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

Written2009-03Yoshiro Suzuki, Matthias A Hediger
Institute of Biochemistry, Molecular Medicine, University of Bern, Bühlstrasse 28, 3012 Bern, Switzerland

(Note : for Links provided by Atlas : click)

Identity

Alias_namesECAC2
epithelial calcium channel 2
transient receptor potential cation channel, subfamily V, member 6
Alias_symbol (synonym)CaT1
Other aliasECaC2
CATL
ABP/ZF
LP6728
ZFAB
HGNC (Hugo) TRPV6
LocusID (NCBI) 55503
Atlas_Id 44425
Location 7q34  [Link to chromosome band 7q34]
Location_base_pair Starts at 142871203 and ends at 142885745 bp from pter ( according to hg19-Feb_2009)  [Mapping TRPV6.png]
Local_order Colocalized with another Ca2+-selective epithelial channel gene, TRPV5.
 
  Schematic representation of human TRPV6 gene and neighbouring genes.
Fusion genes
(updated 2016)
TRPV6 (7q34) / KEL (7q34)

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).

Protein

 
  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

Note
  
Entity 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 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.
  

Bibliography

TRPV6 exhibits unusual patterns of polymorphism and divergence in worldwide populations.
Akey JM, Swanson WJ, Madeoy J, Eberle M, Shriver MD.
Hum Mol Genet. 2006 Jul 1;15(13):2106-13. Epub 2006 May 22.
PMID 16717058
 
Marked disturbance of calcium homeostasis in mice with targeted disruption of the Trpv6 calcium channel gene.
Bianco SD, Peng JB, Takanaga H, Suzuki Y, Crescenzi A, Kos CH, Zhuang L, Freeman MR, Gouveia CH, Wu J, Luo H, Mauro T, Brown EM, Hediger MA.
J Bone Miner Res. 2007 Feb;22(2):274-85.
PMID 17129178
 
The role of TRPV6 in breast carcinogenesis.
Bolanz KA, Hediger MA, Landowski CP.
Mol Cancer Ther. 2008 Feb;7(2):271-9. Epub 2008 Feb 1.
PMID 18245667
 
Ca2+-selective transient receptor potential V channel architecture and function require a specific ankyrin repeat.
Erler I, Hirnet D, Wissenbach U, Flockerzi V, Niemeyer BA.
J Biol Chem. 2004 Aug 13;279(33):34456-63. Epub 2004 Jun 10.
PMID 15192090
 
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 Oct 30;22(49):7858-61.
PMID 14586412
 
Calcium absorption across epithelia.
Hoenderop JG, Nilius B, Bindels RJ.
Physiol Rev. 2005 Jan;85(1):373-422.
PMID 15618484
 
Parallel selection on TRPV6 in human populations.
Hughes DA, Tang K, Strotmann R, Schoneberg T, Prenen J, Nilius B, Stoneking M.
PLoS ONE. 2008 Feb 27;3(2):e1686.
PMID 18301763
 
"Compositions Corresponding to a Calcium Transporter and Methods of Making and Using Same".
Inventors: Matthias A. Hediger, Ji-Bin Peng and Edward M Brown.
US patent # 6,534,642.
 
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 Aug 3;282(31):22582-91. Epub 2007 Jun 5.
PMID 17550901
 
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, Watanuki M, Kim S, Shevde NK, Pike JW.
Mol Endocrinol. 2006 Jun;20(6):1447-61. Epub 2006 Mar 30.
PMID 16574738
 
Calcium fluxes in human trophoblast (BeWo) cells: calcium channels, calcium-ATPase, and sodium-calcium exchanger expression.
Moreau R, Simoneau L, Lafond J.
Mol Reprod Dev. 2003 Feb;64(2):189-98.
PMID 12506351
 
Competitive regulation of CaT-like-mediated Ca2+ entry by protein kinase C and calmodulin.
Niemeyer BA, Bergs C, Wissenbach U, Flockerzi V, Trost C.
Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3600-5.
PMID 11248124
 
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, Prenen J, Hoenderop JG, Vennekens R, Hoefs S, Weidema AF, Droogmans G, Bindels RJ.
J Biol Chem. 2002 Aug 23;277(34):30852-8. Epub 2002 Jun 19.
PMID 12077127
 
Structural conservation of the genes encoding CaT1, CaT2, and related cation channels.
Peng JB, Brown EM, Hediger MA.
Genomics. 2001 Aug;76(1-3):99-109.
PMID 11549322
 
Human calcium transport protein CaT1.
Peng JB, Chen XZ, Berger UV, Weremowicz S, Morton CC, Vassilev PM, Brown EM, Hediger MA.
Biochem Biophys Res Commun. 2000 Nov 19;278(2):326-32.
PMID 11097838
 
CaT1 expression correlates with tumor grade in prostate cancer.
Peng JB, Zhuang L, Berger UV, Adam RM, Williams BJ, Brown EM, Hediger MA, Freeman MR.
Biochem Biophys Res Commun. 2001 Apr 6;282(3):729-34.
PMID 11401523
 
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, Dorr J, Lohr C, Deitmer JW, Fecher-Trost C.
J Biol Chem. 2008 Jun 27;283(26):18086-98. Epub 2008 Apr 29.
PMID 18445599
 
Calcium channel TRPV6 is involved in murine maternal-fetal calcium transport.
Suzuki Y, Kovacs CS, Takanaga H, Peng JB, Landowski CP, Hediger MA.
J Bone Miner Res. 2008 Aug;23(8):1249-56.
PMID 18348695
 
Mechanisms and regulation of epithelial Ca2+ absorption in health and disease.
Suzuki Y, Landowski CP, Hediger MA.
Annu Rev Physiol. 2008;70:257-71.
PMID 17850211
 
Gain-of-function haplotype in the epithelial calcium channel TRPV6 is a risk factor for renal calcium stone formation.
Suzuki Y, Pasch A, Bonny O, Mohaupt MG, Hediger MA, Frey FJ.
Hum Mol Genet. 2008 Jun 1;17(11):1613-8. Epub 2008 Feb 13.
PMID 18276610
 
Duodenal calcium absorption in vitamin D receptor-knockout mice: functional and molecular aspects.
Van Cromphaut SJ, Dewerchin M, Hoenderop JG, Stockmans I, Van Herck E, Kato S, Bindels RJ, Collen D, Carmeliet P, Bouillon R, Carmeliet G.
Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):13324-9. Epub 2001 Oct 30.
PMID 11687634
 
Expression of CaT-like, a novel calcium-selective channel, correlates with the malignancy of prostate cancer.
Wissenbach U, Niemeyer BA, Fixemer T, Schneidewind A, Trost C, Cavalie A, Reus K, Meese E, Bonkhoff H, Flockerzi V.
J Biol Chem. 2001 Jun 1;276(22):19461-8. Epub 2001 Feb 2.
PMID 11278579
 
Calcium-selective ion channel, CaT1, is apically localized in gastrointestinal tract epithelia and is aberrantly expressed in human malignancies.
Zhuang L, Peng JB, Tou L, Takanaga H, Adam RM, Hediger MA, Freeman MR.
Lab Invest. 2002 Dec;82(12):1755-64.
PMID 12480925
 

Citation

This paper should be referenced as such :
Suzuki, Y ; Hediger, MA
TRPV6 (transient receptor potential cation channel, subfamily V, member 6)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(3):267-269.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/TRPV6ID44425ch7q34.html


External links

Nomenclature
HGNC (Hugo)TRPV6   14006
Cards
AtlasTRPV6ID44425ch7q34
Entrez_Gene (NCBI)TRPV6  55503  transient receptor potential cation channel subfamily V member 6
AliasesABP/ZF; CAT1; CATL; ECAC2; 
HSA277909; LP6728; ZFAB
GeneCards (Weizmann)TRPV6
Ensembl hg19 (Hinxton)ENSG00000165125 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000165125 [Gene_View]  chr7:142871203-142885745 [Contig_View]  TRPV6 [Vega]
ICGC DataPortalENSG00000165125
TCGA cBioPortalTRPV6
AceView (NCBI)TRPV6
Genatlas (Paris)TRPV6
WikiGenes55503
SOURCE (Princeton)TRPV6
Genetics Home Reference (NIH)TRPV6
Genomic and cartography
GoldenPath hg38 (UCSC)TRPV6  -     chr7:142871203-142885745 -  7q34   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)TRPV6  -     7q34   [Description]    (hg19-Feb_2009)
EnsemblTRPV6 - 7q34 [CytoView hg19]  TRPV6 - 7q34 [CytoView hg38]
Mapping of homologs : NCBITRPV6 [Mapview hg19]  TRPV6 [Mapview hg38]
OMIM606680   
Gene and transcription
Genbank (Entrez)AF304463 AF365927 AF365928 AJ243500 AJ243501
RefSeq transcript (Entrez)NM_014274 NM_018646
RefSeq genomic (Entrez)NC_000007 NC_018918 NG_050669 NT_187562
Consensus coding sequences : CCDS (NCBI)TRPV6
Cluster EST : UnigeneHs.302740 [ NCBI ]
CGAP (NCI)Hs.302740
Alternative Splicing GalleryENSG00000165125
Gene ExpressionTRPV6 [ NCBI-GEO ]   TRPV6 [ EBI - ARRAY_EXPRESS ]   TRPV6 [ SEEK ]   TRPV6 [ MEM ]
Gene Expression Viewer (FireBrowse)TRPV6 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)55503
GTEX Portal (Tissue expression)TRPV6
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9H1D0   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9H1D0  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9H1D0
Splice isoforms : SwissVarQ9H1D0
PhosPhoSitePlusQ9H1D0
Domaine pattern : Prosite (Expaxy)ANK_REP_REGION (PS50297)    ANK_REPEAT (PS50088)   
Domains : Interpro (EBI)Ankyrin_rpt    Ankyrin_rpt-contain_dom    Ion_trans_dom    TRP_channel    TRPV    TRPV5/TRPV6    TRPV6_channel   
Domain families : Pfam (Sanger)Ank (PF00023)    Ank_2 (PF12796)    Ion_trans (PF00520)   
Domain families : Pfam (NCBI)pfam00023    pfam12796    pfam00520   
Domain families : Smart (EMBL)ANK (SM00248)  
Conserved Domain (NCBI)TRPV6
DMDM Disease mutations55503
Blocks (Seattle)TRPV6
SuperfamilyQ9H1D0
Human Protein AtlasENSG00000165125
Peptide AtlasQ9H1D0
HPRD05982
IPIIPI00152950   IPI00556588   IPI00003427   IPI00749291   IPI00927482   
Protein Interaction databases
DIP (DOE-UCLA)Q9H1D0
IntAct (EBI)Q9H1D0
FunCoupENSG00000165125
BioGRIDTRPV6
STRING (EMBL)TRPV6
ZODIACTRPV6
Ontologies - Pathways
QuickGOQ9H1D0
Ontology : AmiGOcalcium channel activity  calcium channel activity  protein binding  calmodulin binding  plasma membrane  plasma membrane  integral component of plasma membrane  integral component of plasma membrane  integral component of plasma membrane  calcium ion transport  calcium ion transport  regulation of calcium ion-dependent exocytosis  metal ion binding  response to calcium ion  calcium ion homeostasis  extracellular exosome  calcium ion transmembrane transport  calcium ion transmembrane transport  calcium ion import across plasma membrane  calcium ion import across plasma membrane  
Ontology : EGO-EBIcalcium channel activity  calcium channel activity  protein binding  calmodulin binding  plasma membrane  plasma membrane  integral component of plasma membrane  integral component of plasma membrane  integral component of plasma membrane  calcium ion transport  calcium ion transport  regulation of calcium ion-dependent exocytosis  metal ion binding  response to calcium ion  calcium ion homeostasis  extracellular exosome  calcium ion transmembrane transport  calcium ion transmembrane transport  calcium ion import across plasma membrane  calcium ion import across plasma membrane  
Pathways : KEGGSalivary secretion    Mineral absorption   
REACTOMEQ9H1D0 [protein]
REACTOME PathwaysR-HSA-3295583 [pathway]   
NDEx NetworkTRPV6
Atlas of Cancer Signalling NetworkTRPV6
Wikipedia pathwaysTRPV6
Orthology - Evolution
OrthoDB55503
GeneTree (enSembl)ENSG00000165125
Phylogenetic Trees/Animal Genes : TreeFamTRPV6
HOVERGENQ9H1D0
HOGENOMQ9H1D0
Homologs : HomoloGeneTRPV6
Homology/Alignments : Family Browser (UCSC)TRPV6
Gene fusions - Rearrangements
Fusion: TCGATRPV6 7q34 KEL 7q34 BRCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerTRPV6 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TRPV6
dbVarTRPV6
ClinVarTRPV6
1000_GenomesTRPV6 
Exome Variant ServerTRPV6
ExAC (Exome Aggregation Consortium)TRPV6 (select the gene name)
Genetic variants : HAPMAP55503
Genomic Variants (DGV)TRPV6 [DGVbeta]
DECIPHERTRPV6 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisTRPV6 
Mutations
ICGC Data PortalTRPV6 
TCGA Data PortalTRPV6 
Broad Tumor PortalTRPV6
OASIS PortalTRPV6 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICTRPV6  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDTRPV6
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch TRPV6
DgiDB (Drug Gene Interaction Database)TRPV6
DoCM (Curated mutations)TRPV6 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)TRPV6 (select a term)
intoGenTRPV6
NCG5 (London)TRPV6
Cancer3DTRPV6(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM606680   
Orphanet
MedgenTRPV6
Genetic Testing Registry TRPV6
NextProtQ9H1D0 [Medical]
TSGene55503
GENETestsTRPV6
Target ValidationTRPV6
Huge Navigator TRPV6 [HugePedia]
snp3D : Map Gene to Disease55503
BioCentury BCIQTRPV6
ClinGenTRPV6
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD55503
Chemical/Pharm GKB GenePA37832
Clinical trialTRPV6
Miscellaneous
canSAR (ICR)TRPV6 (select the gene name)
Probes
Litterature
PubMed99 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineTRPV6
EVEXTRPV6
GoPubMedTRPV6
iHOPTRPV6
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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