TRPV6 (transient receptor potential cation channel, subfamily V, member 6)
2009-03-01 Yoshiro Suzuki , Matthias A Hediger AffiliationInstitute of Biochemistry, Molecular Medicine, University of Bern, Bühlstrasse 28, 3012 Bern, Switzerland
Identity
HGNC
LOCATION
7q34
IMAGE
LEGEND
Schematic representation of human TRPV6 gene and neighbouring genes.
LOCUSID
ALIAS
CaT1,ECaC2,CATL,ABP/ZF,LP6728,ZFAB
FUSION GENES
DNA/RNA
Genomic structure of human TRPV6. The coding region is shown by open bars. The non-translated regions are shown by filled bars.
Description
TRPV6 gene consists of 15 exons and 14 introns including a coding, and a 5-/3- non-coding region. The regions encoding the ankyrin repeats, 6 transmembrane domains and a pore region are indicated. Several VDREs (vitamin D responsive element) have been identified in its promoter region.
A haplotype containing 3 non-synonymous polymorphisms (C157R+M378V+M681T) represent a recent positive selection in human evolution. The same haplotype seems to be associated with renal calcium stone formation.
A haplotype containing 3 non-synonymous polymorphisms (C157R+M378V+M681T) represent a recent positive selection in human evolution. The same haplotype seems to be associated with renal calcium stone formation.
Transcription
There is an alterative splice variant which missed 25-192 (a.a.). In EST database, there seems to be at least one more variant using different exon 1 (V2) and a variant starting from another site (P3) just upstream of exon 2 (V3).
Proteins
Schematic representation of TRPV6 protein. Four subunits makes one channel pore. Several ankyrin repeats, one N-glycosylation site and several calmodulin binding sites (CaM) are indicated.
Description
Glycosylated membrane protein (725 a.a., MW ~70 kDa) with 6 transmembrane regions and a pore-forming loop. N- and C-terminal tails are in cytoplasmic side. This protein forms a Ca2+-selective ion channel in the plasma membrane.
TRPV6 interacts with calmodulin which contribute to the intracellular Ca2+-dependent inactivation to avoid an increase of free Ca2+ concentration.
The ankyrin repeats may play a role in the interaction between subunits. TRPV6 can form a homo-tetramer as well as a hetero-tetramer with TRPV5, which exhibits distinct channel properties.
TRPV6 interacts with calmodulin which contribute to the intracellular Ca2+-dependent inactivation to avoid an increase of free Ca2+ concentration.
The ankyrin repeats may play a role in the interaction between subunits. TRPV6 can form a homo-tetramer as well as a hetero-tetramer with TRPV5, which exhibits distinct channel properties.
Expression
Highly expressed in placenta, moderately expressed in exocrine pancreas, mammary gland and salivary gland. Highly induced in small intestine under low calcium conditions or by 1,25-dihydroxyvitamin D3 treatment. Highly induced in prostate, breast and other cancer tissues during tumor progression.
Localisation
Plasma membrane. Localized in the apical membrane of the epithelial cells in the duodenum, and syncytiotrophoblasts in placenta.
Function
Apical Ca2+ entry pathway for total body calcium homeostasis in the small intestine under the control of 1,25-dihydroxyvitamin D3. TRPV6 likely also be involved in the placental Ca2+ transport from mother to fetus to maintain fetal bone mineralization.
TRPV6 may play a role in the Ca2+ entry pathway essential for keratinocyte differentiation. Although its exact function in cancer cells and tumor progression is still under investigation, TRPV6 is involved in an increase in proliferation and apoptotic resistance in cancer cells.
TRPV6 may play a role in the Ca2+ entry pathway essential for keratinocyte differentiation. Although its exact function in cancer cells and tumor progression is still under investigation, TRPV6 is involved in an increase in proliferation and apoptotic resistance in cancer cells.
Homology
73% identity with human TRPV5. 89% identity with mouse TRPV6.
Implicated in
Entity name
Prostate cancer
Oncogenesis
Expression of TRPV6 may be a predictor for prostate cancer progression since TRPV6 mRNA and protein levels are elevated in prostatic carcinoma compared to benign prostatic hyperplasia and positively correlated with Gleason grade/score in prostatic carcinoma.
TRPV6 is involved in an increase in proliferation and apoptotic resistance in cancer cells, suggesting that TRPV6 could be a new therapeutic target for the treatment for advanced prostate cancer.
TRPV6 is involved in an increase in proliferation and apoptotic resistance in cancer cells, suggesting that TRPV6 could be a new therapeutic target for the treatment for advanced prostate cancer.
Entity name
Breast cancer
Oncogenesis
TRPV6 mRNA was also found to be increased in breast cancer tissues compared to normal breast tissues. TRPV6 could be a prognostic marker for breast cancer and therapeutic target for breast cancer treatment.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 16717058 | 2006 | TRPV6 exhibits unusual patterns of polymorphism and divergence in worldwide populations. | Akey JM et al |
| 17129178 | 2007 | Marked disturbance of calcium homeostasis in mice with targeted disruption of the Trpv6 calcium channel gene. | Bianco SD et al |
| 18245667 | 2008 | The role of TRPV6 in breast carcinogenesis. | Bolanz KA et al |
| 15192090 | 2004 | Ca2+-selective transient receptor potential V channel architecture and function require a specific ankyrin repeat. | Erler I et al |
| 14586412 | 2003 | Expression of the Ca2+-selective cation channel TRPV6 in human prostate cancer: a novel prognostic marker for tumor progression. | Fixemer T et al |
| 15618484 | 2005 | Calcium absorption across epithelia. | Hoenderop JG et al |
| 18301763 | 2008 | Parallel selection on TRPV6 in human populations. | Hughes DA et al |
| 17550901 | 2007 | TRPV6 is a Ca2+ entry channel essential for Ca2+-induced differentiation of human keratinocytes. | Lehen'kyi V et al |
| 16574738 | 2006 | 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 MB et al |
| 12506351 | 2003 | Calcium fluxes in human trophoblast (BeWo) cells: calcium channels, calcium-ATPase, and sodium-calcium exchanger expression. | Moreau R et al |
| 11248124 | 2001 | Competitive regulation of CaT-like-mediated Ca2+ entry by protein kinase C and calmodulin. | Niemeyer BA et al |
| 12077127 | 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. | Nilius B et al |
| 11549322 | 2001 | Structural conservation of the genes encoding CaT1, CaT2, and related cation channels. | Peng JB et al |
| 11097838 | 2000 | Human calcium transport protein CaT1. | Peng JB et al |
| 11401523 | 2001 | CaT1 expression correlates with tumor grade in prostate cancer. | Peng JB et al |
| 18445599 | 2008 | The human TRPV6 channel protein is associated with cyclophilin B in human placenta. | Stumpf T et al |
| 18348695 | 2008 | Calcium channel TRPV6 is involved in murine maternal-fetal calcium transport. | Suzuki Y et al |
| 17850211 | 2008 | Mechanisms and regulation of epithelial Ca2+ absorption in health and disease. | Suzuki Y et al |
| 18276610 | 2008 | Gain-of-function haplotype in the epithelial calcium channel TRPV6 is a risk factor for renal calcium stone formation. | Suzuki Y et al |
| 11687634 | 2001 | Duodenal calcium absorption in vitamin D receptor-knockout mice: functional and molecular aspects. | Van Cromphaut SJ et al |
| 11278579 | 2001 | Expression of CaT-like, a novel calcium-selective channel, correlates with the malignancy of prostate cancer. | Wissenbach U et al |
| 12480925 | 2002 | Calcium-selective ion channel, CaT1, is apically localized in gastrointestinal tract epithelia and is aberrantly expressed in human malignancies. | Zhuang L et al |
Other Information
Locus ID:
NCBI: 55503
MIM: 606680
HGNC: 14006
Ensembl: ENSG00000165125
Variants:
dbSNP: 55503
ClinVar: 55503
TCGA: ENSG00000165125
COSMIC: TRPV6
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000165125 | ENST00000359396 | A0A1X7SBT1 |
| ENSG00000165125 | ENST00000431833 | C9JHY1 |
| ENSG00000165125 | ENST00000436401 | C9J9W0 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 36599151 | 2023 | The Coexistence of TRPV6 Variants With Other Pancreatitis-Associated Genes Affects Pediatric-Onset Pancreatitis. | 1 |
| 36858649 | 2023 | Biochemistry and pathophysiology of the Transient Potential Receptor Vanilloid 6 (TRPV6) calcium channel. | 3 |
| 37098383 | 2023 | An overlooked African gene variant linked to the calcium selective channel TRPV6: A mini-review. | 0 |
| 36599151 | 2023 | The Coexistence of TRPV6 Variants With Other Pancreatitis-Associated Genes Affects Pediatric-Onset Pancreatitis. | 1 |
| 36858649 | 2023 | Biochemistry and pathophysiology of the Transient Potential Receptor Vanilloid 6 (TRPV6) calcium channel. | 3 |
| 37098383 | 2023 | An overlooked African gene variant linked to the calcium selective channel TRPV6: A mini-review. | 0 |
| 34923708 | 2022 | Functionally deficient TRPV6 variants contribute to hereditary and familial chronic pancreatitis. | 3 |
| 35031425 | 2022 | Calcium selective channel TRPV6: Structure, function, and implications in health and disease. | 18 |
| 35181592 | 2022 | Down-regulation of TRPV6 Is Associated With Adverse Prognosis in Hepatocellular Carcinoma Treated With Curative Resection. | 1 |
| 35705057 | 2022 | TRPV6 channel mediates alcohol-induced gut barrier dysfunction and systemic response. | 5 |
| 35740929 | 2022 | TRPV6 Regulation by Cis-22a and Cholesterol. | 2 |
| 36162385 | 2022 | Vital but vulnerable: Human TRPV6 is a trade-off of powerful Ca(2+) uptake and susceptibility to epithelial barrier dysfunction. | 1 |
| 34923708 | 2022 | Functionally deficient TRPV6 variants contribute to hereditary and familial chronic pancreatitis. | 3 |
| 35031425 | 2022 | Calcium selective channel TRPV6: Structure, function, and implications in health and disease. | 18 |
| 35181592 | 2022 | Down-regulation of TRPV6 Is Associated With Adverse Prognosis in Hepatocellular Carcinoma Treated With Curative Resection. | 1 |
Citation
Yoshiro Suzuki ; Matthias A Hediger
TRPV6 (transient receptor potential cation channel, subfamily V, member 6)
Atlas Genet Cytogenet Oncol Haematol. 2009-03-01
Online version: http://atlasgeneticsoncology.org/gene/44425/trpv6-(transient-receptor-potential-cation-channel-subfamily-v-member-6)
