TRPV6_HUMAN
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 03-AUG-2022, entry version 186.
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:0007744|PDB:6BO8, ECO:0007744|PDB:6BO9, ECO:0007744|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 PDB; 7K4A; EM; 3.26 A; A/B/C/D=41-707.
DR PDB; 7K4B; EM; 3.10 A; A/B/C/D=41-707.
DR PDB; 7K4C; EM; 3.78 A; A/B/C/D=41-707.
DR PDB; 7K4D; EM; 3.66 A; A/B/C/D=41-707.
DR PDB; 7K4E; EM; 4.34 A; A/B/C/D=41-707.
DR PDB; 7K4F; EM; 3.75 A; A/B/C/D=41-707.
DR PDB; 7S88; EM; 2.69 A; A/B/C/D=41-707.
DR PDB; 7S89; EM; 2.54 A; A/B/C/D=41-707.
DR PDB; 7S8B; EM; 2.43 A; A/B/C/D=41-707.
DR PDB; 7S8C; EM; 2.85 A; A/B/C/D=41-707.
DR PDBsum; 6BO8; -.
DR PDBsum; 6BO9; -.
DR PDBsum; 6BOA; -.
DR PDBsum; 6D7S; -.
DR PDBsum; 6D7T; -.
DR PDBsum; 6E2F; -.
DR PDBsum; 7K4A; -.
DR PDBsum; 7K4B; -.
DR PDBsum; 7K4C; -.
DR PDBsum; 7K4D; -.
DR PDBsum; 7K4E; -.
DR PDBsum; 7K4F; -.
DR PDBsum; 7S88; -.
DR PDBsum; 7S89; -.
DR PDBsum; 7S8B; -.
DR PDBsum; 7S8C; -.
DR AlphaFoldDB; Q9H1D0; -.
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; 211 antibodies from 32 providers.
DR DNASU; 55503; -.
DR Ensembl; ENST00000359396.9; ENSP00000352358.5; ENSG00000165125.22. [Q9H1D0-1]
DR GeneID; 55503; -.
DR KEGG; hsa:55503; -.
DR MANE-Select; ENST00000359396.9; ENSP00000352358.5; NM_018646.6; NP_061116.5.
DR UCSC; uc003wbx.4; human. [Q9H1D0-1]
DR CTD; 55503; -.
DR DisGeNET; 55503; -.
DR GeneCards; TRPV6; -.
DR GeneReviews; TRPV6; -.
DR HGNC; HGNC:14006; TRPV6.
DR HPA; ENSG00000165125; Tissue enhanced (pancreas, prostate, salivary gland).
DR MalaCards; TRPV6; -.
DR MIM; 606680; gene.
DR MIM; 618188; phenotype.
DR neXtProt; NX_Q9H1D0; -.
DR OpenTargets; ENSG00000165125; -.
DR Orphanet; 417; Neonatal severe primary hyperparathyroidism.
DR PharmGKB; PA37832; -.
DR VEuPathDB; HostDB:ENSG00000165125; -.
DR eggNOG; KOG3676; Eukaryota.
DR GeneTree; ENSGT00940000156687; -.
DR HOGENOM; CLU_012795_2_0_1; -.
DR InParanoid; Q9H1D0; -.
DR OMA; ILCLWNK; -.
DR OrthoDB; 693004at2759; -.
DR TreeFam; TF314711; -.
DR PathwayCommons; Q9H1D0; -.
DR Reactome; R-HSA-3295583; TRP channels.
DR SignaLink; Q9H1D0; -.
DR SIGNOR; Q9H1D0; -.
DR BioGRID-ORCS; 55503; 7 hits in 1071 CRISPR screens.
DR ChiTaRS; TRPV6; human.
DR GeneWiki; TRPV6; -.
DR GenomeRNAi; 55503; -.
DR Pharos; Q9H1D0; Tchem.
DR PRO; PR:Q9H1D0; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9H1D0; protein.
DR Bgee; ENSG00000165125; Expressed in body of pancreas and 94 other tissues.
DR ExpressionAtlas; Q9H1D0; baseline and differential.
DR Genevisible; Q9H1D0; HS.
DR GO; GO:0034704; C:calcium channel complex; IEA:Ensembl.
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:0042802; F:identical protein binding; IEA:Ensembl.
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:0035898; P:parathyroid hormone secretion; IEA:Ensembl.
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; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
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.
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 BINDING 582
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_note="ligand shared between two neighboring
FT 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"
FT HELIX 68..82
FT /evidence="ECO:0007829|PDB:7S8B"
FT TURN 83..86
FT /evidence="ECO:0007829|PDB:7S8B"
FT TURN 89..96
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 99..106
FT /evidence="ECO:0007829|PDB:7S8B"
FT STRAND 107..109
FT /evidence="ECO:0007829|PDB:7S88"
FT STRAND 117..119
FT /evidence="ECO:0007829|PDB:7K4A"
FT HELIX 122..128
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 134..141
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:7S8B"
FT STRAND 152..155
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 160..166
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 171..176
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 177..179
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 190..192
FT /evidence="ECO:0007829|PDB:7S8B"
FT STRAND 193..195
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 206..212
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 216..223
FT /evidence="ECO:0007829|PDB:7S8B"
FT TURN 224..226
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 239..244
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 249..260
FT /evidence="ECO:0007829|PDB:7S8B"
FT STRAND 266..268
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 272..274
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 283..290
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 293..300
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 301..303
FT /evidence="ECO:0007829|PDB:7S8B"
FT STRAND 304..310
FT /evidence="ECO:0007829|PDB:7S8B"
FT STRAND 313..318
FT /evidence="ECO:0007829|PDB:7S8B"
FT TURN 321..323
FT /evidence="ECO:0007829|PDB:7S8B"
FT STRAND 327..329
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 332..337
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 343..349
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 353..363
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 365..388
FT /evidence="ECO:0007829|PDB:7S8B"
FT STRAND 392..394
FT /evidence="ECO:0007829|PDB:7S8B"
FT TURN 403..405
FT /evidence="ECO:0007829|PDB:7K4A"
FT STRAND 408..410
FT /evidence="ECO:0007829|PDB:7S8B"
FT TURN 413..415
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 420..441
FT /evidence="ECO:0007829|PDB:7S8B"
FT TURN 445..448
FT /evidence="ECO:0007829|PDB:7S8B"
FT STRAND 452..454
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 455..458
FT /evidence="ECO:0007829|PDB:7S8B"
FT TURN 459..462
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 465..484
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 491..503
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 504..511
FT /evidence="ECO:0007829|PDB:7S8B"
FT TURN 513..515
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 516..526
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 529..551
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 552..554
FT /evidence="ECO:0007829|PDB:7S8B"
FT TURN 557..559
FT /evidence="ECO:0007829|PDB:7S8B"
FT STRAND 562..565
FT /evidence="ECO:0007829|PDB:7K4B"
FT HELIX 566..577
FT /evidence="ECO:0007829|PDB:7S8B"
FT STRAND 587..589
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 593..621
FT /evidence="ECO:0007829|PDB:7S8B"
FT TURN 622..625
FT /evidence="ECO:0007829|PDB:7S8B"
FT HELIX 629..646
FT /evidence="ECO:0007829|PDB:7S8B"
FT TURN 650..652
FT /evidence="ECO:0007829|PDB:7S89"
FT STRAND 656..659
FT /evidence="ECO:0007829|PDB:7S8B"
FT STRAND 661..665
FT /evidence="ECO:0007829|PDB:7S8B"
FT STRAND 669..676
FT /evidence="ECO:0007829|PDB:7S8B"
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
