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TPC2

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Target not currently curated in GtoImmuPdb

Target id: 393

Nomenclature: TPC2

Family: CatSper and Two-Pore channels (TPC)

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 12 0 752 11q13.3 TPCN2 two pore segment channel 2
Mouse 12 0 731 7 F5 Tpcn2 two pore segment channel 2
Rat 6 0 711 1q42 Tpcn2 two pore segment channel 2
Previous and Unofficial Names Click here for help
two pore calcium channel protein 2
Database Links Click here for help
Alphafold
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Functional Characteristics Click here for help
Organelle voltage-independent Na+-selective channel (Na+>>K+>>Ca2+). Sensitive to the levels of PI(3,5)P2. Activated by decreases in [ATP] or depletion of extracellular amino acids

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Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
phosphatidyl (3,5) inositol bisphosphate Small molecule or natural product Click here for species-specific activity table Hs Activation 6.4 pEC50 - - 4
pEC50 6.4 (EC50 4x10-7 M) [4]
TPC2-A1-N Small molecule or natural product Hs Activation 5.1 pEC50 - - 1
pEC50 5.1 (EC50 7.8x10-6 M) [1]
Description: In cells stably expressing hTPC2L11A/L12A using a FLIPR-based Ca2+ assay
TPC2-A1-P Small molecule or natural product Hs Activation 5.0 pEC50 - - 1
pEC50 5.0 (EC50 1.05x10-5 M) [1]
Description: In cells stably expressing hTPC2L11A/L12A using a FLIPR-based Ca2+ assay
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
SG-005 Small molecule or natural product Hs Inhibition 5.6 pIC50 - - 2
pIC50 5.6 (IC50 2.5x10-6 M) [2]
Description: Inhibition of TPC2-A1-N-mediated activation of hTPC2.
MT-8 Small molecule or natural product Hs Inhibition 5.6 pIC50 - - 3
pIC50 5.6 (IC50 2.6x10-6 M) [3]
Description: Inhibition of hTPC2 stably overexpressed in HEK293 cells, in endolysosomal patch clamp experiments
SG-094 Small molecule or natural product Hs Inhibition 5.1 pIC50 - - 2
pIC50 5.1 (IC50 8.3x10-6 M) [2]
Description: Inhibition of TPC2-A1-P-mediated activation of hTPC2.
UM-9 Small molecule or natural product Hs Inhibition 5.0 pIC50 - - 3
pIC50 5.0 (IC50 9.5x10-6 M) [3]
Description: Inhibition of hTPC2 stably overexpressed in HEK293 cells, in endolysosomal patch clamp experiments
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
verapamil Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 5.0 pIC50 - - 4
pIC50 5.0 (IC50 1x10-5 M) [4]
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Tpcn2Gt(YHD437)Byg Tpcn2Gt(YHD437)Byg/Tpcn2Gt(YHD437)Byg
involves: 129P2/OlaHsd * C57BL/6
MGI:2385297  MP:0003562 abnormal pancreatic beta cell physiology PMID: 19387438 

References

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1. Gerndt S, Chen CC, Chao YK, Yuan Y, Burgstaller S, Scotto Rosato A, Krogsaeter E, Urban N, Jacob K, Nguyen ONP et al.. (2020) Agonist-mediated switching of ion selectivity in TPC2 differentially promotes lysosomal function. Elife, 9. DOI: 10.7554/eLife.54712 [PMID:32167471]

2. Müller M, Gerndt S, Chao YK, Zisis T, Nguyen ONP, Gerwien A, Urban N, Müller C, Gegenfurtner FA, Geisslinger F et al.. (2021) Gene editing and synthetically accessible inhibitors reveal role for TPC2 in HCC cell proliferation and tumor growth. Cell Chem Biol, 28 (8): 1119-1131.e27. [PMID:33626324]

3. Netcharoensirisuk P, Abrahamian C, Tang R, Chen CC, Rosato AS, Beyers W, Chao YK, Filippini A, Di Pietro S, Bartel K et al.. (2021) Flavonoids increase melanin production and reduce proliferation, migration and invasion of melanoma cells by blocking endolysosomal/melanosomal TPC2. Sci Rep, 11 (1): 8515. [PMID:33875769]

4. Wang X, Zhang X, Dong XP, Samie M, Li X, Cheng X, Goschka A, Shen D, Zhou Y, Harlow J et al.. (2012) TPC proteins are phosphoinositide- activated sodium-selective ion channels in endosomes and lysosomes. Cell, 151 (2): 372-83. [PMID:23063126]

Contributors

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