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Q9H1D0 (TRPV6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Transient receptor potential cation channel subfamily V member 6

Short name=TrpV6
Alternative name(s):
CaT-like
Short name=CaT-L
Calcium transport protein 1
Short name=CaT1
Epithelial calcium channel 2
Short name=ECaC2
Gene names
Name:TRPV6
Synonyms:ECAC2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length725 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Calcium selective cation channel probably involved in Ca2+ uptake in various tissues, including Ca2+ reabsorption in intestine. The channel is activated by low internal calcium level, probably including intracellular calcium store depletion, and the current exhibits an inward rectification. Inactivation includes both, a rapid Ca2+-dependent and a slower Ca2+-calmodulin-dependent mechanism, the latter may be regulated by phosphorylation. In vitro, is slowly inhibited by Mg2+ in a voltage-independent manner. Heteromeric assembly with TRPV5 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating By similarity. Ref.1 Ref.4 Ref.10 Ref.11

Subunit structure

Homotetramer and probably heterotetramer with TRPV5. Interacts with TRPV5. Interacts with S100A10 and probably with the ANAX2-S100A10 heterotetramer. The interaction with S100A10 is required for the trafficking to the plasma membrane. Interacts with BSPRY By similarity. Interacts with calmodulin. Ref.10

Subcellular location

Cell membrane; Multi-pass membrane protein By similarity.

Tissue specificity

Expressed at high levels in the gastrointestinal tract, including esophagus, stomach, duodenum, jejunum, ileum and colon, and in pancreas, placenta, prostate and salivary gland. Expressed at moderate levels in liver, kidney and testis. Expressed in locally advanced prostate cancer, metastatic and androgen-insensitive prostatic lesions but not detected in healthy prostate tissue and benign prostatic hyperplasia. Ref.1 Ref.4

Post-translational modification

Glycosylated By similarity.

Phosphorylation at Tyr-161 by SRC leads to an increased calcium influx through the channel. Probably dephosphorylated at this site by PTPN1 By similarity. Phosphorylation by PRKCA at the calmodulin binding site delays channel inactivation. Ref.10

Sequence similarities

Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV6 sub-subfamily. [View classification]

Contains 6 ANK repeats.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PTPN1P180316EBI-7198335,EBI-968788

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9H1D0-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9H1D0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     25-192: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 725725Transient receptor potential cation channel subfamily V member 6
PRO_0000215354

Regions

Topological domain1 – 328328Cytoplasmic Potential
Transmembrane329 – 34921Helical; Potential
Topological domain350 – 38738Extracellular Potential
Transmembrane388 – 40821Helical; Potential
Topological domain409 – 41911Cytoplasmic Potential
Transmembrane420 – 44021Helical; Potential
Topological domain441 – 4488Extracellular Potential
Transmembrane449 – 46921Helical; Potential
Topological domain470 – 49223Cytoplasmic Potential
Transmembrane493 – 51321Helical; Potential
Intramembrane524 – 54421Pore-forming; By similarity
Transmembrane557 – 57721Helical; Potential
Topological domain578 – 725148Cytoplasmic Potential
Repeat44 – 7431ANK 1
Repeat78 – 10730ANK 2
Repeat116 – 14530ANK 3
Repeat162 – 19130ANK 4
Repeat195 – 23743ANK 5
Repeat239 – 26830ANK 5
Region93 – 10311Interaction with calmodulin By similarity
Region598 – 6025Interaction with S100A10 By similarity
Region691 – 71121Interaction with calmodulin
Motif541 – 5455Selectivity filter By similarity

Amino acid modifications

Modified residue1611Phosphotyrosine; by SRC By similarity
Modified residue7021Phosphothreonine; by PKC/PRKCA Ref.10
Glycosylation3581N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence25 – 192168Missing in isoform 2.
VSP_013439
Natural variant1571C → R. Ref.4 Ref.7
Corresponds to variant rs4987657 [ dbSNP | Ensembl ].
VAR_022251
Natural variant3591R → Q.
Corresponds to variant rs4987665 [ dbSNP | Ensembl ].
VAR_052393
Natural variant3781M → V. Ref.4 Ref.7
Corresponds to variant rs4987667 [ dbSNP | Ensembl ].
VAR_022252
Natural variant6811M → T. Ref.4 Ref.7
Corresponds to variant rs4987682 [ dbSNP | Ensembl ].
VAR_022253

Experimental info

Mutagenesis5421D → A: Abolishes channel activity. Ref.11
Mutagenesis7021T → A: Abolishes phosphorylation by PKC/PRKCA, achieves faster channel inactivation and no effect on binding to calmodulin. Ref.10
Sequence conflict371N → D in AAG41951. Ref.1
Sequence conflict741Q → H in AAG41951. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 1, 2002. Version 2.
Checksum: 3DA775E7D4E1CC65

FASTA72583,210
        10         20         30         40         50         60 
MGLSLPKEKG LILCLWSKFC RWFQRRESWA QSRDEQNLLQ QKRIWESPLL LAAKDNDVQA 

        70         80         90        100        110        120 
LNKLLKYEDC KVHQRGAMGE TALHIAALYD NLEAAMVLME AAPELVFEPM TSELYEGQTA 

       130        140        150        160        170        180 
LHIAVVNQNM NLVRALLARR ASVSARATGT AFRRSPCNLI YFGEHPLSFA ACVNSEEIVR 

       190        200        210        220        230        240 
LLIEHGADIR AQDSLGNTVL HILILQPNKT FACQMYNLLL SYDRHGDHLQ PLDLVPNHQG 

       250        260        270        280        290        300 
LTPFKLAGVE GNTVMFQHLM QKRKHTQWTY GPLTSTLYDL TEIDSSGDEQ SLLELIITTK 

       310        320        330        340        350        360 
KREARQILDQ TPVKELVSLK WKRYGRPYFC MLGAIYLLYI ICFTMCCIYR PLKPRTNNRT 

       370        380        390        400        410        420 
SPRDNTLLQQ KLLQEAYMTP KDDIRLVGEL VTVIGAIIIL LVEVPDIFRM GVTRFFGQTI 

       430        440        450        460        470        480 
LGGPFHVLII TYAFMVLVTM VMRLISASGE VVPMSFALVL GWCNVMYFAR GFQMLGPFTI 

       490        500        510        520        530        540 
MIQKMIFGDL MRFCWLMAVV ILGFASAFYI IFQTEDPEEL GHFYDYPMAL FSTFELFLTI 

       550        560        570        580        590        600 
IDGPANYNVD LPFMYSITYA AFAIIATLLM LNLLIAMMGD THWRVAHERD ELWRAQIVAT 

       610        620        630        640        650        660 
TVMLERKLPR CLWPRSGICG REYGLGDRWF LRVEDRQDLN RQRIQRYAQA FHTRGSEDLD 

       670        680        690        700        710        720 
KDSVEKLELG CPFSPHLSLP MPSVSRSTSR SSANWERLRQ GTLRRDLRGI INRGLEDGES 


WEYQI 

« Hide

Isoform 2 [UniParc].

Checksum: 40C1A0C54EEC3D5A
Show »

FASTA55764,370

References

« Hide 'large scale' references
[1]"Human calcium transport protein CaT1."
Peng J.-B., Chen X.Z., Berger U.V., Weremowicz S., Morton C.C., Vassilev P.M., Brown E.M., Hediger M.A.
Biochem. Biophys. Res. Commun. 278:326-332(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY.
[2]"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. 1:11-11(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Kidney.
[3]"Structural conservation of the genes encoding CaT1, CaT2, and related cation channels."
Peng J.-B., Brown E.M., Hediger M.A.
Genomics 76:99-109(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Kidney.
[4]"Expression of CaT-like, a novel calcium selective channel, correlates with the malignancy of prostate cancer."
Wissenbach U., Niemeyer B.A., Fixemer T., Schneidewind A., Trost C., Cavalie A., Reus K., Meese E., Bonkhoff H., Flockerzi V.
J. Biol. Chem. 276:19461-19468(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS ARG-157; VAL-378 AND THR-681, FUNCTION, TISSUE SPECIFICITY.
Tissue: Placenta.
[5]"A CaT1 splice variant lacking ankyrin repeats."
Peng J.-B., Brown E.M., Hediger M.A.
Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[6]Kelsell R.E.
Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[7]SeattleSNPs variation discovery resource
Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-157; VAL-378 AND THR-681.
[8]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Placenta.
[9]"Human chromosome 7: DNA sequence and biology."
Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. expand/collapse author list , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]"Competitive regulation of CaT-like-mediated Ca2+ entry by protein kinase C and calmodulin."
Niemeyer B.A., Bergs C., Wissenbach U., Flockerzi V., Trost C.
Proc. Natl. Acad. Sci. U.S.A. 98:3600-3605(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CALMODULIN, PHOSPHORYLATION AT THR-702, MUTAGENESIS OF THR-702.
[11]"Ca2+ dependence of the Ca2+-selective TRPV6 channel."
Bodding M., Flockerzi V.
J. Biol. Chem. 279:36546-36552(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF ASP-542.
[12]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF304463 mRNA. Translation: AAG41951.1.
AF365927 mRNA. Translation: AAL40230.1.
AF365928 mRNA. Translation: AAM00356.1.
AH010730 Genomic DNA. Translation: AAK50426.1.
AJ243500 mRNA. Translation: CAC20416.2.
AJ243501 mRNA. Translation: CAC20417.2.
AJ487964 mRNA. Translation: CAD32311.1.
AY225461 Genomic DNA. Translation: AAO38052.1.
AK291707 mRNA. Translation: BAF84396.1.
CH236959 Genomic DNA. Translation: EAL23776.1.
PIRJC7531.
RefSeqNP_061116.3. NM_018646.4.
UniGeneHs.302740.

3D structure databases

ProteinModelPortalQ9H1D0.
SMRQ9H1D0. Positions 44-308.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120683. 6 interactions.
IntActQ9H1D0. 2 interactions.
MINTMINT-1472896.
STRING9606.ENSP00000352358.

Chemistry

ChEMBLCHEMBL1628465.
GuidetoPHARMACOLOGY512.

Protein family/group databases

TCDB1.A.4.2.11. the transient receptor potential ca(2+) channel (trp-cc) family.

PTM databases

PhosphoSiteQ9H1D0.

Polymorphism databases

DMDM62901469.

Proteomic databases

PaxDbQ9H1D0.
PRIDEQ9H1D0.

Protocols and materials databases

DNASU55503.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000359396; ENSP00000352358; ENSG00000165125. [Q9H1D0-1]
GeneID55503.
KEGGhsa:55503.
UCSCuc003wbw.1. human. [Q9H1D0-1]

Organism-specific databases

CTD55503.
GeneCardsGC07M142568.
H-InvDBHIX0007162.
HGNCHGNC:14006. TRPV6.
HPAHPA062864.
MIM606680. gene.
neXtProtNX_Q9H1D0.
PharmGKBPA37832.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG278734.
HOVERGENHBG061442.
InParanoidQ9H1D0.
KOK04975.
OMAPRVTGLY.
OrthoDBEOG70087C.
PhylomeDBQ9H1D0.
TreeFamTF314711.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressQ9H1D0.
BgeeQ9H1D0.
CleanExHS_TRPV6.
GenevestigatorQ9H1D0.

Family and domain databases

Gene3D1.25.40.20. 2 hits.
InterProIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR005821. Ion_trans_dom.
IPR004729. TRP_channel.
IPR024862. TRPV.
IPR008344. TRPV5/TRPV6.
IPR008345. TRPV6_channel.
[Graphical view]
PANTHERPTHR10582. PTHR10582. 1 hit.
PTHR10582:SF1. PTHR10582:SF1. 1 hit.
PfamPF12796. Ank_2. 2 hits.
PF00520. Ion_trans. 1 hit.
[Graphical view]
PRINTSPR01415. ANKYRIN.
PR01765. ECACCHANNEL.
PR01766. ECACCHANNEL1.
SMARTSM00248. ANK. 5 hits.
[Graphical view]
SUPFAMSSF48403. SSF48403. 1 hit.
TIGRFAMsTIGR00870. trp. 1 hit.
PROSITEPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiTRPV6.
GenomeRNAi55503.
NextBio59887.
PROQ9H1D0.
SOURCESearch...

Entry information

Entry nameTRPV6_HUMAN
AccessionPrimary (citable) accession number: Q9H1D0
Secondary accession number(s): A4D2I8 expand/collapse secondary AC list , Q8TDL3, Q8WXR8, Q96LC5, Q9H1D1, Q9H296
Entry history
Integrated into UniProtKB/Swiss-Prot: April 26, 2005
Last sequence update: June 1, 2002
Last modified: April 16, 2014
This is version 124 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM