KH domain-containing proteins of yeast: Absence of a fragile X gene homologue

KH domain-containing proteins of yeast: Absence of a fragile X gene homologue
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DOI:
10.1002/(sici)1096-8628(19990528)84:3
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发表时间:
1999-05-28
期刊:
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子:
--
通讯作者:
Brown, WT
Brown, WT
中科院分区:
其他
文献类型:
--
作者:
Currie, JR;Brown, WT

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KH结构域是由其与异质核核糖核蛋白K(hnRNPK)的RNA结合结构域的同源性定义的区域,FMR 1蛋白中有两个这样的结构域,在脆性X综合征中表达不足。我们开发了一种计算机方法来搜索S。酿酒酵母蛋白序列,因为它们变得可用于FMR 1蛋白的KH结构域。使用我们的基序和GCG的威斯康星州包的FINDPATTERMS,在完整的酵母ORF数据库中鉴定出9个含有KH结构域的蛋白质。五种蛋白质具有已知或预测的功能;四种蛋白质等待功能分析。使用GeneWorks和GeneJockeyII比对,我们发现与FMR 1 P KH结构域最相似的酵母蛋白KH结构域是HX/SCP 160中的KH结构域。其序列与FMR 1 P的第二个KH结构域有50%的同源性,但SCP 160含有8个保守的KH结构域和6个简并的KH结构域。进一步的分析表明SCP 160与脊椎动物和C. elegans蛋白Vigilin也含有14个KH结构域。其次相似的酵母KH结构域发现于YB 83中,YB 83是一种比FMR 1 P短的蛋白质,包含三个KH结构域,其中一个与FMR 1 P中的第二个KH结构域共享45%的同一性。该酵母蛋白和FMR 1 P之间没有显著的整体序列相似性。因此,虽然酵母中的几种蛋白含有KH结构域,但脆性X基因家族的FMR 1蛋白不存在明显的酵母同源物。(C)1999 Wiley-Liss,Inc.
The KH domain is a region defined by its homology to the RNA-binding domains of the heterogeneous nuclear ribonucleoprotein K (hnRNPK), There are two such domains in the FMR1 protein which is underexpressed in the fragile X syndrome. We developed a computer method to search the S. cerevisiae protein sequences as they became available for the KH domain of the FMR1 protein. Using our motif and FINDPATTERNS of the Wisconsin Package of GCG, nine proteins were identified in the completed yeast ORF database that contain KH domains. Five proteins have known or predicted functions; four await functional analysis. Using GeneWorks and GeneJockeyII alignments, we found that the yeast protein KH domain showing the most similarity to either FMR1P KH domain was a KH domain in HX/SCP160. Its sequence is 50% identical to the second KH domain of FMR1P, However, SCP160 contains eight conserved and six degenerate KH domains. Further analysis showed that SCP160 is a better match overall to the vertebrate and C. elegans protein Vigilin, which also contains 14 KH domains. The next most similar yeast KH domain was found in YB83, a protein shorter than FMR1P and containing three KH domains, one of which shares 45% identity with the second KH domain in FMR1P. There is no significant overall sequence similarity between this yeast protein and FMR1P. Thus, while several proteins in yeast contain KH domains, no apparent yeast homologue exists for the FMR1 protein of the fragile X gene family. (C) 1999 Wiley-Liss, Inc.