Q91WD2 (TRPV6_MOUSE) 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):
Calcium transport protein 1
Short name=CaT1
Epithelial calcium channel 2
Short name=ECaC2

Gene names

Name:

Trpv6

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	727 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. Ref.4 Ref.5
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 calmodulin. Interacts with BSPRY. Ref.1 Ref.5 Ref.6 Ref.8 Ref.9
Subcellular location	Cell membrane; Multi-pass membrane protein Ref.6.
Tissue specificity	Abundantly expressed in pancreas and placenta, and to a much lesser extend in stomach and kidney. Not detected in intestine. Ref.1
Post-translational modification	Glycosylated. Ref.1 Ref.5 Phosphorylation at Tyr-161 and Tyr-162 by SRC leads to an increased calcium influx through the channel. Probably dephosphorylated at these sites by PTPN1 By similarity.
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
Domain	ANK repeat Repeat Transmembrane Transmembrane helix
Ligand	Calcium Calmodulin-binding
Molecular function	Calcium channel Ion channel
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	integral to membrane Inferred from sequence or structural similarity PubMed 12077127. Source: MGI plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	calcium channel activity Inferred from direct assay PubMed 12077127. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 727

727

Transient receptor potential cation channel subfamily V member 6

PRO_0000215355

Regions

Topological domain

1 – 327

327

Cytoplasmic Potential

Transmembrane

328 – 348

21

Helical; Potential

Topological domain

349 – 386

38

Extracellular Potential

Transmembrane

387 – 407

21

Helical; Potential

Topological domain

408 – 418

11

Cytoplasmic Potential

Transmembrane

419 – 439

21

Helical; Potential

Topological domain

440 – 447

8

Extracellular Potential

Transmembrane

448 – 468

21

Helical; Potential

Topological domain

469 – 491

23

Cytoplasmic Potential

Transmembrane

492 – 512

21

Helical; Potential

Intramembrane

523 – 545

23

Pore-forming

Transmembrane

558 – 578

21

Helical; Potential

Topological domain

579 – 727

149

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 – 236

42

ANK 5

Repeat

238 – 267

30

ANK 6

Region

93 – 103

11

Interaction with calmodulin

Region

597 – 601

5

Interaction with S100A10 By similarity

Region

649 – 667

19

Interaction with calmodulin

Motif

540 – 544

5

Selectivity filter

Amino acid modifications

Modified residue

161

1

Phosphotyrosine; by SRC By similarity

Modified residue

162

1

Phosphotyrosine; by SRC By similarity

Glycosylation

357

1

N-linked (GlcNAc...) Potential

Experimental info

Mutagenesis

537

1

L → C: Abolishes channel activity. Ref.7

Mutagenesis

541

1

D → A: Abolishes binding of Mg(2+) and increases pore diameter. Ref.4 Ref.7

Mutagenesis

541

1

D → C: Abolishes channel activity. Ref.4 Ref.7

Mutagenesis

541

1

D → G: Increases pore diameter. Ref.4 Ref.7

Mutagenesis

546

1

Y → C: Abolishes channel activity. Ref.7

Mutagenesis

599

1

T → A: Abolishes plasma membrane localization and channel activity. Ref.6

Secondary structure

1

.

.

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.

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727

Helix Strand Turn

Details...

Helix

48 – 54

7

Helix

58 – 65

8

Helix

82 – 88

7

Helix

92 – 101

10

Helix

103 – 107

5

Turn

113 – 117

5

Helix

120 – 126

7

Helix

130 – 138

9

Helix

150 – 152

3

Helix

166 – 173

8

Helix

176 – 184

9

Helix

199 – 204

6

Helix

209 – 221

13

Helix

231 – 233

3

Helix

242 – 249

8

Helix

252 – 264

13

Sequences

	Sequence		Length	Mass (Da)
	Q91WD2 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 410DC8AC9B24F97A	FASTA	727	83,195
	10 20 30 40 50 60 MGWSLPKEKG LILCLWNKFC RWFHRQESWA QSRDEQNLLQ QKRIWESPLL LAAKENDVQA 70 80 90 100 110 120 LSKLLKFEGC EVHQRGAMGE TALHIAALYD NLEAAMVLME AAPELVFEPM TSELYEGQTA 130 140 150 160 170 180 LHIAVINQNV NLVRALLARG ASVSARATGS VFHYRPHNLI YYGEHPLSFA ACVGSEEIVR 190 200 210 220 230 240 LLIEHGADIR AQDSLGNTVL HILILQPNKT FACQMYNLLL SYDGGDHLKS LELVPNNQGL 250 260 270 280 290 300 TPFKLAGVEG NIVMFQHLMQ KRKHIQWTYG PLTSTLYDLT EIDSSGDDQS LLELIVTTKK 310 320 330 340 350 360 REARQILDQT PVKELVSLKW KRYGRPYFCV LGAIYVLYII CFTMCCVYRP LKPRITNRTN 370 380 390 400 410 420 PRDNTLMQQK LLQEAYVTPK DDLRLVGELV SIVGAVIILL VEIPDIFRLG VTRFFGQTIL 430 440 450 460 470 480 GGPFHVIIIT YAFMVLVTMV MRLTNVDGEV VPMSFALVLG WCNVMYFARG FQMLGPFTIM 490 500 510 520 530 540 IQKMIFGDLM RFCWLMAVVI LGFASAFYII FQTEDPDELG HFYDYPMALF STFELFLTII 550 560 570 580 590 600 DGPANYDVDL PFMYSVTYAA FAIIATLLML NLLIAMMGDT HWRVAHERDE LWRAQVVATT 610 620 630 640 650 660 VMLERKLPRC LWPRSGICGR EYGLGDRWFL RVEDRQDLNR QRIRRYAQAF QQQDGLYSED 670 680 690 700 710 720 LEKDSGEKLE TARPFGAYLS FPTPSVSRST SRSSTNWERL RQGALRKDLR GIINRGLEDG EGWEYQI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The TRPV6 gene, cDNA and protein." Hirnet D., Olausson J., Fecher-Trost C., Boedding M., Nastainczyk W., Wissenbach U., Flockerzi V., Freichel M. Cell Calcium 33:509-518(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], GLYCOSYLATION, INTERACTION WITH CALMODULIN, TISSUE SPECIFICITY. Strain: 129/SvJ. Tissue: Placenta.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Ovary and Uterus.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N. Tissue: Salivary gland.
[4]	"Mg2+-dependent gating and strong inward rectification of the cation channel TRPV6." Voets T., Janssens A., Prenen J., Droogmans G., Nilius B. J. Gen. Physiol. 121:245-260(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF ASP-541.
[5]	"Homo- and heterotetrameric architecture of the epithelial Ca2+ channels TRPV5 and TRPV6." Hoenderop J.G., Voets T., Hoefs S., Weidema F., Prenen J., Nilius B., Bindels R.J.M. EMBO J. 22:776-785(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, GLYCOSYLATION.
[6]	"Functional expression of the epithelial Ca(2+) channels (TRPV5 and TRPV6) requires association of the S100A10-annexin 2 complex." van de Graaf S.F., Hoenderop J.G., Gkika D., Lamers D., Prenen J., Rescher U., Gerke V., Staub O., Nilius B., Bindels R.J.M. EMBO J. 22:1478-1487(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH S100A10 AND ANAX2, MUTAGENESIS OF THR-599.
[7]	"Outer pore architecture of a Ca2+-selective TRP channel." Voets T., Janssens A., Droogmans G., Nilius B. J. Biol. Chem. 279:15223-15230(2004) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF CHANNEL PORE, MUTAGENESIS OF LEU-537; ASP-541 AND TYR-546.
[8]	"Regulation of the mouse epithelial Ca2(+) channel TRPV6 by the Ca(2+)-sensor calmodulin." Lambers T.T., Weidema A.F., Nilius B., Hoenderop J.G., Bindels R.J.M. J. Biol. Chem. 279:28855-28861(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CALMODULIN.
[9]	"Identification of BSPRY as a novel auxiliary protein inhibiting TRPV5 activity." van de Graaf S.F.J., van der Kemp A.W.C.M., van den Berg D., van Oorschot M., Hoenderop J.G.J., Bindels R.J.M. J. Am. Soc. Nephrol. 17:26-30(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BSPRY.
[10]	"Structural analyses of the ankyrin repeat domain of TRPV6 and related TRPV ion channels." Phelps C.B., Huang R.J., Lishko P.V., Wang R.R., Gaudet R. Biochemistry 47:2476-2484(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 44-265, ANKYRIN REPEATS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AJ542487 mRNA. Translation: CAD62684.1.
AK077234 mRNA. Translation: BAC36699.1.
BC016101 mRNA. Translation: AAH16101.1.

IPI

IPI00121894.

PIR

JC7796.

RefSeq

NP_071858.2. NM_022413.4.

UniGene

Mm.296889.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2RFA	X-ray	1.70	A	44-265	[»]

ProteinModelPortal

Q91WD2.

SMR

Q91WD2. Positions 41-303.

ModBase

Search...

PTM databases

PhosphoSite

Q91WD2.

Proteomic databases

PaxDb

Q91WD2.

PRIDE

Q91WD2.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000031902; ENSMUSP00000031902; ENSMUSG00000029868.

GeneID

64177.

KEGG

mmu:64177.

Organism-specific databases

CTD

55503.

MGI

MGI:1927259. Trpv6.

Phylogenomic databases

eggNOG

NOG278734.

GeneTree

ENSGT00550000074425.

HOGENOM

HOG000234397.

HOVERGEN

HBG061442.

InParanoid

Q91WD2.

KO

K04975.

OMA

QESWAQS.

Gene expression databases

ArrayExpress

Q91WD2.

Bgee

Q91WD2.

Genevestigator

Q91WD2.

GermOnline

ENSMUSG00000029868. Mus musculus.

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

EvolutionaryTrace

Q91WD2.

NextBio

319950.

SOURCE

Search...

Entry information

Entry name

TRPV6_MOUSE

Accession

Primary (citable) accession number: Q91WD2

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 26, 2005
Last sequence update:	December 1, 2001
Last modified:	May 1, 2013
This is version 100 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program