Cloning and Characterization of the Human and Rat Islet-specific Glucose-6-phosphatase Catalytic Subunit-related Protein (IGRP) Genes

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 restr...

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Veröffentlicht in:The Journal of biological chemistry 2001-07, Vol.276 (27), p.25197-25207
Hauptverfasser: Martin, C C, Bischof, L J, Bergman, B, Hornbuckle, L A, Hilliker, C, Frigeri, C, Wahl, D, Svitek, C A, Wong, R, Goldman, J K, Oeser, J K, Leprêtre, F, Froguel, P, O'Brien, R M, Hutton, J C
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container_end_page 25207
container_issue 27
container_start_page 25197
container_title The Journal of biological chemistry
container_volume 276
creator Martin, C C
Bischof, L J
Bergman, B
Hornbuckle, L A
Hilliker, C
Frigeri, C
Wahl, D
Svitek, C A
Wong, R
Goldman, J K
Oeser, J K
Leprêtre, F
Froguel, P
O'Brien, R M
Hutton, J C
description 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.
doi_str_mv 10.1074/jbc.M101549200
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subjects Amino Acid Sequence
Animals
Base Sequence
Catalytic Domain
Cloning, Molecular
Conserved Sequence
Genetics
Glucose-6-Phosphatase
Glucose-6-Phosphatase - chemistry
Glucose-6-Phosphatase - genetics
Human genetics
Humans
IGRP gene
Immunoenzyme Techniques
Life Sciences
Mice
Molecular Sequence Data
Promoter Regions (Genetics)
Promoter Regions, Genetic
Proteins
Proteins - chemistry
Proteins - genetics
Rats
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger
RNA, Messenger - analysis
Sequence Alignment
title Cloning and Characterization of the Human and Rat Islet-specific Glucose-6-phosphatase Catalytic Subunit-related Protein (IGRP) Genes
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