Chloride Intracellular Channel Protein 2
From Proteopedia
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== Structure == | == Structure == | ||
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| + | == CLIC2 fonctions == | ||
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Revision as of 09:16, 16 November 2009
Contents |
CLIC2
Introduction
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CLIC proteins are a new class of soluble and membrane-bound proteins that have been grouped together on the basis of their sequence similarity. The proteins were named CLIC because the first members of this family to be characterized formed intracellular chloride channels (Heiss & Poustka, 1997). They display broad tissue and cellular distribution. They have been implicated in kidney function, cell division, and bone resorption. (Brett A. Cromer and al, 2007 1) They differ from the other classes of chloride ion channels in primary structure and in the transmembrane regions of the tertiary structure. Since the first member of CLIC, p64 (CLIC5), was discovered in bovine kidney, several members of the CLIC family have been found in other tissues from many species, including NCC27 (CLIC1), CLIC2, CLIC3, mtCLIC (CLIC4), and parchorin (CLIC6). (X. Meng and al, 2009) With the exception of p64 and parchorin, these proteins contain a conserved region of approximately 240 residues. (Brett A. Cromer and al, 2007 2) CLIC proteins can localize to distinct cellular membranes, including the nuclear membrane, lysosomal membranes, mitochondria, Golgi membranes, cell–cell junctions, and the plasma membrane. (Brett A. Cromer and al, 2007 1) The CLIC proteins show sequence homology with members of the glutathione-S-transferase (GST) superfamily. Another feature of CLIC proteins distinguishable from other ion channels is that they exist in two different forms: either as soluble globular proteins, or as an integral membrane protein that is incorporated into lipid bilayers and forms ion channels. (X. Meng and al, 2009) These features that are reminiscent of many bacterial pore-forming toxins. (Brett A. Cromer and al, 2007 2)
CLIC2 is one of the least characterized CLIC family members. At least two isoforms are known to exist, with the difference being an 18-residue insert occurring immediately after the first β-strand. (Brett A. Cromer and al, 2007 1) It has a molecular weight of 28.4 kDa and a calculated isoelectric point of 5.44. (Wei Mi and al, 2008) Human CLIC2 protein is composed of 247 amino acid residues and is found in many organs, including the spleen, lung, liver, and in both skeletal and cardiac muscles. (X. Meng and al, 2009) The CLIC2 gene locates in the telomeric region of Xq28 and is composed of six coding exons and five introns. Since this region of the X chromosome is closely associated with many hereditary diseases, CLIC2 has thus been proposed as a candidate gene for some genetic disorders linked to Xq28.9. (Wei Mi and al, 2008) Consistent with their high degree of primary structure homology, CLIC2 is similar to CLIC1 and CLIC4 in terms of tertiary structure. Like other members of the CLIC family, CLIC2 can exist as a soluble globular protein, or incorporate into a lipid bilayer to form a Cl– channel. (X. Meng and al, 2009 ) CLIC2 inhibits cardiac ryanodine receptor (RyR) calciumrelease channels, suggesting that CLIC2 may function to regulate calcium release from intracellular stores in the heart and skeletal muscles. (Brett A. Cromer and al, 2007 1) The N-terminal domain of CLIC2 lacks the cysteine equivalent to Cys59 of CLIC1, but contains another cysteine Cys33 that together with the conserved Cys30 (equivalent to Cys24 in CLIC1) forms a CxxC motif similar to glutaredoxin. (Brett A. Cromer and al, 2007 2)
Structure
Links between CLIC2 and the GST superfamily members
CLIC2 fonctions
References
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Céline Debarnot, Alexander Berchansky, Michal Harel, David Canner, Eran Hodis
