TPCN2
entrez
219931
canonical
uniprot
Q8NHX9
canonical
ensembl
ENSG00000162341
resolver
ensp
ENSP00000294309
resolver
enst
ENST00000294309
resolver
genesymbol
TPCN2
resolver
genesymbol_syn
TPC2
resolver
hgnc
HGNC:20820
resolver
uniprot
Q59G56
resolver
uniprot
Q9NT82
resolver
uniprot_entry
Q59G56_HUMAN
resolver
uniprot_entry
TPC2_HUMAN
resolver
uniprot_sec
Q9NT82
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 (PubMed:24502975). 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:0000269|PubMed:23394946, ECO:0000269|PubMed:24502975, ECO:0000269|PubMed:25722412, ECO:0000269|PubMed:32221306}.
uniprot
proteins
amino_acid_sequence
MAEPQAESEPLLGGARGGGGDWPAGLTTYRSIQVGPGAAARWDLCIDQAVVFIEDAIQYRSINHRVDASSMWLYRRYYSNVCQRTLSFTIFLILFLAFIETPSSLTSTADVRYRAAPWEPPCGLTESVEVLCLLVFAADLSVKGYLFGWAHFQKNLWLLGYLVVLVVSLVDWTVSLSLVCHEPLRIRRLLRPFFLLQNSSMMKKTLKCIRWSLPEMASVGLLLAIHLCLFTMFGMLLFAGGKQDDGQDRERLTYFQNLPESLTSLLVLLTTANNPDVMIPAYSKNRAYAIFFIVFTVIGSLFLMNLLTAIIYSQFRGYLMKSLQTSLFRRRLGTRAAFEVLSSMVGEGGAFPQAVGVKPQNLLQVLQKVQLDSSHKQAMMEKVRSYGSVLLSAEEFQKLFNELDRSVVKEHPPRPEYQSPFLQSAQFLFGHYYFDYLGNLIALANLVSICVFLVLDADVLPAERDDFILGILNCVFIVYYLLEMLLKVFALGLRGYLSYPSNVFDGLLTVVLLVLEISTLAVYRLPHPGWRPEMVGLLSLWDMTRMLNMLIVFRFLRIIPSMKLMAVVASTVLGLVQNMRAFGGILVVVYYVFAIIGINLFRGVIVALPGNSSLAPANGSAPCGSFEQLEYWANNFDDFAAALVTLWNLMVVNNWQVFLDAYRRYSGPWSKIYFVLWWLVSSVIWVNLFLALILENFLHKWDPRSHLQPLAGTPEATYQMTVELLFRDILEEPGEDELTERLSQHPHLWLCR
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:19620632, PubMed:20880839, PubMed:23063126, PubMed:23394946, PubMed:24502975, PubMed:24776928, PubMed:30860481, PubMed:31825310, PubMed:32167471). 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:18488028, PubMed:23394946, PubMed:32167471). 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 (PubMed:24502975, PubMed:31825310, PubMed:32167471). As calcium channel, it increases the pH in the lysosomal lumen, as sodium channel, it promotes lysosomal exocytosis (PubMed:31825310, 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 (By similarity) (PubMed:18488028, PubMed:19387438, PubMed:19620632, PubMed:20880839, PubMed:23063126, PubMed:23394946, PubMed:24502975, PubMed:24776928, PubMed:31825310, PubMed:32167471, PubMed:32679067). 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:27140606). 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 (PubMed:30860481). {ECO:0000250|UniProtKB:Q8BWC0, ECO:0000269|PubMed:18488028, ECO:0000269|PubMed:19387438, ECO:0000269|PubMed:19620632, ECO:0000269|PubMed:20880839, ECO:0000269|PubMed:23063126, ECO:0000269|PubMed:23394946, ECO:0000269|PubMed:24502975, ECO:0000269|PubMed:24776928, ECO:0000269|PubMed:27140606, ECO:0000269|PubMed:30860481, ECO:0000269|PubMed:31825310, ECO:0000269|PubMed:32167471, ECO:0000269|PubMed:32679067}.; 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}.; FUNCTION: (Microbial infection) Required for cell entry of coronaviruses SARS-CoV and SARS-CoV-2, as well as human coronavirus EMC (HCoV-EMC), by endocytosis. {ECO:0000269|PubMed:32221306}.
uniprot
proteins
mass_dalton
85243
uniprot
proteins
mutagenesis
MUTAGEN 11..12; /note="LL->AA: Localizes at the plasma membrane."; /evidence="ECO:0000269|PubMed:20880839, ECO:0000269|PubMed:24502975"; MUTAGEN 203; /note="K->A: Strongly reduces binding with phosphatidylinositol 3,5-bisphosphate."; /evidence="ECO:0000269|PubMed:30860481"; MUTAGEN 204; /note="K->A: Strongly reduces binding with phosphatidylinositol 3,5-bisphosphate. Decreases sodium transport. No effect on calcium release."; /evidence="ECO:0000269|PubMed:30860481, ECO:0000269|PubMed:32167471"; MUTAGEN 207; /note="K->A: Reduces binding with phosphatidylinositol 3,5-bisphosphate."; /evidence="ECO:0000269|PubMed:30860481"; MUTAGEN 265; /note="L->P: No effect on lysosomal location. Loss of NAADP-sensitive calcium-release channel activity. Inhibits Ebola virus infection."; /evidence="ECO:0000269|PubMed:20880839, ECO:0000269|PubMed:25722412"; MUTAGEN 276; /note="D->K: Not activated by phosphatidylinositol 3,5-bisphosphate."; /evidence="ECO:0000269|PubMed:23063126"; MUTAGEN 322; /note="S->A: Reduces binding with phosphatidylinositol 3,5-bisphosphate."; /evidence="ECO:0000269|PubMed:30860481"; MUTAGEN 329; /note="R->A: Reduces binding with phosphatidylinositol 3,5-bisphosphate."; /evidence="ECO:0000269|PubMed:30860481"; MUTAGEN 551; /note="I->R: Requires both phosphatidylinositol 3,5-bisphosphate and a positive membrane potential for activation."; /evidence="ECO:0000269|PubMed:30860481
uniprot
proteins
post_translational_modification
PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q8BWC0}.
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
16554811
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18488028
uniprot
proteins
pubmed
19387438
uniprot
proteins
pubmed
19620632
uniprot
proteins
pubmed
20880839
uniprot
proteins
pubmed
22012985
uniprot
proteins
pubmed
23063126
uniprot
proteins
pubmed
23394946
uniprot
proteins
pubmed
24188827
uniprot
proteins
pubmed
24502975
uniprot
proteins
pubmed
24776928
uniprot
proteins
pubmed
25722412
uniprot
proteins
pubmed
27140606
uniprot
proteins
pubmed
30860481
uniprot
proteins
pubmed
31825310
uniprot
proteins
pubmed
32167471
uniprot
proteins
pubmed
32221306
uniprot
proteins
pubmed
32679067
uniprot
proteins
pubmed
33795662
uniprot
proteins
pubmed
34362892
uniprot
proteins
sequence_length
752
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Late endosome membrane {ECO:0000269|PubMed:32167471}; Multi-pass membrane protein {ECO:0000255}. Lysosome membrane {ECO:0000269|PubMed:20880839, ECO:0000269|PubMed:23063126, ECO:0000269|PubMed:31825310, ECO:0000269|PubMed:32167471}; Multi-pass membrane protein {ECO:0000255}. Melanosome membrane {ECO:0000269|PubMed:27140606}; Multi-pass membrane protein {ECO:0000255}.
uniprot
proteins
transmembrane_region
TRANSMEM 85..105; /note="Helical; Name=S1 of repeat I"; /evidence="ECO:0000255"; TRANSMEM 128..148; /note="Helical; Name=S2 of repeat I"; /evidence="ECO:0000255"; TRANSMEM 156..176; /note="Helical; Name=S3 of repeat I"; /evidence="ECO:0000255"; TRANSMEM 184..204; /note="Helical; Name=S4 of repeat I"; /evidence="ECO:0000255"; TRANSMEM 219..239; /note="Helical; Name=S5 of repeat I"; /evidence="ECO:0000255"; TRANSMEM 290..310; /note="Helical; Name=S6 of repeat I"; /evidence="ECO:0000255"; TRANSMEM 437..459; /note="Helical; Name=S1 of repeat II"; /evidence="ECO:0000255"; TRANSMEM 466..486; /note="Helical; Name=S2 of repeat II"; /evidence="ECO:0000255"; TRANSMEM 503..523; /note="Helical; Name=S3 of repeat II"; /evidence="ECO:0000255"; TRANSMEM 555..575; /note="Helical; Name=S4 of repeat II"; /evidence="ECO:0000255"; TRANSMEM 581..601; /note="Helical; Name=S5 of repeat II"; /evidence="ECO:0000255"; TRANSMEM 674..694; /note="Helical; Name=S6 of repeat II"; /evidence="ECO:0000255
uniprot
proteins