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Protein

Transient receptor potential cation channel subfamily V member 6

Gene

Trpv6

Organism
Rattus norvegicus (Rat)
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:10428857, PubMed:11287959, PubMed:27296226, PubMed:28878326). Important for normal Ca2+ ion homeostasis in the body, including bone and skin (By similarity). The channel is activated by low internal calcium level, probably including intracellular calcium store depletion, and the current exhibits an inward rectification (PubMed:10428857, PubMed:11287959, PubMed:27296226). 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).By similarity4 Publications

Caution

It is uncertain whether Met-1 or Met-41 is the initiator. In human and mouse, initiation starts at a conserved non-canonical ACG threonine codon decoded as Met-1 upstream of the canonical initiation at Met-41.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi581Calcium; shared with neighboring subunitsCombined sources1 Publication1

GO - Molecular functioni

  • calcium activated cation channel activity Source: RGD
  • calcium channel activity Source: UniProtKB
  • calmodulin binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

  • calcium ion homeostasis Source: UniProtKB
  • calcium ion import Source: RGD
  • calcium ion import across plasma membrane Source: UniProtKB
  • calcium ion transmembrane transport Source: UniProtKB
  • protein homotetramerization Source: UniProtKB
  • response to calcium ion Source: UniProtKB

Keywordsi

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

Protein family/group databases

TCDBi1.A.4.2.7 the transient receptor potential ca(2+) channel (trp-cc) family

Names & Taxonomyi

Protein namesi
Recommended name:
Transient receptor potential cation channel subfamily V member 6
Short name:
TrpV6
Alternative name(s):
Calcium transport protein 11 Publication
Short name:
CaT11 Publication
Epithelial calcium channel 2
Short name:
ECaC2
Gene namesi
Name:Trpv6
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi69335 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 – 366Cytoplasmic2 PublicationsAdd BLAST366
Transmembranei367 – 387Helical2 PublicationsAdd BLAST21
Topological domaini388 – 424Extracellular2 PublicationsAdd BLAST37
Transmembranei425 – 447Helical2 PublicationsAdd BLAST23
Topological domaini448 – 462Cytoplasmic2 PublicationsAdd BLAST15
Transmembranei463 – 482Helical2 PublicationsAdd BLAST20
Topological domaini483 – 488Extracellular2 Publications6
Transmembranei489 – 508Helical2 PublicationsAdd BLAST20
Topological domaini509 – 528Cytoplasmic2 PublicationsAdd BLAST20
Transmembranei529 – 551Helical2 PublicationsAdd BLAST23
Topological domaini552 – 564Extracellular2 PublicationsAdd BLAST13
Intramembranei565 – 584Pore-forming2 PublicationsAdd BLAST20
Topological domaini585 – 595Extracellular2 PublicationsAdd BLAST11
Transmembranei596 – 616Helical2 PublicationsAdd BLAST21
Topological domaini617 – 767Cytoplasmic2 PublicationsAdd BLAST151

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi201Y → F: Prevents up-regulation of the channel by phosphorylation; when associated with F-202. 1 Publication1
Mutagenesisi202Y → F: Prevents up-regulation of the channel by phosphorylation; when associated with F-201. 1 Publication1
Mutagenesisi535L → Q: Alters subunit assembly via domain swapping and reduces channel activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002153561 – 767Transient receptor potential cation channel subfamily V member 6Add BLAST767

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei201Phosphotyrosine; by SRC1 Publication1
Modified residuei202Phosphotyrosine; by SRC1 Publication1
Glycosylationi397N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Glycosylated.By similarity
Phosphorylation at Tyr-201 and Tyr-202 by SRC leads to an increased calcium influx through the channel. Probably dephosphorylated at these sites by PTPN1.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ9R186

PTM databases

iPTMnetiQ9R186
PhosphoSitePlusiQ9R186

Expressioni

Tissue specificityi

Expressed in duodenum, proximal jejunum, cecum, and colon.1 Publication

Interactioni

Subunit structurei

Homotetramer (PubMed:27296226, PubMed:29258289, PubMed:28878326). Probably forms also heterotetramers 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. Interacts with TCAF1 and TCAF2 (By similarity).By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-7198720,EBI-7198720

GO - Molecular functioni

  • calmodulin binding Source: UniProtKB
  • identical protein binding Source: IntAct

Protein-protein interaction databases

DIPiDIP-47769N
IntActiQ9R186, 1 interactor
MINTiQ9R186
STRINGi10116.ENSRNOP00000020616

Structurei

Secondary structure

1767
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi70 – 86Combined sources17
Helixi88 – 94Combined sources7
Helixi98 – 105Combined sources8
Turni106 – 108Combined sources3
Helixi122 – 128Combined sources7
Helixi132 – 141Combined sources10
Helixi143 – 146Combined sources4
Turni154 – 157Combined sources4
Helixi160 – 166Combined sources7
Helixi170 – 178Combined sources9
Helixi190 – 192Combined sources3
Helixi206 – 212Combined sources7
Helixi216 – 224Combined sources9
Helixi239 – 244Combined sources6
Helixi249 – 261Combined sources13
Beta strandi267 – 269Combined sources3
Turni271 – 273Combined sources3
Helixi282 – 289Combined sources8
Helixi292 – 300Combined sources9
Beta strandi303 – 309Combined sources7
Beta strandi312 – 317Combined sources6
Turni320 – 322Combined sources3
Beta strandi323 – 326Combined sources4
Turni327 – 329Combined sources3
Helixi331 – 337Combined sources7
Helixi341 – 346Combined sources6
Helixi352 – 361Combined sources10
Turni362 – 364Combined sources3
Helixi365 – 387Combined sources23
Helixi397 – 399Combined sources3
Turni401 – 404Combined sources4
Turni418 – 420Combined sources3
Helixi421 – 442Combined sources22
Helixi463 – 481Combined sources19
Turni482 – 484Combined sources3
Helixi487 – 489Combined sources3
Helixi490 – 501Combined sources12
Helixi504 – 510Combined sources7
Helixi515 – 530Combined sources16
Helixi533 – 552Combined sources20
Turni556 – 558Combined sources3
Helixi565 – 576Combined sources12
Beta strandi586 – 588Combined sources3
Helixi592 – 613Combined sources22
Turni614 – 617Combined sources4
Turni618 – 620Combined sources3
Helixi622 – 646Combined sources25
Beta strandi649 – 652Combined sources4
Beta strandi655 – 659Combined sources5
Beta strandi662 – 664Combined sources3
Beta strandi668 – 675Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5IWKX-ray3.25A41-709[»]
5IWPX-ray3.65A41-709[»]
5IWRX-ray3.85A41-709[»]
5IWTX-ray3.80A41-709[»]
5WO6X-ray3.31A41-708[»]
5WO7X-ray3.25A41-709[»]
5WO8X-ray3.40A41-709[»]
5WO9X-ray3.70A41-709[»]
5WOAX-ray3.90A41-709[»]
6BOBelectron microscopy3.90A/B/C/D41-708[»]
SMRiQ9R186
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

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

Region

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

Motif

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

Sequence similaritiesi

Keywords - Domaini

ANK repeat, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3676 Eukaryota
ENOG4110DG4 LUCA
HOGENOMiHOG000234397
HOVERGENiHBG061442
InParanoidiQ9R186
KOiK04975

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.

Q9R186-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGPLQREGRP ALGDANVAPG SSPGGVWHQP QPPKDSAFHP MGWSLPKEKG
60 70 80 90 100
LILCLWNKFC RWFHRRESWA QSRDEQNLLQ QKRIWESPLL LAAKENNVQA
110 120 130 140 150
LIKLLKFEGC EVHQKGAMGE 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
PRDNTLLQQK LLQEAYVTPK DDLRLVGELV SIVGAVIILL VEIPDIFRLG
460 470 480 490 500
VTRFFGQTIL GGPFHVIIVT YAFMVLVTMV MRLTNSDGEV VPMSFALVLG
510 520 530 540 550
WCNVMYFARG FQMLGPFTIM IQKMIFGDLM RFCWLMAVVI LGFASAFYII
560 570 580 590 600
FQTEDPDELG HFYDYPMALF STFELFLTII DGPANYDVDL PFMYSITYAA
610 620 630 640 650
FAIIATLLML NLLIAMMGDT HWRVAHERDE LWRAQVVATT VMLERKLPRC
660 670 680 690 700
LWPRSGICGR EYGLGDRWFL RVEDRQDLNR QRIRRYAQAF QQQDDLYSED
710 720 730 740 750
LEKDSGEKLE MARPFGAYLS FPTPSVSRST SRSSTNWDRL RQGALRKDLQ
760
GIINRGLEDG EGWEYQI
Length:767
Mass (Da):87,362
Last modified:April 1, 2015 - v2
Checksum:i2197726C2F583720
GO

Sequence cautioni

The sequence AAD47636 differs from that shown. Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.By similarity

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF160798 mRNA Translation: AAD47636.1 Sequence problems.
RefSeqiNP_446138.1, NM_053686.1
UniGeneiRn.205943

Genome annotation databases

GeneIDi114246
KEGGirno:114246
UCSCiRGD:69335 rat

Similar proteinsi

Entry informationi

Entry nameiTRPV6_RAT
AccessioniPrimary (citable) accession number: Q9R186
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 26, 2005
Last sequence update: April 1, 2015
Last modified: May 23, 2018
This is version 129 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health