TPC2_DANRE
ID TPC2_DANRE Reviewed; 774 AA.
AC A0JMD4;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 12-DEC-2006, sequence version 1.
DT 03-AUG-2022, entry version 81.
DE RecName: Full=Two pore channel protein 2;
DE AltName: Full=Two pore calcium channel protein 2;
DE AltName: Full=Voltage-dependent calcium channel protein TPC2;
GN Name=tpcn2; Synonyms=tpc2; ORFNames=zgc:152898;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=AB;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
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). Localizes to the lysosomal and late endosome membranes
CC where it regulates organellar membrane excitability, membrane
CC trafficking, and pH homeostasis. {ECO:0000250|UniProtKB:Q8NHX9}.
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 -!- CATALYTIC ACTIVITY:
CC Reaction=Ca(2+)(in) = Ca(2+)(out); Xref=Rhea:RHEA:29671,
CC ChEBI:CHEBI:29108; Evidence={ECO:0000250|UniProtKB:Q8NHX9};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:29673;
CC Evidence={ECO:0000250|UniProtKB:Q8NHX9};
CC -!- SUBUNIT: Homodimer (By similarity). {ECO:0000250|UniProtKB:Q8BWC0,
CC ECO:0000250|UniProtKB:Q8NHX9}.
CC -!- SUBCELLULAR LOCATION: Late endosome membrane
CC {ECO:0000250|UniProtKB:Q8NHX9}; Multi-pass membrane protein
CC {ECO:0000255}. Lysosome membrane {ECO:0000250|UniProtKB:Q8NHX9}; Multi-
CC pass membrane protein {ECO:0000255}.
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:0000250|UniProtKB:Q8BWC0}.
CC -!- SIMILARITY: Belongs to the calcium channel alpha-1 subunit (TC
CC 1.A.1.11) family. Two pore calcium channel subfamily. {ECO:0000305}.
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DR EMBL; BC125833; AAI25834.1; -; mRNA.
DR RefSeq; NP_001071190.1; NM_001077722.1.
DR AlphaFoldDB; A0JMD4; -.
DR SMR; A0JMD4; -.
DR STRING; 7955.ENSDARP00000077125; -.
DR PaxDb; A0JMD4; -.
DR GeneID; 777614; -.
DR KEGG; dre:777614; -.
DR CTD; 219931; -.
DR ZFIN; ZDB-GENE-061103-202; tpcn2.
DR eggNOG; KOG2301; Eukaryota.
DR InParanoid; A0JMD4; -.
DR OrthoDB; 761764at2759; -.
DR PhylomeDB; A0JMD4; -.
DR Reactome; R-DRE-2672351; Stimuli-sensing channels.
DR PRO; PR:A0JMD4; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
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; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISS: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; ISS:UniProtKB.
DR GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; ISS:UniProtKB.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; ISS:UniProtKB.
DR GO; GO:0019722; P:calcium-mediated signaling; IMP:ZFIN.
DR GO; GO:0075509; P:endocytosis involved in viral entry into host cell; IBA:GO_Central.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:2000290; P:regulation of myotome development; IMP:ZFIN.
DR GO; GO:0014866; P:skeletal myofibril assembly; IMP:ZFIN.
DR GO; GO:0006939; P:smooth muscle contraction; ISS: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 2: Evidence at transcript level;
KW Calcium; Calcium channel; Calcium transport; Endosome; Glycoprotein;
KW Ion channel; Ion transport; Lysosome; Membrane; Reference proteome; Repeat;
KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..774
FT /note="Two pore channel protein 2"
FT /id="PRO_0000276858"
FT TOPO_DOM 1..92
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 93..113
FT /note="Helical; Name=S1 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 114..140
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 141..161
FT /note="Helical; Name=S2 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 162..170
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 171..191
FT /note="Helical; Name=S3 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 192..197
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 198..218
FT /note="Helical; Name=S4 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 219..232
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 233..253
FT /note="Helical; Name=S5 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 254..267
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 268..292
FT /note="Helical; Pore-forming"
FT /evidence="ECO:0000255"
FT TOPO_DOM 293..302
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 303..323
FT /note="Helical; Name=S6 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 324..452
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 453..475
FT /note="Helical; Name=S1 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 476..486
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 487..507
FT /note="Helical; Name=S2 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 508..518
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 519..539
FT /note="Helical; Name=S3 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 540..564
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 565..585
FT /note="Helical; Name=S4 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 586..596
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 597..617
FT /note="Helical; Name=S5 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 618..658
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 659..681
FT /note="Helical; Pore-forming"
FT /evidence="ECO:0000255"
FT TOPO_DOM 682..696
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 697..717
FT /note="Helical; Name=S6 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 718..774
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 217..221
FT /note="Interaction with phosphatidylinositol 3,5-
FT bisphosphate"
FT /evidence="ECO:0000250|UniProtKB:Q8NHX9"
FT CARBOHYD 626
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 632
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 637
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 774 AA; 89184 MW; 25C167D2C54FEA9E CRC64;
MEEEPLLAGS INQGSGDYGA HSESCLHYPD EHTPRSRRLS YSVTDDSCNV EEDADADLYV
QQAVVFIEDA IKYRSINHRV DSGSLRLYRW YYSNLCQWGL GLTIAVVLAL AFIERPSSLT
YTSDIRVKPK PWEPPCGMTE GIEIVCLCIF ILDVTAKGYL IGWEEFRMNK WLLAYLIVIT
ASVIDWMLSI SMLCDENLRV RRLIRPFFLL QNSSLMKKTL KCIKRTLPEI ASVILLLALH
ICLFTMIGML IFAKSDDPKQ NGEWQTYFRN LPKALSSLLV LLTTANNPDV MIPAYSLNRG
YSIFFILFSV FGTYLLMNLM TAIIYNQFRG YLLMSVQTSI IRRRLGIRAA FEVLCCPGRG
HTSTQAEGHV ERVAVSMFLK VMERVHMKSY CRQAIVKAAR RFPDGFISGE DFQRLFNELD
KDFVKEHPPK PEYSSSGLQH IQYVYSHYYI SVLGNAVALA NVICICTVLV LNAEKSASEK
NYFYMEIINC IFILYYLIEM LLKIVAFGWK GYLSYRNNIF DGFLTVLLLA IQIVIFITFK
IPYVDVDPVP RHVMALWEMI RLVNMLIVFR FLRIIPEIKL MAVVASTIVD LVKNLRAFAG
ILLVVYYMFA VLGIWLFQGA ISPPSNMSLV SNSSLENITG PYSMECGTFE QLEYWPNNFD
DFASSLILLY NIMVVNNWHV FTDAYARYTT DWSLVYFVVW WLTSSVMWVN LFVALILENF
TYKWDRSNGL SVEDVERIAY QSTVQLMFKE HVKEPTEEEL LAQLHQHPHL HLSW
