Emes R D, Ponting C P
MRC Functional Genetics Unit, Department of Human Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
Hum Mol Genet. 2001 Nov 15;10(24):2813-20. doi: 10.1093/hmg/10.24.2813.
A previously unidentified sequence motif has been identified in the products of genes mutated in Miller-Dieker lissencephaly, Treacher Collins, oral-facial-digital type 1 and contiguous syndrome ocular albinism with late onset sensorineural deafness syndromes. An additional homologous motif was detected in a gene product fused to the fibroblast growth factor receptor type 1 in patients with an atypical stem cell myeloproliferative disorder. In total, over 100 eukaryotic intracellular proteins are shown to possess a LIS1 homology (LisH) motif, including several katanin p60 subunits, muskelin, tonneau, LEUNIG, Nopp140, aimless and numerous WD repeat-containing beta-propeller proteins. It is suggested that LisH motifs contribute to the regulation of microtubule dynamics, either by mediating dimerization, or else by binding cytoplasmic dynein heavy chain or microtubules directly. The predicted secondary structure of LisH motifs, and their occurrence in homologues of Gbeta beta-propeller subunits, suggests that they are analogues of Ggamma subunits, and might associate with the periphery of beta-propeller domains. The finding of LisH motifs in both treacle and Nopp140 reinforces previous observations of functional similarities between these nucleolar proteins. Uncharacterized LisH motif-containing proteins represent candidates for other diseases associated with aberrant microtubule dynamics and defects of cell migration, nucleokinesis or chromosome segregation.
在米勒 - 迪克尔无脑回畸形、特雷彻·柯林斯综合征、口面指综合征1型以及伴有迟发性感音神经性耳聋综合征的连续性综合征性眼白化病中发生突变的基因产物中，已鉴定出一种先前未识别的序列基序。在非典型干细胞骨髓增殖性疾病患者中，在与成纤维细胞生长因子受体1融合的基因产物中检测到另一个同源基序。总共超过100种真核细胞内蛋白质被证明具有LIS1同源性（LisH）基序，包括几种katanin p60亚基、肌动蛋白、桶蛋白、LEUNIG、Nopp140、无目标蛋白以及众多含WD重复序列的β - 螺旋桨蛋白。有人提出，LisH基序通过介导二聚化，或者直接结合胞质动力蛋白重链或微管，有助于调节微管动力学。LisH基序的预测二级结构及其在Gββ - 螺旋桨亚基同源物中的出现表明，它们是Gγ亚基的类似物，可能与β - 螺旋桨结构域的周边结合。在treacle和Nopp140中均发现LisH基序，这强化了之前关于这些核仁蛋白之间功能相似性的观察结果。未表征的含LisH基序的蛋白质代表了与异常微管动力学以及细胞迁移、核运动或染色体分离缺陷相关的其他疾病的候选蛋白。
