TPCN1
Description
The TPCN1 (two pore segment channel 1) is a protein-coding gene located on chromosome 12.
TPCN1 is a human protein encoded by the TPCN1 gene. It is an ion channel that differs from other calcium and sodium channels in its structure. Unlike those channels which have four homologous domains, each containing six transmembrane segments (S1 to S6), TPCN1 only contains two domains (each containing segments S1 to S6). The structure of a TPCN1 ortholog from Arabidopsis thaliana has been solved using X-ray crystallography, revealing a fold similar to that of voltage-gated ion channels with EF hands. Only one voltage sensor domain appears to be responsible for voltage sensing. Genetic knockout and pharmacological inhibition experiments have shown that TPCN1, along with TPC2, is essential for infection by Ebola and Marburg viruses in mice.
TPCN1 is an intracellular channel that was initially identified as a non-selective calcium-permeable channel activated by NAADP (nicotinic acid adenine dinucleotide phosphate). It has also been found to be a voltage-gated, highly selective sodium channel that is activated directly by PI(3,5)P2 (phosphatidylinositol 3,5-bisphosphate) and senses pH changes, conferring electrical excitability to organelles. TPCN1 is localized to the early and recycling endosomal membranes, where it is involved in the uptake and processing of proteins and regulates organellar membrane excitability, membrane trafficking, and pH homeostasis. The ion selectivity of TPCN1 is not fixed but is agonist-dependent. Under specific ionic conditions, it can be activated by both NAADP and PI(3,5)P2. TPCN1 is required for mTOR-dependent nutrient sensing.
TPCN1 is also known as TPC1.
Associated Diseases
- familial idiopathic steroid-resistant nephrotic syndrome
- hemoglobin D disease
- Imerslund-Grasbeck syndrome type 2
- hereditary persistence of fetal hemoglobin-sickle cell disease syndrome
- proteinuria, chronic benign
- dominant beta-thalassemia
- delta-beta-thalassemia
- nail-patella-like renal disease
- hemoglobin E-beta-thalassemia syndrome
- hemoglobin E disease
- hemoglobin C-beta-thalassemia syndrome
- alpha-thalassemia-myelodysplastic syndrome
- hemolytic anemia due to pyrimidine 5' nucleotidase deficiency
