Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q8BWC0

- TPC2_MOUSE

UniProt

Q8BWC0 - TPC2_MOUSE

Protein

Two pore calcium channel protein 2

Gene

Tpcn2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 92 (01 Oct 2014)
      Sequence version 1 (01 Mar 2003)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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

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

    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

    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 2PRO_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.By similarity

    Structurei

    3D structure databases

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

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 6868CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini90 – 11122ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini133 – 1397CytoplasmicSequence Analysis
    Topological domaini161 – 1677ExtracellularSequence Analysis
    Topological domaini189 – 20315CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini225 – 23814ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini264 – 2707ExtracellularSequence Analysis
    Topological domaini292 – 417126CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini439 – 44911ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini471 – 48616CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini508 – 52417ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini543 – 56422CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini586 – 61833ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini642 – 65615ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini678 – 73154CytoplasmicSequence AnalysisAdd
    BLAST

    Intramembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Intramembranei239 – 26325Helical; Pore-formingSequence AnalysisAdd
    BLAST
    Intramembranei619 – 64123Helical; Pore-formingSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei69 – 8921Helical; Name=S1 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei112 – 13221Helical; Name=S2 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei140 – 16021Helical; Name=S3 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei168 – 18821Helical; Name=S4 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei204 – 22421Helical; Name=S5 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei271 – 29121Helical; Name=S6 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei418 – 43821Helical; Name=S1 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei450 – 47021Helical; Name=S2 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei487 – 50721Helical; Name=S3 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei525 – 54218Helical; Name=S4 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei565 – 58521Helical; Name=S5 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei657 – 67721Helical; Name=S6 of repeat IISequence AnalysisAdd
    BLAST

    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

    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.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti127 – 1271K → E in BAC41072. (PubMed:16141072)Curated
    Sequence conflicti224 – 2241I → V in BAC41072. (PubMed:16141072)Curated
    Sequence conflicti272 – 2721F → L in BAC41072. (PubMed:16141072)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 526526Missing in isoform 3. 1 PublicationVSP_023008Add
    BLAST
    Alternative sequencei1 – 453453Missing in isoform 2. 1 PublicationVSP_023009Add
    BLAST
    Alternative sequencei454 – 51461GILDY…PHSGW → MAAWDLGVSYGWAQPPLLLG AFSAWCPYSDYCCLFTPAAS SPHPSAPPDFLTCLLCLPR in isoform 2. 1 PublicationVSP_023010Add
    BLAST

    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

    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: October 1, 2014
    This is version 92 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