Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Gene: CLIC2 - chloride intracellular channel 2

Homo sapiens

Synonyms: Chloride intracellular channel protein 2, CLIC2b, XAP121

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Dulhunty, A.F., Board, P.G., Heiss, N.S., Fan, L.

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Disease relevance of CLIC2

Since a direct association exists between a number of human chloride channel genes and a range of hereditary diseases, CLIC2 possibly represents a candidate for one of the many diseases linked to Xq28 [1].

High impact information on CLIC2

Sequence alignments showed that CLIC-2 has a high degree of sequence similarity with CLIC-1 and some similarity to the omega class of glutathione transferases (GSTO) [2].
Functional studies showed that CLIC-2 inhibited cardiac ryanodine receptor Ca2+ release channels in lipid bilayers when added to the cytoplasmic side of the channels and inhibited Ca2+ release from cardiac sarcoplasmic reticulum vesicles [2].
While the CXXC active site motif is conserved between CLIC-2 and the glutaredoxins, no thiol transferase activity was detected [2].
CLIC-2 was found to be widely distributed in tissues including heart and skeletal muscle [2].
Sedlin also associated with CLIC2 in yeast two-hybrid assays [3].

Biological context of CLIC2

CLIC-2 is one of only a few cytosolic inhibitors of cardiac RyR2 channels, and may suppress their activity during diastole and during stress [4].

Associations of CLIC2 with chemical compounds

CLIC-2 reduced increases in activity induced by ATP or adenosine 5'-[beta,gamma-imido]triphosphate [4].
The results show that CLIC-2 interacts with the RyR protein by a mechanism that does not require oxidation, but is influenced by a conserved Cys residue at position 30 [4].

Other interactions of CLIC2

While the human NCC27 and XAP121 homologs encode small peptides of 241 and 243 amino acids, respectively, the bovine peptide has a length of 437 amino acids [1].
CLIC-2 provides a unique probe for substate activity, coupled gating and ligand-induced activation of cardiac RyR channels [4].
CLIC-2 (0.2-10 microM) added to the cytoplasmic side of RyR2 channels in lipid bilayers depressed activity in a reversible, voltage-independent, manner in the presence of activating (10-100 microM) or sub-activating (100 nM) cytoplasmic Ca2+ concentrations [4].

References

Genomic structure of a novel chloride channel gene, CLIC2, in Xq28. Heiss, N.S., Poustka, A. Genomics (1997)
CLIC-2 modulates cardiac ryanodine receptor Ca2+ release channels. Board, P.G., Coggan, M., Watson, S., Gage, P.W., Dulhunty, A.F. Int. J. Biochem. Cell Biol. (2004)
Interaction of Sedlin with chloride intracellular channel proteins. Fan, L., Yu, W., Zhu, X. FEBS Lett. (2003)
A recently identified member of the glutathione transferase structural family modifies cardiac RyR2 substate activity, coupled gating and activation by Ca2+ and ATP. Dulhunty, A.F., Pouliquin, P., Coggan, M., Gage, P.W., Board, P.G. Biochem. J. (2005)