Tissue-specific regulation by vitamin D3 of a novel protein containing ankyrin-like repeats

Vitamin D3 is the precursor of the steroid hormone 1,25-dihydroxyvitamin D3 which is involved in the regulation of calcium metabolism, growth and differentiation. We used differential display of mRNA populations from kidney and intestine of vitamin D3-deficient and -replete chicks to determine the steady-state abundance of approximately 5000 mRNAs. One of these sequences, whose differential expression in kidney and down-regulation by vitamin D3 was confirmed by Northern analysis, was used to screen a cDNA library from vitamin D3-deficient chick kidney in order to obtain a full length cDNA. Subcloning and sequencing revealed that this cDNA encodes a novel protein containing ankyrin-like repeats and a C-terminal Fe-S binding region signature. The encoded protein consists of 617 amino acids and contains two sets of four ankyrin-like repeats separated by 146 amino acids. This motif consists of approximately 33 amino acids containing a highly conserved central hydrophobic alpha helix and is abundant in a wide variety of proteins, particularly those participating in the protein-protein or protein-membrane interactions involved in signal transduction, regulation of the cell cycle and control of transcription. Outside of the ankyrin-like domains, no homologies with other proteins in existing data bases were found. Our results have revealed a novel protein containing ankyrin-like repeats tissue-specifically down-regulated by vitamin D3 in the kidney.