Structure of the gene encoding mouse reticulocalbin, a novel endoplasmic reticulum-resident Ca(2+)-binding protein with multiple EF-hand motifs.
Reticulocalbin, an endoplasmic reticulum (ER)-resident Ca(2+)-binding protein, is a member of the EF-hand Ca(2+)-binding protein superfamily [Ozawa, M. and Muramatsu, T. (1993) J. Biol. Chem. 268, 699-705]. Reticulocalbin has six repeats of a domain containing the EF-hand motif. In addition, the protein has an amino-terminal leader sequence which serves as a signal for transfer of the protein into the lumen of the ER, and a His-Asp-Glu-Leu sequence at its carboxy terminus which functions as a signal to retain the protein in the ER. In this paper, we describe the genomic structure of this unique Ca(2+)-binding protein. Southern blot analysis of mouse genomic DNA revealed that there is a single copy of the reticulocalbin gene per haploid genome. The gene spans over 13 kilobase pairs and encodes six separate exons. Thus, reticulocalbin differs from the cytosolic Ca(2+)-binding protein calbindin D28 which also has six EF-hand motif domains, but the gene for which is divided into 11 exons. While there is some correlation between exon division and protein domain structure, these relationships are not as clear as they are in other genes. Comparison of the gene organization of reticulocalbin with that of other EF-hand proteins revealed that reticulocalbin diverged very early from other members of the EF-hand protein super-family.