FIG. 1.

The Neuregulin 1 gene encodes an abundance of related but functionally distinct proteins. The Neuregulin 1 gene is schematized at the top. Boxes represent coding exons drawn approximately to scale. Introns are not shown to scale. In primates, six families of Nrg1 isoforms have been described and are thought to all be transcribed from distinct core promoters (I–VI) (Steinthorsdottir et al 2004). Only types I–III appear to be present in non-primates. Each of the six families of isoforms has a unique N-terminal sequence that is encoded by 6 different 5′ exons (I = E592, II= E1006, III = E1160, IV = E187, V = E92 and VI = E290). No clear signal sequence is present in E592, E187, E92 or E290. E1006 encodes a classic signal peptide and E1160 enocodes a transmembrane domain that anchors the Type III isoforms in the membrane. Other domains of interest include the Ig domain (encoded by exons 3 and 4), the EGF domain encoded by exon 8, the C-terminal EGF-like domain encoded by combinations of exons 9–12, the common transmembrane domain encoded by exon 13 and the intracellular domain, encoded by exons 14–19. The functions associated with these domains are described in the text. What is clear from this diagram is that combinations of differential promoter usage with differential splicing gives rise to families of proteins with distinct signalling strategies.