Family 2.A.19 - The Ca2+ Cation Antiporter Family       

Family ID: 52624

Proteins of the CaCA family are found ubiquitously, having been identified in animals, plants, yeast, archaea and divergent bacteria. They exhibit widely divergent sequences, and several have been shown to have arisen by a tandem intragenic duplication event (Saier et al., 1999). The most conserved portions of this repeat element, a1 and a2, are found in TMSs 2-3 and TMSs 7-8 in the model of Iwamoto et al. (1999). These sequences are important for transport function and may form an intramembranous pore/loop-like structure.

Members of the CaCA family vary in size from 302 amino acyl residues (Methanococcus jannaschii) to 1199 residues (Bos taurus). Even within the animal kingdom, they vary in size from 461 to 1199 residues. The bacterial and archaeal proteins are in general smaller than the eukaryotic proteins (Chung et al., 2001). They have been suggested to traverse the membrane 9 (mammals) or 10 (bacteria) times as a-helical spanners. The E. coli ChaB(YrbG) homologue has been found to have 10 TMSs with both the N- and C-termini localized to the periplasm. Each homologous half of the internally duplicated protein has 5 TMS with opposite orientation in the membrane (Saaf et al., 2001).

The mammalian cardiac muscle homologue probably has 9 TMSs. The N-terminus of this protein is believed to be extracellular, while the C-terminus is intracellular (Iwamoto et al., 1999). A large central loop is not required for transport function and plays a role in regulation. In the preferred 9 TMS model for this mammalian protein, the polypeptide chain loops into the membrane after TMS 2 and after TMS 7. The large central loop separates TMS 5 from TMS 6. TMS 2 plus the following loop show sequence similarity to TMS 7 and its loop. TMS 7 may be close to TMSs 2 and 3 in the 3-D structure of the protein (Qui et al., 2001).