The present invention provides nucleic acid molecules encoding novel red fluorescent proteins from Entacmaea quadricolor and mutants thereof. Also of interest are proteins that are substantially similar to the novel red fluorescent proteins. In addition, host cells, stable cell lines and transgenic organisms comprising the nucleic acid molecules encoding the novel red fluorescent proteins are provided. The subject proteins and nucleic acid compositions find use in a variety of different applications and methods, particularly for labeling of biomolecules, cells, or cell organelles. Finally, kits for use in such methods and applications are provided.