Details of the Target
General Information of Target
Target ID | LDTP09270 | |||||
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Target Name | Two pore channel protein 2 (TPCN2) | |||||
Gene Name | TPCN2 | |||||
Gene ID | 219931 | |||||
Synonyms |
TPC2; Two pore channel protein 2; Two pore calcium channel protein 2 |
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3D Structure | ||||||
Sequence |
MAEPQAESEPLLGGARGGGGDWPAGLTTYRSIQVGPGAAARWDLCIDQAVVFIEDAIQYR
SINHRVDASSMWLYRRYYSNVCQRTLSFTIFLILFLAFIETPSSLTSTADVRYRAAPWEP PCGLTESVEVLCLLVFAADLSVKGYLFGWAHFQKNLWLLGYLVVLVVSLVDWTVSLSLVC HEPLRIRRLLRPFFLLQNSSMMKKTLKCIRWSLPEMASVGLLLAIHLCLFTMFGMLLFAG GKQDDGQDRERLTYFQNLPESLTSLLVLLTTANNPDVMIPAYSKNRAYAIFFIVFTVIGS LFLMNLLTAIIYSQFRGYLMKSLQTSLFRRRLGTRAAFEVLSSMVGEGGAFPQAVGVKPQ NLLQVLQKVQLDSSHKQAMMEKVRSYGSVLLSAEEFQKLFNELDRSVVKEHPPRPEYQSP FLQSAQFLFGHYYFDYLGNLIALANLVSICVFLVLDADVLPAERDDFILGILNCVFIVYY LLEMLLKVFALGLRGYLSYPSNVFDGLLTVVLLVLEISTLAVYRLPHPGWRPEMVGLLSL WDMTRMLNMLIVFRFLRIIPSMKLMAVVASTVLGLVQNMRAFGGILVVVYYVFAIIGINL FRGVIVALPGNSSLAPANGSAPCGSFEQLEYWANNFDDFAAALVTLWNLMVVNNWQVFLD AYRRYSGPWSKIYFVLWWLVSSVIWVNLFLALILENFLHKWDPRSHLQPLAGTPEATYQM TVELLFRDILEEPGEDELTERLSQHPHLWLCR |
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Target Type |
Literature-reported
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Target Bioclass |
Transporter and channel
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Family |
Calcium channel alpha-1 subunit (TC 1.A.1.11) family, Two pore calcium channel subfamily
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Subcellular location |
Late endosome membrane
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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) . 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. 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. 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. 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. 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.; (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.; (Microbial infection) Required for cell entry of coronaviruses SARS-CoV and SARS-CoV-2, as well as human coronavirus EMC (HCoV-EMC), by endocytosis.
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TTD ID | ||||||
Uniprot ID | ||||||
DrugMap ID | ||||||
Ensemble ID | ||||||
HGNC ID |
Probe(s) Labeling This Target
ABPP Probe
Probe name | Structure | Binding Site(Ratio) | Interaction ID | Ref | |
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IPM Probe Info |
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C82(0.77) | LDD1701 | [1] | |
NAIA_4 Probe Info |
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N.A. | LDD2226 | [2] | |
TFBX Probe Info |
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N.A. | LDD0027 | [3] |
Competitor(s) Related to This Target
The Interaction Atlas With This Target
The Protein(s) Related To This Target
Enzyme
Protein name | Family | Uniprot ID | |||
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Serine/threonine-protein kinase mTOR (MTOR) | PI3/PI4-kinase family | P42345 |
Transporter and channel
Other
Protein name | Family | Uniprot ID | |||
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HCLS1-associated protein X-1 (HAX1) | HAX1 family | O00165 |
References