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Extracellular signal-regulated kinase 3 (ERK3) is a distantly related member of the mitogen-activated protein (MAP) kinase family of serine/threonine kinases. Here, we report the characterization of the genomic loci encoding ERK3 in mice and humans. The mouse ERK3 gene (Mapk6) spans more than 20 kb and is split into six exons. Its structure is similar to that of the human MAPK6 gene, which extends over 40 kb. We also identified and characterized a mouse Mapk6 processed pseudogene. In humans, database analysis has revealed the presence of six MAPK6 processed pseudogenes localized on four different chromosomes. We further show that the structure of MAPK6 is closely related to that of the gene encoding the homologous protein kinase p63MAPK (MAPK4), suggesting that the two genes arose by duplication. Our analysis demonstrates that the ERK3 subfamily of MAP kinase genes is composed of two functional genes, MAPK6 and MAPK4, and several pseudogenes. [Copyright &y& Elsevier]