Fig. 6. Potential amino acid signals in the human ClC-2 sequence. Proposed membrane topology of the ClC-2 Cl^– channel based on a high resolution X-ray diffraction study of a ClC from Salmonella typhimurium (Dutzler et al., 2003). The extracellular side is up. There is high homology in the transmembrane helices but the bacterial structure lacks the large (300 aa) C-terminus of ClC-2. Portions labeled CBS are cystathionine beta synthase domains highly conserved in eukaryotic ClCs. The amino acids shown are potential tyrosine- or di-leucine-containing basolateral sorting signals.