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Protein

Two pore calcium channel protein 2

Gene

Tpcn2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

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

GO - Biological processi

Keywordsi

Molecular functionCalcium channel, Ion channel, Voltage-gated channel
Biological processCalcium transport, Ion transport, Transport
LigandCalcium

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:2385297 Tpcn2

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 – 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

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...) asparagine1 Publication1
Glycosylationi601N-linked (GlcNAc...) asparagine1 Publication1

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ8BWC0
PRIDEiQ8BWC0

PTM databases

iPTMnetiQ8BWC0
PhosphoSitePlusiQ8BWC0

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSMUSG00000048677 Expressed in 105 organ(s), highest expression level in bone marrow macrophage
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
OMAiPHPGWRP
OrthoDBiEOG091G045K
PhylomeDBiQ8BWC0
TreeFamiTF328550

Family and domain databases

Gene3Di1.20.120.350, 2 hits
InterProiView protein in InterPro
IPR005821 Ion_trans_dom
IPR028798 TPC2
IPR027359 Volt_channel_dom_sf
PANTHERiPTHR10037:SF92 PTHR10037:SF92, 1 hit
PfamiView protein in Pfam
PF00520 Ion_trans, 2 hits

Sequences (3+)i

Sequence statusi: Complete.

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

This entry has 3 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A140LJI3A0A140LJI3_MOUSE
Two pore calcium channel protein 2
Tpcn2
479Annotation score:
A0A140LIA1A0A140LIA1_MOUSE
Two pore calcium channel protein 2
Tpcn2
503Annotation score:
A0A140LHT5A0A140LHT5_MOUSE
Two pore calcium channel protein 2
Tpcn2
533Annotation score:
A0A140LJE2A0A140LJE2_MOUSE
Two pore calcium channel protein 2
Tpcn2
490Annotation score:
A0A140LIT7A0A140LIT7_MOUSE
Two pore calcium channel protein 2
Tpcn2
132Annotation score:

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

Similar proteinsi

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

iPTMnetiQ8BWC0
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
OMAiPHPGWRP
OrthoDBiEOG091G045K
PhylomeDBiQ8BWC0
TreeFamiTF328550

Enzyme and pathway databases

ReactomeiR-MMU-2672351 Stimuli-sensing channels

Miscellaneous databases

PROiPR:Q8BWC0
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000048677 Expressed in 105 organ(s), highest expression level in bone marrow macrophage
CleanExiMM_TPCN2
ExpressionAtlasiQ8BWC0 baseline and differential
GenevisibleiQ8BWC0 MM

Family and domain databases

Gene3Di1.20.120.350, 2 hits
InterProiView protein in InterPro
IPR005821 Ion_trans_dom
IPR028798 TPC2
IPR027359 Volt_channel_dom_sf
PANTHERiPTHR10037:SF92 PTHR10037:SF92, 1 hit
PfamiView protein in Pfam
PF00520 Ion_trans, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiTPC2_MOUSE
AccessioniPrimary (citable) accession number: Q8BWC0
Secondary accession number(s): Q6NSV0, Q8BTJ7, Q8R396
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 6, 2007
Last sequence update: March 1, 2003
Last modified: November 7, 2018
This is version 121 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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