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

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.