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J. Biol. Chem., Vol. 276, Issue 27, 25197-25207, July 6, 2001
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From the 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.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AF283835 (human IGRP gene excluding the promoter),
AF283575 (human IGRP promoter), AF321459-AF321463 (human IGRP exons 1-5, respectively), AF323433 (rat IGRP promoter and exon 1), AF323434-AF323436 (rat IGRP exons 2, 3, and 5, respectively), NM021331
(mouse IGRP cDNA), AF118761 (mouse IGRP promoter), and AF
118762-AF118766 (mouse IGRP exons 1-5, respectively).
Cloning and Characterization of the Human and Rat
Islet-specific Glucose-6-phosphatase Catalytic Subunit-related Protein
(IGRP) Genes*
§,,
,,,,,, and
Department of Molecular Physiology and
Biophysics, Vanderbilt University Medical School, Nashville, Tennessee
37232, ¶ Barbara Davis Center for Childhood Diabetes, University
of Colorado Health Sciences Center, Denver, Colorado 80262, and
Institut de Biologie-CNRS 8090, Institut Pasteur de
Lille, Lille Cedex, France
*
This work was supported by a grant from Juvenile Diabetes
Foundation International (JDFI) and Vanderbilt Diabetes Core Laboratory Grant P60 DK20593 (to R. O'B.), American Diabetes Association Grant
9901-116 and Barbara Davis Center Diabetes and Endocrinology Research
Center Grant P30 DK57516 (to J. C. H.), and by a grant from the
Nord-Pas de Calais Region (to F. L.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Recipient of Vanderbilt Molecular Endocrinology Training
Program Award 5 T 32 DK07563-12).
To whom correspondence may be addressed: Dept. of Molecular
Physiology and Biophysics, 761 MRB II, Vanderbilt University Medical School, Nashville, TN 37232-0615. Tel.: 615-936-1503; Fax:
615-322-7236; E-mail: richard.obrien@mcmail.vanderbilt.edu (R. O'B.)
or Tel.: 303-315-8197; Fax: 303-315-4892; E-mail:
john.hutton@uchsc.edu (J. C. H.).
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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