COMPLETE GENOMIC ORGANIZATION OF THE HUMAN ERYTHROID P55 GENE (MPP1),A MEMBRANE-ASSOCIATED GUANYLATE KINASE HOMOLOG

Human p55 is an abundantly palmitoylated phospho protein of the erythr oid membrane. It is the prototype of a newly discovered family of memb rane-associated proteins termed MAGUKs (membrane-associated guanylate kinase homologues). The MAGUKs interact with the cytoskeleton and regu late cell proliferation, signaling pathways, and intercellular junctio ns, Here, we report the complete intron-exon map of the human erythroi d p55 gene (HGMW-approved symbol MPP1), The structure of the p55 gene was determined from cosmid clones isolated from a cosmid library speci fic for the human X chromosome. There is a single copy of the p55 gene , composed of 12 exons and spanning approximately 28 kb in the q28 reg ion of the human X chromosome. The exon sizes range from 69 (exon 5) t o 203 (exon 10) bp, whereas the intron sizes vary from 280 bp (intron 2) to similar to 14 kb (intron 1), The intron-exon boundaries conform to the donor/acceptor consensus sequence, GT-AG, for splice junctions. Several of the exon boundaries correspond to the boundaries of functi onal domains in the p55 protein. These domains include a SH3 motif and a region that binds to cytoskeletal protein 4.1. In addition, a compa rison of the genomic and the primary structures of p55 reveals a highl y conserved phosphotyrosine domain located between the protein 4.1 bin ding domain and the guanylate kinase domain, Finally, promoter activit y measurements of the region immediately upstream of the p55 gene, whi ch contains several cis-elements commonly found in housekeeping genes, suggest that a CpG island may be associated with the p55 gene express ion in vivo. (C) 1996 Academic Press, Inc.