Does an Uncharacterized Gene/Protein Play a Role in Melanocortin Signaling?

Abstract

Melanocortin 3‐receptor (MC3R) is mainly expressed in the brain and plays an important role in a number biological processes, energy homeostasis, neuroendocrine regulation, sodium metabolism, and insulin signaling. Although many reports show that MCRs are involved in activating the cAMP pathway and they are important in a variety of cellular functions, post‐receptor mechanisms are not completely understood. As an initial approach, we performed microarray analyses to identify genes that are up‐regulated following MC3R activation/internalization by gamma‐melanocortin stimulating hormone (gamma‐MSH) in a mouse neuronal cell line over‐expressing MC3R. One gene, referred to as the uncharacterized gene (UNCG), had the highest expression (13 fold) in MC3R containing cells and was confirmed by real‐time PCR analysis. The UNCG mRNA is a single open‐reading frame of 415 bases that encodes a 137 amino acid protein with a predicted molecular mass of 16327 Daltons. Analysis of RNA from multiple mouse tissues reveals wide expression. A form of the gene has been identified in other organisms, rat and human. Preliminary localization studies indicate that the encoded protein is located in the cytoplasm in untreated cells. This data will enhance our knowledge of the molecular mechanisms involved in MC3R signaling. Supported: NIH/RCMI/G12RR17581‐05 (RCMI funded Histology and Molecular and Cell Biology core facilities).