Cloning and characterization of the human and rat islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) genes.

Martin CC, Bischof LJ, Bergman B, Hornbuckle LA, Hilliker C, Frigeri C, Wahl D, Svitek CA, Wong R, Goldman JK, Oeser JK, LeprĂȘtre F, Froguel P, O'Brien RM, Hutton JC
J Biol Chem. 2001 276 (27): 25197-207

PMID: 11297555 · DOI:10.1074/jbc.M101549200

Islet-specific glucose-6-phosphatase (G6Pase) catalytic subunit-related protein (IGRP) is a homolog of the catalytic subunit of G6Pase, the enzyme that catalyzes the terminal step of the gluconeogenic pathway. Its catalytic activity, however, has not been defined. Since IGRP gene expression is restricted to islets, this suggests a possible role in the regulation of islet metabolism and, hence, insulin secretion induced by metabolites. We report here a comparative analysis of the human, mouse, and rat IGRP genes. These studies aimed to identify conserved sequences that may be critical for IGRP function and that specify its restricted tissue distribution. The single copy human IGRP gene has five exons of similar length and coding sequence to the mouse IGRP gene and is located on human chromosome 2q28-32 adjacent to the myosin heavy chain 1B gene. In contrast, the rat IGRP gene does not appear to encode a protein as a result of a series of deletions and insertions in the coding sequence. Moreover, rat IGRP mRNA, unlike mouse and human IGRP mRNA, is not expressed in islets or islet-derived cell lines, an observation that was traced by fusion gene analysis to a mutation of the TATA box motif in the mouse/human IGRP promoters to TGTA in the rat sequence. The results provide a framework for the further analysis of the molecular basis for the tissue-restricted expression of the IGRP gene and the identification of key amino acid sequences that determine its biological activity.

MeSH Terms (17)

Amino Acid Sequence Animals Base Sequence Catalytic Domain Cloning, Molecular Conserved Sequence Glucose-6-Phosphatase Humans Immunoenzyme Techniques Mice Molecular Sequence Data Promoter Regions, Genetic Proteins Rats Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Sequence Alignment

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