Five members of a novel Ca2+-binding protein (CABP) subfamily with similarity to calmodulin

Five members of a novel Ca2+-binding protein subfamily (CaBP), with 46-58% sequence similarity to calmodulin (CaM), were identified in the vertebrate retina. Important differences between these Ca2+-binding proteins and CaM i nclude alterations within their second EF-hand loop that render these motif s inactive in Ca2+ coordination and the fact that their central alpha-helix es are extended by one alpha-helical turn. CaBP1 and CaBP2 contain a consen sus sequence for N-terminal myristoylation, similar to members of the recov erin subfamily and are fatty acid acylated in vitro. The patterns of expres sion differ for each of the various members. Expression of CaBP5, for examp le, is restricted to retinal rod and cone bipolar cells. In contrast, CaBP1 has a more widespread pattern of expression. In the brain, CaBP1 is found in the cerebral cortex and hippocampus, and in the retina this protein is f ound in cone bipolar and amacrine cells. CaBP1 and CaBP2 are expressed as m ultiple, alternatively spliced variants, and in heterologous expression sys tems these forms show different patterns of subcellular localization. In re constitution assays, CaBPs are able to substitute functionally for CaM. The se data suggest that these novel CaBPs are an important component of Ca2+-m ediated cellular signal transduction in the central nervous system where th ey may augment or substitute for CaM.