Protein Details: Two pore channel protein 1

Protein ID

ICDB_Pro_1673

Protein Name

Two pore channel protein 1

Gene Name

TPCN1; KIAA1169; TPC1

Organism

Homo sapiens (Human)

Length

816 amino acids

AlphaFoldDB

AF-Q9ULQ1-F1-model_v4.pdb

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 voltage-gated highly-selective Na(+) channel activated directly by PI(3;5)P2 (phosphatidylinositol 3;5-bisphosphate) that senses pH changes and confers electrical excitability to organelles. Localizes to the early and recycling endosomes membranes where it plays a role in the uptake and processing of proteins and regulates organellar membrane excitability; membrane trafficking and pH homeostasis (Probable). 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 (Probable). Required for mTOR-dependent nutrient sensing (Probable). (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.

Sequence

MAVSLDDDVPLILTLDEGGSAPLAPSNGLGQEELPSKNGGSYAIHDSQAPSLSSGGESSPSSPAHNWEMNYQEAAIYLQEGENNDKFFTHPKDAKALAAYLFAHNHLFYLMELATALLLLLLSLCEAPAVPALRLGIYVHATLELFALMVVVFELCMKLRWLGLHTFIRHKRTMVKTSVLVVQFVEAIVVLVRQMSHVRVTRALRCIFLVDCRYCGGVRRNLRQIFQSLPPFMDILLLLLFFMIIFAILGFYLFSPNPSDPYFSTLENSIVSLFVLLTTANFPDVMMPSYSRNPWSCVFFIVYLSIELYFIMNLLLAVVFDTFNDIEKRKFKSLLLHKRTAIQHAYRLLISQRRPAGISYRQFEGLMRFYKPRMSARERYLTFKALNQNNTPLLSLKDFYDIYEVAALKWKAKKNREHWFDELPRTALLIFKGINILVKSKAFQYFMYLVVAVNGVWILVETFMLKGGNFFSKHVPWSYLVFLTIYGVELFLKVAGLGPVEYLSSGWNLFDFSVTVFAFLGLLALALNMEPFYFIVVLRPLQLLRLFKLKERYRNVLDTMFELLPRMASLGLTLLIFYYSFAIVGMEFFCGIVFPNCCNTSTVADAYRWRNHTVGNRTVVEEGYYYLNNFDNILNSFVTLFELTVVNNWYIIMEGVTSQTSHWSRLYFMTFYIVTMVVMTIIVAFILEAFVFRMNYSRKNQDSEVDGGITLEKEISKEELVAVLELYREARGASSDVTRLLETLSQMERYQQHSMVFLGRRSRTKSDLSLKMYQEEIQEWYEEHAREQEQQRQLSSSAAPAAQQPPGSRQRSQTVT

PDB Structures

Ligand Binding

1. DICL_CP

2. DICL_Pep

Binding Site

Disease

Scleredema Adultorum and Coffin-Siris Syndrome

Location

Highest expression found in the heart and kidney; and lowest expression found in the spleen

DOI ID

10.1038/nature08030; 10.1093/dnares/6.5.329; 10.1093/dnares/9.3.99; 10.1038/ng1285; 10.1038/nature04569; 10.1101/gr.2596504; 10.1083/jcb.200904073; 10.1074/jbc.m110.162073; 10.1016/j.cell.2012.08.036; 10.1016/j.cell.2013.01.023; 10.1038/nchembio.1522; 10.1016/j.jprot.2013.11.014; 10.1126/science.1258758; 10.1016/j.tips.2020.06.002; 10.1126/scisignal.abd5605; 10.1038/s41467-021-24735-z

RefSeq

NP_001137291.1 [Q9ULQ1-3]; NP_001288143.1; NP_060371.2 [Q9ULQ1-1]; XP_011536792.1; XP_011536794.1 [Q9ULQ1-1];