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Gene Review

TRPV6  -  transient receptor potential cation...

Homo sapiens

Synonyms: ABP/ZF, CAT1, CATL, CaT-L, CaT-like, ...
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Disease relevance of TRPV6


Psychiatry related information on TRPV6


High impact information on TRPV6

  • A major breakthrough in completing the molecular details of these pathways was the identification of the epithelial Ca(2+) channel family consisting of two members: TRPV5 and TRPV6 [6].
  • The derepression requires binding of HuR, an AU-rich-element binding protein, to the 3'UTR of CAT-1 mRNA [7].
  • The derepression of CAT-1 mRNA is accompanied by its release from cytoplasmic processing bodies and its recruitment to polysomes [7].
  • Of these five amino acids, the first threonine plays a crucial role since the corresponding mutants (TRPV5 T599A and TRPV6 T600A) exhibited a diminished capacity to bind S100A10, were redistributed to a subplasma membrane area and did not display channel activity [8].
  • In conclusion, the S100A10-annexin 2 complex plays a crucial role in routing of TRPV5 and TRPV6 to plasma membrane [8].

Chemical compound and disease context of TRPV6


Biological context of TRPV6

  • To obtain insight in the pore architecture of TRPV6, a Ca(2+)-selective member of the TRPV subfamily, we probed the dimensions of its pore and determined pore-lining segments using cysteine-scanning mutagenesis [10].
  • Only one ECaC gene seems to exist in the F. rubripes genome, and the corresponding protein clusters together with ECaC2 from mammals upon phylogenetic analysis [11].
  • Importantly, downregulation of annexin 2 using annexin 2-specific small interfering RNA inhibited TRPV5 and TRPV6-mediated currents in transfected HEK293 cells [8].
  • This S100 protein forms a heterotetrameric complex with annexin 2 and associates specifically with the conserved sequence VATTV located in the C-terminal tail of TRPV5 and TRPV6 [8].
  • These data strongly suggest that the TRPV6 haplotype defined by the derived alleles at C157R, M378V and M681T conferred a selective advantage that varied spatially, and perhaps temporally, during human history [12].

Anatomical context of TRPV6


Associations of TRPV6 with chemical compounds


Physical interactions of TRPV6


Regulatory relationships of TRPV6

  • The mRNA for CaT1 was expressed more abundantly than that for CaT2 in three major tissues involved in transcellular calcium transport, namely intestine, kidney, and placenta, as determined by quantitative PCR [21].

Other interactions of TRPV6

  • Within the TRPV subgroup, TRPV5 and TRPV6 show exclusive calcium selectivity and play an important role in calcium uptake [15].
  • With the exception of TRPV5 and TRPV6, TRPV channel subunits preferentially assemble into homomeric complexes [22].
  • Of the two identified interaction domains within the N-terminal region, we showed that the first domain encompassing the third ankyrin repeat is the stringent requirement for physical assembly of TRPV6 subunits and when transferred to an unrelated protein enables its interaction with TRPV6 [15].
  • Moreover, the increase in CaT1 mRNA expression preceded by several hours the vitamin D induction of calbindin D9K, a putative cytosolic calcium transport protein [14].
  • The TRPC1 and TRPV6 members of the transient receptor potential (TRP) channel family are the most likely molecular candidates for the formation of prostate-specific endogenous SOCs [23].
  • A significant increase of TRPV6-mediated calcium uptake was observed after CypB/TRPV6 co-expression [24].

Analytical, diagnostic and therapeutic context of TRPV6

  • Whole cell recordings from non-transfected HEK cells and cells expressing human TRPV6 revealed the presence of a basal inward current in both types of cells when the internal solution contained 0.1 mm EGTA and 100 nm [Ca(2+)](i) or if the cytosolic Ca(2+) buffering remained undisturbed in perforated patch-clamp experiments [25].
  • In vivo interaction of TRPV6 with PTP1B was visualized using the bimolecular fluorescence complementation (BiFC) method and proved by co-immunoprecipitation of both proteins [19].
  • In prostatectomy specimens from 97 clinically organ-confined tumors, TRPV6 expression correlated significantly with the Gleason score (P=0.032), pathological stage (P<0.001) and extraprostatic extension (P=0.025) [2].
  • Based upon the hormonal responsiveness of a 7-kb TRPV6 promoter fragment in intestinal cell lines, we used a chromatin immunoprecipitation (ChIP) scanning method to search for possible vitamin D receptor (VDR) and retinoid X receptor (RXR) regulatory regions within the TRPV6 locus [20].
  • Reverse transcriptase-polymerase chain reaction revealed significant increases in messenger RNA abundance of transient potential receptor (TRP) V5 (223 +/- 10%), TRPV6 (177 +/- 9%), calbindin-D28k (231 +/- 8%), and TRPM6 (165 +/- 8%) in diabetic rats [26].


  1. Epithelial Ca2+ entry channels: transcellular Ca2+ transport and beyond. Peng, J.B., Brown, E.M., Hediger, M.A. J. Physiol. (Lond.) (2003) [Pubmed]
  2. Expression of the Ca2+-selective cation channel TRPV6 in human prostate cancer: a novel prognostic marker for tumor progression. Fixemer, T., Wissenbach, U., Flockerzi, V., Bonkhoff, H. Oncogene (2003) [Pubmed]
  3. The novel vitamin D analog ZK191784 as an intestine-specific vitamin D antagonist. Nijenhuis, T., van der Eerden, B.C., Z??gel, U., Steinmeyer, A., Weinans, H., Hoenderop, J.G., van Leeuwen, J.P., Bindels, R.J. FASEB J. (2006) [Pubmed]
  4. TRPV6 mediates capsaicin-induced apoptosis in gastric cancer cells-Mechanisms behind a possible new "hot" cancer treatment. Chow, J., Norng, M., Zhang, J., Chai, J. Biochim. Biophys. Acta (2007) [Pubmed]
  5. Cytosolic free calcium in lymphoblasts from young, aged and Alzheimer subjects. Gibson, G.E., Toral-Barza, L. Mech. Ageing Dev. (1992) [Pubmed]
  6. Calcium absorption across epithelia. Hoenderop, J.G., Nilius, B., Bindels, R.J. Physiol. Rev. (2005) [Pubmed]
  7. Relief of microRNA-mediated translational repression in human cells subjected to stress. Bhattacharyya, S.N., Habermacher, R., Martine, U., Closs, E.I., Filipowicz, W. Cell (2006) [Pubmed]
  8. Functional expression of the epithelial Ca(2+) channels (TRPV5 and TRPV6) requires association of the S100A10-annexin 2 complex. van de Graaf, S.F., Hoenderop, J.G., Gkika, D., Lamers, D., Prenen, J., Rescher, U., Gerke, V., Staub, O., Nilius, B., Bindels, R.J. EMBO J. (2003) [Pubmed]
  9. Calcium-transport in quiescent and 1,25-dihydroxycholecalciferol-stimulated human osteosarcoma cells. Role in 24 hydroxylase enhancement. Rebut-Bonneton, C., Ly, S.Y., Cancela, L. Horm. Metab. Res. (1988) [Pubmed]
  10. Outer pore architecture of a Ca2+-selective TRP channel. Voets, T., Janssens, A., Droogmans, G., Nilius, B. J. Biol. Chem. (2004) [Pubmed]
  11. Functional characterisation and genomic analysis of an epithelial calcium channel (ECaC) from pufferfish, Fugu rubripes. Qiu, A., Hogstrand, C. Gene (2004) [Pubmed]
  12. TRPV6 exhibits unusual patterns of polymorphism and divergence in worldwide populations. Akey, J.M., Swanson, W.J., Madeoy, J., Eberle, M., Shriver, M.D. Hum. Mol. Genet. (2006) [Pubmed]
  13. Diverse Calcium Channel Types are Present in the Human Placental Syncytiotrophoblast Basal Membrane. Bernucci, L., Henríquez, M., Díaz, P., Riquelme, G. Placenta (2006) [Pubmed]
  14. 1,25-Dihydroxyvitamin D3 increases the expression of the CaT1 epithelial calcium channel in the Caco-2 human intestinal cell line. Wood, R.J., Tchack, L., Taparia, S. BMC Physiol. (2001) [Pubmed]
  15. Ca2+-selective transient receptor potential V channel architecture and function require a specific ankyrin repeat. Erler, I., Hirnet, D., Wissenbach, U., Flockerzi, V., Niemeyer, B.A. J. Biol. Chem. (2004) [Pubmed]
  16. Regulation of the epithelial Ca2+ channels TRPV5 and TRPV6 by 1alpha,25-dihydroxy Vitamin D3 and dietary Ca2+. van de Graaf, S.F., Boullart, I., Hoenderop, J.G., Bindels, R.J. J. Steroid Biochem. Mol. Biol. (2004) [Pubmed]
  17. Store-operated Ca2+ current and TRPV6 channels in lymph node prostate cancer cells. Bödding, M., Fecher-Trost, C., Flockerzi, V. J. Biol. Chem. (2003) [Pubmed]
  18. TRPV6 is a Ca2+ entry channel essential for Ca2+-induced differentiation of human keratinocytes. Lehen'kyi, V., Beck, B., Polakowska, R., Charveron, M., Bordat, P., Skryma, R., Prevarskaya, N. J. Biol. Chem. (2007) [Pubmed]
  19. Tyrosine phosphatase PTP1B interacts with TRPV6 in vivo and plays a role in TRPV6-mediated calcium influx in HEK293 cells. Sternfeld, L., Krause, E., Schmid, A., Anderie, I., Latas, A., Al-Shaldi, H., Köhl, A., Evers, K., Hofer, H.W., Schulz, I. Cell. Signal. (2005) [Pubmed]
  20. The human transient receptor potential vanilloid type 6 distal promoter contains multiple vitamin D receptor binding sites that mediate activation by 1,25-dihydroxyvitamin D3 in intestinal cells. Meyer, M.B., Watanuki, M., Kim, S., Shevde, N.K., Pike, J.W. Mol. Endocrinol. (2006) [Pubmed]
  21. Structural conservation of the genes encoding CaT1, CaT2, and related cation channels. Peng, J.B., Brown, E.M., Hediger, M.A. Genomics (2001) [Pubmed]
  22. Homo- and heteromeric assembly of TRPV channel subunits. Hellwig, N., Albrecht, N., Harteneck, C., Schultz, G., Schaefer, M. J. Cell. Sci. (2005) [Pubmed]
  23. Store-operated Ca2+ channels in prostate cancer epithelial cells: function, regulation, and role in carcinogenesis. Vanden Abeele, F., Shuba, Y., Roudbaraki, M., Lemonnier, L., Vanoverberghe, K., Mariot, P., Skryma, R., Prevarskaya, N. Cell Calcium (2003) [Pubmed]
  24. The human TRPV6 channel protein is associated with cyclophilin B in human placenta. Stumpf, T., Zhang, Q., Hirnet, D., Lewandrowski, U., Sickmann, A., Wissenbach, U., Dörr, J., Lohr, C., Deitmer, J.W., Fecher-Trost, C. J. Biol. Chem. (2008) [Pubmed]
  25. Ca2+ dependence of the Ca2+-selective TRPV6 channel. Bödding, M., Flockerzi, V. J. Biol. Chem. (2004) [Pubmed]
  26. Increased renal calcium and magnesium transporter abundance in streptozotocin-induced diabetes mellitus. Lee, C.T., Lien, Y.H., Lai, L.W., Chen, J.B., Lin, C.R., Chen, H.C. Kidney Int. (2006) [Pubmed]
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