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Database: UniProt
Entry: Q9H1D0
LinkDB: Q9H1D0
Original site: Q9H1D0 
ID   TRPV6_HUMAN             Reviewed;         765 AA.
AC   Q9H1D0; A4D2I8; Q8TDL3; Q8WXR8; Q96LC5; Q9H1D1; Q9H296;
DT   26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-2015, sequence version 3.
DT   10-FEB-2021, entry version 180.
DE   RecName: Full=Transient receptor potential cation channel subfamily V member 6;
DE            Short=TrpV6;
DE   AltName: Full=CaT-like {ECO:0000303|PubMed:11278579};
DE            Short=CaT-L {ECO:0000303|PubMed:11278579};
DE   AltName: Full=Calcium transport protein 1 {ECO:0000303|PubMed:11097838};
DE            Short=CaT1 {ECO:0000303|PubMed:11097838};
DE   AltName: Full=Epithelial calcium channel 2;
DE            Short=ECaC2;
GN   Name=TRPV6; Synonyms=ECAC2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, AND
RP   TISSUE SPECIFICITY.
RX   PubMed=11097838; DOI=10.1006/bbrc.2000.3716;
RA   Peng J.-B., Chen X.Z., Berger U.V., Weremowicz S., Morton C.C.,
RA   Vassilev P.M., Brown E.M., Hediger M.A.;
RT   "Human calcium transport protein CaT1.";
RL   Biochem. Biophys. Res. Commun. 278:326-332(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Kidney;
RX   PubMed=11545681; DOI=10.1186/1472-6793-1-11;
RA   Wood R.J., Tchack L., Taparia S.;
RT   "1,25-dihydroxyvitamin D3 increases the expression of the CaT1 epithelial
RT   calcium channel in the Caco-2 human intestinal cell line.";
RL   BMC Physiol. 1:11-11(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Kidney;
RX   PubMed=11549322; DOI=10.1006/geno.2001.6606;
RA   Peng J.-B., Brown E.M., Hediger M.A.;
RT   "Structural conservation of the genes encoding CaT1, CaT2, and related
RT   cation channels.";
RL   Genomics 76:99-109(2001).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS ARG-197; VAL-418 AND
RP   THR-721, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC   TISSUE=Placenta;
RX   PubMed=11278579; DOI=10.1074/jbc.m009895200;
RA   Wissenbach U., Niemeyer B.A., Fixemer T., Schneidewind A., Trost C.,
RA   Cavalie A., Reus K., Meese E., Bonkhoff H., Flockerzi V.;
RT   "Expression of CaT-like, a novel calcium selective channel, correlates with
RT   the malignancy of prostate cancer.";
RL   J. Biol. Chem. 276:19461-19468(2001).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA   Peng J.-B., Brown E.M., Hediger M.A.;
RT   "A CaT1 splice variant lacking ankyrin repeats.";
RL   Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA   Kelsell R.E.;
RL   Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-197; VAL-418 AND
RP   THR-721.
RG   SeattleSNPs variation discovery resource;
RL   Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Placenta;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] OF 41-765.
RX   PubMed=12690205; DOI=10.1126/science.1083423;
RA   Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA   Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA   Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA   Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA   Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA   Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA   Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA   Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA   Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA   Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA   Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA   Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA   Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA   Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA   Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA   Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA   Adams M.D., Tsui L.-C.;
RT   "Human chromosome 7: DNA sequence and biology.";
RL   Science 300:767-772(2003).
RN   [10]
RP   FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CALMODULIN,
RP   PHOSPHORYLATION AT THR-742, AND MUTAGENESIS OF THR-742.
RX   PubMed=11248124; DOI=10.1073/pnas.051511398;
RA   Niemeyer B.A., Bergs C., Wissenbach U., Flockerzi V., Trost C.;
RT   "Competitive regulation of CaT-like-mediated Ca2+ entry by protein kinase C
RT   and calmodulin.";
RL   Proc. Natl. Acad. Sci. U.S.A. 98:3600-3605(2001).
RN   [11]
RP   FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-582, AND
RP   CALMODULIN-BINDING REGION.
RX   PubMed=15184369; DOI=10.1074/jbc.m404679200;
RA   Bodding M., Flockerzi V.;
RT   "Ca2+ dependence of the Ca2+-selective TRPV6 channel.";
RL   J. Biol. Chem. 279:36546-36552(2004).
RN   [12]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [13]
RP   IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, IDENTIFICATION OF
RP   NON-CANONICAL INITIATION CODON, SUBCELLULAR LOCATION, GLYCOSYLATION, AND
RP   TISSUE SPECIFICITY.
RX   PubMed=23612980; DOI=10.1074/jbc.m113.469726;
RA   Fecher-Trost C., Wissenbach U., Beck A., Schalkowsky P., Stoerger C.,
RA   Doerr J., Dembek A., Simon-Thomas M., Weber A., Wollenberg P., Ruppert T.,
RA   Middendorff R., Maurer H.H., Flockerzi V.;
RT   "The in vivo TRPV6 protein starts at a non-AUG triplet, decoded as
RT   methionine, upstream of canonical initiation at AUG.";
RL   J. Biol. Chem. 288:16629-16644(2013).
RN   [14]
RP   INTERACTION WITH TCAF1 AND TCAF2.
RX   PubMed=25559186; DOI=10.1083/jcb.201402076;
RA   Gkika D., Lemonnier L., Shapovalov G., Gordienko D., Poux C.,
RA   Bernardini M., Bokhobza A., Bidaux G., Degerny C., Verreman K., Guarmit B.,
RA   Benahmed M., de Launoit Y., Bindels R.J., Fiorio Pla A., Prevarskaya N.;
RT   "TRP channel-associated factors are a novel protein family that regulates
RT   TRPM8 trafficking and activity.";
RL   J. Cell Biol. 208:89-107(2015).
RN   [15] {ECO:0000244|PDB:6BO8, ECO:0000244|PDB:6BO9, ECO:0000244|PDB:6BOA}
RP   STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) OF 41-765, FUNCTION,
RP   SUBCELLULAR LOCATION, SUBUNIT, TOPOLOGY, AND MUTAGENESIS OF ARG-510;
RP   GLN-523 AND ALA-606.
RX   PubMed=29258289; DOI=10.1038/nature25182;
RA   McGoldrick L.L., Singh A.K., Saotome K., Yelshanskaya M.V., Twomey E.C.,
RA   Grassucci R.A., Sobolevsky A.I.;
RT   "Opening of the human epithelial calcium channel TRPV6.";
RL   Nature 553:233-237(2018).
RN   [16]
RP   VARIANTS HRPTTN TYR-212; THR-223; GLN-425; ARG-428; GLU-451 AND TRP-483,
RP   VARIANT SER-18, CHARACTERIZATION OF VARIANTS HRPTTN TYR-212; THR-223;
RP   GLN-425; GLU-451; ARG-428 AND TRP-483, CHARACTERIZATION OF VARIANT SER-18,
RP   INVOLVEMENT IN HRPTTN, FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=29861107; DOI=10.1016/j.ajhg.2018.04.006;
RA   Suzuki Y., Chitayat D., Sawada H., Deardorff M.A., McLaughlin H.M.,
RA   Begtrup A., Millar K., Harrington J., Chong K., Roifman M., Grand K.,
RA   Tominaga M., Takada F., Shuster S., Obara M., Mutoh H., Kushima R.,
RA   Nishimura G.;
RT   "TRPV6 Variants Interfere with Maternal-Fetal Calcium Transport through the
RT   Placenta and Cause Transient Neonatal Hyperparathyroidism.";
RL   Am. J. Hum. Genet. 102:1104-1114(2018).
RN   [17]
RP   VARIANTS HRPTTN THR-223 AND ARG-428.
RX   PubMed=30820485; DOI=10.1210/js.2018-00374;
RA   Yamashita S., Mizumoto H., Sawada H., Suzuki Y., Hata D.;
RT   "TRPV6 gene mutation in a dizygous twin with transient neonatal
RT   hyperparathyroidism.";
RL   J. Endocr. Soc. 3:602-606(2019).
CC   -!- FUNCTION: Calcium selective cation channel that mediates Ca(2+) uptake
CC       in various tissues, including the intestine (PubMed:11097838,
CC       PubMed:11278579, PubMed:11248124 PubMed:15184369, PubMed:23612980,
CC       PubMed:29258289). Important for normal Ca(2+) ion homeostasis in the
CC       body, including bone and skin (By similarity). The channel is activated
CC       by low internal calcium level, probably including intracellular calcium
CC       store depletion, and the current exhibits an inward rectification
CC       (PubMed:15184369). Inactivation includes both a rapid Ca(2+)-dependent
CC       and a slower Ca(2+)-calmodulin-dependent mechanism; the latter may be
CC       regulated by phosphorylation. In vitro, is slowly inhibited by Mg(2+)
CC       in a voltage-independent manner. Heteromeric assembly with TRPV5 seems
CC       to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers
CC       exhibit voltage-dependent gating. {ECO:0000250|UniProtKB:Q91WD2,
CC       ECO:0000269|PubMed:11097838, ECO:0000269|PubMed:11248124,
CC       ECO:0000269|PubMed:11278579, ECO:0000269|PubMed:15184369,
CC       ECO:0000269|PubMed:23612980, ECO:0000269|PubMed:29258289,
CC       ECO:0000269|PubMed:29861107}.
CC   -!- SUBUNIT: Homotetramer (PubMed:29258289). Probably forms also
CC       heterotetramers with TRPV5. Interacts with TRPV5. Interacts with
CC       S100A10 and probably with the ANAX2-S100A10 heterotetramer. The
CC       interaction with S100A10 is required for the trafficking to the plasma
CC       membrane. Interacts with BSPRY (By similarity). Interacts with TCAF1
CC       and TCAF2 isoform 2 (PubMed:25559186). Interacts with calmodulin
CC       (PubMed:11248124). {ECO:0000250|UniProtKB:Q91WD2,
CC       ECO:0000269|PubMed:11248124, ECO:0000269|PubMed:25559186,
CC       ECO:0000269|PubMed:29258289}.
CC   -!- INTERACTION:
CC       Q9H1D0; P18031: PTPN1; NbExp=6; IntAct=EBI-7198335, EBI-968788;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11097838,
CC       ECO:0000269|PubMed:11248124, ECO:0000269|PubMed:11278579,
CC       ECO:0000269|PubMed:15184369, ECO:0000269|PubMed:23612980,
CC       ECO:0000269|PubMed:29258289, ECO:0000269|PubMed:29861107}; Multi-pass
CC       membrane protein {ECO:0000269|PubMed:29258289}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9H1D0-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9H1D0-2; Sequence=VSP_013439;
CC   -!- TISSUE SPECIFICITY: Expressed at high levels in the gastrointestinal
CC       tract, including esophagus, stomach, duodenum, jejunum, ileum and
CC       colon, and in pancreas, placenta, prostate and salivary gland.
CC       Expressed at moderate levels in liver, kidney and testis. Expressed in
CC       trophoblasts of placenta villus trees (at protein
CC       level)(PubMed:23612980). Expressed in locally advanced prostate cancer,
CC       metastatic and androgen-insensitive prostatic lesions but not detected
CC       in healthy prostate tissue and benign prostatic hyperplasia.
CC       {ECO:0000269|PubMed:11097838, ECO:0000269|PubMed:11278579,
CC       ECO:0000269|PubMed:23612980}.
CC   -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:Q91WD2,
CC       ECO:0000269|PubMed:23612980}.
CC   -!- PTM: Phosphorylation at Tyr-201 by SRC leads to an increased calcium
CC       influx through the channel. Probably dephosphorylated at this site by
CC       PTPN1 (By similarity). Phosphorylation by PRKCA at the calmodulin
CC       binding site delays channel inactivation (PubMed:11248124).
CC       {ECO:0000250|UniProtKB:Q9R186, ECO:0000269|PubMed:11248124}.
CC   -!- DISEASE: Hyperparathyroidism, transient neonatal (HRPTTN) [MIM:618188]:
CC       An autosomal recessive disease characterized by impaired transplacental
CC       maternal-fetal transport of calcium, high serum PTH levels and signs of
CC       metabolic bone disease in the neonatal period. Skeletal anomalies
CC       include generalized osteopenia, narrow chest, short ribs with multiple
CC       healing fractures, and bowing or fractures of long bones. Affected
CC       individuals experience postnatal respiratory and feeding difficulties.
CC       The condition improves within a short time after birth once calcium is
CC       provided orally. {ECO:0000269|PubMed:29861107,
CC       ECO:0000269|PubMed:30820485}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the transient receptor (TC 1.A.4) family. TrpV
CC       subfamily. TRPV6 sub-subfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAK50426.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.; Evidence={ECO:0000305|PubMed:23612980};
CC       Sequence=AAL40230.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.; Evidence={ECO:0000305|PubMed:23612980};
CC       Sequence=AAM00356.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.; Evidence={ECO:0000305|PubMed:23612980};
CC       Sequence=AAO38052.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.; Evidence={ECO:0000305|PubMed:23612980};
CC       Sequence=BAF84396.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.; Evidence={ECO:0000305|PubMed:23612980};
CC       Sequence=CAC20416.2; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.; Evidence={ECO:0000305|PubMed:23612980};
CC       Sequence=CAC20417.2; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.; Evidence={ECO:0000305|PubMed:23612980};
CC       Sequence=CAD32311.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.; Evidence={ECO:0000305|PubMed:23612980};
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=TRPV6 entry;
CC       URL="https://en.wikipedia.org/wiki/TRPV6";
CC   -!- WEB RESOURCE: Name=SeattleSNPs;
CC       URL="http://pga.gs.washington.edu/data/trpv5/";
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/TRPV6ID44425ch7q34.html";
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DR   EMBL; AF304463; AAG41951.1; -; mRNA.
DR   EMBL; AF365927; AAL40230.1; ALT_SEQ; mRNA.
DR   EMBL; AF365928; AAM00356.1; ALT_SEQ; mRNA.
DR   EMBL; AH010730; AAK50426.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; AJ243500; CAC20416.2; ALT_SEQ; mRNA.
DR   EMBL; AJ243501; CAC20417.2; ALT_SEQ; mRNA.
DR   EMBL; AJ487964; CAD32311.1; ALT_SEQ; mRNA.
DR   EMBL; AY225461; AAO38052.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; AK291707; BAF84396.1; ALT_SEQ; mRNA.
DR   EMBL; CH236959; EAL23776.1; -; Genomic_DNA.
DR   CCDS; CCDS5874.2; -. [Q9H1D0-1]
DR   PIR; JC7531; JC7531.
DR   RefSeq; NP_061116.5; NM_018646.5. [Q9H1D0-1]
DR   PDB; 6BO8; EM; 3.60 A; A/B/C/D=41-765.
DR   PDB; 6BO9; EM; 4.00 A; A/B/C/D=41-765.
DR   PDB; 6BOA; EM; 4.20 A; A/B/C/D=41-765.
DR   PDB; 6D7S; EM; 4.34 A; A/B/C/D=41-765.
DR   PDB; 6D7T; EM; 4.44 A; A/B/C/D=41-765.
DR   PDB; 6E2F; EM; 3.90 A; A/B/C/D=41-765.
DR   PDBsum; 6BO8; -.
DR   PDBsum; 6BO9; -.
DR   PDBsum; 6BOA; -.
DR   PDBsum; 6D7S; -.
DR   PDBsum; 6D7T; -.
DR   PDBsum; 6E2F; -.
DR   SMR; Q9H1D0; -.
DR   BioGRID; 120683; 16.
DR   IntAct; Q9H1D0; 4.
DR   MINT; Q9H1D0; -.
DR   STRING; 9606.ENSP00000352358; -.
DR   BindingDB; Q9H1D0; -.
DR   ChEMBL; CHEMBL1628465; -.
DR   DrugBank; DB11093; Calcium citrate.
DR   DrugBank; DB11348; Calcium Phosphate.
DR   DrugBank; DB14481; Calcium phosphate dihydrate.
DR   TCDB; 1.A.4.2.11; the transient receptor potential ca(2+) channel (trp-cc) family.
DR   GlyGen; Q9H1D0; 1 site.
DR   iPTMnet; Q9H1D0; -.
DR   PhosphoSitePlus; Q9H1D0; -.
DR   BioMuta; TRPV6; -.
DR   DMDM; 62901469; -.
DR   MassIVE; Q9H1D0; -.
DR   PaxDb; Q9H1D0; -.
DR   PeptideAtlas; Q9H1D0; -.
DR   PRIDE; Q9H1D0; -.
DR   ProteomicsDB; 80400; -. [Q9H1D0-1]
DR   ProteomicsDB; 80401; -. [Q9H1D0-2]
DR   Antibodypedia; 32586; 189 antibodies.
DR   DNASU; 55503; -.
DR   GeneID; 55503; -.
DR   KEGG; hsa:55503; -.
DR   UCSC; uc003wbx.4; human. [Q9H1D0-1]
DR   CTD; 55503; -.
DR   DisGeNET; 55503; -.
DR   GeneCards; TRPV6; -.
DR   HGNC; HGNC:14006; TRPV6.
DR   HPA; ENSG00000165125; Tissue enhanced (pancreas, placenta, salivary gland).
DR   MalaCards; TRPV6; -.
DR   MIM; 606680; gene.
DR   MIM; 618188; phenotype.
DR   neXtProt; NX_Q9H1D0; -.
DR   PharmGKB; PA37832; -.
DR   VEuPathDB; HostDB:ENSG00000165125.17; -.
DR   eggNOG; KOG3676; Eukaryota.
DR   HOGENOM; CLU_012795_2_0_1; -.
DR   InParanoid; Q9H1D0; -.
DR   OrthoDB; 693004at2759; -.
DR   TreeFam; TF314711; -.
DR   PathwayCommons; Q9H1D0; -.
DR   Reactome; R-HSA-3295583; TRP channels.
DR   SIGNOR; Q9H1D0; -.
DR   BioGRID-ORCS; 55503; 2 hits in 874 CRISPR screens.
DR   ChiTaRS; TRPV6; human.
DR   GeneWiki; TRPV6; -.
DR   GenomeRNAi; 55503; -.
DR   Pharos; Q9H1D0; Tchem.
DR   PRO; PR:Q9H1D0; -.
DR   Proteomes; UP000005640; Unplaced.
DR   RNAct; Q9H1D0; protein.
DR   Bgee; ENSG00000165125; Expressed in placenta and 195 other tissues.
DR   ExpressionAtlas; Q9H1D0; baseline and differential.
DR   Genevisible; Q9H1D0; HS.
DR   GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0005262; F:calcium channel activity; IDA:UniProtKB.
DR   GO; GO:0005516; F:calmodulin binding; IDA:UniProtKB.
DR   GO; GO:0005216; F:ion channel activity; IBA:GO_Central.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0055074; P:calcium ion homeostasis; ISS:UniProtKB.
DR   GO; GO:0098703; P:calcium ion import across plasma membrane; IDA:UniProtKB.
DR   GO; GO:0070588; P:calcium ion transmembrane transport; IDA:UniProtKB.
DR   GO; GO:0006816; P:calcium ion transport; IDA:UniProtKB.
DR   GO; GO:0017158; P:regulation of calcium ion-dependent exocytosis; NAS:UniProtKB.
DR   GO; GO:0051592; P:response to calcium ion; ISS:UniProtKB.
DR   DisProt; DP01767; -.
DR   Gene3D; 1.25.40.20; -; 2.
DR   InterPro; IPR002110; Ankyrin_rpt.
DR   InterPro; IPR020683; Ankyrin_rpt-contain_dom.
DR   InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR   InterPro; IPR005821; Ion_trans_dom.
DR   InterPro; IPR024862; TRPV.
DR   InterPro; IPR008344; TRPV5/TRPV6.
DR   InterPro; IPR008345; TRPV6_channel.
DR   PANTHER; PTHR10582; PTHR10582; 1.
DR   Pfam; PF00023; Ank; 1.
DR   Pfam; PF12796; Ank_2; 1.
DR   Pfam; PF00520; Ion_trans; 1.
DR   PRINTS; PR01415; ANKYRIN.
DR   PRINTS; PR01765; ECACCHANNEL.
DR   PRINTS; PR01766; ECACCHANNEL1.
DR   SMART; SM00248; ANK; 5.
DR   SUPFAM; SSF48403; SSF48403; 1.
DR   PROSITE; PS50297; ANK_REP_REGION; 1.
DR   PROSITE; PS50088; ANK_REPEAT; 2.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; ANK repeat; Calcium; Calcium channel;
KW   Calcium transport; Calmodulin-binding; Cell membrane; Disease variant;
KW   Glycoprotein; Ion channel; Ion transport; Membrane; Metal-binding;
KW   Phosphoprotein; Reference proteome; Repeat; Transmembrane;
KW   Transmembrane helix; Transport.
FT   CHAIN           1..765
FT                   /note="Transient receptor potential cation channel
FT                   subfamily V member 6"
FT                   /id="PRO_0000215354"
FT   TOPO_DOM        1..367
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305|PubMed:29258289"
FT   TRANSMEM        368..388
FT                   /note="Helical"
FT                   /evidence="ECO:0000305|PubMed:29258289"
FT   TOPO_DOM        389..425
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305|PubMed:29258289"
FT   TRANSMEM        426..448
FT                   /note="Helical"
FT                   /evidence="ECO:0000305|PubMed:29258289"
FT   TOPO_DOM        449..463
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305|PubMed:29258289"
FT   TRANSMEM        464..483
FT                   /note="Helical"
FT                   /evidence="ECO:0000305|PubMed:29258289"
FT   TOPO_DOM        484..489
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305|PubMed:29258289"
FT   TRANSMEM        490..509
FT                   /note="Helical"
FT                   /evidence="ECO:0000305|PubMed:29258289"
FT   TOPO_DOM        510..529
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305|PubMed:29258289"
FT   TRANSMEM        530..552
FT                   /note="Helical"
FT                   /evidence="ECO:0000305|PubMed:29258289"
FT   TOPO_DOM        553..565
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305|PubMed:29258289"
FT   INTRAMEM        566..585
FT                   /note="Pore-forming"
FT                   /evidence="ECO:0000305|PubMed:29258289"
FT   TOPO_DOM        586..596
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305|PubMed:29258289"
FT   TRANSMEM        597..617
FT                   /note="Helical"
FT                   /evidence="ECO:0000305|PubMed:29258289"
FT   TOPO_DOM        618..765
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305|PubMed:29258289"
FT   REPEAT          84..114
FT                   /note="ANK 1"
FT   REPEAT          118..147
FT                   /note="ANK 2"
FT   REPEAT          156..185
FT                   /note="ANK 3"
FT   REPEAT          202..231
FT                   /note="ANK 4"
FT   REPEAT          235..277
FT                   /note="ANK 5"
FT   REPEAT          279..308
FT                   /note="ANK 5"
FT   REGION          133..143
FT                   /note="Interaction with calmodulin"
FT                   /evidence="ECO:0000250"
FT   REGION          638..642
FT                   /note="Interaction with S100A10"
FT                   /evidence="ECO:0000250"
FT   REGION          731..751
FT                   /note="Interaction with calmodulin"
FT                   /evidence="ECO:0000269|PubMed:11248124,
FT                   ECO:0000269|PubMed:15184369"
FT   MOTIF           581..585
FT                   /note="Selectivity filter"
FT                   /evidence="ECO:0000305|PubMed:29258289"
FT   METAL           582
FT                   /note="Calcium; shared with neighboring subunits"
FT                   /evidence="ECO:0000305|PubMed:29258289"
FT   MOD_RES         201
FT                   /note="Phosphotyrosine; by SRC"
FT                   /evidence="ECO:0000250|UniProtKB:Q9R186"
FT   MOD_RES         742
FT                   /note="Phosphothreonine; by PKC/PRKCA"
FT                   /evidence="ECO:0000269|PubMed:11248124"
FT   CARBOHYD        398
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         65..232
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.5"
FT                   /id="VSP_013439"
FT   VARIANT         18
FT                   /note="A -> S (likely benign variant; no effect on
FT                   localization at the plasma membrane; no change in calcium
FT                   ion import across plasma membrane; dbSNP:rs17881456)"
FT                   /evidence="ECO:0000269|PubMed:29861107"
FT                   /id="VAR_081865"
FT   VARIANT         197
FT                   /note="C -> R (in dbSNP:rs4987657)"
FT                   /evidence="ECO:0000269|PubMed:11278579, ECO:0000269|Ref.7"
FT                   /id="VAR_022251"
FT   VARIANT         212
FT                   /note="C -> Y (in HRPTTN; decreased localization at the
FT                   plasma membrane; loss of calcium ion import across plasma
FT                   membrane)"
FT                   /evidence="ECO:0000269|PubMed:29861107"
FT                   /id="VAR_081866"
FT   VARIANT         223
FT                   /note="I -> T (in HRPTTN; decreased localization at the
FT                   plasma membrane; no change in calcium ion import across
FT                   plasma membrane)"
FT                   /evidence="ECO:0000269|PubMed:29861107,
FT                   ECO:0000269|PubMed:30820485"
FT                   /id="VAR_081867"
FT   VARIANT         399
FT                   /note="R -> Q (in dbSNP:rs4987665)"
FT                   /id="VAR_052393"
FT   VARIANT         418
FT                   /note="M -> V (in dbSNP:rs4987667)"
FT                   /evidence="ECO:0000269|PubMed:11278579, ECO:0000269|Ref.7"
FT                   /id="VAR_022252"
FT   VARIANT         425
FT                   /note="R -> Q (in HRPTTN; decreased localization at the
FT                   plasma membrane; loss of calcium ion import across plasma
FT                   membrane)"
FT                   /evidence="ECO:0000269|PubMed:29861107"
FT                   /id="VAR_081868"
FT   VARIANT         428
FT                   /note="G -> R (in HRPTTN; decreased localization at the
FT                   plasma membrane; loss of calcium ion import across plasma
FT                   membrane)"
FT                   /evidence="ECO:0000269|PubMed:29861107,
FT                   ECO:0000269|PubMed:30820485"
FT                   /id="VAR_081869"
FT   VARIANT         451
FT                   /note="G -> E (in HRPTTN; induces cell death most likely
FT                   through intracellular calcium overload; increased calcium
FT                   ion import across plasma membrane; may lack intracellular
FT                   calcium-dependent inactivation)"
FT                   /evidence="ECO:0000269|PubMed:29861107"
FT                   /id="VAR_081870"
FT   VARIANT         483
FT                   /note="R -> W (in HRPTTN; decreased localization at the
FT                   plasma membrane; loss of calcium ion import across plasma
FT                   membrane)"
FT                   /evidence="ECO:0000269|PubMed:29861107"
FT                   /id="VAR_081871"
FT   VARIANT         721
FT                   /note="M -> T (in dbSNP:rs4987682)"
FT                   /evidence="ECO:0000269|PubMed:11278579, ECO:0000269|Ref.7"
FT                   /id="VAR_022253"
FT   MUTAGEN         510
FT                   /note="R->E: Decreases channel opening, and thereby
FT                   decreases channel activity."
FT                   /evidence="ECO:0000269|PubMed:29258289"
FT   MUTAGEN         523
FT                   /note="Q->A: Decreases channel activity."
FT                   /evidence="ECO:0000269|PubMed:29258289"
FT   MUTAGEN         582
FT                   /note="D->A: Abolishes channel activity."
FT                   /evidence="ECO:0000269|PubMed:15184369"
FT   MUTAGEN         606
FT                   /note="A->T: Decreases channel opening, and thereby
FT                   strongly decreases channel activity."
FT                   /evidence="ECO:0000269|PubMed:29258289"
FT   MUTAGEN         742
FT                   /note="T->A: Abolishes phosphorylation by PKC/PRKCA,
FT                   achieves faster channel inactivation and no effect on
FT                   binding to calmodulin."
FT                   /evidence="ECO:0000269|PubMed:11248124"
FT   CONFLICT        77
FT                   /note="N -> D (in Ref. 1; AAG41951)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        114
FT                   /note="Q -> H (in Ref. 1; AAG41951)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   765 AA;  87286 MW;  626D515E12112546 CRC64;
     MGPLQGDGGP ALGGADVAPR LSPVRVWPRP QAPKEPALHP MGLSLPKEKG LILCLWSKFC
     RWFQRRESWA QSRDEQNLLQ QKRIWESPLL LAAKDNDVQA LNKLLKYEDC KVHQRGAMGE
     TALHIAALYD NLEAAMVLME AAPELVFEPM TSELYEGQTA LHIAVVNQNM NLVRALLARR
     ASVSARATGT AFRRSPCNLI YFGEHPLSFA ACVNSEEIVR LLIEHGADIR AQDSLGNTVL
     HILILQPNKT FACQMYNLLL SYDRHGDHLQ PLDLVPNHQG LTPFKLAGVE GNTVMFQHLM
     QKRKHTQWTY GPLTSTLYDL TEIDSSGDEQ SLLELIITTK KREARQILDQ TPVKELVSLK
     WKRYGRPYFC MLGAIYLLYI ICFTMCCIYR PLKPRTNNRT SPRDNTLLQQ KLLQEAYMTP
     KDDIRLVGEL VTVIGAIIIL LVEVPDIFRM GVTRFFGQTI LGGPFHVLII TYAFMVLVTM
     VMRLISASGE VVPMSFALVL GWCNVMYFAR GFQMLGPFTI MIQKMIFGDL MRFCWLMAVV
     ILGFASAFYI IFQTEDPEEL GHFYDYPMAL FSTFELFLTI IDGPANYNVD LPFMYSITYA
     AFAIIATLLM LNLLIAMMGD THWRVAHERD ELWRAQIVAT TVMLERKLPR CLWPRSGICG
     REYGLGDRWF LRVEDRQDLN RQRIQRYAQA FHTRGSEDLD KDSVEKLELG CPFSPHLSLP
     MPSVSRSTSR SSANWERLRQ GTLRRDLRGI INRGLEDGES WEYQI
//
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