Protein Details: Two pore calcium channel protein 1

Protein ID

ICDB_Pro_1476

Protein Name

Two pore calcium channel protein 1

Gene Name

Tpcn1; Kiaa1169; Tpc1

Organism

Mus musculus (Mouse)

Length

817 amino acids

AlphaFoldDB

AF-Q9EQJ0-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. 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 (By similarity). Required for mTOR-dependent nutrient sensing.

Sequence

MAVSLDDDVPLILTLDEAESAPLPPSNSLGQEQLPSKNGGSHSIHNSQVPSLVSGADSPPSSPTGHNWEMNYQEAAIYLQEGQNNDKFFTHPKDARALAAYLFVHNHFFYMMELLTALLLLLLSLCESPAVPVLKLHTYVHATLELFALMVVVFELCMKLRWLGFHTFVRHKRTMVKTSVLVVQFIEAIVVLVRQTSHVRVTRALRCIFLVDCRYCGGVRRNLRQIFQSLPPFMDILLLLLFFMIIFAILGFYLFSTNPSDPYFSTLENSIVNLFVLLTTANFPDVMMPSYSRNPWSCVFFIVYLSIELYFIMNLLLAVVFDTFNDIEKHKFKSLLLHKRTAIQHAYGLLASQRRPAGISYRQFEGLMRFYKPRMSARERFLTFKALNQSNTPLLSLKDFYDIYEVAALQWKAKRNRQHWFDELPRTAFLIFKGINILVNSKAFQYFMYLVVAVNGVWILVETFMLKGGNFTSKHVPWSYLVFLTIYGVELFMKVAGLGPVEYLSSGWNLFDFSVTAFAFLGLLALTLNMEPFYFIVVLRPLQLLRLFKLKKRYRNVLDTMFELLPRMASLGLTLLTFYYSFAIVGMEFFNGRLTPNCCNTSTVADAYRFINHTVGNKTKVEEGYYYLNNFDNILNSFVTLFELTVVNNWYIIMEGVTSQTSHWSRLYFMTFYIVTMVVMTIIVAFILEAFVFRMNYSRKSQDSEVDSGIVIEKEMSKEELMAVLELYREERGTSSDVTRLLDTLSQMEKYQQNSMVFLGRRSRTKSDLSLKMYQEEIQEWYEEHAREQEQQKLRGSVPGPAAQQPPGSRQRSQTVT

PDB Structures

Ligand Binding

1. DICL_CP

2. DICL_Pep

Binding Site

Disease

Location

Mainly expressed in epithelial tissues like lung; kidney; colon; spleen and liver (at protein level)

DOI ID

10.1073/pnas.142287799; 10.1126/science.1112014; 10.1101/gr.2596504; 10.1093/dnares/10.4.167; 10.1016/j.cell.2010.12.001; 10.1016/j.cell.2012.08.036; 10.1016/j.cell.2013.01.023; 10.1038/nchembio.1522; 10.1126/science.1258758; 10.1038/s41598-017-10607-4

RefSeq

NP_665852.1 [Q9EQJ0-1]; XP_011246503.1

Feature