Protein Details: Two pore calcium channel protein 1

Protein ID

ICDB_Pro_1686

Protein Name

Two pore calcium channel protein 1

Gene Name

Tpcn1; Tpc1

Organism

Rattus norvegicus (Rat)

Length

817 amino acids

AlphaFoldDB

AF-Q9WTN5-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. Required for mTOR-dependent nutrient sensing.

Sequence

MSVILDDDVLLILTLDEELSAPLTPSNGLGQEDLPSKNGGGQSGPNSQVPSLVSGADSPPSSPPGHNWEMNYQEAAIYLQEGQNNDKFFTHPKDARALAAYLFVHNHFFYMMELLTALLLLLLSLCESPAVPALKLRTYVHATLELFALMVVVFELCMKLRWLGFHTFVRHKRTMVKTSVLVVQFIEAIVVLVRQTSHVRVTRALRCIFLVDCRYCGGVRRNLRQIFQSLPPFMDILLLLLFFMIIFAILGFYLFSTNPSDPYFNTLENSIVNLFVLLTTANFPDVMMPSYSRNPWSCVFFIVYLSIELYFIMNLLLAVVFDTFNDIEKHKFKSLLLHKRTAIQHAYHLLVSQRRPAGISYRQFEGLMRFYKPRMSARERFLTFKALNQSNTPLLSLKDFYDIYEVAALQWKAKKNRQHWFDELPRTAFLIFKGINILVNSKAFQYFMYLVVAVNGVWILVETFMLKGGNFISKHVPWSYLVFLTIYGVELFMKVAGLGPVEYLSSGWNLFDFSVTAFAFLGLLALTLNMEPFYFIVVLRPLQLLRLFKLKKRYRNVLDTMFELLPRMASLGLTLLTFYYSFAIVGMEFFSGRLSPNCCNSSTVADAYRFINHTVGNKTKVEEGYYYLNNFDNILNSFVTLFELTVVNNWYIIMEGVTSQTSHWSRLYFMTFYIVTMVVMTIIVAFILEAFVFRMNYSRKSQESEVDSGIVIEKEMSKEELLAILELHREARGTSSDVTRLLDTLSQMEKYQQNSMVFLGRRSRTKSDLSLKMYQEEIQEWYEEHAREQEQQQLRGSAPSPAAQQTPGSRQRSQTVT

PDB Structures

Ligand Binding

1. DICL_CP

2. DICL_Pep

Binding Site

Disease

Location

Widely expressed. Expressed at relatively high level in kidney; liver and lung; and in the kidney it is expressed at inner medullary collecting ducts. . . .

DOI ID

10.1006/bbrc.2000.2435; 10.1101/gr.2596504

RefSeq

NP_647548.2;

Feature