Protein: Two pore calcium channel protein 1 (Voltage-dependent calcium channel protein TPC1) (Q9EQJ0)
Organism: Mus musculus (Mouse)
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.
Subcellular location: Lysosome membrane {ECO:0000250|UniProtKB:Q9ULQ1}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q9ULQ1}. Endosome membrane {ECO:0000250|UniProtKB:Q9ULQ1}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q9ULQ1}. Early endosome membrane {ECO:0000269|PubMed:28855648}; Multi-pass membrane protein {ECO:0000269|PubMed:28855648}. Recycling endosome membrane {ECO:0000269|PubMed:28855648}; Multi-pass membrane protein {ECO:0000269|PubMed:28855648}.
Sequence: MAVSLDDDVPLILTLDEAESAPLPPSNSLGQEQLPSKNGGSHSIHNSQVPSLVSGADSPPSSPTGHNWEMNYQEAAIYLQEGQNNDKFFTHPKDARALAAYLFVHNHFFYMMELLTALLLLLLSLCESPAVPVLKLHTYVHATLELFALMVVVFELCMKLRWLGFHTFVRHKRTMVKTSVLVVQFIEAIVVLVRQTSHVRVTRALRCIFLVDCRYCGGVRRNLRQIFQSLPPFMDILLLLLFFMIIFAILGFYLFSTNPSDPYFSTLENSIVNLFVLLTTANFPDVMMPSYSRNPWSCVFFIVYLSIELYFIMNLLLAVVFDTFNDIEKHKFKSLLLHKRTAIQHAYGLLASQRRPAGISYRQFEGLMRFYKPRMSARERFLTFKALNQSNTPLLSLKDFYDIYEVAALQWKAKRNRQHWFDELPRTAFLIFKGINILVNSKAFQYFMYLVVAVNGVWILVETFMLKGGNFTSKHVPWSYLVFLTIYGVELFMKVAGLGPVEYLSSGWNLFDFSVTAFAFLGLLALTLNMEPFYFIVVLRPLQLLRLFKLKKRYRNVLDTMFELLPRMASLGLTLLTFYYSFAIVGMEFFNGRLTPNCCNTSTVADAYRFINHTVGNKTKVEEGYYYLNNFDNILNSFVTLFELTVVNNWYIIMEGVTSQTSHWSRLYFMTFYIVTMVVMTIIVAFILEAFVFRMNYSRKSQDSEVDSGIVIEKEMSKEELMAVLELYREERGTSSDVTRLLDTLSQMEKYQQNSMVFLGRRSRTKSDLSLKMYQEEIQEWYEEHAREQEQQKLRGSVPGPAAQQPPGSRQRSQTVT
InterPro domains: - IPR005821: Ion transport domain (domain) [107-692]
- IPR028801: Two pore channel protein 1 (family) [1-793]
- IPR027359: Voltage-dependent channel domain superfamily (homologous_superfamily) [434-558]
Interaction partners: - Two pore channel protein 2
- ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005215 (transporter activity), GO:0022857 (transmembrane transporter activity), GO:0005515 (protein binding), GO:1901702 (salt transmembrane transporter activity), GO:0015075 (monoatomic ion transmembrane transporter activity), GO:0042802 (identical protein binding), GO:0022803 (passive transmembrane transporter activity), GO:0015318 (inorganic molecular entity transmembrane transporter activity), GO:0005216 (monoatomic ion channel activity), GO:0022890 (inorganic cation transmembrane transporter activity), GO:0015085 (calcium ion transmembrane transporter activity), GO:0015267 (channel activity), GO:0008324 (monoatomic cation transmembrane transporter activity), GO:0005261 (monoatomic cation channel activity), GO:0005262 (calcium channel activity), GO:0022839 (monoatomic ion gated channel activity), GO:0022836 (gated channel activity), GO:0046873 (metal ion transmembrane transporter activity), GO:0140828 (metal cation:monoatomic cation antiporter activity), GO:0099604 (ligand-gated calcium channel activity), GO:0070727 (cellular macromolecule localization), GO:0022832 (voltage-gated channel activity), GO:0005245 (voltage-gated calcium channel activity), GO:0008332 (low voltage-gated calcium channel activity)
Biological Process (BP): GO:0008150 (biological process), GO:0009987 (cellular process), GO:0065007 (biological regulation), GO:0051179 (localization), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0016032 (viral process), GO:0044419 (biological process involved in interspecies interaction between organisms), GO:0051234 (establishment of localization), GO:0009893 (positive regulation of metabolic process), GO:0055085 (transmembrane transport), GO:0046794 (transport of virus), GO:0019058 (viral life cycle), GO:0044403 (biological process involved in symbiotic interaction), GO:0019222 (regulation of metabolic process), GO:0050794 (regulation of cellular process), GO:0048522 (positive regulation of cellular process), GO:0051701 (biological process involved in interaction with host), GO:0009894 (regulation of catabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0034220 (monoatomic ion transmembrane transport), GO:0046718 (viral entry into host cell), GO:0075509 (endocytosis involved in viral entry into host cell), GO:0031325 (positive regulation of cellular metabolic process), GO:0009896 (positive regulation of catabolic process), GO:0006810 (transport), GO:0010506 (regulation of autophagy), GO:0031331 (positive regulation of cellular catabolic process), GO:0016192 (vesicle-mediated transport), GO:0010508 (positive regulation of autophagy), GO:0031329 (regulation of cellular catabolic process), GO:0006811 (monoatomic ion transport), GO:0044000 (movement in host), GO:0044409 (entry into host), GO:0006897 (endocytosis)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0031090 (organelle membrane), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0005768 (endosome), GO:0005773 (vacuole), GO:0043227 (membrane-bounded organelle), GO:0036019 (endolysosome), GO:0000323 (lytic vacuole), GO:0043231 (intracellular membrane-bounded organelle), GO:0098588 (bounding membrane of organelle), GO:0012506 (vesicle membrane), GO:0005774 (vacuolar membrane), GO:0010008 (endosome membrane), GO:0031982 (vesicle), GO:0030659 (cytoplasmic vesicle membrane), GO:0005764 (lysosome), GO:0097708 (intracellular vesicle), GO:0098852 (lytic vacuole membrane), GO:0005765 (lysosomal membrane)