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Q8BWC0

- TPC2_MOUSE

UniProt

Q8BWC0 - TPC2_MOUSE

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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

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

Topology

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

MaxQBiQ8BWC0.
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...

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

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

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:
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_146206.4. [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:
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 .
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

MaxQBi Q8BWC0.
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

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: November 26, 2014
This is version 94 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