NARG2 encodes a novel nuclear protein with (S/T)PXX motifs that is expressed during development

We previously identified a partial expressed sequence tag clone corresponding to NARG2 in a screen for genes that are expressed in developing neurons and misexpressed in transgenic mice that lack functional N-methyl-d-aspartate receptors. Here we report the first characterization of the mouse and human NARG2 genes, cDNAs and the proteins that they encode. Mouse and human NARG2 consist of 988 and 982 amino acids, respectively, and share 74% identity. NARG2 does not display significant homology to other known genes, and lower organisms such as Saccharomyces cerevisiae, Drosophila melanogaster and Fugu rubripes appear to lack NARG2 orthologs. In vitro translation of the mouse cDNA yields a 150 kDa protein. NARG2 localizes to the nucleus in transfected cells, and deletion of a canonical basic nuclear localization signal suggests that this and other sequences in the protein cooperate for nuclear targeting. NARG2 consists of 16 exons in both mice and humans, 11 of which are identical in length, and alternative splicing is evident in both species. Exon 10 is the largest, and exhibits a much higher rate of nonsynonymous nucleotide substitution than the others. In addition, NARG2 contains (S/T)PXX motifs (11 in mouse NARG2, six in human NARG2). Northern blot analysis and RNase protection demonstrated that NARG2 is expressed at relatively high levels in dividing and immature cells, and that it is down-regulated upon terminal differentiation. The results indicate that NARG2 encodes a novel (S/T)PXX motif-containing nuclear protein, and suggest that NARG2 may play an important role in the early development of a number of different cell types.