Molecular and biochemical characterization of mouse Ellis Van Creveld protein

Ellis van Creveld (EvC) syndrome is a rare human genetic disorder resulting from abnormal bone and muscle development, and is characterized by short‐limb dwarfism, postaxial polydactyly, dysplastic nails and teeth and heart defects. The EvC gene, EVC , is one of the genes mutated in individuals suffering from the syndrome. In mouse, the EVC gene encodes a novel 1005‐ amino acid protein with putative transmembrane region, nuclear localization signals, and a leucine‐zipper motif. EVC is a regulator of the hedgehog signal transduction pathway that controls development and growth of bones during embryogenesis. As a first step towards elucidating the function of the EVC protein, we have successfully cloned fragment and full‐length EVC genes, and have expressed and purified their protein products. We report here that mouse EVC protein binds and hydrolyzes ATP. This result corroborates our earlier observation from bioinformatic analyses that EVC protein contains the P loop, a motif found in many nucleotide‐binding proteins. We have also cloned and expressed the combined P‐loop and leucine‐zipper domain of both mouse and human genes, and are purifying the protein products for structure determination. This work is supported by ORSP, SFA University.