A Unified Nomenclature System for the Nuclear Receptor Superfamily

Abstract

Letter to the Editor this criteria correspond to known functional groups of A Unified Nomenclature System for receptors. This procedure yields six subfamilies. All the the Nuclear Receptor Superfamily unusual receptors that contain only one of the two conserved domains (C or E) were grouped into a separate subfamily (subfamily 0) irrespective of their evolutionary Nuclear hormone receptors (NRs) are important tranorigin. Within subfamilies, groups of receptors are descriptional regulators involved in widely diverse physiofined as the most internal branches with bootstrap vallogical functions such as control of embryonic developues above 90%. In this nomenclature system, the numment, cell differentiation, and homeostasis (Gronemeyer ber of a given receptor inside a group does not carry and Laudet, 1995; Mangelsdorf et al., 1995). In addition, any specific information. In many cases these groups these molecules are extremely important in medical recontain arthropod and vertebrate members. The various search since a large number of them are implicated in homologs of the same gene in invertebrates (e.g., Drodiseases such as cancer, diabetes, or hormone resissophila and Caenorhabditis) have the same name. It is tance syndromes. Some of the NRs act as ligand-inducible transcription factors, while a large number of them have no defined ligand and are hence described as "orphan" receptors (Enmark and Gustafsson, 1996). Over the last decade, workers in the field have described more than 300 sequences of NRs using an increasingly complex and baroque nomenclature. The existence of several names for the same gene is an acute problem for the orphan receptors, which often cannot be described by their function, particularly at the moment of their discovery. As discussed during the Seventh International CBT Symposium on "Nuclear Orphan Receptors" in Huddinge, Sweden (September 9-12, 1995), this plethora of names has become more and more confusing and now constitutes a barrier for understanding of newly acquired knowledge to researchers outside as well as within the field. For that reason, four of us (V. L., J. A., J.-A. G., and W. W.) agreed to form a committee for the nomenclature of NRs. It is the purpose of this paper to recommend names for the subfamilies and groups of receptors based on a phylogenetic tree connecting all known NR sequences. This system, based on the evolution of the two well-conserved domains of NRs (the DNA-binding C domain and the ligand-binding E domain), offers a practical and significant framework to which subsequent genes can be easily added. The resulting nomenclature has now been endorsed by over 40 scientists 1 many of whom contributed to defining the nomenclature and to preparing this letter. This nomenclature has been discussed with the International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR). A subcommittee of NC-IUPHAR entitled "Nuclear Receptors" will be set up to further clarify receptor nomenclature to integrate structure and function.A summa...

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