CLIC3
Domain
The active G-site contains a dithiol Cys-X-X-Cys 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 chloride channel. The redox status of the active cysteine in Cys-X-X-Cys 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 (By similarity).
Function
In the soluble state, catalyzes glutaredoxin-like thiol disulfide exchange reactions with reduced glutathione as electron donor (PubMed:28198360, PubMed:37759794). Reduced in a glutathione-dependent way and secreted into the extracellular matrix where it activates TGM2 and promotes blood vessel growth during tissue remodeling as occurs in tumorigenesis. Can reduce specific cysteines in TGM2 and regulate cofactor binding (PubMed:28198360). Can insert into membranes and form outwardly rectifying chloride ion channels. May participate in cellular growth control.
Sequence Similarities
Belongs to the chloride channel CLIC family.
Tissue Specificity
Detected in placenta (at protein level). Widely expressed. High expression is found in placenta followed by lung and heart. Low expression in skeletal muscle, kidney and pancreas.
Cellular localization
- Nucleus
- Membrane
- Single-pass membrane protein
- Cell membrane
- Single-pass membrane protein
- Cytoplasm
- Secreted
- Extracellular space
- Extracellular matrix
- Predominantly nuclear. Some protein was found in the cytoplasm. Exists both as soluble cytoplasmic protein and as membrane protein with probably a single transmembrane domain (By similarity). Secreted into the extracellular matrix by activated fibroblasts.
Alternative names
Chloride intracellular channel protein 3, Glutaredoxin-like oxidoreductase CLIC3, CLIC3