CHARACTERIZATION OF THE MAMMALIAN YAP (YES-ASSOCIATED PROTEIN) GENE AND ITS ROLE IN DEFINING A NOVEL PROTEIN MODULE, THE WW DOMAIN
CHARACTERIZATION OF THE MAMMALIAN YAP (YES-ASSOCIATED PROTEIN) GENE AND ITS ROLE IN DEFINING A NOVEL PROTEIN MODULE, THE WW DOMAIN
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DOI：
10.1074/jbc.270.24.14733
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发表时间：
1995-06-16
影响因子：
4.8
通讯作者：
LEHMAN, D
中科院分区：
文献类型：
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作者：
SUDOL, M;BORK, P;LEHMAN, D
我们报道了鸡YAP （Yes相关蛋白）基因的人和小鼠同源基因的cDNA克隆和表征，该基因编码一种结合Yes原癌基因产物的SH3 （Src同源3）结构域的新蛋白。小鼠、人类和鸡YAP蛋白的序列比较显示，小鼠YAP中插入的序列代表上游序列的不完美重复。对该序列的进一步分析揭示了一个假定的蛋白质模块，该模块存在于酵母、线虫和哺乳动物（包括人类肌营养不良蛋白）的各种结构、调节和信号分子中。由于该序列基序的一个突出特征是两个色氨酸(W)，我们将其命名为WW结构域(Bork， P., and Sudol， M. (1994) Trends Biochem。科学学报，19,531-533)。自它的描述以来，越来越多的蛋白质被证明含有这个结构域，我们在这里报道了WW模块的广泛分布，并对其可能的功能进行了讨论。我们还表明，人类YAP基因在高等真核生物中很好地保守，但在酵母中可能不保守。它在成人组织中的RNA水平表达几乎无处不在，在胎盘、前列腺、卵巢和睾丸中表达量相对较高，但在外周血白细胞中检测不到。利用人类中期染色体的荧光原位杂交技术，并通过Southern blot杂交和聚合酶链反应扩增对鼠人杂交体进行分析，我们将人类YAP基因定位在染色体11q13带上，该区域已被定位为多发性内分泌肿瘤I型基因。
We report cDNA cloning and characterization of the human and mouse orthologs of the chicken YAP (Yes-associated protein) gene which encodes a novel protein that binds to the SH3 (Src homology 3) domain of the Yes proto-oncogene product. Sequence comparison between mouse, human, and chicken YAP proteins showed an inserted sequence in the mouse YAP that represented an imperfect repeat of an upstream sequence. Further analysis of this sequence revealed a putative protein module that is found in various structural, regulatory, and signaling molecules in yeast, nematode, and mammals including human dystrophin. Because one of the prominent features of this sequence motif is two tryptophans (W), we named it the WW domain (Bork, P., and Sudol, M. (1994) Trends Biochem. Sci. 19, 531-533). Since its delineation, more proteins have been shown to contain this domain, and we report here on the widespread distribution of the WW module and present a discussion of its possible function. We have also shown that the human YAP gene is well conserved among higher eukaryotes, but it may not be conserved in yeast. Its expression at the RNA level in adult human tissues is nearly ubiquitous, being relatively high in placenta, prostate, ovary, and testis, but is not detectable in peripheral blood leukocytes. Using fluorescence in situ hybridization on human metaphase chromosomes and by analyzing rodent-human hybrids by Southern blot hybridization and polymerase chain reaction amplification, we mapped the human YAP gene to chromosome band 11q13, a region to which the multiple endocrine neoplasia type I gene has been mapped.