3 Ontology Annotations
| GO Term | Gene Name |
|---|---|
| GO:0005247 | IPR002247 |
| GO:0006821 | IPR002247 |
| GO:0016020 | IPR002247 |
| Type: | Family | Name: | Chloride channel ClC-5 |
| Description: | Chloride channels (CLCs) constitute an evolutionarily well-conserved family of voltage-gated channels that are structurally unrelated to the other known voltage-gated channels. They are found in organisms ranging from bacteria to yeasts and plants, and also to animals. Their functions in higher animals likely include the regulation of cell volume, control of electrical excitability and trans-epithelial transport [].The first member of the family (CLC-0) was expression-cloned from the electric organ of Torpedo marmorata [], and subsequently nine CLC-like proteins have been cloned from mammals. They are thought to function as multimers of two or more identical or homologous subunits, and they have varying tissue distributions and functional properties. To date, CLC-0, CLC-1, CLC-2, CLC-4 and CLC-5 have been demonstrated to form functional Cl- channels; whether the remaining isoforms do so is either contested or unproven. One possible explanation for the difficulty in expressing activatable Cl- channels is that some of the isoforms may function as Cl- channels of intracellular compartments, rather than of the plasma membrane. However, they are all thought to have a similar transmembrane (TM) topology, initial hydropathy analysis suggesting 13 hydrophobic stretches long enough to form putative TM domains []. Recently, the postulated TM topology has been revised, and it now seems likely that the CLCs have 10 (or possibly 12) TM domains, with both N- and C-termini residing in the cytoplasm [].A number of human disease-causing mutations have been identified in the genes encoding CLCs. Mutations in CLCN1, the gene encoding CLC-1, the major skeletal muscle Cl- channel, lead to both recessively and dominantly-inherited forms of muscle stiffness or myotonia []. Similarly, mutations in CLCN5, which encodes CLC-5, a renal Cl- channel, lead to several forms of inherited kidney stone disease []. These mutations have been demonstrated to reduce or abolish CLC function.CLC-5, with 746 amino acid residues, is a member of the CLC family that shows most similarity to the CLC-3 and CLC-4 channels, to which it is ~80%identical at the amino acid level. It is predominantly expressed in the kidney, but can be found in the brain and liver []. As mentioned above,mutations in the CLCN5 gene cause certain hereditary kidney stone diseases, including Dent's disease, an X-chromosome linked syndrome characterised byproteinuria, hypercalciuria, and kidney stones (nephrolithiasis), leading to progressive renal failure. When the native protein is expressed, it givesrises to strongly outwardly-rectifying Cl-currents; however, the mutated channel forms show loss-of-function [, ]. Recent studies have suggestedthat CLC-5 may play an important role in endocytosis in renal proximal tubule cells (probably by providing a shunt for the potential generated bythe H+-ATPase), and that disruption of this function may impair endocytosis, accounting for the proteinuria observed in Dent's disease []. | Short Name: | Cl_channel-5 |
| GO Term | Gene Name |
|---|---|
| GO:0005247 | IPR002247 |
| GO:0006821 | IPR002247 |
| GO:0016020 | IPR002247 |
