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Q8BWC0

- TPC2_MOUSE

UniProt

Q8BWC0 - TPC2_MOUSE

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Protein
Two pore calcium channel protein 2
Gene
Tpcn2, Tpc2
Organism
Mus musculus (Mouse)
Status
Reviewed - 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

  1. NAADP-sensitive calcium-release channel activity Source: UniProtKB
  2. voltage-gated calcium channel activity Source: UniProtKB

GO - Biological processi

  1. membrane depolarization during action potential Source: RefGenome
  2. release of sequestered calcium ion into cytosol Source: UniProtKB
  3. 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

ReactomeiREACT_196640. 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
ProteomesiUP000000589: Chromosome 7

Organism-specific databases

MGIiMGI:2385297. Tpcn2.

Subcellular locationi

Lysosome membrane; Multi-pass membrane protein
Note: Only the acidic lysosomal fraction is sensitive to NAADP.2 Publications

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 6868Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei69 – 8921Helical; Name=S1 of repeat I; Reviewed prediction
Add
BLAST
Topological domaini90 – 11122Extracellular Reviewed prediction
Add
BLAST
Transmembranei112 – 13221Helical; Name=S2 of repeat I; Reviewed prediction
Add
BLAST
Topological domaini133 – 1397Cytoplasmic Reviewed prediction
Transmembranei140 – 16021Helical; Name=S3 of repeat I; Reviewed prediction
Add
BLAST
Topological domaini161 – 1677Extracellular Reviewed prediction
Transmembranei168 – 18821Helical; Name=S4 of repeat I; Reviewed prediction
Add
BLAST
Topological domaini189 – 20315Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei204 – 22421Helical; Name=S5 of repeat I; Reviewed prediction
Add
BLAST
Topological domaini225 – 23814Extracellular Reviewed prediction
Add
BLAST
Intramembranei239 – 26325Helical; Pore-forming; Reviewed prediction
Add
BLAST
Topological domaini264 – 2707Extracellular Reviewed prediction
Transmembranei271 – 29121Helical; Name=S6 of repeat I; Reviewed prediction
Add
BLAST
Topological domaini292 – 417126Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei418 – 43821Helical; Name=S1 of repeat II; Reviewed prediction
Add
BLAST
Topological domaini439 – 44911Extracellular Reviewed prediction
Add
BLAST
Transmembranei450 – 47021Helical; Name=S2 of repeat II; Reviewed prediction
Add
BLAST
Topological domaini471 – 48616Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei487 – 50721Helical; Name=S3 of repeat II; Reviewed prediction
Add
BLAST
Topological domaini508 – 52417Extracellular Reviewed prediction
Add
BLAST
Transmembranei525 – 54218Helical; Name=S4 of repeat II; Reviewed prediction
Add
BLAST
Topological domaini543 – 56422Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei565 – 58521Helical; Name=S5 of repeat II; Reviewed prediction
Add
BLAST
Topological domaini586 – 61833Extracellular Reviewed prediction
Add
BLAST
Intramembranei619 – 64123Helical; Pore-forming; Reviewed prediction
Add
BLAST
Topological domaini642 – 65615Extracellular Reviewed prediction
Add
BLAST
Transmembranei657 – 67721Helical; Name=S6 of repeat II; Reviewed prediction
Add
BLAST
Topological domaini678 – 73154Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. endosome membrane Source: Ensembl
  2. integral component of membrane Source: UniProtKB-KW
  3. lysosomal membrane Source: UniProtKB
  4. lysosome Source: UniProtKB
  5. plasma membrane Source: RefGenome
Complete GO annotation...

Keywords - Cellular componenti

Lysosome, Membrane

Pathology & Biotechi

Disruption phenotypei

Loss of NAADP-mediated calcium release.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi257 – 2571N → A: Complete loss of selectivity for calcium over monocovalent cations. 1 Publication
Mutagenesisi594 – 5941N → A: Loss of N-glycosylation; when associated with N-601. 1 Publication
Mutagenesisi601 – 6011N → A: Loss of N-glycosylation; when associated with N-594. 1 Publication
Mutagenesisi643 – 6431E → A: Partial loss of selectivity for calcium over monocovalent cations. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 731731Two pore calcium channel protein 2
PRO_0000276857Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi594 – 5941N-linked (GlcNAc...)1 Publication
Glycosylationi601 – 6011N-linked (GlcNAc...)1 Publication

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Glycoprotein

Proteomic databases

PRIDEiQ8BWC0.

PTM databases

PhosphoSiteiQ8BWC0.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiQ8BWC0.
CleanExiMM_TPCN2.
GenevestigatoriQ8BWC0.

Interactioni

Subunit structurei

Homodimer. Interacts with LRRK2 By similarity.1 Publication

Structurei

3D structure databases

ProteinModelPortaliQ8BWC0.
SMRiQ8BWC0. Positions 199-301, 569-692.

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.

Sequence similaritiesi

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG299468.
GeneTreeiENSGT00530000063660.
HOGENOMiHOG000154668.
HOVERGENiHBG079776.
InParanoidiQ8BWC0.
KOiK14077.
OMAiSSVIWVN.
OrthoDBiEOG72ZCDF.
PhylomeDBiQ8BWC0.
TreeFamiTF328550.

Family and domain databases

Gene3Di1.20.120.350. 1 hit.
InterProiIPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
IPR028798. TPC2.
[Graphical view]
PANTHERiPTHR10037:SF175. PTHR10037:SF175. 1 hit.
PfamiPF00520. Ion_trans. 2 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

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

MAAEEQPLLG RDRGSGQVHS GAAADQELCI DQAVVFIEDA IKYRSIYHRM    50
DAGSLWLYRW YYSNVCQRVL GFIIFLILIL AFVEVPSSFT KTADVRYRSQ 100
PWQPPCGLTE TIEAFCLLAF LVDLSVKGYL VGQAQLQQNL WLLAYFMVLV 150
VSVVDWIVSL SLACEEPLRM RRLLRPFFLL QNSSMMKKTL KCIRWSLPEM 200
ASVGLLLAIH LCLFTIIGML LFTIGEKDEA QDQERLAYFR NLPEALTSLL 250
VLLTTSNNPD VMIPAYTQNR AFALFFIVFT LIGSLFLMNL LTAIIYNQFR 300
GYLMKSLQTS LFRRRLGARA AYEVLASRAG PAGTTPELVG VNPETFLPVL 350
QKTQLNKTHK QAIMQKVQSY EGRPMLADEF QKLFDEVDKG LAKERPLKPQ 400
YQSPFLQTAQ FIFSHHYFDY LGNLVALGNL LSICVFLVLD SDLLPGERDD 450
FVLGILDYIF ILYYLLELLF KVFALGLPGY LSYHSNVFDG LLTIILLVSE 500
ICTLAVYRLP HSGWKPEQYG PLSLWDMTRL MNTLIVFRFL RIIPNIKPMA 550
EVANTILGLI PNLRAFGGIL VVAYYVFAMI GINLFRGVIV PPGNSSLVPD 600
NNSAVCGSFE QLGYWPNNFD DFAAALITLW NVMVVNNWQV ILEAYKRYAG 650
PWSMVYFVLW WLVSSVIWIN LFLALLLENF LHRWDPQGHK QLLVGTKQMS 700
VELMFRDILE EPKEEELMEK LHKHPHLHLC R 731
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 BAC41072.1 differs from that shown. Reason: Frameshift at position 318.

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 526526Missing in isoform 3.
VSP_023008Add
BLAST
Alternative sequencei1 – 453453Missing in isoform 2.
VSP_023009Add
BLAST
Alternative sequencei454 – 51461GILDY…PHSGW → MAAWDLGVSYGWAQPPLLLG AFSAWCPYSDYCCLFTPAAS SPHPSAPPDFLTCLLCLPR in isoform 2.
VSP_023010Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti127 – 1271K → E in BAC41072. 1 Publication
Sequence conflicti224 – 2241I → V in BAC41072. 1 Publication
Sequence conflicti272 – 2721F → L in BAC41072. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_146206.4. [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:
EMBL
GenBank
DDBJ
Links Updated
AK052930 mRNA. Translation: BAC35207.1 .
AK090059 mRNA. Translation: BAC41072.1 . Frameshift.
BC025890 mRNA. Translation: AAH25890.1 .
BC069857 mRNA. Translation: AAH69857.1 .
CCDSi CCDS40203.1. [Q8BWC0-1 ]
RefSeqi NP_666318.2. NM_146206.4. [Q8BWC0-1 ]
UniGenei Mm.102235.

3D structure databases

ProteinModelPortali Q8BWC0.
SMRi Q8BWC0. Positions 199-301, 569-692.
ModBasei Search...
MobiDBi Search...

PTM databases

PhosphoSitei Q8BWC0.

Proteomic databases

PRIDEi Q8BWC0.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000058022 ; ENSMUSP00000061308 ; ENSMUSG00000048677 . [Q8BWC0-1 ]
GeneIDi 233979.
KEGGi mmu:233979.
UCSCi uc009kqw.1. mouse. [Q8BWC0-2 ]
uc009kqx.1. mouse. [Q8BWC0-1 ]

Organism-specific databases

CTDi 219931.
MGIi MGI:2385297. Tpcn2.

Phylogenomic databases

eggNOGi NOG299468.
GeneTreei ENSGT00530000063660.
HOGENOMi HOG000154668.
HOVERGENi HBG079776.
InParanoidi Q8BWC0.
KOi K14077.
OMAi SSVIWVN.
OrthoDBi EOG72ZCDF.
PhylomeDBi Q8BWC0.
TreeFami TF328550.

Enzyme and pathway databases

Reactomei REACT_196640. Stimuli-sensing channels.

Miscellaneous databases

ChiTaRSi TPCN2. mouse.
NextBioi 381977.
PROi Q8BWC0.
SOURCEi Search...

Gene expression databases

Bgeei Q8BWC0.
CleanExi MM_TPCN2.
Genevestigatori Q8BWC0.

Family and domain databases

Gene3Di 1.20.120.350. 1 hit.
InterProi IPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
IPR028798. TPC2.
[Graphical view ]
PANTHERi PTHR10037:SF175. PTHR10037:SF175. 1 hit.
Pfami PF00520. Ion_trans. 2 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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.

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: September 3, 2014
This is version 91 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

External Data

Dasty 3

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