Top ▲
GtoPdb is requesting financial support from commercial users. Please see our sustainability page for more information.
Target has curated data in GtoImmuPdb
Target id: 512
Nomenclature: TRPV6
Family: Transient Receptor Potential channels (TRP)
Annotation status:
Annotated and reviewed, awaiting update
» Email us
Gene and Protein Information ![]() |
|||||||
Species | TM | P Loops | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 6 | 1 | 765 | 7q34 | TRPV6 | transient receptor potential cation channel subfamily V member 6 | 19 |
Mouse | 6 | 1 | 767 | 6 B2.1 | Trpv6 | transient receptor potential cation channel, subfamily V, member 6 | 6 |
Rat | 6 | 1 | 767 | 4q23 | Trpv6 | transient receptor potential cation channel, subfamily V, member 6 | 18 |
Database Links ![]() |
|
Alphafold | Q9H1D0 (Hs), Q91WD2 (Mm), Q9R186 (Rn) |
CATH/Gene3D | 1.25.40.20 |
ChEMBL Target | CHEMBL1628465 (Hs) |
Ensembl Gene | ENSG00000165125 (Hs), ENSMUSG00000029868 (Mm), ENSRNOG00000014714 (Rn) |
Entrez Gene | 55503 (Hs), 64177 (Mm), 114246 (Rn) |
Human Protein Atlas | ENSG00000165125 (Hs) |
KEGG Gene | hsa:55503 (Hs), mmu:64177 (Mm), rno:114246 (Rn) |
OMIM | 606680 (Hs) |
Pharos | Q9H1D0 (Hs) |
RefSeq Nucleotide | NM_018646 (Hs), NM_022413 (Mm), NM_053686 (Rn) |
RefSeq Protein | NP_061116 (Hs), NP_071858 (Mm), NP_446138 (Rn) |
UniProtKB | Q9H1D0 (Hs), Q91WD2 (Mm), Q9R186 (Rn) |
Wikipedia | TRPV6 (Hs) |
Associated Proteins ![]() |
||||||||||||||||||||||||||||
|
|
|
Ion Selectivity and Conductance ![]() |
||||||
|
||||||
|
||||||
Ion Selectivity and Conductance Comments | ||||||
Overall single channel conductance is 42-58 pS [34]. Subject to Mg2+ block. PCa:PNa ratio > 100. |
Voltage Dependence Comments |
Only block by intracellular Mg2+ displays voltage dependency (V0.5 is approx -50 mV at 1 mM intracellular Mg2+, no extracellular Mg2+, symmetric Na+ [28]. |
Activators (Human) |
constitutively active (with strong buffering of intracellular Ca2+) |
Download all structure-activity data for this target as a CSV file
Activators | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Activator Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
TRPV6 is constitutively active [18-19]. Extracellular 2-aminoethoxydiphenylborane potentiates TRPV6 [29]. |
Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Channel Blockers | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | Click column headers to sort | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
View species-specific channel blocker tables |
Immunopharmacology Comments |
Expressed on human T cells [15]. |
Tissue Distribution ![]() |
||||||||
|
||||||||
|
||||||||
|
||||||||
|
Functional Assays ![]() |
||||||||||
|
||||||||||
|
||||||||||
|
Physiological Functions ![]() |
||||||||
|
||||||||
|
||||||||
|
||||||||
|
Physiological Consequences of Altering Gene Expression ![]() |
||||||||||
|
||||||||||
|
||||||||||
|
Phenotypes, Alleles and Disease Models ![]() |
Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Gene Expression and Pathophysiology ![]() |
||||||||||||
|
||||||||||||
|
General Comments |
In Vivo Detection of Human TRPV6-Rich Tumors with Anti-Cancer Peptides Derived from Soricidin, namely SOR-C13 and SOR-C27, which target tumor sites in mice bearing ovarian or prostate tumors, has been demonstrated [3]. |
1. Barley NF, Howard A, O'Callaghan D, Legon S, Walters JR. (2001) Epithelial calcium transporter expression in human duodenum. Am J Physiol Gastrointest Liver Physiol, 280 (2): G285-90. [PMID:11208552]
2. Bianco SD, Peng JB, Takanaga H, Suzuki Y, Crescenzi A, Kos CH, Zhuang L, Freeman MR, Gouveia CH, Wu J et al.. (2007) Marked disturbance of calcium homeostasis in mice with targeted disruption of the Trpv6 calcium channel gene. J Bone Miner Res, 22 (2): 274-85. [PMID:17129178]
3. Bowen CV, DeBay D, Ewart HS, Gallant P, Gormley S, Ilenchuk TT, Iqbal U, Lutes T, Martina M, Mealing G et al.. (2013) In vivo detection of human TRPV6-rich tumors with anti-cancer peptides derived from soricidin. PLoS ONE, 8 (3): e58866. [PMID:23554944]
4. Brooks CA, Barton LS, Behm DJ, Brnardic EJ, Costell MH, Holt DA, Jolivette LJ, Matthews JM, McAtee JJ, McCleland BW et al.. (2019) Discovery of GSK3527497: A Candidate for the Inhibition of Transient Receptor Potential Vanilloid-4 (TRPV4). J Med Chem, 62 (20): 9270-9280. [PMID:31532662]
5. Gkika D, Hsu YJ, van der Kemp AW, Christakos S, Bindels RJ, Hoenderop JG. (2006) Critical role of the epithelial Ca2+ channel TRPV5 in active Ca2+ reabsorption as revealed by TRPV5/calbindin-D28K knockout mice. J Am Soc Nephrol, 17 (11): 3020-7. [PMID:17005931]
6. Hirnet D, Olausson J, Fecher-Trost C, Bödding M, Nastainczyk W, Wissenbach U, Flockerzi V, Freichel M. (2003) The TRPV6 gene, cDNA and protein. Cell Calcium, 33 (5-6): 509-18. [PMID:12765696]
7. Hoenderop JG, Vennekens R, Müller D, Prenen J, Droogmans G, Bindels RJ, Nilius B. (2001) Function and expression of the epithelial Ca(2+) channel family: comparison of mammalian ECaC1 and 2. J Physiol (Lond.), 537 (Pt 3): 747-61. [PMID:11744752]
8. 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]
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, 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]
11. Meena AS, Shukla PK, Bell B, Giorgianni F, Caires R, Fernández-Peña C, Beranova S, Aihara E, Montrose MH, Chaib M et al.. (2022) TRPV6 channel mediates alcohol-induced gut barrier dysfunction and systemic response. Cell Rep, 39 (11): 110937. [PMID:35705057]
12. Niemeyer BA, Bergs C, Wissenbach U, Flockerzi V, Trost C. (2001) Competitive regulation of CaT-like-mediated Ca2+ entry by protein kinase C and calmodulin. Proc Natl Acad Sci USA, 98 (6): 3600-5. [PMID:11248124]
13. Nijenhuis T, Hoenderop JG, van der Kemp AW, Bindels RJ. (2003) Localization and regulation of the epithelial Ca2+ channel TRPV6 in the kidney. J Am Soc Nephrol, 14 (11): 2731-40. [PMID:14569082]
14. Nilius B, Prenen J, Hoenderop JG, Vennekens R, Hoefs S, Weidema AF, Droogmans G, Bindels RJ. (2002) Fast and slow inactivation kinetics of the Ca2+ channels ECaC1 and ECaC2 (TRPV5 and TRPV6). Role of the intracellular loop located between transmembrane segments 2 and 3. J Biol Chem, 277 (34): 30852-8. [PMID:12077127]
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, Brown EM, Hediger MA. (2001) Structural conservation of the genes encoding CaT1, CaT2, and related cation channels. Genomics, 76 (1-3): 99-109. [PMID:11549322]
17. 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]
18. Peng JB, Chen XZ, Berger UV, Vassilev PM, Tsukaguchi H, Brown EM, Hediger MA. (1999) Molecular cloning and characterization of a channel-like transporter mediating intestinal calcium absorption. J Biol Chem, 274 (32): 22739-46. [PMID:10428857]
19. Peng JB, Chen XZ, Berger UV, Weremowicz S, Morton CC, Vassilev PM, Brown EM, Hediger MA. (2000) Human calcium transport protein CaT1. Biochem Biophys Res Commun, 278 (2): 326-32. [PMID:11097838]
20. Peng JB, Zhuang L, Berger UV, Adam RM, Williams BJ, Brown EM, Hediger MA, Freeman MR. (2001) CaT1 expression correlates with tumor grade in prostate cancer. Biochem Biophys Res Commun, 282 (3): 729-34. [PMID:11401523]
21. Schoeber JP, Topala CN, Lee KP, Lambers TT, Ricard G, van der Kemp AW, Huynen MA, Hoenderop JG, Bindels RJ. (2008) Identification of Nipsnap1 as a novel auxiliary protein inhibiting TRPV6 activity. Pflugers Arch, 457 (1): 91-101. [PMID:18392847]
22. Simonin C, Awale M, Brand M, van Deursen R, Schwartz J, Fine M, Kovacs G, Häfliger P, Gyimesi G, Sithampari A et al.. (2015) Optimization of TRPV6 Calcium Channel Inhibitors Using a 3D Ligand-Based Virtual Screening Method. Angew Chem Int Ed Engl, 54 (49): 14748-52. [PMID:26457814]
23. Van Cromphaut SJ, Dewerchin M, Hoenderop JG, Stockmans I, Van Herck E, Kato S, Bindels RJ, Collen D, Carmeliet P, Bouillon R et al.. (2001) Duodenal calcium absorption in vitamin D receptor-knockout mice: functional and molecular aspects. Proc Natl Acad Sci USA, 98 (23): 13324-9. [PMID:11687634]
24. 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]
25. 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]
26. 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]
27. Voets T, Janssens A, Droogmans G, Nilius B. (2004) Outer pore architecture of a Ca2+-selective TRP channel. J Biol Chem, 279 (15): 15223-30. [PMID:14736889]
28. Voets T, Janssens A, Prenen J, Droogmans G, Nilius B. (2003) Mg2+-dependent gating and strong inward rectification of the cation channel TRPV6. J Gen Physiol, 121 (3): 245-60. [PMID:12601087]
29. Voets T, Prenen J, Fleig A, Vennekens R, Watanabe H, Hoenderop JG, Bindels RJ, Droogmans G, Penner R, Nilius B. (2001) CaT1 and the calcium release-activated calcium channel manifest distinct pore properties. J Biol Chem, 276 (51): 47767-70. [PMID:11687570]
30. 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]
31. Weissgerber P, Kriebs U, Tsvilovskyy V, Olausson J, Kretz O, Stoerger C, Mannebach S, Wissenbach U, Vennekens R, Middendorff R et al.. (2012) Excision of Trpv6 gene leads to severe defects in epididymal Ca2+ absorption and male fertility much like single D541A pore mutation. J Biol Chem, 287 (22): 17930-41. [PMID:22427671]
32. Weissgerber P, Kriebs U, Tsvilovskyy V, Olausson J, Kretz O, Stoerger C, Vennekens R, Wissenbach U, Middendorff R, Flockerzi V et al.. (2011) Male fertility depends on Ca²+ absorption by TRPV6 in epididymal epithelia. Sci Signal, 4 (171): ra27. [PMID:21540454]
33. Wissenbach U, Niemeyer BA, Fixemer T, Schneidewind A, Trost C, Cavalie A, Reus K, Meese E, Bonkhoff H, Flockerzi V. (2001) Expression of CaT-like, a novel calcium-selective channel, correlates with the malignancy of prostate cancer. J Biol Chem, 276 (22): 19461-8. [PMID:11278579]
34. Yue L, Peng JB, Hediger MA, Clapham DE. (2001) CaT1 manifests the pore properties of the calcium-release-activated calcium channel. Nature, 410 (6829): 705-9. [PMID:11287959]
35. Zhuang L, Peng JB, Tou L, Takanaga H, Adam RM, Hediger MA, Freeman MR. (2002) Calcium-selective ion channel, CaT1, is apically localized in gastrointestinal tract epithelia and is aberrantly expressed in human malignancies. Lab Invest, 82 (12): 1755-64. [PMID:12480925]