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UniProtKB - Q91WD2 (TRPV6_MOUSE)

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Protein

Transient receptor potential cation channel subfamily V member 6

Gene

Trpv6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Calcium selective cation channel that mediates Ca2+ uptake in various tissues, including the intestine (PubMed:12765696, PubMed:12601087, PubMed:12574114, PubMed:14736889, PubMed:15123711, PubMed:17129178). Important for normal Ca2+ ion homeostasis in the body, including bone and skin (PubMed:17129178, PubMed:22878123). 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 (PubMed:15123711). In vitro, is slowly inhibited by Mg2+ in a voltage-independent manner (PubMed:12601087). Heteromeric assembly with TRPV5 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating (PubMed:12574114).8 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi581Calcium; shared with neighboring subunitsBy similarity1

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

  • calcium ion homeostasis Source: UniProtKB
  • calcium ion import Source: MGI
  • calcium ion import across plasma membrane Source: UniProtKB
  • calcium ion transmembrane transport Source: MGI
  • calcium ion transport Source: MGI
  • parathyroid hormone secretion Source: MGI
  • protein homotetramerization Source: MGI
  • response to calcium ion Source: UniProtKB
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionCalcium channel, Calmodulin-binding, Ion channel
Biological processCalcium transport, Ion transport, Transport
LigandCalcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-MMU-3295583 TRP channels

Names & Taxonomyi

Protein namesi
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 namesi
Name:Trpv6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:1927259 Trpv6

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 366CytoplasmicBy similarityAdd BLAST366
Transmembranei367 – 387HelicalBy similarityAdd BLAST21
Topological domaini388 – 424ExtracellularBy similarityAdd BLAST37
Transmembranei425 – 447HelicalBy similarityAdd BLAST23
Topological domaini448 – 462CytoplasmicBy similarityAdd BLAST15
Transmembranei463 – 482HelicalBy similarityAdd BLAST20
Topological domaini483 – 488ExtracellularBy similarity6
Transmembranei489 – 508HelicalBy similarityAdd BLAST20
Topological domaini509 – 528CytoplasmicBy similarityAdd BLAST20
Transmembranei529 – 551HelicalBy similarityAdd BLAST23
Topological domaini552 – 564ExtracellularBy similarityAdd BLAST13
Intramembranei565 – 584Pore-formingBy similarityAdd BLAST20
Topological domaini585 – 595ExtracellularBy similarityAdd BLAST11
Transmembranei596 – 616HelicalBy similarityAdd BLAST21
Topological domaini617 – 767CytoplasmicBy similarityAdd BLAST151

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Mutant mice have lower body weight than their littermates throughout their lifespan and low fertility, due to impaired calcium homeostasis. Mutant mice display strongly impaired intestinal Ca2+ uptake and increased urinary Ca2+ levels (PubMed:17129178). Still, their serum Ca2+ levels are normal, probably due to compensation by another calcium channel (PubMed:17129178, PubMed:20399919). In spite of this, mutant mice display decreased femoral mineral density; also when they are fed a high-calcium diet (PubMed:17129178). In contrast, no difference in bone density was observed in another study; mutant and wild-type mice displayed similar values when fed a normal diet, and a similar reduction in bone mass when fed a low-calcium diet (PubMed:20399919). Besides, the majority of mutant mice display alopecia and develop dermatitis (PubMed:17129178).2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi577L → C: Abolishes channel activity. 1 Publication1
Mutagenesisi581D → A: Abolishes binding of Mg(2+) and increases pore diameter. Impairs intestinal Ca(2+) uptake. 3 Publications1
Mutagenesisi581D → C: Abolishes channel activity. 2 Publications1
Mutagenesisi581D → G: Increases pore diameter. 2 Publications1
Mutagenesisi586Y → C: Abolishes channel activity. 1 Publication1
Mutagenesisi639T → A: Abolishes plasma membrane localization and channel activity. 1 Publication1

Chemistry databases

GuidetoPHARMACOLOGYi512

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002153551 – 767Transient receptor potential cation channel subfamily V member 6Add BLAST767

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei201Phosphotyrosine; by SRCBy similarity1
Modified residuei202Phosphotyrosine; by SRCBy similarity1
Glycosylationi397N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Glycosylated.3 Publications
Phosphorylation at Tyr-201 and Tyr-202 by SRC leads to an increased calcium influx through the channel. Probably dephosphorylated at these sites by PTPN1 (By similarity).By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ91WD2
PRIDEiQ91WD2

PTM databases

iPTMnetiQ91WD2
PhosphoSitePlusiQ91WD2

Expressioni

Tissue specificityi

Detected in intestine (at protein level) (PubMed:17129178). Abundantly expressed in pancreas and placenta, and to a much lesser extent in stomach and kidney (PubMed:12765696). Detected in kidney and duodenum (PubMed:17129178, PubMed:20399919).3 Publications

Inductioni

Up-regulated in intestine by exposure to a low-calcium diet (PubMed:17129178, PubMed:22878123). Down-regulated in intestine in response to a high-calcium diet (PubMed:17129178).2 Publications

Gene expression databases

ExpressionAtlasiQ91WD2 baseline and differential

Interactioni

Subunit structurei

Interacts with TCAF1 and TCAF2 (By similarity). Homotetramer and probably heterotetramer with TRPV5 (PubMed:12574114). Interacts with TRPV5 (PubMed:12574114). Interacts with S100A10 and probably with the ANAX2-S100A10 heterotetramer. The interaction with S100A10 is required for the trafficking to the plasma membrane (PubMed:12660155). Interacts with calmodulin (PubMed:12765696, PubMed:15123711). Interacts with BSPRY (PubMed:16380433).By similarity5 Publications

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000031902

Structurei

Secondary structure

1767
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi88 – 94Combined sources7
Helixi98 – 105Combined sources8
Helixi122 – 128Combined sources7
Helixi132 – 141Combined sources10
Helixi143 – 147Combined sources5
Turni153 – 157Combined sources5
Helixi160 – 166Combined sources7
Helixi170 – 178Combined sources9
Helixi190 – 192Combined sources3
Helixi206 – 213Combined sources8
Helixi216 – 224Combined sources9
Helixi239 – 244Combined sources6
Helixi249 – 261Combined sources13
Helixi271 – 273Combined sources3
Helixi282 – 289Combined sources8
Helixi292 – 304Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2RFAX-ray1.70A84-305[»]
ProteinModelPortaliQ91WD2
SMRiQ91WD2
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ91WD2

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati84 – 114ANK 1PROSITE-ProRule annotation1 PublicationAdd BLAST31
Repeati118 – 147ANK 2PROSITE-ProRule annotation1 PublicationAdd BLAST30
Repeati156 – 185ANK 3PROSITE-ProRule annotation1 PublicationAdd BLAST30
Repeati202 – 231ANK 4PROSITE-ProRule annotation1 PublicationAdd BLAST30
Repeati235 – 276ANK 5PROSITE-ProRule annotation1 PublicationAdd BLAST42
Repeati278 – 307ANK 6PROSITE-ProRule annotation1 PublicationAdd BLAST30

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni133 – 143Interaction with calmodulinAdd BLAST11
Regioni637 – 641Interaction with S100A10By similarity5
Regioni689 – 707Interaction with calmodulinAdd BLAST19

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi580 – 584Selectivity filter1 Publication5

Sequence similaritiesi

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

Keywords - Domaini

ANK repeat, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3676 Eukaryota
ENOG4110DG4 LUCA
GeneTreeiENSGT00550000074425
HOGENOMiHOG000234397
HOVERGENiHBG061442
InParanoidiQ91WD2
KOiK04975
TreeFamiTF314711

Family and domain databases

CDDicd00204 ANK, 1 hit
Gene3Di1.25.40.20, 2 hits
InterProiView protein in InterPro
IPR002110 Ankyrin_rpt
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
IPR005821 Ion_trans_dom
IPR004729 TRP_channel
IPR024862 TRPV
IPR008344 TRPV5/TRPV6
IPR008345 TRPV6_channel
PANTHERiPTHR10582 PTHR10582, 1 hit
PfamiView protein in Pfam
PF12796 Ank_2, 1 hit
PF00520 Ion_trans, 1 hit
PRINTSiPR01415 ANKYRIN
PR01765 ECACCHANNEL
PR01766 ECACCHANNEL1
SMARTiView protein in SMART
SM00248 ANK, 5 hits
SUPFAMiSSF48403 SSF48403, 1 hit
TIGRFAMsiTIGR00870 trp, 1 hit
PROSITEiView protein in PROSITE
PS50297 ANK_REP_REGION, 1 hit
PS50088 ANK_REPEAT, 2 hits

Sequencei

Sequence statusi: Complete.

Q91WD2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGPLQREDRP ALGGANVAPG SSPVGVWHQP QPPKEPAFHP MGWSLPKEKG 
        60         70         80         90        100
LILCLWNKFC RWFHRQESWA QSRDEQNLLQ QKRIWESPLL LAAKENDVQA 
       110        120        130        140        150
LSKLLKFEGC EVHQRGAMGE TALHIAALYD NLEAAMVLME AAPELVFEPM 
       160        170        180        190        200
TSELYEGQTA LHIAVINQNV NLVRALLARG ASVSARATGS VFHYRPHNLI 
       210        220        230        240        250
YYGEHPLSFA ACVGSEEIVR LLIEHGADIR AQDSLGNTVL HILILQPNKT 
       260        270        280        290        300
FACQMYNLLL SYDGGDHLKS LELVPNNQGL TPFKLAGVEG NIVMFQHLMQ 
       310        320        330        340        350
KRKHIQWTYG PLTSTLYDLT EIDSSGDDQS LLELIVTTKK REARQILDQT 
       360        370        380        390        400
PVKELVSLKW KRYGRPYFCV LGAIYVLYII CFTMCCVYRP LKPRITNRTN 
       410        420        430        440        450
PRDNTLMQQK LLQEAYVTPK DDLRLVGELV SIVGAVIILL VEIPDIFRLG 
       460        470        480        490        500
VTRFFGQTIL GGPFHVIIIT YAFMVLVTMV MRLTNVDGEV VPMSFALVLG 
       510        520        530        540        550
WCNVMYFARG FQMLGPFTIM IQKMIFGDLM RFCWLMAVVI LGFASAFYII 
       560        570        580        590        600
FQTEDPDELG HFYDYPMALF STFELFLTII DGPANYDVDL PFMYSVTYAA 
       610        620        630        640        650
FAIIATLLML NLLIAMMGDT HWRVAHERDE LWRAQVVATT VMLERKLPRC 
       660        670        680        690        700
LWPRSGICGR EYGLGDRWFL RVEDRQDLNR QRIRRYAQAF QQQDGLYSED 
       710        720        730        740        750
LEKDSGEKLE TARPFGAYLS FPTPSVSRST SRSSTNWERL RQGALRKDLR 
       760 
GIINRGLEDG EGWEYQI
Length:767
Mass (Da):87,387
Last modified:April 1, 2015 - v2
Checksum:iFBD937FB9C55F9BA
GO

Sequence cautioni

The sequence AAH16101 differs from that shown. Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.1 Publication
The sequence BAC36699 differs from that shown. Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.1 Publication

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1M → E in BAC36699 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK077234 mRNA Translation: BAC36699.1 Sequence problems.
BC016101 mRNA Translation: AAH16101.1 Sequence problems.
AJ542487 mRNA Translation: CAD62684.1
CCDSiCCDS20052.2
PIRiJC7796
RefSeqiNP_071858.3, NM_022413.4
UniGeneiMm.296889

Genome annotation databases

EnsembliENSMUST00000201471; ENSMUSP00000143854; ENSMUSG00000029868
GeneIDi64177
KEGGimmu:64177
UCSCiuc009bqc.2 mouse

Similar proteinsi

Entry informationi

Entry nameiTRPV6_MOUSE
AccessioniPrimary (citable) accession number: Q91WD2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 26, 2005
Last sequence update: April 1, 2015
Last modified: June 20, 2018
This is version 142 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

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