| UniProt functional annotation for O00299 | |||
| UniProt code: O00299. |
| Organism: | Homo sapiens (Human). | |
| Taxonomy: | Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. | |
| Function: | Can insert into membranes and form chloride ion channels. Channel activity depends on the pH. Membrane insertion seems to be redox-regulated and may occur only under oxydizing conditions. Involved in regulation of the cell cycle. {ECO:0000269|PubMed:10834939, ECO:0000269|PubMed:11195932, ECO:0000269|PubMed:11551966, ECO:0000269|PubMed:11940526, ECO:0000269|PubMed:11978800, ECO:0000269|PubMed:14613939, ECO:0000269|PubMed:9139710}. | |
| Subunit: | Monomer. Homodimer (in vitro). Interacts with TRAPPC2. Dimerization requires a conformation change that leads to the exposure of a large hydrophobic surface. In vivo, this may lead to membrane insertion. Interacts with AKAP9. {ECO:0000269|PubMed:11551966, ECO:0000269|PubMed:12163479, ECO:0000269|PubMed:12681486, ECO:0000269|PubMed:14613939}. | |
| Subcellular location: | Nucleus {ECO:0000269|PubMed:12681486, ECO:0000269|PubMed:9139710}. Nucleus membrane {ECO:0000269|PubMed:9139710}; Single-pass membrane protein {ECO:0000255}. Cytoplasm {ECO:0000269|PubMed:10793131, ECO:0000269|PubMed:11551966, ECO:0000269|PubMed:12681486, ECO:0000269|PubMed:9139710, ECO:0000305|PubMed:11978800, ECO:0000305|PubMed:14613939}. Cell membrane {ECO:0000269|PubMed:11551966, ECO:0000269|PubMed:11940526, ECO:0000269|PubMed:14613939, ECO:0000305|PubMed:11978800}; Single-pass membrane protein {ECO:0000269|PubMed:11551966, ECO:0000269|PubMed:14613939}. Note=Mostly in the nucleus including in the nuclear membrane (PubMed:9139710, PubMed:12681486). Small amount in the cytoplasm and the plasma membrane (PubMed:9139710). Exists both as soluble cytoplasmic protein and as membrane protein with probably a single transmembrane domain (PubMed:11940526, PubMed:11551966, PubMed:14613939). {ECO:0000269|PubMed:11551966, ECO:0000269|PubMed:11940526, ECO:0000269|PubMed:12681486, ECO:0000269|PubMed:14613939, ECO:0000269|PubMed:9139710}. | |
| Tissue specificity: | Expression is prominent in heart, placenta, liver, kidney and pancreas. {ECO:0000269|PubMed:10793131}. | |
| Domain: | Members of this family may change from a globular, soluble state to a state where the N-terminal domain is inserted into the membrane and functions as chloride channel. A conformation change of the N-terminal domain is thought to expose hydrophobic surfaces that trigger membrane insertion. {ECO:0000269|PubMed:14613939, ECO:0000269|PubMed:18850721}. | |
| Ptm: | Hydrogen peroxide treatment causes a conformation change, leading to dimerization and formation of an intramolecular disulfide bond between Cys-24 and Cys-59. | |
| Miscellaneous: | The protein seems to have very low affinity for glutathione, even though glutathione binding was observed in protein crystals. | |
| Similarity: | Belongs to the chloride channel CLIC family. {ECO:0000305}. | |
Annotations taken from UniProtKB at the EBI.