Q9H1D0 (TRPV6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	725 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Calcium transport Ion transport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	ANK repeat Repeat Transmembrane Transmembrane helix
Ligand	Calcium Calmodulin-binding
Molecular function	Calcium channel Ion channel
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	regulation of calcium ion-dependent exocytosis Non-traceable author statement Ref.4. Source: UniProtKB
Cellular_component	integral to plasma membrane Traceable author statement Ref.4. Source: UniProtKB
Molecular_function	calcium channel activity Inferred from direct assay Ref.11. Source: UniProtKB calmodulin binding Inferred from direct assay Ref.4. Source: UniProtKB
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 725	725	Transient receptor potential cation channel subfamily V member 6		PRO_0000215354
Regions
	Topological domain	1 – 328	328	Cytoplasmic Potential
	Transmembrane	329 – 349	21	Helical; Potential
	Topological domain	350 – 387	38	Extracellular Potential
	Transmembrane	388 – 408	21	Helical; Potential
	Topological domain	409 – 419	11	Cytoplasmic Potential
	Transmembrane	420 – 440	21	Helical; Potential
	Topological domain	441 – 448	8	Extracellular Potential
	Transmembrane	449 – 469	21	Helical; Potential
	Topological domain	470 – 492	23	Cytoplasmic Potential
	Transmembrane	493 – 513	21	Helical; Potential
	Intramembrane	524 – 544	21	Pore-forming; By similarity
	Transmembrane	557 – 577	21	Helical; Potential
	Topological domain	578 – 725	148	Cytoplasmic Potential
	Repeat	44 – 74	31	ANK 1
	Repeat	78 – 107	30	ANK 2
	Repeat	116 – 145	30	ANK 3
	Repeat	162 – 191	30	ANK 4
	Repeat	195 – 237	43	ANK 5
	Repeat	239 – 268	30	ANK 5
	Region	93 – 103	11	Interaction with calmodulin By similarity
	Region	598 – 602	5	Interaction with S100A10 By similarity
	Region	691 – 711	21	Interaction with calmodulin
	Motif	541 – 545	5	Selectivity filter By similarity
Amino acid modifications
	Modified residue	161	1	Phosphotyrosine; by SRC By similarity
	Modified residue	702	1	Phosphothreonine; by PKC/PRKCA Ref.10
	Glycosylation	358	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	25 – 192	168	Missing in isoform 2.		VSP_013439
	Natural variant	157	1	C → R. Ref.4 Ref.7 Corresponds to variant rs4987657 [ dbSNP | Ensembl ].		VAR_022251
	Natural variant	359	1	R → Q. Corresponds to variant rs4987665 [ dbSNP | Ensembl ].		VAR_052393
	Natural variant	378	1	M → V. Ref.4 Ref.7 Corresponds to variant rs4987667 [ dbSNP | Ensembl ].		VAR_022252
	Natural variant	681	1	M → T. Ref.4 Ref.7 Corresponds to variant rs4987682 [ dbSNP | Ensembl ].		VAR_022253
Experimental info
	Mutagenesis	542	1	D → A: Abolishes channel activity. Ref.11
	Mutagenesis	702	1	T → A: Abolishes phosphorylation by PKC/PRKCA, achieves faster channel inactivation and no effect on binding to calmodulin. Ref.10
	Sequence conflict	37	1	N → D in AAG41951. Ref.1
	Sequence conflict	74	1	Q → H in AAG41951. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2002. Version 2. Checksum: 3DA775E7D4E1CC65	FASTA	725	83,210
	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
	Isoform 2 [UniParc]. Checksum: 40C1A0C54EEC3D5A	FASTA	557	64,370
	10 20 30 40 50 60 MGLSLPKEKG LILCLWSKFC RWFQDSLGNT VLHILILQPN KTFACQMYNL LLSYDRHGDH 70 80 90 100 110 120 LQPLDLVPNH QGLTPFKLAG VEGNTVMFQH LMQKRKHTQW TYGPLTSTLY DLTEIDSSGD 130 140 150 160 170 180 EQSLLELIIT TKKREARQIL DQTPVKELVS LKWKRYGRPY FCMLGAIYLL YIICFTMCCI 190 200 210 220 230 240 YRPLKPRTNN RTSPRDNTLL QQKLLQEAYM TPKDDIRLVG ELVTVIGAII ILLVEVPDIF 250 260 270 280 290 300 RMGVTRFFGQ TILGGPFHVL IITYAFMVLV TMVMRLISAS GEVVPMSFAL VLGWCNVMYF 310 320 330 340 350 360 ARGFQMLGPF TIMIQKMIFG DLMRFCWLMA VVILGFASAF YIIFQTEDPE ELGHFYDYPM 370 380 390 400 410 420 ALFSTFELFL TIIDGPANYN VDLPFMYSIT YAAFAIIATL LMLNLLIAMM GDTHWRVAHE 430 440 450 460 470 480 RDELWRAQIV ATTVMLERKL PRCLWPRSGI CGREYGLGDR WFLRVEDRQD LNRQRIQRYA 490 500 510 520 530 540 QAFHTRGSED LDKDSVEKLE LGCPFSPHLS LPMPSVSRST SRSSANWERL RQGTLRRDLR 550 GIINRGLEDG ESWEYQI

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.

Web resources

Wikipedia

TRPV6 entry

SeattleSNPs

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.
IPI	IPI00152950. IPI00556588.
PIR	JC7531.
RefSeq	NP_061116.2. NM_018646.3.
UniGene	Hs.302740. Hs.638966.
3D structure databases
ProteinModelPortal	Q9H1D0.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-1472896.
STRING	9606.ENSP00000352358.
Protein family/group databases
TCDB	1.A.4.2.11. transient receptor potential Ca2+ channel (TRP-CC) family.
PTM databases
PhosphoSite	Q9H1D0.
Polymorphism databases
DMDM	62901469.
Proteomic databases
PaxDb	Q9H1D0.
PRIDE	Q9H1D0.
Protocols and materials databases
DNASU	55503.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000359396; ENSP00000352358; ENSG00000165125.
GeneID	55503.
KEGG	hsa:55503.
UCSC	uc003wbw.1. human.
Organism-specific databases
CTD	55503.
GeneCards	GC07M142568.
H-InvDB	HIX0007162.
HGNC	HGNC:14006. TRPV6.
MIM	606680. gene.
neXtProt	NX_Q9H1D0.
PharmGKB	PA37832.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG278734.
HOVERGEN	HBG061442.
InParanoid	Q9H1D0.
KO	K04975.
OMA	QESWAQS.
OrthoDB	EOG4SBDXG.
PhylomeDB	Q9H1D0.
Enzyme and pathway databases
Pathway_Interaction_DB	ptp1bpathway. Signaling events mediated by PTP1B. tcrpathway. TCR signaling in naive CD4+ T cells. cd8tcrpathway. TCR signaling in naive CD8+ T cells.
Gene expression databases
ArrayExpress	Q9H1D0.
Bgee	Q9H1D0.
CleanEx	HS_TRPV6.
Genevestigator	Q9H1D0.
GermOnline	ENSG00000165125. Homo sapiens.
Family and domain databases
Gene3D	1.25.40.20. 2 hits.
InterPro	IPR002110. Ankyrin_rpt. IPR020683. Ankyrin_rpt-contain_dom. IPR005821. Ion_trans_dom. IPR004729. TRP_channel. IPR008344. TRPV5/TRPV6_channel. IPR008345. TRPV6_channel. IPR024862. TRPV_channel. [Graphical view]
PANTHER	PTHR10582. PTHR10582. 1 hit. PTHR10582:SF1. PTHR10582:SF1. 1 hit.
Pfam	PF12796. Ank_2. 2 hits. PF00520. Ion_trans. 1 hit. [Graphical view]
PRINTS	PR01415. ANKYRIN. PR01765. ECACCHANNEL. PR01766. ECACCHANNEL1.
SMART	SM00248. ANK. 5 hits. [Graphical view]
SUPFAM	SSF48403. ANK. 1 hit.
TIGRFAMs	TIGR00870. trp. 1 hit.
PROSITE	PS50297. ANK_REP_REGION. 1 hit. PS50088. ANK_REPEAT. 2 hits. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL1628465.
GenomeRNAi	55503.
NextBio	59887.
SOURCE	Search...

Entry information

Entry name

TRPV6_HUMAN

Accession

Primary (citable) accession number: Q9H1D0
Secondary accession number(s): A4D2I8 , Q8TDL3, Q8WXR8, Q96LC5, Q9H1D1, Q9H296

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 26, 2005
Last sequence update:	June 1, 2002
Last modified:	May 1, 2013
This is version 113 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.