Title: The MurinePolycomb-Group Geneeedand Its Human Orthologue: Functional Implications of Evolutionary Conservation
Abstract: Similar toDrosophila,murinePolycomb-group (PcG) genes regulate anterior–posterior patterning of segmented axial structures by transcriptional repression of homeotic gene expression. The murinePcGgeneeed(embryonic ectoderm development) encodes a 441-amino-acid protein with five WD motifs which, except for the amino terminus, is highly homologous toDrosophilaESC (Extra Sex Combs). Here, sequence and expression analysis as well as chromosomal mapping of the human orthologue ofeedis described. Absolute conservation of the humaneedprotein along with significant divergence at the nucleotide level reveals functional constraints operating on all residues. The human orthologue appears to be ubiquitously expressed and maps to chromsome 11q14.2–q22.3. Using the first WD motif of the β-subunit of the bovine G protein as a structural reference, the predicted locations of two previously identifiedeedpoint mutations (A. Schumacheret al.,1996,Nature383: 250–253) are also reported herein. The proline substitution (L196P) in the second WD motif of thel7Rn53354SBnull allele maps to the internal core of the inner end of the β-propeller blade and is likely to disrupt protein folding. In contrast, the asparagine substitution (I193N) in the second WD motif of the hypomorphicl7Rn51989SBallele maps onto the surface of the β-propeller blade near the central cavity and may affect surface interactions without compromising propeller packing. These results illustrate the critical importance of all residues foreedfunction in mammals and support a model whereby the amino terminus might implement function(s) related to embryonic development in higher organisms.
Publication Year: 1998
Publication Date: 1998-11-01
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 36
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