Two short domains are responsible for the nuclear localization of the mouse spermine oxidase mu isoform

In mouse, at least two catalytically active splice variants (mSMOalfa and mSMOmu) of the flavin-containing spermine oxidase enzyme are present. We have demonstrated previously that the cytosolic mSMOalfa is the major isoform, while the mSMOmu enzyme is present in both nuclear and cytoplasmic compartments and has an extra protein domain corresponding to the additional exon VIa. By amino acid sequence comparison and molecular modeling of mSMO proteins, we identified a second domain that is necessary for nuclear localization of the mSMOmu splice variant. A deletion mutant enzyme of this region was constructed to demonstrate its role in protein nuclear targeting by means of transient expression in the murine neuroblastoma cell line, N18TG2.