Menin acts as contextual a tumor suppressor and a tumor promoter, partly via epigenetic regulation of gene transcription. While menin is phosphorylated, it remains unclear whether wild type menin has other post-translational modifications. Here, we report that menin is SUMOylated by SUMO1 in vivo and in vitro, and the SUMOylation is reduced by a SUMO protease. Lysine 591 of menin was covalently modified by SUMO1 and K591R mutation in menin blocked SUMOylation of the C-terminal part of menin in transfected cells. Full-length menin with K591 mutation was still SUMOylated in vivo, suggesting the existence of multiple SUMOylation sites. Menin K591R mutant or menin-SUMO fusion protein still retains the ability to regulate cell proliferation and the expression of the examined menin target genes.