CLIC1
Domain
The active G-site contains a monothiol Cys-X-X-Ser motif which mediates glutathione-dependent redox catalysis.
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 a channel. The redox status of the active cysteine in Cys-X-X-Cys/Ser motif likely determines the capacity to adopt a soluble or membrane-inserted state. A conformation change of the N-terminal domain is thought to expose hydrophobic surfaces that trigger membrane insertion.
Function
In the soluble state, catalyzes glutaredoxin-like thiol disulfide exchange reactions with reduced glutathione as electron donor. Reduces selenite and dehydroascorbate and may act as an antioxidant during oxidative stress response (PubMed:25581026, PubMed:37759794). Can insert into membranes and form voltage-dependent multi-ion conductive channels. Membrane insertion seems to be redox-regulated and may occur only under oxidizing conditions. Involved in regulation of the cell cycle.
Post-translational modifications
Hydrogen peroxide treatment causes a conformation change, leading to dimerization and formation of an intramolecular disulfide bond between Cys-24 and Cys-59.
Sequence Similarities
Belongs to the chloride channel CLIC family.
Tissue Specificity
Expression is prominent in heart, placenta, liver, kidney and pancreas.
Cellular localization
- Nucleus
- Nucleus membrane
- Single-pass membrane protein
- Cytoplasm
- Cell membrane
- Single-pass membrane protein
- Endoplasmic reticulum
- Mostly in the nucleus including in the nuclear membrane (PubMed:12681486, PubMed:9139710). 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:11551966, PubMed:11940526, PubMed:12681486, PubMed:14613939, PubMed:9139710). Might not be present in the nucleus of cardiac cells (By similarity).
Alternative names
G6, NCC27, CLIC1, Chloride intracellular channel protein 1, Chloride channel ABP, Glutaredoxin-like oxidoreductase CLIC1, Glutathione-dependent dehydroascorbate reductase CLIC1, Nuclear chloride ion channel 27, Regulatory nuclear chloride ion channel protein, hRNCC