Dysregulated expression of Maf proteins (namely c‐Maf, MafA and MafB) leads to multiple myeloma in humans and oncogenic transformation of chicken embryonic fibroblasts. Maf proteins are transcriptional activators of tissue‐specific gene expression and regulators of cell differentiation. For example, MafA is a critical regulator of crystallin genes and the lens differentiation program in chickens. In mammals, MafA is essential for the development of mature insulin‐producing β‐cells of pancreas. It has been shown that MafA protein stability is regulated by phosphorylations at multiple serine and threonine residues. Here, we report that Maf proteins are also post‐translationally modified by small ubiquitin‐like modifier (SUMO) proteins at a conserved lysine residue in the amino‐terminal transactivator domain. A SUMOylation‐deficient mutant of MafA (K32R) was more potent than wild‐type MafA in transactivating luciferase reporter construct driven by αA‐crystallin or insulin gene promoter. In ovo electroporation into developing chicken embryo showed that the K32R mutant induced ectopic δ‐crystallin gene expression more efficiently than the wild‐type MafA. We also demonstrated that the K32R mutant had enhanced ability to induce colony formation of a chicken fibroblast cell line DF‐1. Therefore, SUMOylation is a functional post‐translational modification of MafA that negatively regulates its transcriptional and transforming activities.