This paper describes three distinct estrogen receptor (ER) subtypes: ER alpha, ER beta, and a unique type. ER gamma, cloned from a teleost fish, the Atlantic croaker Micropogonias undulatus; the first identification of a third type of classical ER in vertebrate species. Phylogenetic analysis shows that ER gamma arose through gene duplication from ER beta early in the teleost lineage and indicates that ER gamma is present in other teleosts. although it has not been recognized as such. The Atlantic croaker ER gamma shows amino acid differences in regions important for ligand binding and receptor activation that are conserved in all other ER gamma s. The three ER subtypes are genetically distinct and have different distribution patterns in Atlantic croaker tissues. In addition, ER beta and ER gamma fusion proteins can each bind estradiol-17 beta with high affinity. The presence of three functional ERs in one species expands the role of ER multiplicity in estrogen signaling systems and provides a unique opportunity to investigate the dynamics and mechanisms of ER evolution. References: 37
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