Journal Article

Characterization of the Myotubularin Dual Specificity Phosphatase Gene Family from Yeast to Human

Jocelyn Laporte, François Blondeau, Anna Buj-Bello, Dimtry Tentler, Christine Kretz, Niklas Dahl and Jean-Louis Mandel

in Human Molecular Genetics

Volume 7, issue 11, pages 1703-1712
Published in print October 1998 | ISSN: 0964-6906
Published online October 1998 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/7.11.1703
Characterization of the Myotubularin Dual Specificity Phosphatase Gene Family from Yeast to Human

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X-linked myotubular myopathy (XLMTM) is a severe congenital muscle disorder due to mutations in the MTM1 gene. The corresponding protein, myotubularin, contains the consensus active site of tyrosine phosphatases (PTP) but otherwise shows no homology to other phosphatases. Myotubularin is able to hydrolyze a synthetic analogue of tyrosine phosphate, in a reaction inhibited by orthovanadate, and was recently shown to act on both phosphotyrosine and phosphoserine. This gene is conserved down to yeast and strong homologies were found with human ESTs, thus defining a new dual specificity phosphatase (DSP) family. We report the presence of novel members of the MTM gene family in Schizosaccharomyces pombe, Caenorhabditis elegans, zebrafish, Drosophila, mouse and man. This represents the largest family of DSPs described to date. Eight MTM-related genes were found in the human genome and we determined the chromosomal localization and expression pattern for most of them. A subclass of the myotubularin homologues lacks a functional PTP active site. Missense mutations found in XLMTM patients affect residues conserved in a Drosophila homologue. Comparison of the various genes allowed construction of a phylogenetic tree and reveals conserved residues which may be essential for function. These genes may be good candidates for other genetic diseases.

Journal Article.  7369 words.  Illustrated.

Subjects: Genetics and Genomics

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