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Protein

Two pore calcium channel protein 2

Gene

Tpcn2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Nicotinic acid adenine dinucleotide phosphate (NAADP) receptor that may function as one of the major voltage-gated Ca2+ channels (VDCC) across the lysosomal membrane. Involved in smooth muscle contraction.3 Publications

GO - Molecular functioni

  • NAADP-sensitive calcium-release channel activity Source: UniProtKB
  • protein kinase binding Source: MGI
  • voltage-gated calcium channel activity Source: UniProtKB

GO - Biological processi

  • calcium-mediated signaling Source: MGI
  • cellular calcium ion homeostasis Source: MGI
  • lysosome organization Source: MGI
  • membrane depolarization during action potential Source: GO_Central
  • regulation of autophagy Source: MGI
  • release of sequestered calcium ion into cytosol Source: UniProtKB
  • response to vitamin D Source: Ensembl
  • smooth muscle contraction Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Calcium channel, Ion channel, Voltage-gated channel

Keywords - Biological processi

Calcium transport, Ion transport, Transport

Keywords - Ligandi

Calcium

Enzyme and pathway databases

ReactomeiR-MMU-2672351. Stimuli-sensing channels.

Names & Taxonomyi

Protein namesi
Recommended name:
Two pore calcium channel protein 2
Alternative name(s):
Voltage-dependent calcium channel protein TPC2
Gene namesi
Name:Tpcn2
Synonyms:Tpc2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:2385297. Tpcn2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 68CytoplasmicSequence analysisAdd BLAST68
Transmembranei69 – 89Helical; Name=S1 of repeat ISequence analysisAdd BLAST21
Topological domaini90 – 111ExtracellularSequence analysisAdd BLAST22
Transmembranei112 – 132Helical; Name=S2 of repeat ISequence analysisAdd BLAST21
Topological domaini133 – 139CytoplasmicSequence analysis7
Transmembranei140 – 160Helical; Name=S3 of repeat ISequence analysisAdd BLAST21
Topological domaini161 – 167ExtracellularSequence analysis7
Transmembranei168 – 188Helical; Name=S4 of repeat ISequence analysisAdd BLAST21
Topological domaini189 – 203CytoplasmicSequence analysisAdd BLAST15
Transmembranei204 – 224Helical; Name=S5 of repeat ISequence analysisAdd BLAST21
Topological domaini225 – 238ExtracellularSequence analysisAdd BLAST14
Intramembranei239 – 263Helical; Pore-formingSequence analysisAdd BLAST25
Topological domaini264 – 270ExtracellularSequence analysis7
Transmembranei271 – 291Helical; Name=S6 of repeat ISequence analysisAdd BLAST21
Topological domaini292 – 417CytoplasmicSequence analysisAdd BLAST126
Transmembranei418 – 438Helical; Name=S1 of repeat IISequence analysisAdd BLAST21
Topological domaini439 – 449ExtracellularSequence analysisAdd BLAST11
Transmembranei450 – 470Helical; Name=S2 of repeat IISequence analysisAdd BLAST21
Topological domaini471 – 486CytoplasmicSequence analysisAdd BLAST16
Transmembranei487 – 507Helical; Name=S3 of repeat IISequence analysisAdd BLAST21
Topological domaini508 – 524ExtracellularSequence analysisAdd BLAST17
Transmembranei525 – 542Helical; Name=S4 of repeat IISequence analysisAdd BLAST18
Topological domaini543 – 564CytoplasmicSequence analysisAdd BLAST22
Transmembranei565 – 585Helical; Name=S5 of repeat IISequence analysisAdd BLAST21
Topological domaini586 – 618ExtracellularSequence analysisAdd BLAST33
Intramembranei619 – 641Helical; Pore-formingSequence analysisAdd BLAST23
Topological domaini642 – 656ExtracellularSequence analysisAdd BLAST15
Transmembranei657 – 677Helical; Name=S6 of repeat IISequence analysisAdd BLAST21
Topological domaini678 – 731CytoplasmicSequence analysisAdd BLAST54

GO - Cellular componenti

  • endosome membrane Source: MGI
  • integral component of membrane Source: UniProtKB-KW
  • lysosomal membrane Source: UniProtKB
  • lysosome Source: UniProtKB
  • plasma membrane Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Lysosome, Membrane

Pathology & Biotechi

Disruption phenotypei

Loss of NAADP-mediated calcium release.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi257N → A: Complete loss of selectivity for calcium over monocovalent cations. 1 Publication1
Mutagenesisi594N → A: Loss of N-glycosylation; when associated with N-601. 1 Publication1
Mutagenesisi601N → A: Loss of N-glycosylation; when associated with N-594. 1 Publication1
Mutagenesisi643E → A: Partial loss of selectivity for calcium over monocovalent cations. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002768571 – 731Two pore calcium channel protein 2Add BLAST731

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi594N-linked (GlcNAc...)1 Publication1
Glycosylationi601N-linked (GlcNAc...)1 Publication1

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ8BWC0.
PRIDEiQ8BWC0.

PTM databases

PhosphoSitePlusiQ8BWC0.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSMUSG00000048677.
CleanExiMM_TPCN2.
ExpressionAtlasiQ8BWC0. baseline and differential.
GenevisibleiQ8BWC0. MM.

Interactioni

Subunit structurei

Homodimer (PubMed:19557428). Interacts with LRRK2. Interacts with HAX1 (By similarity).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000061308.

Structurei

3D structure databases

ProteinModelPortaliQ8BWC0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

Each of the two internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position (By similarity).By similarity

Sequence similaritiesi

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410KCTV. Eukaryota.
ENOG4111V21. LUCA.
GeneTreeiENSGT00530000063660.
HOGENOMiHOG000154668.
HOVERGENiHBG079776.
InParanoidiQ8BWC0.
KOiK14077.
OMAiFVFGHYY.
OrthoDBiEOG091G045K.
PhylomeDBiQ8BWC0.
TreeFamiTF328550.

Family and domain databases

Gene3Di1.20.120.350. 1 hit.
InterProiIPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
[Graphical view]
PfamiPF00520. Ion_trans. 2 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8BWC0-1) [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
MAAEEQPLLG RDRGSGQVHS GAAADQELCI DQAVVFIEDA IKYRSIYHRM
60 70 80 90 100
DAGSLWLYRW YYSNVCQRVL GFIIFLILIL AFVEVPSSFT KTADVRYRSQ
110 120 130 140 150
PWQPPCGLTE TIEAFCLLAF LVDLSVKGYL VGQAQLQQNL WLLAYFMVLV
160 170 180 190 200
VSVVDWIVSL SLACEEPLRM RRLLRPFFLL QNSSMMKKTL KCIRWSLPEM
210 220 230 240 250
ASVGLLLAIH LCLFTIIGML LFTIGEKDEA QDQERLAYFR NLPEALTSLL
260 270 280 290 300
VLLTTSNNPD VMIPAYTQNR AFALFFIVFT LIGSLFLMNL LTAIIYNQFR
310 320 330 340 350
GYLMKSLQTS LFRRRLGARA AYEVLASRAG PAGTTPELVG VNPETFLPVL
360 370 380 390 400
QKTQLNKTHK QAIMQKVQSY EGRPMLADEF QKLFDEVDKG LAKERPLKPQ
410 420 430 440 450
YQSPFLQTAQ FIFSHHYFDY LGNLVALGNL LSICVFLVLD SDLLPGERDD
460 470 480 490 500
FVLGILDYIF ILYYLLELLF KVFALGLPGY LSYHSNVFDG LLTIILLVSE
510 520 530 540 550
ICTLAVYRLP HSGWKPEQYG PLSLWDMTRL MNTLIVFRFL RIIPNIKPMA
560 570 580 590 600
EVANTILGLI PNLRAFGGIL VVAYYVFAMI GINLFRGVIV PPGNSSLVPD
610 620 630 640 650
NNSAVCGSFE QLGYWPNNFD DFAAALITLW NVMVVNNWQV ILEAYKRYAG
660 670 680 690 700
PWSMVYFVLW WLVSSVIWIN LFLALLLENF LHRWDPQGHK QLLVGTKQMS
710 720 730
VELMFRDILE EPKEEELMEK LHKHPHLHLC R
Length:731
Mass (Da):83,595
Last modified:March 1, 2003 - v1
Checksum:i3C76487441344AD7
GO
Isoform 2 (identifier: Q8BWC0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-453: Missing.
     454-514: GILDYIFILY...AVYRLPHSGW → MAAWDLGVSY...FLTCLLCLPR

Show »
Length:276
Mass (Da):31,501
Checksum:i4F77688937BFCE4A
GO
Isoform 3 (identifier: Q8BWC0-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-526: Missing.

Show »
Length:205
Mass (Da):23,727
Checksum:iDE59E952F4A6D049
GO

Sequence cautioni

The sequence BAC41072 differs from that shown. Reason: Frameshift at position 318.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti127K → E in BAC41072 (PubMed:16141072).Curated1
Sequence conflicti224I → V in BAC41072 (PubMed:16141072).Curated1
Sequence conflicti272F → L in BAC41072 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0230081 – 526Missing in isoform 3. 1 PublicationAdd BLAST526
Alternative sequenceiVSP_0230091 – 453Missing in isoform 2. 1 PublicationAdd BLAST453
Alternative sequenceiVSP_023010454 – 514GILDY…PHSGW → MAAWDLGVSYGWAQPPLLLG AFSAWCPYSDYCCLFTPAAS SPHPSAPPDFLTCLLCLPR in isoform 2. 1 PublicationAdd BLAST61

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK052930 mRNA. Translation: BAC35207.1.
AK090059 mRNA. Translation: BAC41072.1. Frameshift.
BC025890 mRNA. Translation: AAH25890.1.
BC069857 mRNA. Translation: AAH69857.1.
CCDSiCCDS40203.1. [Q8BWC0-1]
RefSeqiNP_666318.2. NM_146206.5. [Q8BWC0-1]
UniGeneiMm.102235.

Genome annotation databases

EnsembliENSMUST00000058022; ENSMUSP00000061308; ENSMUSG00000048677. [Q8BWC0-1]
GeneIDi233979.
KEGGimmu:233979.
UCSCiuc009kqw.1. mouse. [Q8BWC0-2]
uc009kqx.1. mouse. [Q8BWC0-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK052930 mRNA. Translation: BAC35207.1.
AK090059 mRNA. Translation: BAC41072.1. Frameshift.
BC025890 mRNA. Translation: AAH25890.1.
BC069857 mRNA. Translation: AAH69857.1.
CCDSiCCDS40203.1. [Q8BWC0-1]
RefSeqiNP_666318.2. NM_146206.5. [Q8BWC0-1]
UniGeneiMm.102235.

3D structure databases

ProteinModelPortaliQ8BWC0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000061308.

PTM databases

PhosphoSitePlusiQ8BWC0.

Proteomic databases

PaxDbiQ8BWC0.
PRIDEiQ8BWC0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000058022; ENSMUSP00000061308; ENSMUSG00000048677. [Q8BWC0-1]
GeneIDi233979.
KEGGimmu:233979.
UCSCiuc009kqw.1. mouse. [Q8BWC0-2]
uc009kqx.1. mouse. [Q8BWC0-1]

Organism-specific databases

CTDi219931.
MGIiMGI:2385297. Tpcn2.

Phylogenomic databases

eggNOGiENOG410KCTV. Eukaryota.
ENOG4111V21. LUCA.
GeneTreeiENSGT00530000063660.
HOGENOMiHOG000154668.
HOVERGENiHBG079776.
InParanoidiQ8BWC0.
KOiK14077.
OMAiFVFGHYY.
OrthoDBiEOG091G045K.
PhylomeDBiQ8BWC0.
TreeFamiTF328550.

Enzyme and pathway databases

ReactomeiR-MMU-2672351. Stimuli-sensing channels.

Miscellaneous databases

PROiQ8BWC0.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000048677.
CleanExiMM_TPCN2.
ExpressionAtlasiQ8BWC0. baseline and differential.
GenevisibleiQ8BWC0. MM.

Family and domain databases

Gene3Di1.20.120.350. 1 hit.
InterProiIPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
[Graphical view]
PfamiPF00520. Ion_trans. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTPC2_MOUSE
AccessioniPrimary (citable) accession number: Q8BWC0
Secondary accession number(s): Q6NSV0, Q8BTJ7, Q8R396
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 6, 2007
Last sequence update: March 1, 2003
Last modified: November 30, 2016
This is version 110 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.