Mouse Nope (Neighbor Of Punc E11) was discovered as a gene proximal to the Punc gene on chromosome 9 (1). Punc and Nope are distant members of a subgroup of the immunoglobulin (Ig) superfamily, which include DCC (Deleted in Colorectal Cancer) (2), Caenorhabditis elegans UNC5 (UNC = behaviorally uncoordinated) and its mammalian homologues (rat UNC5H1 and H2, mouse UNC5H2 and H3, and human UNC5H3 and H4) (3), Drosophila Frazzled (4), vertebrate Neogenin (5), and mouse Nope and mouse Punc. Members of this subgroup of the Ig superfamily are type I transmembrane proteins with four Ig domains in their extracellular regions.
Mouse Nope consists of a 21 amino acid (aa) signal peptide, a 933 aa extracellular domain (including four Ig domains, five fibronectin-type III (FnIII) repeats), a 24 aa transmembrane segment, and a 274 aa cytoplasmic domain (1). The extracellular domain of mouse Nope shares 45% aa sequence similarity with mouse Punc. However, the cytoplasmic domains of mouse Nope and mouse Punc do not share aa sequence similarity. Compared to other members of the subgroup of the Ig superfamily, mouse Nope extracellular domain shares 25.8% and 25.2% aa similarity with mouse DCC and mouse Neogenin, respectively. Mouse and human Nope share 90.8% aa sequence similarity. Mouse Nope is expressed mostly in embryonic muscle tissues and in developing and adult nervous systems. The structural similarities between Nope and the guidance receptor of the DCC family suggest that Nope may have similar functions as the DCC family (6‑8).
