General Information of Target

Target ID LDTP09270
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
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MAEPQAESEPLLGGARGGGGDWPAGLTTYRSIQVGPGAAARWDLCIDQAVVFIEDAIQYR
SINHRVDASSMWLYRRYYSNVCQRTLSFTIFLILFLAFIETPSSLTSTADVRYRAAPWEP
PCGLTESVEVLCLLVFAADLSVKGYLFGWAHFQKNLWLLGYLVVLVVSLVDWTVSLSLVC
HEPLRIRRLLRPFFLLQNSSMMKKTLKCIRWSLPEMASVGLLLAIHLCLFTMFGMLLFAG
GKQDDGQDRERLTYFQNLPESLTSLLVLLTTANNPDVMIPAYSKNRAYAIFFIVFTVIGS
LFLMNLLTAIIYSQFRGYLMKSLQTSLFRRRLGTRAAFEVLSSMVGEGGAFPQAVGVKPQ
NLLQVLQKVQLDSSHKQAMMEKVRSYGSVLLSAEEFQKLFNELDRSVVKEHPPRPEYQSP
FLQSAQFLFGHYYFDYLGNLIALANLVSICVFLVLDADVLPAERDDFILGILNCVFIVYY
LLEMLLKVFALGLRGYLSYPSNVFDGLLTVVLLVLEISTLAVYRLPHPGWRPEMVGLLSL
WDMTRMLNMLIVFRFLRIIPSMKLMAVVASTVLGLVQNMRAFGGILVVVYYVFAIIGINL
FRGVIVALPGNSSLAPANGSAPCGSFEQLEYWANNFDDFAAALVTLWNLMVVNNWQVFLD
AYRRYSGPWSKIYFVLWWLVSSVIWVNLFLALILENFLHKWDPRSHLQPLAGTPEATYQM
TVELLFRDILEEPGEDELTERLSQHPHLWLCR
Target Type
Literature-reported
Target Bioclass
Transporter and channel
Family
Calcium channel alpha-1 subunit (TC 1.A.1.11) family, Two pore calcium channel subfamily
Subcellular location
Late endosome membrane
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.
TTD ID
T97754
Uniprot ID
Q8NHX9
DrugMap ID
TTZWC8B
Ensemble ID
ENST00000294309.8
HGNC ID
HGNC:20820

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 3 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
IPM
 Probe Info 
C82(0.77)  LDD1701  [1]
NAIA_4
 Probe Info 
N.A.  LDD2226  [2]
TFBX
 Probe Info 
N.A.  LDD0027  [3]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0023  KB03 MDA-MB-231 C82(0.77)  LDD1701  [1]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Serine/threonine-protein kinase mTOR (MTOR) PI3/PI4-kinase family P42345
Transporter and channel
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Two pore channel protein 1 (TPCN1) Calcium channel alpha-1 subunit (TC 1.A.1.11) family Q9ULQ1
Two pore channel protein 2 (TPCN2) Calcium channel alpha-1 subunit (TC 1.A.1.11) family Q8NHX9
Other
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
HCLS1-associated protein X-1 (HAX1) HAX1 family O00165

The Drug(s) Related To This Target

Investigative
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Phosphatidyl (3,5) Inositol Biphosphate Small molecular drug D01ZCI

References

1 Nucleophilic covalent ligand discovery for the cysteine redoxome. Nat Chem Biol. 2023 Nov;19(11):1309-1319. doi: 10.1038/s41589-023-01330-5. Epub 2023 May 29.
Mass spectrometry data entry: PXD039908 , PXD029761
2 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264
3 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255