Phosphoglucomutase 1: a gene with two promoters and a duplicated first exon

Abstract

In view of its central role in glycolysis and gluconeogenesis and its polymorphic genetic variability, the phosphoglucomutase 1 (PGM1) gene in man has been the target of protein structural studies and genetic analysis for more than 25 years. We have now isolated genomic clones containing the complete PGM1 gene and have shown that it spans over 65 kb and contains 11 exons. We have also shown that the sites of the two mutations which form the molecular basis for the common PGM1 protein polymorphism lie in exons 4 and 8 and are 18 kb apart. Within this region there is a site of intragenic recombination. We have discovered two alternatively spliced first exons, one of which, exon 1A, is transcribed in a wide variety of cell types; the other, exon 1B, is transcribed in fast muscle. Exon 1A is transcribed from a promoter which has the structural hallmarks of a housekeeping promoter but lies more than 35 kb upstream of exon 2. Exon 1B lies 6 kb upstream of exon 2 within the large first intron of the ubiquitously expressed PGM1 transcript. The fast-muscle form of PGM1 is characterized by 18 extra amino acid residues at its N-terminal end. Sequence comparisons show that exons 1A and 1B are structurally related and have arisen by duplication.

Immunolocalization of the exocytosis-sensitive phosphoprotein, PP63/parafusin, in Paramecium cells using antibodies against recombinant protein

“…In muscle, PGM can associate with desmosomes ), extra-junctional acetylcholine receptors (Belkin and Burridge 1994) or dystrophin (Moiseeva et al 1996). Functional diversity has been inferred in mammals from the genetic variability of PGM (Putt et al 1993). Similarly, we have found two P63/pf genes (Hauser et al 1997).…”

Sequence Differences between Human Muscle and Liver cDNAs for UDPglucose Pyrophosphorylase and Kinetic Properties of the Recombinant Enzymes Expressed in Escherichia Coli

“…This is unlikely to occur if the two cDNAs arise from different genes and we suggest that they may result from the use of a different first exon in these two transcripts. A similar situation has been reported (Putt et al, 1993) to occur in the preceding enzyme of UDP-Glc formation, phosphoglucomutase.…”

Regulation of phosphoglucomutase 1 phosphorylation and activity by a signaling kinase

“…In the other direction, conversion of G-6-P to G-1-P generates a substrate for synthesis of UDP-glucose, which is required for synthesis of a variety of cellular constituents, including cell wall polymers and glycoproteins. PGM has been used extensively as a genetic marker for isozyme polymorphism among humans (Putt et al, 1993). PGM is known to be post-translationally modified by cytoplasmic glycosylation that does not seem to regulate its enzymatic activity but rather is implicated in the localization of the protein (Dey et al, 1994).…”