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Q8BWC0 (TPC2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 77. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Two pore calcium channel protein 2
Alternative name(s):
Voltage-dependent calcium channel protein TPC2
Gene names
Name:Tpcn2
Synonyms:Tpc2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length731 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.3 Ref.5 Ref.6

Subunit structure

Homodimer. Interacts with LRRK2 By similarity. Ref.4

Subcellular location

Lysosome membrane; Multi-pass membrane protein. Note: Only the acidic lysosomal fraction is sensitive to NAADP. Ref.4 Ref.5

Tissue specificity

Widely expressed. Ref.4

Domain

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.

Post-translational modification

N-glycosylated. Ref.4

Disruption phenotype

Loss of NAADP-mediated calcium release. Ref.3

Sequence similarities

Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. Two pore calcium channel subfamily. [View classification]

Sequence caution

The sequence BAC41072.1 differs from that shown. Reason: Frameshift at position 318.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8BWC0-1)

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.
Isoform 2 (identifier: Q8BWC0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-453: Missing.
     454-514: GILDYIFILY...AVYRLPHSGW → MAAWDLGVSY...FLTCLLCLPR
Isoform 3 (identifier: Q8BWC0-3)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 731731Two pore calcium channel protein 2
PRO_0000276857

Regions

Topological domain1 – 6868Cytoplasmic Potential
Transmembrane69 – 8921Helical; Name=S1 of repeat I; Potential
Topological domain90 – 11122Extracellular Potential
Transmembrane112 – 13221Helical; Name=S2 of repeat I; Potential
Topological domain133 – 1397Cytoplasmic Potential
Transmembrane140 – 16021Helical; Name=S3 of repeat I; Potential
Topological domain161 – 1677Extracellular Potential
Transmembrane168 – 18821Helical; Name=S4 of repeat I; Potential
Topological domain189 – 20315Cytoplasmic Potential
Transmembrane204 – 22421Helical; Name=S5 of repeat I; Potential
Topological domain225 – 23814Extracellular Potential
Intramembrane239 – 26325Helical; Pore-forming; Potential
Topological domain264 – 2707Extracellular Potential
Transmembrane271 – 29121Helical; Name=S6 of repeat I; Potential
Topological domain292 – 417126Cytoplasmic Potential
Transmembrane418 – 43821Helical; Name=S1 of repeat II; Potential
Topological domain439 – 44911Extracellular Potential
Transmembrane450 – 47021Helical; Name=S2 of repeat II; Potential
Topological domain471 – 48616Cytoplasmic Potential
Transmembrane487 – 50721Helical; Name=S3 of repeat II; Potential
Topological domain508 – 52417Extracellular Potential
Transmembrane525 – 54218Helical; Name=S4 of repeat II; Potential
Topological domain543 – 56422Cytoplasmic Potential
Transmembrane565 – 58521Helical; Name=S5 of repeat II; Potential
Topological domain586 – 61833Extracellular Potential
Intramembrane619 – 64123Helical; Pore-forming; Potential
Topological domain642 – 65615Extracellular Potential
Transmembrane657 – 67721Helical; Name=S6 of repeat II; Potential
Topological domain678 – 73154Cytoplasmic Potential

Amino acid modifications

Glycosylation5941N-linked (GlcNAc...) Ref.4
Glycosylation6011N-linked (GlcNAc...) Ref.4

Natural variations

Alternative sequence1 – 526526Missing in isoform 3.
VSP_023008
Alternative sequence1 – 453453Missing in isoform 2.
VSP_023009
Alternative sequence454 – 51461GILDY…PHSGW → MAAWDLGVSYGWAQPPLLLG AFSAWCPYSDYCCLFTPAAS SPHPSAPPDFLTCLLCLPR in isoform 2.
VSP_023010

Experimental info

Mutagenesis2571N → A: Complete loss of selectivity for calcium over monocovalent cations. Ref.5
Mutagenesis5941N → A: Loss of N-glycosylation; when associated with N-601. Ref.4
Mutagenesis6011N → A: Loss of N-glycosylation; when associated with N-594. Ref.4
Mutagenesis6431E → A: Partial loss of selectivity for calcium over monocovalent cations. Ref.5
Sequence conflict1271K → E in BAC41072. Ref.1
Sequence conflict2241I → V in BAC41072. Ref.1
Sequence conflict2721F → L in BAC41072. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 1, 2003. Version 1.
Checksum: 3C76487441344AD7

FASTA73183,595
        10         20         30         40         50         60 
MAAEEQPLLG RDRGSGQVHS GAAADQELCI DQAVVFIEDA IKYRSIYHRM DAGSLWLYRW 

        70         80         90        100        110        120 
YYSNVCQRVL GFIIFLILIL AFVEVPSSFT KTADVRYRSQ PWQPPCGLTE TIEAFCLLAF 

       130        140        150        160        170        180 
LVDLSVKGYL VGQAQLQQNL WLLAYFMVLV VSVVDWIVSL SLACEEPLRM RRLLRPFFLL 

       190        200        210        220        230        240 
QNSSMMKKTL KCIRWSLPEM ASVGLLLAIH LCLFTIIGML LFTIGEKDEA QDQERLAYFR 

       250        260        270        280        290        300 
NLPEALTSLL VLLTTSNNPD VMIPAYTQNR AFALFFIVFT LIGSLFLMNL LTAIIYNQFR 

       310        320        330        340        350        360 
GYLMKSLQTS LFRRRLGARA AYEVLASRAG PAGTTPELVG VNPETFLPVL QKTQLNKTHK 

       370        380        390        400        410        420 
QAIMQKVQSY EGRPMLADEF QKLFDEVDKG LAKERPLKPQ YQSPFLQTAQ FIFSHHYFDY 

       430        440        450        460        470        480 
LGNLVALGNL LSICVFLVLD SDLLPGERDD FVLGILDYIF ILYYLLELLF KVFALGLPGY 

       490        500        510        520        530        540 
LSYHSNVFDG LLTIILLVSE ICTLAVYRLP HSGWKPEQYG PLSLWDMTRL MNTLIVFRFL 

       550        560        570        580        590        600 
RIIPNIKPMA EVANTILGLI PNLRAFGGIL VVAYYVFAMI GINLFRGVIV PPGNSSLVPD 

       610        620        630        640        650        660 
NNSAVCGSFE QLGYWPNNFD DFAAALITLW NVMVVNNWQV ILEAYKRYAG PWSMVYFVLW 

       670        680        690        700        710        720 
WLVSSVIWIN LFLALLLENF LHRWDPQGHK QLLVGTKQMS VELMFRDILE EPKEEELMEK 

       730 
LHKHPHLHLC R

« Hide

Isoform 2 [UniParc].

Checksum: 4F77688937BFCE4A
Show »

FASTA27631,501
Isoform 3 [UniParc].

Checksum: DE59E952F4A6D049
Show »

FASTA20523,727

References

« Hide 'large scale' references
[1]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Strain: C57BL/6J.
Tissue: Bone marrow and Heart.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
Strain: Czech II.
Tissue: Eye and Mammary gland.
[3]"NAADP mobilizes calcium from acidic organelles through two-pore channels."
Calcraft P.J., Ruas M., Pan Z., Cheng X., Arredouani A., Hao X., Tang J., Rietdorf K., Teboul L., Chuang K.T., Lin P., Xiao R., Wang C., Zhu Y., Lin Y., Wyatt C.N., Parrington J., Ma J. expand/collapse author list , Evans A.M., Galione A., Zhu M.X.
Nature 459:596-600(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[4]"The two-pore channel TPCN2 mediates NAADP-dependent Ca(2+)-release from lysosomal stores."
Zong X., Schieder M., Cuny H., Fenske S., Gruner C., Roetzer K., Griesbeck O., Harz H., Biel M., Wahl-Schott C.
Pflugers Arch. 458:891-899(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-594 AND ASN-601, SUBCELLULAR LOCATION, SUBUNIT, TISSUE SPECIFICITY, TOPOLOGY, MUTAGENESIS OF ASN-594 AND ASN-601.
[5]"Characterizatgmion of two-pore channel 2 (TPCN2)-mediated Ca2+ currents in isolated lysosomes."
Schieder M., Roetzer K., Brueggemann A., Biel M., Wahl-Schott C.A.
J. Biol. Chem. 285:21219-21222(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF ASN-257 AND GLU-643, SUBCELLULAR LOCATION.
[6]"TPC2 proteins mediate nicotinic acid adenine dinucleotide phosphate (NAADP)- and agonist-evoked contractions of smooth muscle."
Tugba Durlu-Kandilci N., Ruas M., Chuang K.T., Brading A., Parrington J., Galione A.
J. Biol. Chem. 285:24925-24932(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AK052930 mRNA. Translation: BAC35207.1.
AK090059 mRNA. Translation: BAC41072.1. Frameshift.
BC025890 mRNA. Translation: AAH25890.1.
BC069857 mRNA. Translation: AAH69857.1.
IPIIPI00226229.
IPI00828406.
IPI00828561.
RefSeqNP_666318.2. NM_146206.4.
UniGeneMm.102235.

3D structure databases

ProteinModelPortalQ8BWC0.
SMRQ8BWC0. Positions 199-301.
ModBaseSearch...

PTM databases

PhosphoSiteQ8BWC0.

Proteomic databases

PRIDEQ8BWC0.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000058022; ENSMUSP00000061308; ENSMUSG00000048677.
GeneID233979.
KEGGmmu:233979.
UCSCuc009kqw.1. mouse.
uc009kqx.1. mouse.

Organism-specific databases

CTD219931.
MGIMGI:2385297. Tpcn2.

Phylogenomic databases

eggNOGNOG299468.
GeneTreeENSGT00530000063660.
HOGENOMHOG000154668.
HOVERGENHBG079776.
InParanoidQ8BWC0.
KOK14077.
OMALLSLWDM.
OrthoDBEOG4XWFXH.

Gene expression databases

BgeeQ8BWC0.
CleanExMM_TPCN2.
GenevestigatorQ8BWC0.

Family and domain databases

InterProIPR005821. Ion_trans_dom.
[Graphical view]
PfamPF00520. Ion_trans. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTPCN2. mouse.
NextBio381977.
SOURCESearch...

Entry information

Entry nameTPC2_MOUSE
AccessionPrimary (citable) accession number: Q8BWC0
Secondary accession number(s): Q6NSV0, Q8BTJ7, Q8R396
Entry history
Integrated into UniProtKB/Swiss-Prot: February 6, 2007
Last sequence update: March 1, 2003
Last modified: May 1, 2013
This is version 77 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

MGD cross-references

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

SIMILARITY comments

Index of protein domains and families

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