Predict Functionally Important Residues Responsible for Estrogen Receptor Subtype Divergence
Feng Wang, Hirohisa Kishino, Yasuhiko Wada · Proceedings Genome Informatics Workshop/Genome informatics · 2003
The estrogen receptor (ER) is a ligand-activated transcription factor that mediates the physiologicale ects of the female sex steroid hormone 17 beta estradiol (E2), and regulates the expression of genesinvolved in the growth, development and function of a diverge range of tissues. The ER is a memberof nuclear receptor (NR) superfamily, which shares a common structural organization including sixindependent but interacting functional domains. Two ER subtypes, although related, are separategenes and code for proteins of di ering lengths. We are interested in the selection constraint actingon the functional domains of ER subtypes after gene duplication. Because the sequence di erences ofER subtype in ligand binding domain (LBD) provide the molecular basis for the subtype physiologicalfunction, it is necessary to identify those functional related sites in order to investigate the functionaldivergence between two subtypes. In this study, we utilize the evolutionary rate analysis approach,combined with structural mapping, to predict the functionally important residues responsible for ERsubtype divergence.