Complete Genomic Organization of the Human Erythroid p55 Gene (MPP1), a Membrane-Associated Guanylate Kinase Homologue

• Published in: Genomics (San Diego, Calif.) Calif.), 1996-01, Vol.31 (2), p.223-229
• Main Authors: Kim, Anthony C., Metzenberg, Aida B., Sahr, Kenneth E., Marfatia, Shirin M., Chishti, Athar H.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Base Sequence; Biological and medical sciences; Blood Proteins - genetics; Chromosome Mapping; Conserved Sequence; DNA - genetics; Exons; Fundamental and applied biological sciences. Psychology; Genes. Genome; Genome, Human; Guanylate Kinases; HeLa Cells; Humans; Introns; Membrane Proteins - genetics; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Nucleoside-Phosphate Kinase - genetics; Promoter Regions, Genetic; Transcription, Genetic; X Chromosome - genetics
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1006/geno.1996.0035

Human p55 is an abundantly palmitoylated phosphoprotein of the erythroid membrane. It is the prototype of a newly discovered family of membrane-associated proteins termed MAGUKs (membrane-associated guanylate kinase homologues). The MAGUKs interact with the cytoskeleton and regulate cell proliferation, signaling pathways, and intercellular junctions. Here, we report the complete intron–exon map of the human erythroid p55 gene (HGMW-approved symbol MPP1). The structure of the p55 gene was determined from cosmid clones isolated from a cosmid library specific 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 region of the human X chromosome. The exon sizes range from 69 (exon 5) to 203 (exon 10) bp, whereas the intron sizes vary from 280 bp (intron 2) 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 functional domains in the p55 protein. These domains include a SH3 motif and a region that binds to cytoskeletal protein 4.1. In addition, a comparison of the genomic and the primary structures of p55 reveals a highly conserved phosphotyrosine domain located between the protein 4.1 binding domain and the guanylate kinase domain. Finally, promoter activity measurements of the region immediately upstream of the p55 gene, which contains severalcis-elements commonly found in housekeeping genes, suggest that a CpG island may be associated with the p55 gene expressionin vivo.