TPC2_MOUSE
ID TPC2_MOUSE Reviewed; 731 AA.
AC Q8BWC0; Q6NSV0; Q8BTJ7; Q8R396;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Two pore channel protein 2;
DE AltName: Full=Two pore calcium channel protein 2 {ECO:0000305};
DE AltName: Full=Voltage-dependent calcium channel protein TPC2;
GN Name=Tpcn2 {ECO:0000312|MGI:MGI:2385297}; Synonyms=Tpc2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, and Heart;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC STRAIN=Czech II; TISSUE=Eye, and Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19387438; DOI=10.1038/nature08030;
RA Calcraft P.J., Ruas M., Pan Z., Cheng X., Arredouani A., Hao X., Tang J.,
RA Rietdorf K., Teboul L., Chuang K.T., Lin P., Xiao R., Wang C., Zhu Y.,
RA Lin Y., Wyatt C.N., Parrington J., Ma J., Evans A.M., Galione A., Zhu M.X.;
RT "NAADP mobilizes calcium from acidic organelles through two-pore
RT channels.";
RL Nature 459:596-600(2009).
RN [4]
RP GLYCOSYLATION AT ASN-594 AND ASN-601, SUBCELLULAR LOCATION, SUBUNIT, TISSUE
RP SPECIFICITY, TOPOLOGY, AND MUTAGENESIS OF ASN-594 AND ASN-601.
RX PubMed=19557428; DOI=10.1007/s00424-009-0690-y;
RA Zong X., Schieder M., Cuny H., Fenske S., Gruner C., Roetzer K.,
RA Griesbeck O., Harz H., Biel M., Wahl-Schott C.;
RT "The two-pore channel TPCN2 mediates NAADP-dependent Ca(2+)-release from
RT lysosomal stores.";
RL Pflugers Arch. 458:891-899(2009).
RN [5]
RP FUNCTION, MUTAGENESIS OF ASN-257 AND GLU-643, AND SUBCELLULAR LOCATION.
RX PubMed=20495006; DOI=10.1074/jbc.c110.143123;
RA Schieder M., Roetzer K., Brueggemann A., Biel M., Wahl-Schott C.A.;
RT "Characterizatgmion of two-pore channel 2 (TPCN2)-mediated Ca2+ currents in
RT isolated lysosomes.";
RL J. Biol. Chem. 285:21219-21222(2010).
RN [6]
RP FUNCTION.
RX PubMed=20547763; DOI=10.1074/jbc.m110.129833;
RA Tugba Durlu-Kandilci N., Ruas M., Chuang K.T., Brading A., Parrington J.,
RA Galione A.;
RT "TPC2 proteins mediate nicotinic acid adenine dinucleotide phosphate
RT (NAADP)- and agonist-evoked contractions of smooth muscle.";
RL J. Biol. Chem. 285:24925-24932(2010).
RN [7]
RP FUNCTION.
RX PubMed=23063126; DOI=10.1016/j.cell.2012.08.036;
RA Wang X., Zhang X., Dong X.P., Samie M., Li X., Cheng X., Goschka A.,
RA Shen D., Zhou Y., Harlow J., Zhu M.X., Clapham D.E., Ren D., Xu H.;
RT "TPC proteins are phosphoinositide- activated sodium-selective ion channels
RT in endosomes and lysosomes.";
RL Cell 151:372-383(2012).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23394946; DOI=10.1016/j.cell.2013.01.023;
RA Cang C., Zhou Y., Navarro B., Seo Y.J., Aranda K., Shi L.,
RA Battaglia-Hsu S., Nissim I., Clapham D.E., Ren D.;
RT "mTOR regulates lysosomal ATP-sensitive two-pore Na(+) channels to adapt to
RT metabolic state.";
RL Cell 152:778-790(2013).
RN [9]
RP FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND CATALYTIC
RP ACTIVITY.
RX PubMed=25144390; DOI=10.1038/ncomms5699;
RA Grimm C., Holdt L.M., Chen C.C., Hassan S., Mueller C., Joers S., Cuny H.,
RA Kissing S., Schroeder B., Butz E., Northoff B., Castonguay J., Luber C.A.,
RA Moser M., Spahn S., Luellmann-Rauch R., Fendel C., Klugbauer N.,
RA Griesbeck O., Haas A., Mann M., Bracher F., Teupser D., Saftig P., Biel M.,
RA Wahl-Schott C.;
RT "High susceptibility to fatty liver disease in two-pore channel 2-deficient
RT mice.";
RL Nat. Commun. 5:4699-4699(2014).
RN [10]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=25722412; DOI=10.1126/science.1258758;
RA Sakurai Y., Kolokoltsov A.A., Chen C.C., Tidwell M.W., Bauta W.E.,
RA Klugbauer N., Grimm C., Wahl-Schott C., Biel M., Davey R.A.;
RT "Ebola virus. Two-pore channels control Ebola virus host cell entry and are
RT drug targets for disease treatment.";
RL Science 347:995-998(2015).
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=32167471; DOI=10.7554/elife.54712;
RA Gerndt S., Chen C.C., Chao Y.K., Yuan Y., Burgstaller S., Scotto Rosato A.,
RA Krogsaeter E., Urban N., Jacob K., Nguyen O.N.P., Miller M.T., Keller M.,
RA Vollmar A.M., Gudermann T., Zierler S., Schredelseker J., Schaefer M.,
RA Biel M., Malli R., Wahl-Schott C., Bracher F., Patel S., Grimm C.;
RT "Agonist-mediated switching of ion selectivity in TPC2 differentially
RT promotes lysosomal function.";
RL Elife 9:0-0(2020).
CC -!- FUNCTION: Intracellular channel initially characterized as a non-
CC selective Ca(2+)-permeable channel activated by NAADP (nicotinic acid
CC adenine dinucleotide phosphate), it is also a highly-selective Na(+)
CC channel activated directly by PI(3,5)P2 (phosphatidylinositol 3,5-
CC bisphosphate) (PubMed:19387438, PubMed:20495006, PubMed:20547763,
CC PubMed:25144390). Localizes to the lysosomal and late endosome
CC membranes where it regulates organellar membrane excitability, membrane
CC trafficking, and pH homeostasis. Is associated with a plethora of
CC physiological processes, including mTOR-dependent nutrient sensing,
CC skin pigmentation and autophagy (PubMed:25144390, PubMed:23394946,
CC PubMed:23063126). Ion selectivity is not fixed but rather agonist-
CC dependent and under defined ionic conditions, can be readily activated
CC by both NAADP and PI(3,5)P2. As calcium channel, it increases the pH in
CC the lysosomal lumen, as sodium channel, it promotes lysosomal
CC exocytosis (PubMed:32167471). Plays a crucial role in endolysosomal
CC trafficking in the endolysosomal degradation pathway and is potentially
CC involved in the homeostatic control of many macromolecules and cell
CC metabolites (PubMed:25144390). Unlike the voltage-dependent TPCN1,
CC TPCN2 is voltage independent and can be activated solely by PI(3,5)P2
CC binding. In contrast, PI(4,5)P2, PI(3,4)P2, PI(3)P and PI(5)P have no
CC obvious effect on channel activation (By similarity).
CC {ECO:0000250|UniProtKB:Q8NHX9, ECO:0000269|PubMed:19387438,
CC ECO:0000269|PubMed:20495006, ECO:0000269|PubMed:20547763,
CC ECO:0000269|PubMed:23063126, ECO:0000269|PubMed:23394946,
CC ECO:0000269|PubMed:25144390, ECO:0000269|PubMed:32167471}.
CC -!- FUNCTION: (Microbial infection) During Ebola virus (EBOV) infection,
CC controls the movement of endosomes containing virus particles and is
CC required by EBOV to escape from the endosomal network into the cell
CC cytoplasm. {ECO:0000269|PubMed:25722412}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Ca(2+)(in) = Ca(2+)(out); Xref=Rhea:RHEA:29671,
CC ChEBI:CHEBI:29108; Evidence={ECO:0000269|PubMed:25144390};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:29673;
CC Evidence={ECO:0000269|PubMed:25144390};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Na(+)(in) = Na(+)(out); Xref=Rhea:RHEA:34963,
CC ChEBI:CHEBI:29101; Evidence={ECO:0000250|UniProtKB:Q8NHX9};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:34965;
CC Evidence={ECO:0000250|UniProtKB:Q8NHX9};
CC -!- ACTIVITY REGULATION: Regulated by Mg(2+) ions, cytosolic Mg(2+)
CC selectively inhibits outward current while lysosomal Mg(2+) modestly
CC inhibits both the outward and inward currents. In the absence of
CC Mg(2+), NAADP readily activates TPCN2, with properties similar to
CC PI(3,5)P2 (By similarity). Na(+) current is inhibited by ATP in a
CC MTORC-dependent manner. ATP sensitivity is independent of PI(3,5)P2
CC (PubMed:23394946). Both current elicited by PI(3,5)P2 as well as NAADP
CC are inhibited by tetrandrine. {ECO:0000250|UniProtKB:Q8NHX9,
CC ECO:0000269|PubMed:23394946, ECO:0000269|PubMed:25722412}.
CC -!- SUBUNIT: Homodimer (Probable). Interacts with LRRK2. Interacts with
CC HAX1. Interacts with MTOR; the interaction is required for TPCN2 ATP
CC sensitivity (By similarity). Found in a complex with LSM12, TPCN1 and
CC TPCN2 (By similarity). Interacts with LSM12 (By similarity).
CC {ECO:0000250|UniProtKB:Q8NHX9, ECO:0000305|PubMed:19557428}.
CC -!- SUBCELLULAR LOCATION: Late endosome membrane
CC {ECO:0000305|PubMed:25144390}; Multi-pass membrane protein
CC {ECO:0000255}. Lysosome membrane {ECO:0000269|PubMed:19557428,
CC ECO:0000269|PubMed:20495006, ECO:0000269|PubMed:25144390,
CC ECO:0000269|PubMed:32167471}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:19557428, ECO:0000269|PubMed:20495006}. Note=Only
CC the acidic lysosomal fraction is sensitive to NAADP.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8BWC0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BWC0-2; Sequence=VSP_023009, VSP_023010;
CC Name=3;
CC IsoId=Q8BWC0-3; Sequence=VSP_023008;
CC -!- TISSUE SPECIFICITY: Widely expressed. Highly expressed in macrophages
CC (PubMed:32167471). {ECO:0000269|PubMed:19557428,
CC ECO:0000269|PubMed:32167471}.
CC -!- DOMAIN: Each of the two internal repeats contains five hydrophobic
CC transmembrane segments (S1, S2, S3, S5, S6) and one positively charged
CC transmembrane segment (S4). S4 segments probably represent the voltage-
CC sensor and are characterized by a series of positively charged amino
CC acids at every third position (By similarity). {ECO:0000250}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:19557428}.
CC -!- DISRUPTION PHENOTYPE: Loss of NAADP-mediated calcium release
CC (PubMed:19387438). Mutant mice are highly susceptible to hepatic
CC cholesterol overload, have hyperlipoproteinaemia and liver damage
CC consistent with non-alcoholic fatty liver hepatitis (PubMed:25144390).
CC TPCN1 and TPCN2 double knockouts are viable, fertile, have no obvious
CC morphological abnormalities, and no obvious behavioral defects. After
CC fasting for 3 days, they are less active and endurance performance is
CC reduced by 8.3 fold in contrast to wild-type littermates that show no
CC changes. Two days after re-introduction of food, mutants regain
CC endurance and become as active as before fasting (PubMed:23394946).
CC {ECO:0000269|PubMed:19387438, ECO:0000269|PubMed:23394946,
CC ECO:0000269|PubMed:25144390}.
CC -!- SIMILARITY: Belongs to the calcium channel alpha-1 subunit (TC
CC 1.A.1.11) family. Two pore calcium channel subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC41072.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK052930; BAC35207.1; -; mRNA.
DR EMBL; AK090059; BAC41072.1; ALT_FRAME; mRNA.
DR EMBL; BC025890; AAH25890.1; -; mRNA.
DR EMBL; BC069857; AAH69857.1; -; mRNA.
DR CCDS; CCDS40203.1; -. [Q8BWC0-1]
DR RefSeq; NP_666318.2; NM_146206.5. [Q8BWC0-1]
DR AlphaFoldDB; Q8BWC0; -.
DR SMR; Q8BWC0; -.
DR BioGRID; 231481; 1.
DR STRING; 10090.ENSMUSP00000061308; -.
DR GlyGen; Q8BWC0; 2 sites.
DR iPTMnet; Q8BWC0; -.
DR PhosphoSitePlus; Q8BWC0; -.
DR MaxQB; Q8BWC0; -.
DR PaxDb; Q8BWC0; -.
DR PRIDE; Q8BWC0; -.
DR ProteomicsDB; 258825; -. [Q8BWC0-1]
DR ProteomicsDB; 258826; -. [Q8BWC0-2]
DR ProteomicsDB; 258827; -. [Q8BWC0-3]
DR DNASU; 233979; -.
DR Ensembl; ENSMUST00000058022; ENSMUSP00000061308; ENSMUSG00000048677. [Q8BWC0-1]
DR GeneID; 233979; -.
DR KEGG; mmu:233979; -.
DR UCSC; uc009kqw.1; mouse. [Q8BWC0-2]
DR UCSC; uc009kqx.1; mouse. [Q8BWC0-1]
DR CTD; 219931; -.
DR MGI; MGI:2385297; Tpcn2.
DR VEuPathDB; HostDB:ENSMUSG00000048677; -.
DR eggNOG; KOG2301; Eukaryota.
DR GeneTree; ENSGT00940000159763; -.
DR HOGENOM; CLU_019500_1_0_1; -.
DR InParanoid; Q8BWC0; -.
DR OMA; FTESIEM; -.
DR OrthoDB; 761764at2759; -.
DR PhylomeDB; Q8BWC0; -.
DR TreeFam; TF328550; -.
DR Reactome; R-MMU-2672351; Stimuli-sensing channels.
DR BioGRID-ORCS; 233979; 2 hits in 73 CRISPR screens.
DR PRO; PR:Q8BWC0; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q8BWC0; protein.
DR Bgee; ENSMUSG00000048677; Expressed in granulocyte and 101 other tissues.
DR ExpressionAtlas; Q8BWC0; baseline and differential.
DR Genevisible; Q8BWC0; MM.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0036020; C:endolysosome membrane; ISS:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0097682; F:intracellular phosphatidylinositol-3,5-bisphosphate-sensitive cation channel activity; ISS:UniProtKB.
DR GO; GO:0015280; F:ligand-gated sodium channel activity; ISS:UniProtKB.
DR GO; GO:0072345; F:NAADP-sensitive calcium-release channel activity; IDA:UniProtKB.
DR GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; IMP:UniProtKB.
DR GO; GO:0019722; P:calcium-mediated signaling; IMP:UniProtKB.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISO:MGI.
DR GO; GO:0075509; P:endocytosis involved in viral entry into host cell; IMP:UniProtKB.
DR GO; GO:0090117; P:endosome to lysosome transport of low-density lipoprotein particle; IMP:UniProtKB.
DR GO; GO:0007040; P:lysosome organization; ISO:MGI.
DR GO; GO:0019065; P:receptor-mediated endocytosis of virus by host cell; ISO:MGI.
DR GO; GO:0010506; P:regulation of autophagy; ISO:MGI.
DR GO; GO:0017157; P:regulation of exocytosis; IMP:UniProtKB.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IMP:UniProtKB.
DR GO; GO:0033280; P:response to vitamin D; IEA:Ensembl.
DR GO; GO:0006939; P:smooth muscle contraction; IMP:UniProtKB.
DR GO; GO:0035725; P:sodium ion transmembrane transport; ISS:UniProtKB.
DR Gene3D; 1.20.120.350; -; 2.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR028798; TPC2.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR46768; PTHR46768; 1.
DR Pfam; PF00520; Ion_trans; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Calcium channel; Calcium transport;
KW Endosome; Glycoprotein; Ion channel; Ion transport; Lysosome; Membrane;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport;
KW Voltage-gated channel.
FT CHAIN 1..731
FT /note="Two pore channel protein 2"
FT /id="PRO_0000276857"
FT TOPO_DOM 1..68
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 69..89
FT /note="Helical; Name=S1 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 90..111
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 112..132
FT /note="Helical; Name=S2 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 133..139
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 140..160
FT /note="Helical; Name=S3 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 161..167
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 168..188
FT /note="Helical; Name=S4 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 189..203
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 204..224
FT /note="Helical; Name=S5 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 225..238
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 239..263
FT /note="Helical; Pore-forming"
FT /evidence="ECO:0000255"
FT TOPO_DOM 264..270
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 271..291
FT /note="Helical; Name=S6 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 292..417
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 418..438
FT /note="Helical; Name=S1 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 439..449
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 450..470
FT /note="Helical; Name=S2 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 471..486
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 487..507
FT /note="Helical; Name=S3 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 508..524
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 525..542
FT /note="Helical; Name=S4 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 543..564
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 565..585
FT /note="Helical; Name=S5 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 586..618
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 619..641
FT /note="Helical; Pore-forming"
FT /evidence="ECO:0000255"
FT TOPO_DOM 642..656
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 657..677
FT /note="Helical; Name=S6 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 678..731
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 187..191
FT /note="Interaction with phosphatidylinositol 3,5-
FT bisphosphate"
FT /evidence="ECO:0000250|UniProtKB:Q8NHX9"
FT CARBOHYD 594
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19557428"
FT CARBOHYD 601
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19557428"
FT VAR_SEQ 1..526
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023008"
FT VAR_SEQ 1..453
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023009"
FT VAR_SEQ 454..514
FT /note="GILDYIFILYYLLELLFKVFALGLPGYLSYHSNVFDGLLTIILLVSEICTLA
FT VYRLPHSGW -> MAAWDLGVSYGWAQPPLLLGAFSAWCPYSDYCCLFTPAASSPHPSA
FT PPDFLTCLLCLPR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023010"
FT MUTAGEN 257
FT /note="N->A: Complete loss of selectivity for calcium over
FT monocovalent cations."
FT /evidence="ECO:0000269|PubMed:20495006"
FT MUTAGEN 594
FT /note="N->A: Loss of N-glycosylation; when associated with
FT N-601."
FT /evidence="ECO:0000269|PubMed:19557428"
FT MUTAGEN 601
FT /note="N->A: Loss of N-glycosylation; when associated with
FT N-594."
FT /evidence="ECO:0000269|PubMed:19557428"
FT MUTAGEN 643
FT /note="E->A: Partial loss of selectivity for calcium over
FT monocovalent cations."
FT /evidence="ECO:0000269|PubMed:20495006"
FT CONFLICT 127
FT /note="K -> E (in Ref. 1; BAC41072)"
FT /evidence="ECO:0000305"
FT CONFLICT 224
FT /note="I -> V (in Ref. 1; BAC41072)"
FT /evidence="ECO:0000305"
FT CONFLICT 272
FT /note="F -> L (in Ref. 1; BAC41072)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 731 AA; 83595 MW; 3C76487441344AD7 CRC64;
MAAEEQPLLG RDRGSGQVHS GAAADQELCI DQAVVFIEDA IKYRSIYHRM DAGSLWLYRW
YYSNVCQRVL GFIIFLILIL AFVEVPSSFT KTADVRYRSQ PWQPPCGLTE TIEAFCLLAF
LVDLSVKGYL VGQAQLQQNL WLLAYFMVLV VSVVDWIVSL SLACEEPLRM RRLLRPFFLL
QNSSMMKKTL KCIRWSLPEM ASVGLLLAIH LCLFTIIGML LFTIGEKDEA QDQERLAYFR
NLPEALTSLL VLLTTSNNPD VMIPAYTQNR AFALFFIVFT LIGSLFLMNL LTAIIYNQFR
GYLMKSLQTS LFRRRLGARA AYEVLASRAG PAGTTPELVG VNPETFLPVL QKTQLNKTHK
QAIMQKVQSY EGRPMLADEF QKLFDEVDKG LAKERPLKPQ YQSPFLQTAQ FIFSHHYFDY
LGNLVALGNL LSICVFLVLD SDLLPGERDD FVLGILDYIF ILYYLLELLF KVFALGLPGY
LSYHSNVFDG LLTIILLVSE ICTLAVYRLP HSGWKPEQYG PLSLWDMTRL MNTLIVFRFL
RIIPNIKPMA EVANTILGLI PNLRAFGGIL VVAYYVFAMI GINLFRGVIV PPGNSSLVPD
NNSAVCGSFE QLGYWPNNFD DFAAALITLW NVMVVNNWQV ILEAYKRYAG PWSMVYFVLW
WLVSSVIWIN LFLALLLENF LHRWDPQGHK QLLVGTKQMS VELMFRDILE EPKEEELMEK
LHKHPHLHLC R
