Characterization of the myotubularin dual specificity phosphatase gene family from yeast to human
Characterization of the myotubularin dual specificity phosphatase gene family from yeast to human
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DOI：
10.1093/hmg/7.11.1703
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发表时间：
1998-10-01
影响因子：
3.5
通讯作者：
Mandel, JL
中科院分区：
文献类型：
--
作者：
Laporte, J;Blondeau, F;Mandel, JL
X连锁肌管性肌病（XLMTM）是一种严重的先天性肌肉疾病，由于MTM1基因突变。相应的蛋白质，肌管蛋白，含有酪氨酸磷酸酶（PTP）的共识活性位点，但在其他方面没有显示出同源性的其他磷酸酶。肌管菌素能够水解酪氨酸磷酸的合成类似物，在原钒酸盐抑制的反应中，并且最近被证明对磷酸酪氨酸和磷酸丝氨酸都起作用。该基因在酵母中是保守的，与人类EST有很强的同源性，因此定义了一个新的双特异性磷酸酶（DSP）家族。我们报道了在裂殖酵母、秀丽隐杆线虫、斑马鱼、果蝇、小鼠和人中存在MT ′ M基因家族的新成员。这代表了迄今为止描述的最大的DSP家族。在人类基因组中发现了8个MTM相关基因，我们确定了其中大多数基因的Chrome、染色体定位和表达模式。错义突变在XLMTM患者中发现影响果蝇同源物中保守的残基，各种基因的比较允许构建系统发育树，并揭示可能对功能至关重要的保守残基。这些基因可能是其他遗传疾病的良好候选者。
X-linked myotubular myopathy (XLMTM) is a severe congenital muscle disorder due to mutations in the MTM1 gene. The corresponding protein, myotubalarin, 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 MT'M 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 chrome,somal 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.