UniProtKB - Q91WD2 (TRPV6_MOUSE)
Protein
Transient receptor potential cation channel subfamily V member 6
Gene
Trpv6
Organism
Mus musculus (Mouse)
Status
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 581 | Calcium; shared with neighboring subunitsBy similarity | 1 |
GO - Molecular functioni
- calcium channel activity Source: MGI
- calmodulin binding Source: UniProtKB
- identical protein binding Source: MGI
- ion channel activity Source: GO_Central
- metal ion binding Source: UniProtKB-KW
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
Keywordsi
Molecular function | Calcium channel, Calmodulin-binding, Ion channel |
Biological process | Calcium transport, Ion transport, Transport |
Ligand | Calcium, Metal-binding |
Enzyme and pathway databases
Reactomei | R-MMU-3295583 TRP channels |
Names & Taxonomyi
Protein namesi | Recommended name: Transient receptor potential cation channel subfamily V member 6Short name: TrpV6 Alternative name(s): Calcium transport protein 1 Short name: CaT1 Epithelial calcium channel 2 Short name: ECaC2 |
Gene namesi | Name:Trpv6 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1927259 Trpv6 |
Subcellular locationi
Plasma membrane
- Cell membrane 5 Publications; Multi-pass membrane protein 1 Publication
Plasma Membrane
- integral component of plasma membrane Source: UniProtKB
- plasma membrane Source: UniProtKB
Other locations
- cell Source: GOC
- integral component of membrane Source: MGI
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 366 | CytoplasmicBy similarityAdd BLAST | 366 | |
Transmembranei | 367 – 387 | HelicalBy similarityAdd BLAST | 21 | |
Topological domaini | 388 – 424 | ExtracellularBy similarityAdd BLAST | 37 | |
Transmembranei | 425 – 447 | HelicalBy similarityAdd BLAST | 23 | |
Topological domaini | 448 – 462 | CytoplasmicBy similarityAdd BLAST | 15 | |
Transmembranei | 463 – 482 | HelicalBy similarityAdd BLAST | 20 | |
Topological domaini | 483 – 488 | ExtracellularBy similarity | 6 | |
Transmembranei | 489 – 508 | HelicalBy similarityAdd BLAST | 20 | |
Topological domaini | 509 – 528 | CytoplasmicBy similarityAdd BLAST | 20 | |
Transmembranei | 529 – 551 | HelicalBy similarityAdd BLAST | 23 | |
Topological domaini | 552 – 564 | ExtracellularBy similarityAdd BLAST | 13 | |
Intramembranei | 565 – 584 | Pore-formingBy similarityAdd BLAST | 20 | |
Topological domaini | 585 – 595 | ExtracellularBy similarityAdd BLAST | 11 | |
Transmembranei | 596 – 616 | HelicalBy similarityAdd BLAST | 21 | |
Topological domaini | 617 – 767 | CytoplasmicBy similarityAdd BLAST | 151 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & 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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 577 | L → C: Abolishes channel activity. 1 Publication | 1 | |
Mutagenesisi | 581 | D → A: Abolishes binding of Mg(2+) and increases pore diameter. Impairs intestinal Ca(2+) uptake. 3 Publications | 1 | |
Mutagenesisi | 581 | D → C: Abolishes channel activity. 2 Publications | 1 | |
Mutagenesisi | 581 | D → G: Increases pore diameter. 2 Publications | 1 | |
Mutagenesisi | 586 | Y → C: Abolishes channel activity. 1 Publication | 1 | |
Mutagenesisi | 639 | T → A: Abolishes plasma membrane localization and channel activity. 1 Publication | 1 |
Chemistry databases
GuidetoPHARMACOLOGYi | 512 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000215355 | 1 – 767 | Transient receptor potential cation channel subfamily V member 6Add BLAST | 767 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 201 | Phosphotyrosine; by SRCBy similarity | 1 | |
Modified residuei | 202 | Phosphotyrosine; by SRCBy similarity | 1 | |
Glycosylationi | 397 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
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, PhosphoproteinProteomic databases
PaxDbi | Q91WD2 |
PRIDEi | Q91WD2 |
PTM databases
iPTMneti | Q91WD2 |
PhosphoSitePlusi | Q91WD2 |
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
ExpressionAtlasi | Q91WD2 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 PublicationsGO - Molecular functioni
- calmodulin binding Source: UniProtKB
- identical protein binding Source: MGI
Protein-protein interaction databases
STRINGi | 10090.ENSMUSP00000031902 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q91WD2 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q91WD2 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 84 – 114 | ANK 1PROSITE-ProRule annotation1 PublicationAdd BLAST | 31 | |
Repeati | 118 – 147 | ANK 2PROSITE-ProRule annotation1 PublicationAdd BLAST | 30 | |
Repeati | 156 – 185 | ANK 3PROSITE-ProRule annotation1 PublicationAdd BLAST | 30 | |
Repeati | 202 – 231 | ANK 4PROSITE-ProRule annotation1 PublicationAdd BLAST | 30 | |
Repeati | 235 – 276 | ANK 5PROSITE-ProRule annotation1 PublicationAdd BLAST | 42 | |
Repeati | 278 – 307 | ANK 6PROSITE-ProRule annotation1 PublicationAdd BLAST | 30 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 133 – 143 | Interaction with calmodulinAdd BLAST | 11 | |
Regioni | 637 – 641 | Interaction with S100A10By similarity | 5 | |
Regioni | 689 – 707 | Interaction with calmodulinAdd BLAST | 19 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 580 – 584 | Selectivity filter1 Publication | 5 |
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 helixPhylogenomic databases
eggNOGi | KOG3676 Eukaryota ENOG4110DG4 LUCA |
GeneTreei | ENSGT00940000156687 |
HOGENOMi | HOG000234397 |
InParanoidi | Q91WD2 |
KOi | K04975 |
OrthoDBi | 693004at2759 |
TreeFami | TF314711 |
Family and domain databases
Gene3Di | 1.25.40.20, 2 hits |
InterProi | View protein in InterPro IPR002110 Ankyrin_rpt IPR020683 Ankyrin_rpt-contain_dom IPR036770 Ankyrin_rpt-contain_sf IPR005821 Ion_trans_dom IPR024862 TRPV IPR008344 TRPV5/TRPV6 IPR008345 TRPV6_channel |
PANTHERi | PTHR10582 PTHR10582, 1 hit |
Pfami | View protein in Pfam PF12796 Ank_2, 1 hit PF00520 Ion_trans, 1 hit |
PRINTSi | PR01415 ANKYRIN PR01765 ECACCHANNEL PR01766 ECACCHANNEL1 |
SMARTi | View protein in SMART SM00248 ANK, 5 hits |
SUPFAMi | SSF48403 SSF48403, 1 hit |
PROSITEi | View protein in PROSITE PS50297 ANK_REP_REGION, 1 hit PS50088 ANK_REPEAT, 2 hits |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
Q91WD2-1 [UniParc]FASTAAdd to basket
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
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A0J9YMK6 | A0A0J9YMK6_MOUSE | Transient receptor potential cation... | Trpv6 | 767 | Annotation score: |
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 1 | M → E in BAC36699 (PubMed:16141072).Curated | 1 |
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 |
CCDSi | CCDS20052.2 |
PIRi | JC7796 |
RefSeqi | NP_071858.3, NM_022413.4 |
Genome annotation databases
Ensembli | ENSMUST00000201471; ENSMUSP00000143854; ENSMUSG00000029868 |
GeneIDi | 64177 |
KEGGi | mmu:64177 |
UCSCi | uc009bqc.2 mouse |
Similar proteinsi
Cross-referencesi
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 |
CCDSi | CCDS20052.2 |
PIRi | JC7796 |
RefSeqi | NP_071858.3, NM_022413.4 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2RFA | X-ray | 1.70 | A | 84-305 | [»] | |
SMRi | Q91WD2 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
STRINGi | 10090.ENSMUSP00000031902 |
Chemistry databases
GuidetoPHARMACOLOGYi | 512 |
PTM databases
iPTMneti | Q91WD2 |
PhosphoSitePlusi | Q91WD2 |
Proteomic databases
PaxDbi | Q91WD2 |
PRIDEi | Q91WD2 |
Genome annotation databases
Ensembli | ENSMUST00000201471; ENSMUSP00000143854; ENSMUSG00000029868 |
GeneIDi | 64177 |
KEGGi | mmu:64177 |
UCSCi | uc009bqc.2 mouse |
Organism-specific databases
CTDi | 55503 |
MGIi | MGI:1927259 Trpv6 |
Phylogenomic databases
eggNOGi | KOG3676 Eukaryota ENOG4110DG4 LUCA |
GeneTreei | ENSGT00940000156687 |
HOGENOMi | HOG000234397 |
InParanoidi | Q91WD2 |
KOi | K04975 |
OrthoDBi | 693004at2759 |
TreeFami | TF314711 |
Enzyme and pathway databases
Reactomei | R-MMU-3295583 TRP channels |
Miscellaneous databases
ChiTaRSi | Trpv6 mouse |
EvolutionaryTracei | Q91WD2 |
PROi | PR:Q91WD2 |
SOURCEi | Search... |
Gene expression databases
ExpressionAtlasi | Q91WD2 baseline and differential |
Family and domain databases
Gene3Di | 1.25.40.20, 2 hits |
InterProi | View protein in InterPro IPR002110 Ankyrin_rpt IPR020683 Ankyrin_rpt-contain_dom IPR036770 Ankyrin_rpt-contain_sf IPR005821 Ion_trans_dom IPR024862 TRPV IPR008344 TRPV5/TRPV6 IPR008345 TRPV6_channel |
PANTHERi | PTHR10582 PTHR10582, 1 hit |
Pfami | View protein in Pfam PF12796 Ank_2, 1 hit PF00520 Ion_trans, 1 hit |
PRINTSi | PR01415 ANKYRIN PR01765 ECACCHANNEL PR01766 ECACCHANNEL1 |
SMARTi | View protein in SMART SM00248 ANK, 5 hits |
SUPFAMi | SSF48403 SSF48403, 1 hit |
PROSITEi | View protein in PROSITE PS50297 ANK_REP_REGION, 1 hit PS50088 ANK_REPEAT, 2 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | TRPV6_MOUSE | |
Accessioni | Q91WD2Primary (citable) accession number: Q91WD2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 26, 2005 |
Last sequence update: | April 1, 2015 | |
Last modified: | November 13, 2019 | |
This is version 150 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Complete proteome, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families - MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references