TRPV6 (transient receptor potential cation channel, subfamily V, member 6)

2009-03-01   Yoshiro Suzuki  , Matthias A Hediger  

Institute of Biochemistry, Molecular Medicine, University of Bern, Bühlstrasse 28, 3012 Bern, Switzerland

Identity

HGNC
LOCATION
7q34
IMAGE
Atlas Image
LEGEND
Schematic representation of human TRPV6 gene and neighbouring genes.
LOCUSID
ALIAS
CaT1,ECaC2,CATL,ABP/ZF,LP6728,ZFAB
FUSION GENES

DNA/RNA

Atlas Image
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.

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

Atlas Image
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.

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.

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.
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 IDLast YearTitleAuthors

Other Information

Locus ID:

NCBI: 55503
MIM: 606680
HGNC: 14006
Ensembl: ENSG00000165125

Variants:

dbSNP: 55503
ClinVar: 55503
TCGA: ENSG00000165125
COSMIC: TRPV6

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000165125ENST00000359396A0A1X7SBT1
ENSG00000165125ENST00000431833C9JHY1
ENSG00000165125ENST00000436401C9J9W0

Expression (GTEx)

0
10
20
30
40
50
60

Pathways

PathwaySourceExternal ID
Salivary secretionKEGGko04970
Salivary secretionKEGGhsa04970
Mineral absorptionKEGGko04978
Mineral absorptionKEGGhsa04978
Transmembrane transport of small moleculesREACTOMER-HSA-382551
Ion channel transportREACTOMER-HSA-983712
Stimuli-sensing channelsREACTOMER-HSA-2672351
TRP channelsREACTOMER-HSA-3295583

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
365991512023The Coexistence of TRPV6 Variants With Other Pancreatitis-Associated Genes Affects Pediatric-Onset Pancreatitis.1
368586492023Biochemistry and pathophysiology of the Transient Potential Receptor Vanilloid 6 (TRPV6) calcium channel.3
370983832023An overlooked African gene variant linked to the calcium selective channel TRPV6: A mini-review.0
365991512023The Coexistence of TRPV6 Variants With Other Pancreatitis-Associated Genes Affects Pediatric-Onset Pancreatitis.1
368586492023Biochemistry and pathophysiology of the Transient Potential Receptor Vanilloid 6 (TRPV6) calcium channel.3
370983832023An overlooked African gene variant linked to the calcium selective channel TRPV6: A mini-review.0
349237082022Functionally deficient TRPV6 variants contribute to hereditary and familial chronic pancreatitis.3
350314252022Calcium selective channel TRPV6: Structure, function, and implications in health and disease.18
351815922022Down-regulation of TRPV6 Is Associated With Adverse Prognosis in Hepatocellular Carcinoma Treated With Curative Resection.1
357050572022TRPV6 channel mediates alcohol-induced gut barrier dysfunction and systemic response.5
357409292022TRPV6 Regulation by Cis-22a and Cholesterol.2
361623852022Vital but vulnerable: Human TRPV6 is a trade-off of powerful Ca(2+) uptake and susceptibility to epithelial barrier dysfunction.1
349237082022Functionally deficient TRPV6 variants contribute to hereditary and familial chronic pancreatitis.3
350314252022Calcium selective channel TRPV6: Structure, function, and implications in health and disease.18
351815922022Down-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/haematological-explorer/favicon/humanGenome