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Gene Review

CLIC2  -  chloride intracellular channel 2

Homo sapiens

Synonyms: CLIC2b, Chloride intracellular channel protein 2, MRXS32, XAP121
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Disease relevance of CLIC2


High impact information on CLIC2


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].


  1. Genomic structure of a novel chloride channel gene, CLIC2, in Xq28. Heiss, N.S., Poustka, A. Genomics (1997) [Pubmed]
  2. 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) [Pubmed]
  3. Interaction of Sedlin with chloride intracellular channel proteins. Fan, L., Yu, W., Zhu, X. FEBS Lett. (2003) [Pubmed]
  4. 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) [Pubmed]
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