4/19/2023 0 Comments Clc sequence viewer 7.5 download![]() ![]() Based on sequence homology, the nine mammalian ClC proteins can be grouped into three classes, of which the first ( ClC-1, ClC-2, ClC-Ka and ClC-Kb) is expressed primarily in plasma membranes, whereas the other two ( ClC-3, ClC-4, and ClC-5 and ClC-6 and ClC-7) are expressed primarily in organellar membranes. Localization and function ĬlC-5 belongs to the family of voltage gated chloride channel that are regulators of membrane excitability, transepithelial transport and cell volume in different tissues. The proton glutamate is crucial to the H + transport acting as an H + transfer site. The gating glutamate is necessary for both H + transport and ClC-5 voltage dependence. Two important amino acids for the proper ClC-5 function are the glutamic acids at position 211 and 268 called respectively “gating glutamate” and “proton glutamate”. The Cl − selectivity filter is principally driven by helices D, F, N, and R, which are conveyed together near the channel center. Helices B, H, I, O, P, and Q are the six major helices involved in the formation of dimer’s interface and are crucial for proper pore configuration. The canonical 746- amino acid ClC-5 protein has 18 membrane spanning α-helices (named A to R), an intracellular N- terminal domain and a cytoplasmic C-terminus containing two cystathionine beta-synthase (CBS) domains which are known to be involved in the regulation of ClC-5 activity. ClC-5 can form both homo- and hetero- dimers due to its marked sequence homology with ClC-3 and ClC-4. Like all ClC channels, ClC-5 needs to dimerize to create the pore through which the ions pass. The chloride channel H +/Cl − exchanger ClC-5 The three promoters drive with varying degree of efficiency 11 different mRNAs, with transcription initiating from at least three different start sites. ![]() Several different 5’ alternatively used exons have been recognized in the human kidney. Two strong and one weak promoters were predicted to be present in the CLCN5 gene. The 5’ untranslated region (5’UTR) of CLCN5 is complex and not entirely clarified. The CLCN5 gene has 8 paralogues ( CLCN1, CLCN2, CLCN3, CLCN4, CLCN6, CLCN7, CLCNKA, CLCNKB) and 201 orthologues among jawed vertebrates ( Gnathostomata).įive different CLCN5 gene transcripts have been discovered, two of which (transcript variants 3 and 4 ) encode for the canonical 746 amino acid protein, two (transcript variants 1 and 2 ) for the NH 2-terminal extended 816 amino acid protein and one does not encode for any protein (Transcript variant 5, ). It extends over about 170 Kb of genomic DNA, has a coding region of 2,238 bp and consists of 17 exons including 11 coding exons (from 2 to 12). The human CLCN5 gene (MIM#300008, reference sequence NG_007159.2) is localized in the pericentromeric region on chromosome Xp11.23. 3.2 DNA testing and genetic counselling.2 The chloride channel H +/Cl − exchanger ClC-5.Mutations in the CLCN5 gene cause an X-linked recessive nephropathy named Dent disease (Dent disease 1 MIM#300009) characterized by excessive urinary loss of low-molecular-weight proteins and of calcium ( hypercalciuria), nephrocalcinosis (presence of calcium phosphate aggregates in the tubular lumen and/or interstitium) and nephrolithiasis (kidney stones). ClC-5 is mainly expressed in the kidney, in particular in proximal tubules where it participates to the uptake of albumin and low-molecular-weight proteins, which is one of the principal physiological role of proximal tubular cells. The CLCN5 gene encodes the chloride channel Cl-/H+ exchanger ClC-5. regulation of anion transmembrane transport.
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