Tpcn2
entrez
233979
canonical
uniprot
Q8BWC0
canonical
ensembl
ENSMUSG00000048677
resolver
ensp
ENSMUSP00000061308
resolver
ensp
ENSMUSP00000147178
resolver
ensp
ENSMUSP00000239997
resolver
ensp
ENSMUSP00000239998
resolver
ensp
ENSMUSP00000240011
resolver
genesymbol
Tpcn2
resolver
genesymbol_syn
Tpc2
resolver
uniprot
Q6NSV0
resolver
uniprot
Q8BTJ7
resolver
uniprot
Q8R396
resolver
uniprot_entry
TPC2_MOUSE
resolver
uniprot_sec
Q6NSV0
resolver
uniprot_sec
Q8BTJ7
resolver
uniprot_sec
Q8R396
resolver
activity_regulation
ACTIVITY REGULATION: Regulated by Mg(2+) ions, cytosolic Mg(2+) selectively inhibits outward current while lysosomal Mg(2+) modestly inhibits both the outward and inward currents. In the absence of Mg(2+), NAADP readily activates TPCN2, with properties similar to PI(3,5)P2 (By similarity). Na(+) current is inhibited by ATP in a MTORC-dependent manner. ATP sensitivity is independent of PI(3,5)P2 (PubMed:23394946). Both current elicited by PI(3,5)P2 as well as NAADP are inhibited by tetrandrine. {ECO:0000250|UniProtKB:Q8NHX9, ECO:0000269|PubMed:23394946, ECO:0000269|PubMed:25722412}.
uniprot
proteins
amino_acid_sequence
MAAEEQPLLGRDRGSGQVHSGAAADQELCIDQAVVFIEDAIKYRSIYHRMDAGSLWLYRWYYSNVCQRVLGFIIFLILILAFVEVPSSFTKTADVRYRSQPWQPPCGLTETIEAFCLLAFLVDLSVKGYLVGQAQLQQNLWLLAYFMVLVVSVVDWIVSLSLACEEPLRMRRLLRPFFLLQNSSMMKKTLKCIRWSLPEMASVGLLLAIHLCLFTIIGMLLFTIGEKDEAQDQERLAYFRNLPEALTSLLVLLTTSNNPDVMIPAYTQNRAFALFFIVFTLIGSLFLMNLLTAIIYNQFRGYLMKSLQTSLFRRRLGARAAYEVLASRAGPAGTTPELVGVNPETFLPVLQKTQLNKTHKQAIMQKVQSYEGRPMLADEFQKLFDEVDKGLAKERPLKPQYQSPFLQTAQFIFSHHYFDYLGNLVALGNLLSICVFLVLDSDLLPGERDDFVLGILDYIFILYYLLELLFKVFALGLPGYLSYHSNVFDGLLTIILLVSEICTLAVYRLPHSGWKPEQYGPLSLWDMTRLMNTLIVFRFLRIIPNIKPMAEVANTILGLIPNLRAFGGILVVAYYVFAMIGINLFRGVIVPPGNSSLVPDNNSAVCGSFEQLGYWPNNFDDFAAALITLWNVMVVNNWQVILEAYKRYAGPWSMVYFVLWWLVSSVIWINLFLALLLENFLHRWDPQGHKQLLVGTKQMSVELMFRDILEEPKEEELMEKLHKHPHLHLCR
uniprot
proteins
function
FUNCTION: Intracellular channel initially characterized as a non-selective Ca(2+)-permeable channel activated by NAADP (nicotinic acid adenine dinucleotide phosphate), it is also a highly-selective Na(+) channel activated directly by PI(3,5)P2 (phosphatidylinositol 3,5-bisphosphate) (PubMed:19387438, PubMed:20495006, PubMed:20547763, PubMed:25144390, PubMed:27231233). Localizes to the lysosomal and late endosome membranes where it regulates organellar membrane excitability, membrane trafficking, and pH homeostasis. Is associated with a plethora of physiological processes, including mTOR-dependent nutrient sensing, skin pigmentation and autophagy (PubMed:23063126, PubMed:23394946, PubMed:25144390). Ion selectivity is not fixed but rather agonist-dependent and under defined ionic conditions, can be readily activated by both NAADP and PI(3,5)P2. As calcium channel, it increases the pH in the lysosomal lumen, as sodium channel, it promotes lysosomal exocytosis (PubMed:32167471). Plays a crucial role in endolysosomal trafficking in the endolysosomal degradation pathway and is potentially involved in the homeostatic control of many macromolecules and cell metabolites (PubMed:19387438, PubMed:20495006, PubMed:20547763, PubMed:23063126, PubMed:23394946, PubMed:25144390, PubMed:32167471). Also expressed in melanosomes of pigmented cells where mediates a Ca(2+) channel and/or PI(3,5)P2-activated melanosomal Na(+) channel to acidify pH and inhibit tyrosinase activity required for melanogenesis and pigmentation (PubMed:27231233). Unlike the voltage-dependent TPCN1, TPCN2 is voltage independent and can be activated solely by PI(3,5)P2 binding. In contrast, PI(4,5)P2, PI(3,4)P2, PI(3)P and PI(5)P have no obvious effect on channel activation (By similarity). {ECO:0000250|UniProtKB:Q8NHX9, ECO:0000269|PubMed:19387438, ECO:0000269|PubMed:20495006, ECO:0000269|PubMed:20547763, ECO:0000269|PubMed:23063126, ECO:0000269|PubMed:23394946, ECO:0000269|PubMed:25144390, ECO:0000269|PubMed:27231233, ECO:0000269|PubMed:32167471}.; FUNCTION: (Microbial infection) During Ebola virus (EBOV) infection, controls the movement of endosomes containing virus particles and is required by EBOV to escape from the endosomal network into the cell cytoplasm. {ECO:0000269|PubMed:25722412}.
uniprot
proteins
mass_dalton
83595
uniprot
proteins
mutagenesis
MUTAGEN 257; /note="N->A: Complete loss of selectivity for calcium over monocovalent cations."; /evidence="ECO:0000269|PubMed:20495006"; MUTAGEN 594; /note="N->A: Loss of N-glycosylation; when associated with N-601."; /evidence="ECO:0000269|PubMed:19557428"; MUTAGEN 601; /note="N->A: Loss of N-glycosylation; when associated with N-594."; /evidence="ECO:0000269|PubMed:19557428"; MUTAGEN 643; /note="E->A: Partial loss of selectivity for calcium over monocovalent cations."; /evidence="ECO:0000269|PubMed:20495006
uniprot
proteins
post_translational_modification
PTM: N-glycosylated. {ECO:0000269|PubMed:19557428}.
uniprot
proteins
protein_family
Calcium channel alpha-1 subunit (TC 1.A.1.11) family
uniprot
proteins
protein_family
Two pore calcium channel subfamily
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
19387438
uniprot
proteins
pubmed
19557428
uniprot
proteins
pubmed
20495006
uniprot
proteins
pubmed
20547763
uniprot
proteins
pubmed
23063126
uniprot
proteins
pubmed
23394946
uniprot
proteins
pubmed
25144390
uniprot
proteins
pubmed
25722412
uniprot
proteins
pubmed
27231233
uniprot
proteins
pubmed
32167471
uniprot
proteins
sequence_length
731
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Late endosome membrane {ECO:0000305|PubMed:25144390}; Multi-pass membrane protein {ECO:0000255}. Lysosome membrane {ECO:0000269|PubMed:19557428, ECO:0000269|PubMed:20495006, ECO:0000269|PubMed:25144390, ECO:0000269|PubMed:32167471}; Multi-pass membrane protein {ECO:0000269|PubMed:19557428, ECO:0000269|PubMed:20495006}. Melanosome membrane {ECO:0000269|PubMed:27231233}; Multi-pass membrane protein {ECO:0000255}. Note=Only the acidic lysosomal fraction is sensitive to NAADP.
uniprot
proteins
transmembrane_region
TRANSMEM 69..89; /note="Helical; Name=S1 of repeat I"; /evidence="ECO:0000255"; TRANSMEM 112..132; /note="Helical; Name=S2 of repeat I"; /evidence="ECO:0000255"; TRANSMEM 140..160; /note="Helical; Name=S3 of repeat I"; /evidence="ECO:0000255"; TRANSMEM 168..188; /note="Helical; Name=S4 of repeat I"; /evidence="ECO:0000255"; TRANSMEM 204..224; /note="Helical; Name=S5 of repeat I"; /evidence="ECO:0000255"; TRANSMEM 271..291; /note="Helical; Name=S6 of repeat I"; /evidence="ECO:0000255"; TRANSMEM 418..438; /note="Helical; Name=S1 of repeat II"; /evidence="ECO:0000255"; TRANSMEM 450..470; /note="Helical; Name=S2 of repeat II"; /evidence="ECO:0000255"; TRANSMEM 487..507; /note="Helical; Name=S3 of repeat II"; /evidence="ECO:0000255"; TRANSMEM 525..542; /note="Helical; Name=S4 of repeat II"; /evidence="ECO:0000255"; TRANSMEM 565..585; /note="Helical; Name=S5 of repeat II"; /evidence="ECO:0000255"; TRANSMEM 657..677; /note="Helical; Name=S6 of repeat II"; /evidence="ECO:0000255
uniprot
proteins