Structure, function and regulation of BP-3, a member of the CD38/ADP-ribosyl cyclase family

Abstract

The murine BP-3 gene encodes a variably glycosylated phosphatidylinositollinkcd cell surface glycoprotein that is expressed on early B and T lineage cells, myeloid cells, intestinal epithelial cells and a discrete population of reticular cells in peripheral lymphoid tissues. The deduced amino acid sequence of BP-3 cDNA shares significant homology with human and mouse CD38 and molluscan ADPribosyl cyclase, enzymes that generate the calcium mobilizing agent, cyclic ADPribose, from NAD. However, our studies indicate that the recombinant BP-3 molecule has relatively low ADP-ribosyl cyclase enzyme activity, measurable only at pH 4.0. The BP-3 gene was mapped to mouse chromosome 5 very near the CD38 locus, suggesting that this family arose by gene duplication. Analysis of genomic clones indicates that the BP-3 gene consists of 9 exons and spans approximately 27 Kb. The overall exon organization of the BP-3 gene is very similar to that reported for the ADP-ribosyl cyclase gene in the mollusc, Aplysta turodal. As a first step to gain insight into the BP-3 gene regulatory elements, we determined the transcriptions! start sites of the BP-3 gene in a pro-B cell line. The major transcription! start site (-19 from the ATO start codon) contains a weak initiator sequence. The upstream region lacks a TATA box, but consensus recognition sequences for the Pu.l. Ikaros/LvF-1. E2A and TCF-1 transcriptional factors may regulate BP-3 transcription in lymphoid and myeloid cells.