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Protein

Transient receptor potential cation channel subfamily V member 6

Gene

TRPV6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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). 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 similarity5 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi582Calcium; shared with neighboring subunitsBy similarity1

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 into cell 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
Complete GO annotation...

Keywords - Molecular functioni

Calcium channel, Ion channel

Keywords - Biological processi

Calcium transport, Ion transport, Transport

Keywords - Ligandi

Calcium, Calmodulin-binding, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000165125-MONOMER.
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

HGNCiHGNC:14006. TRPV6.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei368 – 388HelicalBy similarityAdd BLAST21
Transmembranei426 – 448HelicalBy similarityAdd BLAST23
Transmembranei464 – 483HelicalBy similarityAdd BLAST20
Transmembranei490 – 509HelicalBy similarityAdd BLAST20
Transmembranei530 – 552HelicalBy similarityAdd BLAST23
Intramembranei566 – 585Pore-formingBy similarityAdd BLAST20
Transmembranei597 – 617HelicalBy similarityAdd BLAST21

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi582D → A: Abolishes 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.
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...)Sequence 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

HPAiHPA062644.
HPA062864.

Interactioni

Subunit structurei

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 BSPRY (By similarity). Interacts with TCAF1 and TCAF2 isoform 2 (PubMed:25559186). Interacts with calmodulin (PubMed:11248124).By similarity2 Publications

Binary interactionsi

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

GO - Molecular functioni

  • calmodulin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi120683. 14 interactors.
IntActiQ9H1D0. 2 interactors.
MINTiMINT-1472896.
STRINGi9606.ENSP00000352358.

Chemistry databases

BindingDBiQ9H1D0.

Structurei

3D structure databases

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 filterBy similarity5

Sequence similaritiesi

Contains 6 ANK repeats.PROSITE-ProRule annotation

Keywords - Domaini

ANK repeat, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3676. Eukaryota.
ENOG4110DG4. LUCA.
HOVERGENiHBG061442.
InParanoidiQ9H1D0.
KOiK04975.
OrthoDBiEOG091G0314.
TreeFamiTF314711.

Family and domain databases

Gene3Di1.25.40.20. 2 hits.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR005821. Ion_trans_dom.
IPR004729. TRP_channel.
IPR008344. TRPV5/TRPV6.
IPR008345. TRPV6_channel.
[Graphical view]
PfamiPF00023. Ank. 1 hit.
PF12796. Ank_2. 1 hit.
PF00520. Ion_trans. 1 hit.
[Graphical view]
PRINTSiPR01415. ANKYRIN.
PR01765. ECACCHANNEL.
PR01766. ECACCHANNEL1.
SMARTiSM00248. ANK. 5 hits.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
TIGRFAMsiTIGR00870. trp. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 2 hits.
[Graphical view]

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 → R.2 PublicationsCorresponds to variant rs4987657dbSNPEnsembl.1
Natural variantiVAR_052393399R → Q.Corresponds to variant rs4987665dbSNPEnsembl.1
Natural variantiVAR_022252418M → V.2 PublicationsCorresponds to variant rs4987667dbSNPEnsembl.1
Natural variantiVAR_022253721M → T.2 PublicationsCorresponds to variant rs4987682dbSNPEnsembl.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

EnsembliENST00000359396; ENSP00000352358; ENSG00000165125.
GeneIDi55503.
KEGGihsa:55503.
UCSCiuc003wbx.4. human. [Q9H1D0-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

TRPV6 entry

SeattleSNPs
Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.

3D structure databases

ProteinModelPortaliQ9H1D0.
SMRiQ9H1D0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120683. 14 interactors.
IntActiQ9H1D0. 2 interactors.
MINTiMINT-1472896.
STRINGi9606.ENSP00000352358.

Chemistry databases

BindingDBiQ9H1D0.
ChEMBLiCHEMBL1628465.

Protein family/group databases

TCDBi1.A.4.2.11. the transient receptor potential ca(2+) channel (trp-cc) family.

PTM databases

iPTMnetiQ9H1D0.
PhosphoSitePlusiQ9H1D0.

Polymorphism and mutation databases

DMDMi62901469.

Proteomic databases

PaxDbiQ9H1D0.
PeptideAtlasiQ9H1D0.
PRIDEiQ9H1D0.

Protocols and materials databases

DNASUi55503.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000359396; ENSP00000352358; ENSG00000165125.
GeneIDi55503.
KEGGihsa:55503.
UCSCiuc003wbx.4. human. [Q9H1D0-1]

Organism-specific databases

CTDi55503.
DisGeNETi55503.
GeneCardsiTRPV6.
H-InvDBHIX0007162.
HGNCiHGNC:14006. TRPV6.
HPAiHPA062644.
HPA062864.
MIMi606680. gene.
neXtProtiNX_Q9H1D0.
PharmGKBiPA37832.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3676. Eukaryota.
ENOG4110DG4. LUCA.
HOVERGENiHBG061442.
InParanoidiQ9H1D0.
KOiK04975.
OrthoDBiEOG091G0314.
TreeFamiTF314711.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000165125-MONOMER.
ReactomeiR-HSA-3295583. TRP channels.
SIGNORiQ9H1D0.

Miscellaneous databases

GeneWikiiTRPV6.
GenomeRNAii55503.
PROiQ9H1D0.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000165125.
CleanExiHS_TRPV6.
ExpressionAtlasiQ9H1D0. baseline and differential.
GenevisibleiQ9H1D0. HS.

Family and domain databases

Gene3Di1.25.40.20. 2 hits.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR005821. Ion_trans_dom.
IPR004729. TRP_channel.
IPR008344. TRPV5/TRPV6.
IPR008345. TRPV6_channel.
[Graphical view]
PfamiPF00023. Ank. 1 hit.
PF12796. Ank_2. 1 hit.
PF00520. Ion_trans. 1 hit.
[Graphical view]
PRINTSiPR01415. ANKYRIN.
PR01765. ECACCHANNEL.
PR01766. ECACCHANNEL1.
SMARTiSM00248. ANK. 5 hits.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
TIGRFAMsiTIGR00870. trp. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTRPV6_HUMAN
AccessioniPrimary (citable) accession number: Q9H1D0
Secondary accession number(s): A4D2I8
, Q8TDL3, Q8WXR8, Q96LC5, Q9H1D1, Q9H296
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 26, 2005
Last sequence update: April 1, 2015
Last modified: November 2, 2016
This is version 149 of the entry and version 3 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.