PGM1

Phosphoglucomutase-1 is an enzyme that in humans is encoded by the PGM1 gene. The protein encoded by this gene is an isozyme of phosphoglucomutase (PGM) and belongs to the phosphohexose mutase family. There are several PGM isozymes, which are encoded by different genes and catalyze the transfer of phosphate between the 1 and 6 positions of glucose. In most cell types, this PGM isozyme is predominant, representing about 90% of total PGM activity. In red blood cells, PGM2 is a major isozyme. This gene is highly polymorphic. Mutations in this gene cause CDG syndrome type 1t (CDG1T, formerly known as glycogen storage disease type XIV). Alternatively spliced transcript variants encoding different isoforms have been identified in this gene.[provided by RefSeq, Mar 2010]

Phosphoglucomutase-1 is an enzyme that in humans is encoded by the PGM1 gene. The protein encoded by this gene is an isozyme of phosphoglucomutase (PGM) and belongs to the phosphohexose mutase family. There are several PGM isozymes, which are encoded by different genes and catalyze the transfer of phosphate between the 1 and 6 positions of glucose. In most cell types, this PGM isozyme is predominant, representing about 90% of total PGM activity. In red blood cells, PGM2 is a major isozyme. This gene is highly polymorphic. Mutations in this gene cause CDG syndrome type 1t (CDG1T, formerly known as glycogen storage disease type XIV). Alternatively spliced transcript variants encoding different isoforms have been identified in this gene.[provided by RefSeq, Mar 2010]

Structure

The PGM1 gene is localized to the first chromosome, with its specific region being 1p31. The complete PGM1 gene spans over 65 kb and contains 11 exons, and 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. There are 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 tissue. Exon 1A is transcribed from a promoter that 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. PGM1 is a monomeric protein with 562 amino acids and four structural domains arranged in an overall heart shape. The active site is located in the large, centrally located cleft, formed by more than 80 residues. The active site can be segregated into four highly conserved regions that contribute to catalysis and substrate binding. These regions are: the phosphoserine residue that participates in phosphoryl transfer; the metal- binding loop; a sugar-binding loop; and the phosphate-binding site that interacts with the phosphate group of the substrate. The active site cleft of PGM1 relies on all four structural domains of the enzyme for its structural integrity.

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