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

C. C. Martin (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23) , L. J. Bischof , B. Bergman , L. A. Hornbuckle , C. Hilliker , C. Frigeri , D. Wahl (24, 25) , C. A. Svitek , R. Wong , J. K. Goldman , J. K. Oeser , F. Leprêtre , P. Froguel (26, 27, 28) , R. M. O'Brien , J. C. Hutton

1 ID-IMAG - Informatique et Distribution
2 PIIM - Physique des interactions ioniques et moléculaires
3 CRISMAT - Laboratoire de cristallographie et sciences des matériaux
4 CALTECH - California Institute of Technology
5 SAS - Sol Agro et hydrosystème Spatialisation
6 LEG - Laboratoire d'électrotechnique de Grenoble
7 LR - Laboratoire de rhéologie
8 IRHiS - Institut de Recherches Historiques du Septentrion (IRHiS) - UMR 8529
9 LAM - Laboratoire d'Astrophysique de Marseille
10 LCL - Laboratoire de catalyse de Lille - UMR 8010
11 UCCS - Unité de Catalyse et Chimie du Solide - UMR 8181
12 LDO - Domaines Océaniques
13 Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques
14 Service de génétique [Rouen]
15 ESPACE - Études des Structures, des Processus d’Adaptation et des Changements de l’Espace
16 SRS - Synchrotron Radiation Source
17 IMB - Institut de Mathématiques de Bourgogne [Dijon]
18 UB - Université de Bourgogne
19 LTPCM - Laboratoire de thermodynamique et physico-chimie métallurgiques
20 LGP2 - Laboratoire Génie des procédés papetiers
21 G2ELab - Laboratoire de Génie Electrique de Grenoble
22 Department of Human Genetics
23 Neurosciences Sensorielles Comportement Cognition
24 Unité de Médecine Interne Thrombose Maladies Vasculaires
25 Nouvelles Approches Anti-Thrombotiques
26 GMM - Génétique des maladies multifactorielles
27 Section of Genomic Medicine
28 Genome Centre

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.

Mots clés: Mice; Humans; Glucose-6-Phosphatase; Conserved Sequence; Cloning; Catalytic Domain; Base Sequence; Animals; Amino Acid Sequence; Molecular Sequence Data; Promoter Regions (Genetics); RNA; Reverse Transcriptase Polymerase Chain Reaction; Sequence Alignment

Mots clés: Molecular; Immunoenzyme Techniques; Proteins; Messenger; Rats

Domaines: Génétique humaine

C. C. Martin, L. J. Bischof, B. Bergman, L. A. Hornbuckle, C. Hilliker, et al.. Cloning and characterization of the human and rat islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) genes.. Journal of Biological Chemistry, 2001, 276 (27), pp.25197-207. ⟨10.1074/jbc.M101549200⟩. ⟨hal-00174787⟩