<p>Spen (split end) proteins regulate the expression of key transcriptional effectors in diverse signalling pathways. They are large proteins characterised by N-terminal RNA-binding motifs and a highly conserved C-terminal SPOC (Spen paralog and ortholog C-terminal) domain. The function of the SPOC domain is unknown, but the SPOC domain of the SHARP Spen protein has been implicated in the interaction of SHARP with the SMRT/NcoR corepressor, where SHARP plays an essential role in the repressor complex [<cite idref="PUB00013949"/>].</p><p>The SPOC domain is folded into a single compact domain consisting of a beta-barrel with seven strands framed by six alpha helices. A number of deep grooves and clefts in the surface, plus two nonpolar loops, render the SPOC domain well suited to protein-protein interactions; most of the conserved residues occur on the protein surface rather than in the core. Other proteins containing a SPOC domain include drosophila Split ends, which promotes sclerite development in the head and restricts it in the thorax, and mouse MINT (homologue of SHARP), which is involved in skeletal and neuronal development via its repression of Msx2.</p>