CLIC5
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 chloride 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 (By similarity).
Function
In the soluble state, catalyzes glutaredoxin-like thiol disulfide exchange reactions with reduced glutathione as electron donor (By similarity). Can insert into membranes and form non-selective ion channels almost equally permeable to Na(+), K(+) and Cl(-) (PubMed:15184393, PubMed:18028448). Required for normal hearing (PubMed:24781754). It is necessary for the formation of stereocilia in the inner ear and normal development of the organ of Corti (By similarity). May play a role in the regulation of transepithelial ion absorption and secretion. Is required for the development and/or maintenance of the proper glomerular endothelial cell and podocyte architecture (PubMed:15184393, PubMed:18028448, PubMed:20335315). Plays a role in formation of the lens suture in the eye, which is important for normal optical properties of the lens (By similarity).
Involvement in disease
Deafness, autosomal recessive, 103
DFNB103
A form of sensorineural deafness with onset in early childhood. Hearing impairment progresses from mild to severe or even profound before the second decade, and is accompanied by vestibular areflexia.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the chloride channel CLIC family.
Tissue Specificity
Widely expressed in both fetal and adult human tissues (PubMed:24781754). Isoform 1 is expressed in renal glomeruli endothelial cells and podocytes (at protein level).
Cellular localization
- Isoform 1
- Cytoplasm
- Cytoskeleton
- Cytoplasm
- Cell cortex
- Membrane
- Single-pass membrane protein
- Apical cell membrane
- Single-pass membrane protein
- Cytoplasm
- Mitochondrion
- Cell projection
- Stereocilium
- Associates with the cortical actin cytoskeleton (PubMed:10793131, PubMed:15184393). Localizes to the apical region of cochlear hair cells, at the base of the actin-rich hair bundle (By similarity). Colocalizes with podocalyxin at the apical cell membrane in renal glomeruli (PubMed:20335315). May localize to the centrosome in lens epithelial cells (By similarity). Exists both as soluble cytoplasmic protein and as membrane protein with probably a single transmembrane domain (By similarity).
- Isoform 2
- Golgi apparatus
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Centrosome
- Colocalizes with AKAP9 at the Golgi apparatus as well as, to a lesser extent, the centrosome.
Alternative names
Chloride intracellular channel protein 5, Glutaredoxin-like oxidoreductase CLIC5, CLIC5