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Protein

Transient receptor potential cation channel subfamily V member 6

Gene

TRPV6

Organism
Homo sapiens (Human)
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:11097838, PubMed:11278579, PubMed:11248124 PubMed:15184369, PubMed:23612980, PubMed:29258289). 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:15184369). 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 similarity6 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi582Calcium; shared with neighboring subunits1 Publication1

GO - Molecular functioni

  • calcium channel activity Source: UniProtKB
  • calmodulin binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

  • calcium ion homeostasis Source: UniProtKB
  • calcium ion import across plasma membrane Source: UniProtKB
  • calcium ion transmembrane transport Source: UniProtKB
  • calcium ion transport Source: UniProtKB
  • regulation of calcium ion-dependent exocytosis 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

Enzyme and pathway databases

ReactomeiR-HSA-3295583 TRP channels
SIGNORiQ9H1D0

Protein family/group databases

TCDBi1.A.4.2.11 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):
CaT-like1 Publication
Short name:
CaT-L1 Publication
Calcium transport protein 11 Publication
Short name:
CaT11 Publication
Epithelial calcium channel 2
Short name:
ECaC2
Gene namesi
Name:TRPV6
Synonyms:ECAC2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000165125.17
HGNCiHGNC:14006 TRPV6
MIMi606680 gene
neXtProtiNX_Q9H1D0

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 – 367Cytoplasmic1 PublicationAdd BLAST367
Transmembranei368 – 388Helical1 PublicationAdd BLAST21
Topological domaini389 – 425Extracellular1 PublicationAdd BLAST37
Transmembranei426 – 448Helical1 PublicationAdd BLAST23
Topological domaini449 – 463Cytoplasmic1 PublicationAdd BLAST15
Transmembranei464 – 483Helical1 PublicationAdd BLAST20
Topological domaini484 – 489Extracellular1 Publication6
Transmembranei490 – 509Helical1 PublicationAdd BLAST20
Topological domaini510 – 529Cytoplasmic1 PublicationAdd BLAST20
Transmembranei530 – 552Helical1 PublicationAdd BLAST23
Topological domaini553 – 565Extracellular1 PublicationAdd BLAST13
Intramembranei566 – 585Pore-forming1 PublicationAdd BLAST20
Topological domaini586 – 596Extracellular1 PublicationAdd BLAST11
Transmembranei597 – 617Helical1 PublicationAdd BLAST21
Topological domaini618 – 765Cytoplasmic1 PublicationAdd BLAST148

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi510R → E: Decreases channel opening, and thereby decreases channel activity. 1 Publication1
Mutagenesisi523Q → A: Decreases channel activity. 1 Publication1
Mutagenesisi582D → A: Abolishes channel activity. 1 Publication1
Mutagenesisi606A → T: Decreases channel opening, and thereby strongly decreases channel activity. 1 Publication1
Mutagenesisi742T → A: Abolishes phosphorylation by PKC/PRKCA, achieves faster channel inactivation and no effect on binding to calmodulin. 1 Publication1

Organism-specific databases

DisGeNETi55503
OpenTargetsiENSG00000165125
PharmGKBiPA37832

Chemistry databases

ChEMBLiCHEMBL1628465

Polymorphism and mutation databases

DMDMi62901469

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002153541 – 765Transient receptor potential cation channel subfamily V member 6Add BLAST765

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei201Phosphotyrosine; by SRCBy similarity1
Glycosylationi398N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei742Phosphothreonine; by PKC/PRKCA1 Publication1

Post-translational modificationi

Glycosylated.By similarity1 Publication
Phosphorylation at Tyr-201 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 (PubMed:11248124).By similarity1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ9H1D0
PeptideAtlasiQ9H1D0
PRIDEiQ9H1D0

PTM databases

iPTMnetiQ9H1D0
PhosphoSitePlusiQ9H1D0

Expressioni

Tissue specificityi

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 trophoblasts of placenta villus trees (at protein level)(PubMed:23612980). Expressed in locally advanced prostate cancer, metastatic and androgen-insensitive prostatic lesions but not detected in healthy prostate tissue and benign prostatic hyperplasia.3 Publications

Gene expression databases

BgeeiENSG00000165125
CleanExiHS_TRPV6
ExpressionAtlasiQ9H1D0 baseline and differential
GenevisibleiQ9H1D0 HS

Organism-specific databases

HPAiHPA062864

Interactioni

Subunit structurei

Homotetramer (PubMed:29258289). 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 BSPRY (By similarity). Interacts with TCAF1 and TCAF2 isoform 2 (PubMed:25559186). Interacts with calmodulin (PubMed:11248124).By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PTPN1P180316EBI-7198335,EBI-968788

GO - Molecular functioni

  • calmodulin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi120683, 15 interactors
IntActiQ9H1D0, 2 interactors
MINTiQ9H1D0
STRINGi9606.ENSP00000352358

Chemistry databases

BindingDBiQ9H1D0

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
6BO8electron microscopy3.60A/B/C/D41-765[»]
6BO9electron microscopy4.00A/B/C/D41-765[»]
6BOAelectron microscopy4.20A/B/C/D41-765[»]
ProteinModelPortaliQ9H1D0
SMRiQ9H1D0
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati84 – 114ANK 1Add BLAST31
Repeati118 – 147ANK 2Add BLAST30
Repeati156 – 185ANK 3Add BLAST30
Repeati202 – 231ANK 4Add BLAST30
Repeati235 – 277ANK 5Add BLAST43
Repeati279 – 308ANK 5Add BLAST30

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni133 – 143Interaction with calmodulinBy similarityAdd BLAST11
Regioni638 – 642Interaction with S100A10By similarity5
Regioni731 – 751Interaction with calmodulin2 PublicationsAdd BLAST21

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi581 – 585Selectivity filter1 Publication5

Sequence similaritiesi

Keywords - Domaini

ANK repeat, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3676 Eukaryota
ENOG4110DG4 LUCA
GeneTreeiENSGT00550000074425
HOVERGENiHBG061442
InParanoidiQ9H1D0
KOiK04975
OrthoDBiEOG091G0314
TreeFamiTF314711

Family and domain databases

CDDicd00204 ANK, 2 hits
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
PF00023 Ank, 1 hit
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

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9H1D0-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGPLQGDGGP ALGGADVAPR LSPVRVWPRP QAPKEPALHP MGLSLPKEKG
60 70 80 90 100
LILCLWSKFC RWFQRRESWA QSRDEQNLLQ QKRIWESPLL LAAKDNDVQA
110 120 130 140 150
LNKLLKYEDC KVHQRGAMGE TALHIAALYD NLEAAMVLME AAPELVFEPM
160 170 180 190 200
TSELYEGQTA LHIAVVNQNM NLVRALLARR ASVSARATGT AFRRSPCNLI
210 220 230 240 250
YFGEHPLSFA ACVNSEEIVR LLIEHGADIR AQDSLGNTVL HILILQPNKT
260 270 280 290 300
FACQMYNLLL SYDRHGDHLQ PLDLVPNHQG LTPFKLAGVE GNTVMFQHLM
310 320 330 340 350
QKRKHTQWTY GPLTSTLYDL TEIDSSGDEQ SLLELIITTK KREARQILDQ
360 370 380 390 400
TPVKELVSLK WKRYGRPYFC MLGAIYLLYI ICFTMCCIYR PLKPRTNNRT
410 420 430 440 450
SPRDNTLLQQ KLLQEAYMTP KDDIRLVGEL VTVIGAIIIL LVEVPDIFRM
460 470 480 490 500
GVTRFFGQTI LGGPFHVLII TYAFMVLVTM VMRLISASGE VVPMSFALVL
510 520 530 540 550
GWCNVMYFAR GFQMLGPFTI MIQKMIFGDL MRFCWLMAVV ILGFASAFYI
560 570 580 590 600
IFQTEDPEEL GHFYDYPMAL FSTFELFLTI IDGPANYNVD LPFMYSITYA
610 620 630 640 650
AFAIIATLLM LNLLIAMMGD THWRVAHERD ELWRAQIVAT TVMLERKLPR
660 670 680 690 700
CLWPRSGICG REYGLGDRWF LRVEDRQDLN RQRIQRYAQA FHTRGSEDLD
710 720 730 740 750
KDSVEKLELG CPFSPHLSLP MPSVSRSTSR SSANWERLRQ GTLRRDLRGI
760
INRGLEDGES WEYQI
Length:765
Mass (Da):87,286
Last modified:April 1, 2015 - v3
Checksum:i626D515E12112546
GO
Isoform 2 (identifier: Q9H1D0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     65-232: Missing.

Show »
Length:597
Mass (Da):68,446
Checksum:i6EB713BE033FD580
GO

Sequence cautioni

The sequence AAK50426 differs from that shown. Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.1 Publication
The sequence AAL40230 differs from that shown. Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.1 Publication
The sequence AAM00356 differs from that shown. Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.1 Publication
The sequence AAO38052 differs from that shown. Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.1 Publication
The sequence BAF84396 differs from that shown. Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.1 Publication
The sequence CAC20416 differs from that shown. Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.1 Publication
The sequence CAC20417 differs from that shown. Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.1 Publication
The sequence CAD32311 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 conflicti77N → D in AAG41951 (PubMed:11097838).Curated1
Sequence conflicti114Q → H in AAG41951 (PubMed:11097838).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_022251197C → R2 PublicationsCorresponds to variant dbSNP:rs4987657Ensembl.1
Natural variantiVAR_052393399R → Q. Corresponds to variant dbSNP:rs4987665Ensembl.1
Natural variantiVAR_022252418M → V2 PublicationsCorresponds to variant dbSNP:rs4987667Ensembl.1
Natural variantiVAR_022253721M → T2 PublicationsCorresponds to variant dbSNP:rs4987682Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01343965 – 232Missing in isoform 2. 1 PublicationAdd BLAST168

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF304463 mRNA Translation: AAG41951.1
AF365927 mRNA Translation: AAL40230.1 Sequence problems.
AF365928 mRNA Translation: AAM00356.1 Sequence problems.
AH010730 Genomic DNA Translation: AAK50426.1 Sequence problems.
AJ243500 mRNA Translation: CAC20416.2 Sequence problems.
AJ243501 mRNA Translation: CAC20417.2 Sequence problems.
AJ487964 mRNA Translation: CAD32311.1 Sequence problems.
AY225461 Genomic DNA Translation: AAO38052.1 Sequence problems.
AK291707 mRNA Translation: BAF84396.1 Sequence problems.
CH236959 Genomic DNA Translation: EAL23776.1
CCDSiCCDS5874.2 [Q9H1D0-1]
PIRiJC7531
RefSeqiNP_061116.5, NM_018646.5 [Q9H1D0-1]
UniGeneiHs.302740

Genome annotation databases

EnsembliENST00000638686; ENSP00000492723; ENSG00000165125 [Q9H1D0-1]
GeneIDi55503
KEGGihsa:55503
UCSCiuc003wbx.4 human [Q9H1D0-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTRPV6_HUMAN
AccessioniPrimary (citable) accession number: Q9H1D0
Secondary accession number(s): A4D2I8
, Q8TDL3, Q8WXR8, Q96LC5, Q9H1D1, Q9H296
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 26, 2005
Last sequence update: April 1, 2015
Last modified: May 23, 2018
This is version 160 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health