TPC1_HUMAN
ID TPC1_HUMAN Reviewed; 816 AA.
AC Q9ULQ1; A7E258; Q86XS9; Q8NC20;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 3.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Two pore channel protein 1 {ECO:0000305};
DE AltName: Full=Two pore calcium channel protein 1;
DE AltName: Full=Voltage-dependent calcium channel protein TPC1;
GN Name=TPCN1 {ECO:0000312|HGNC:HGNC:18182};
GN Synonyms=KIAA1169, TPC1 {ECO:0000303|PubMed:24776928,
GN ECO:0000303|PubMed:25722412};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=10574461; DOI=10.1093/dnares/6.5.329;
RA Hirosawa M., Nagase T., Ishikawa K., Kikuno R., Nomura N., Ohara O.;
RT "Characterization of cDNA clones selected by the GeneMark analysis from
RT size-fractionated cDNA libraries from human brain.";
RL DNA Res. 6:329-336(1999).
RN [3]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [7]
RP FUNCTION, MUTAGENESIS OF LEU-273, AND SUBCELLULAR LOCATION.
RX PubMed=19620632; DOI=10.1083/jcb.200904073;
RA Brailoiu E., Churamani D., Cai X., Schrlau M.G., Brailoiu G.C., Gao X.,
RA Hooper R., Boulware M.J., Dun N.J., Marchant J.S., Patel S.;
RT "Essential requirement for two-pore channel 1 in NAADP-mediated calcium
RT signaling.";
RL J. Cell Biol. 186:201-209(2009).
RN [8]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF 740-LEU-LEU-741.
RX PubMed=20880839; DOI=10.1074/jbc.m110.162073;
RA Brailoiu E., Rahman T., Churamani D., Prole D.L., Brailoiu G.C., Hooper R.,
RA Taylor C.W., Patel S.;
RT "An NAADP-gated two-pore channel targeted to the plasma membrane uncouples
RT triggering from amplifying Ca2+ signals.";
RL J. Biol. Chem. 285:38511-38516(2010).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
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 [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH MTOR.
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 [11]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF 219-ARG--ARG-223 AND ARG-539,
RP AND DOMAIN.
RX PubMed=24776928; DOI=10.1038/nchembio.1522;
RA Cang C., Bekele B., Ren D.;
RT "The voltage-gated sodium channel TPC1 confers endolysosomal
RT excitability.";
RL Nat. Chem. Biol. 10:463-469(2014).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [13]
RP FUNCTION (MICROBIAL INFECTION), ACTIVITY REGULATION, AND SUBCELLULAR
RP LOCATION.
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 [14]
RP REVIEW OF FUNCTION.
RX PubMed=32679067; DOI=10.1016/j.tips.2020.06.002;
RA Jin X., Zhang Y., Alharbi A., Hanbashi A., Alhoshani A., Parrington J.;
RT "Targeting Two-Pore Channels: Current Progress and Future Challenges.";
RL Trends Pharmacol. Sci. 41:582-594(2020).
RN [15]
RP INTERACTION WITH JPT2.
RX PubMed=33758061; DOI=10.1126/scisignal.abd5605;
RA Gunaratne G.S., Brailoiu E., He S., Unterwald E.M., Patel S., Slama J.T.,
RA Walseth T.F., Marchant J.S.;
RT "Essential requirement for JPT2 in NAADP-evoked Ca2+ signaling.";
RL Sci. Signal. 14:0-0(2021).
RN [16]
RP SUBUNIT.
RX PubMed=34362892; DOI=10.1038/s41467-021-24735-z;
RA Zhang J., Guan X., Shah K., Yan J.;
RT "Lsm12 is an NAADP receptor and a two-pore channel regulatory protein
RT required for calcium mobilization from acidic organelles.";
RL Nat. Commun. 12:4739-4739(2021).
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 voltage-gated highly-
CC selective Na(+) channel activated directly by PI(3,5)P2
CC (phosphatidylinositol 3,5-bisphosphate) that senses pH changes and
CC confers electrical excitability to organelles (PubMed:19620632,
CC PubMed:23063126, PubMed:24776928, PubMed:23394946). Localizes to the
CC early and recycling endosomes membranes where it plays a role in the
CC uptake and processing of proteins and regulates organellar membrane
CC excitability, membrane trafficking and pH homeostasis (PubMed:23394946)
CC (Probable). Ion selectivity is not fixed but rather agonist-dependent
CC and under defined ionic conditions, can be readily activated by both
CC NAADP and PI(3,5)P2 (Probable). Required for mTOR-dependent nutrient
CC sensing (PubMed:23394946) (Probable). {ECO:0000269|PubMed:19620632,
CC ECO:0000269|PubMed:23063126, ECO:0000269|PubMed:23394946,
CC ECO:0000269|PubMed:24776928, ECO:0000305|PubMed:32679067}.
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=Na(+)(in) = Na(+)(out); Xref=Rhea:RHEA:34963,
CC ChEBI:CHEBI:29101; Evidence={ECO:0000269|PubMed:23394946,
CC ECO:0000269|PubMed:24776928};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:34965;
CC Evidence={ECO:0000269|PubMed:23394946, ECO:0000269|PubMed:24776928};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Ca(2+)(in) = Ca(2+)(out); Xref=Rhea:RHEA:29671,
CC ChEBI:CHEBI:29108; Evidence={ECO:0000269|PubMed:19387438};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:29673;
CC Evidence={ECO:0000269|PubMed:19387438};
CC -!- ACTIVITY REGULATION: Na(+) current is inhibited by ATP in a MTORC-
CC dependent manner. ATP sensitivity is independent of PI(3,5)P2
CC (PubMed:23394946). Probably 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). Both current elicited by PI(3,5)P2 as well
CC as NAADP are inhibited by tetrandrine. {ECO:0000250|UniProtKB:Q8NHX9,
CC ECO:0000269|PubMed:23394946, ECO:0000269|PubMed:25722412}.
CC -!- SUBUNIT: Dimer. Interacts with MTOR; the interaction is required for
CC TPCN1 ATP sensitivity (PubMed:23394946). Interacts with STX7, STX8 and
CC STX12 (By similarity). Interacts with JPT2 (PubMed:33758061). Found in
CC a complex with LSM12, TPCN1 and TPCN2 (PubMed:34362892).
CC {ECO:0000250|UniProtKB:Q9EQJ0, ECO:0000269|PubMed:23394946,
CC ECO:0000269|PubMed:33758061, ECO:0000269|PubMed:34362892, ECO:0000305}.
CC -!- INTERACTION:
CC Q9ULQ1; O00165: HAX1; NbExp=2; IntAct=EBI-5239895, EBI-357001;
CC Q9ULQ1; Q9ULQ1: TPCN1; NbExp=3; IntAct=EBI-5239895, EBI-5239895;
CC Q9ULQ1; Q8NHX9: TPCN2; NbExp=9; IntAct=EBI-5239895, EBI-5239949;
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:19620632,
CC ECO:0000269|PubMed:23063126, ECO:0000269|PubMed:25722412}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:19620632}. Endosome membrane
CC {ECO:0000269|PubMed:19620632, ECO:0000269|PubMed:20880839,
CC ECO:0000269|PubMed:23063126, ECO:0000269|PubMed:25722412}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:19620632}. Early endosome membrane
CC {ECO:0000250|UniProtKB:Q9EQJ0}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9EQJ0}. Recycling endosome membrane
CC {ECO:0000250|UniProtKB:Q9EQJ0}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9EQJ0}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9ULQ1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9ULQ1-2; Sequence=VSP_023003, VSP_023004, VSP_023005;
CC Name=3;
CC IsoId=Q9ULQ1-3; Sequence=VSP_041346;
CC -!- TISSUE SPECIFICITY: Highest expression found in the heart and kidney,
CC and lowest expression found in the spleen.
CC {ECO:0000269|PubMed:10574461}.
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 represent the voltage-sensor
CC and are characterized by a series of positively charged amino acids at
CC every third position. {ECO:0000269|PubMed:24776928}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q9EQJ0}.
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=AK057414; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAA86483.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY083666; AAM01199.1; -; mRNA.
DR EMBL; AB032995; BAA86483.2; ALT_INIT; mRNA.
DR EMBL; AK057414; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK075071; BAC11385.1; -; mRNA.
DR EMBL; AC010178; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC089999; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC127004; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC136795; AAI36796.1; -; mRNA.
DR EMBL; BC136796; AAI36797.1; -; mRNA.
DR EMBL; BC150203; AAI50204.1; -; mRNA.
DR EMBL; BC152423; AAI52424.1; -; mRNA.
DR CCDS; CCDS31908.1; -. [Q9ULQ1-1]
DR CCDS; CCDS44985.1; -. [Q9ULQ1-3]
DR RefSeq; NP_001137291.1; NM_001143819.2. [Q9ULQ1-3]
DR RefSeq; NP_001288143.1; NM_001301214.1.
DR RefSeq; NP_060371.2; NM_017901.5. [Q9ULQ1-1]
DR RefSeq; XP_011536792.1; XM_011538490.2. [Q9ULQ1-3]
DR RefSeq; XP_011536794.1; XM_011538492.2. [Q9ULQ1-1]
DR AlphaFoldDB; Q9ULQ1; -.
DR SMR; Q9ULQ1; -.
DR BioGRID; 119760; 30.
DR IntAct; Q9ULQ1; 9.
DR MINT; Q9ULQ1; -.
DR STRING; 9606.ENSP00000448083; -.
DR DrugCentral; Q9ULQ1; -.
DR GuidetoPHARMACOLOGY; 392; -.
DR TCDB; 1.A.1.11.25; the voltage-gated ion channel (vic) superfamily.
DR GlyGen; Q9ULQ1; 3 sites.
DR iPTMnet; Q9ULQ1; -.
DR PhosphoSitePlus; Q9ULQ1; -.
DR BioMuta; TPCN1; -.
DR DMDM; 125991219; -.
DR EPD; Q9ULQ1; -.
DR jPOST; Q9ULQ1; -.
DR MassIVE; Q9ULQ1; -.
DR MaxQB; Q9ULQ1; -.
DR PaxDb; Q9ULQ1; -.
DR PeptideAtlas; Q9ULQ1; -.
DR PRIDE; Q9ULQ1; -.
DR ProteomicsDB; 85094; -. [Q9ULQ1-1]
DR ProteomicsDB; 85095; -. [Q9ULQ1-2]
DR ProteomicsDB; 85096; -. [Q9ULQ1-3]
DR Antibodypedia; 31242; 64 antibodies from 18 providers.
DR DNASU; 53373; -.
DR Ensembl; ENST00000335509.11; ENSP00000335300.6; ENSG00000186815.13. [Q9ULQ1-1]
DR Ensembl; ENST00000541517.5; ENSP00000438125.1; ENSG00000186815.13. [Q9ULQ1-3]
DR Ensembl; ENST00000550785.5; ENSP00000448083.1; ENSG00000186815.13. [Q9ULQ1-3]
DR GeneID; 53373; -.
DR KEGG; hsa:53373; -.
DR MANE-Select; ENST00000335509.11; ENSP00000335300.6; NM_017901.6; NP_060371.2.
DR UCSC; uc001tuw.4; human. [Q9ULQ1-1]
DR CTD; 53373; -.
DR DisGeNET; 53373; -.
DR GeneCards; TPCN1; -.
DR HGNC; HGNC:18182; TPCN1.
DR HPA; ENSG00000186815; Low tissue specificity.
DR MIM; 609666; gene.
DR neXtProt; NX_Q9ULQ1; -.
DR OpenTargets; ENSG00000186815; -.
DR PharmGKB; PA134922711; -.
DR VEuPathDB; HostDB:ENSG00000186815; -.
DR eggNOG; KOG2301; Eukaryota.
DR GeneTree; ENSGT00940000158958; -.
DR InParanoid; Q9ULQ1; -.
DR PhylomeDB; Q9ULQ1; -.
DR TreeFam; TF328550; -.
DR PathwayCommons; Q9ULQ1; -.
DR Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR SignaLink; Q9ULQ1; -.
DR BioGRID-ORCS; 53373; 14 hits in 1081 CRISPR screens.
DR ChiTaRS; TPCN1; human.
DR GeneWiki; TPCN1; -.
DR GenomeRNAi; 53373; -.
DR Pharos; Q9ULQ1; Tchem.
DR PRO; PR:Q9ULQ1; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9ULQ1; protein.
DR Bgee; ENSG00000186815; Expressed in right hemisphere of cerebellum and 200 other tissues.
DR ExpressionAtlas; Q9ULQ1; baseline and differential.
DR Genevisible; Q9ULQ1; HS.
DR GO; GO:0031901; C:early endosome membrane; ISS:UniProtKB.
DR GO; GO:0036019; C:endolysosome; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; TAS:ParkinsonsUK-UCL.
DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; TAS:ParkinsonsUK-UCL.
DR GO; GO:0055038; C:recycling endosome membrane; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0097682; F:intracellular phosphatidylinositol-3,5-bisphosphate-sensitive cation channel activity; IDA:UniProtKB.
DR GO; GO:0015280; F:ligand-gated sodium channel activity; IDA:UniProtKB.
DR GO; GO:0072345; F:NAADP-sensitive calcium-release channel activity; IDA:UniProtKB.
DR GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0019905; F:syntaxin binding; IEA:Ensembl.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0005248; F:voltage-gated sodium channel activity; IDA:UniProtKB.
DR GO; GO:0075509; P:endocytosis involved in viral entry into host cell; IMP:UniProtKB.
DR GO; GO:0034220; P:ion transmembrane transport; TAS:Reactome.
DR GO; GO:0010508; P:positive regulation of autophagy; IDA:ParkinsonsUK-UCL.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR Gene3D; 1.20.120.350; -; 1.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR028801; TPC1_animal.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR46474; PTHR46474; 1.
DR Pfam; PF00520; Ion_trans; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Calcium channel; Calcium transport;
KW Coiled coil; Endosome; Glycoprotein; Ion channel; Ion transport; Lysosome;
KW Membrane; Reference proteome; Repeat; Transmembrane; Transmembrane helix;
KW Transport; Voltage-gated channel.
FT CHAIN 1..816
FT /note="Two pore channel protein 1"
FT /id="PRO_0000276853"
FT TOPO_DOM 1..112
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 113..133
FT /note="Helical; Name=S1 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 134
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 135..155
FT /note="Helical; Name=S2 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 156..177
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 178..198
FT /note="Helical; Name=S3 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 199..200
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 201..220
FT /note="Helical; Name=S4 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 221..234
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 235..255
FT /note="Helical; Name=S5 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 256..262
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 263..286
FT /note="Helical; Pore-forming"
FT /evidence="ECO:0000255"
FT TOPO_DOM 287..294
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 295..315
FT /note="Helical; Name=S6 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 316..444
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 445..465
FT /note="Helical; Name=S1 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 466..479
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 480..500
FT /note="Helical; Name=S2 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 501..503
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 504..526
FT /note="Helical; Name=S3 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 527..534
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 535..549
FT /note="Helical; Name=S4 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 550..573
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 574..594
FT /note="Helical; Name=S5 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 595..629
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 630..653
FT /note="Helical; Pore-forming"
FT /evidence="ECO:0000255"
FT TOPO_DOM 654..670
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 671..691
FT /note="Helical; Name=S6 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 692..816
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 17..64
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 782..816
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 769..796
FT /evidence="ECO:0000255"
FT COMPBIAS 41..64
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 791..816
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 599
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 611
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 616
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..366
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_023003"
FT VAR_SEQ 1
FT /note="M -> MESCYIAQAGLELLGSSSSPTLTSQSAEITEDASNGGVSEQHPWPSG
FT FERELKPETISSPGYHILRATGEENM (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041346"
FT VAR_SEQ 569..618
FT /note="SLGLTLLIFYYSFAIVGMEFFCGIVFPNCCNTSTVADAYRWRNHTVGNRT
FT -> RYCQPPPWPAGPGAVWQCPVGAGAEWQSGERSSTKDCNRGPDGAPRSLES (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_023004"
FT VAR_SEQ 619..816
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_023005"
FT MUTAGEN 219..223
FT /note="RRNLR->QQNLQ: Loss of voltage sensitivity."
FT /evidence="ECO:0000269|PubMed:24776928"
FT MUTAGEN 273
FT /note="L->P: Loss of NAADP-mediated cytoplasmic calcium
FT release."
FT /evidence="ECO:0000269|PubMed:19620632"
FT MUTAGEN 539
FT /note="R->I: Loss of voltage sensitivity."
FT /evidence="ECO:0000269|PubMed:24776928"
FT MUTAGEN 740..741
FT /note="LL->AA: No effect on subcellular location."
FT /evidence="ECO:0000269|PubMed:20880839"
FT CONFLICT 621
FT /note="E -> G (in Ref. 4; AK057414)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 816 AA; 94147 MW; D6D26BFAF33E1463 CRC64;
MAVSLDDDVP LILTLDEGGS APLAPSNGLG QEELPSKNGG SYAIHDSQAP SLSSGGESSP
SSPAHNWEMN YQEAAIYLQE GENNDKFFTH PKDAKALAAY LFAHNHLFYL MELATALLLL
LLSLCEAPAV PALRLGIYVH ATLELFALMV VVFELCMKLR WLGLHTFIRH KRTMVKTSVL
VVQFVEAIVV LVRQMSHVRV TRALRCIFLV DCRYCGGVRR NLRQIFQSLP PFMDILLLLL
FFMIIFAILG FYLFSPNPSD PYFSTLENSI VSLFVLLTTA NFPDVMMPSY SRNPWSCVFF
IVYLSIELYF IMNLLLAVVF DTFNDIEKRK FKSLLLHKRT AIQHAYRLLI SQRRPAGISY
RQFEGLMRFY KPRMSARERY LTFKALNQNN TPLLSLKDFY DIYEVAALKW KAKKNREHWF
DELPRTALLI FKGINILVKS KAFQYFMYLV VAVNGVWILV ETFMLKGGNF FSKHVPWSYL
VFLTIYGVEL FLKVAGLGPV EYLSSGWNLF DFSVTVFAFL GLLALALNME PFYFIVVLRP
LQLLRLFKLK ERYRNVLDTM FELLPRMASL GLTLLIFYYS FAIVGMEFFC GIVFPNCCNT
STVADAYRWR NHTVGNRTVV EEGYYYLNNF DNILNSFVTL FELTVVNNWY IIMEGVTSQT
SHWSRLYFMT FYIVTMVVMT IIVAFILEAF VFRMNYSRKN QDSEVDGGIT LEKEISKEEL
VAVLELYREA RGASSDVTRL LETLSQMERY QQHSMVFLGR RSRTKSDLSL KMYQEEIQEW
YEEHAREQEQ QRQLSSSAAP AAQQPPGSRQ RSQTVT
