf SF, Hoenderop JG, Gkika D, Lamers D, Prenen J, Rescher U, Gerke V, Staub O, Nilius B, Bindels RJ. (2003) Functional expression of the epithelial Ca(2+) channels (TRPV5 and TRPV6) requires association of the S100A10-annexin 2 complex. EMBO J, 22 (7): 1478-87. [PMID:12660155]

22. van de Graaf SF, Hoenderop JG, van der Kemp AW, Gisler SM, Bindels RJ. (2006) Interaction of the epithelial Ca2+ channels TRPV5 and TRPV6 with the intestine- and kidney-enriched PDZ protein NHERF4. Pflugers Arch, 452 (4): 407-17. [PMID:16565876]

23. van de Graaf SF, van der Kemp AW, van den Berg D, van Oorschot M, Hoenderop JG, Bindels RJ. (2006) Identification of BSPRY as a novel auxiliary protein inhibiting TRPV5 activity. J Am Soc Nephrol, 17 (1): 26-30. [PMID:16380433]

24. van der Eerden BC, Hoenderop JG, de Vries TJ, Schoenmaker T, Buurman CJ, Uitterlinden AG, Pols HA, Bindels RJ, van Leeuwen JP. (2005) The epithelial Ca2+ channel TRPV5 is essential for proper osteoclastic bone resorption. Proc Natl Acad Sci USA, 102 (48): 17507-12. [PMID:16291808]

25. van Megen WH, Beggs MR, An SW, Ferreira PG, Lee JJ, Wolf MT, Alexander RT, Dimke H. (2022) Gentamicin Inhibits Ca2+ Channel TRPV5 and Induces Calciuresis Independent of the Calcium-Sensing Receptor-Claudin-14 Pathway. J Am Soc Nephrol, 33 (3): 547-564. [PMID:35022312]

26. Vennekens R, Hoenderop JG, Prenen J, Stuiver M, Willems PH, Droogmans G, Nilius B, Bindels RJ. (2000) Permeation and gating properties of the novel epithelial Ca(2+) channel. J Biol Chem, 275 (6): 3963-9. [PMID:10660551]

27. Vennekens R, Prenen J, Hoenderop JG, Bindels RJ, Droogmans G, Nilius B. (2001) Modulation of the epithelial Ca2+ channel ECaC by extracellular pH. Pflugers Arch, 442 (2): 237-42. [PMID:11417220]

28. Weber K, Erben RG, Rump A, Adamski J. (2001) Gene structure and regulation of the murine epithelial calcium channels ECaC1 and 2. Biochem Biophys Res Commun, 289 (5): 1287-94. [PMID:11741335]

29. Yeh BI, Kim YK, Jabbar W, Huang CL. (2005) Conformational changes of pore helix coupled to gating of TRPV5 by protons. EMBO J, 24 (18): 3224-34. [PMID:16121193]

30. Yeh BI, Sun TJ, Lee JZ, Chen HH, Huang CL. (2003) Mechanism and molecular determinant for regulation of rabbit transient receptor potential type 5 (TRPV5) channel by extracellular pH. J Biol Chem, 278 (51): 51044-52. [PMID:14525991]

31. Zhong G, Long H, Chen F, Yu Y. (2021) Oxoglaucine mediates Ca2+ influx and activates autophagy to alleviate osteoarthritis through the TRPV5/calmodulin/CAMK-II pathway. Br J Pharmacol, 178 (15): 2931-2947. [PMID:33786819]

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