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

2009-03-01 Yoshiro Suzuki , Matthias A Hediger Affiliation

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

Identity

HGNC

TRPV6

LOCATION

7q34

IMAGE

LEGEND

Schematic representation of human TRPV6 gene and neighbouring genes.

LOCUSID

55503

ALIAS

CaT1,ECaC2,CATL,ABP/ZF,LP6728,ZFAB

FUSION GENES

Show Gene Fusions

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.

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.

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 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)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Salivary secretion	KEGG	ko04970
Salivary secretion	KEGG	hsa04970
Mineral absorption	KEGG	ko04978
Mineral absorption	KEGG	hsa04978
Transmembrane transport of small molecules	REACTOME	R-HSA-382551
Ion channel transport	REACTOME	R-HSA-983712
Stimuli-sensing channels	REACTOME	R-HSA-2672351
TRP channels	REACTOME	R-HSA-3295583

Protein levels (Protein atlas)

Not detected

Low

Medium

High

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)