MAFG

MAFG, also known as MafG, is a human transcription factor encoded by the MAFG gene. It is a member of the small Maf protein family, which includes MafF and MafK. Small Maf proteins are basic leucine zipper (bZIP) transcription factors that lack a classical transactivation domain and regulate gene expression by dimerizing with other bZIP proteins.

MafG functions primarily through dimerization, forming either homodimers or heterodimers with partner bZIP transcription factors. The most studied partner is Nrf2 (NFE2L2); the Nrf2–MafG complex binds to Maf recognition elements (MARE) and, when paired with Nrf2, activates antioxidant response elements (ARE) to induce genes involved in detoxification and antioxidant defense, such as NQO1, GCLC, and HMOX1. MafG can also participate in repressive complexes with Bach1, competing for MARE/ARE sites to downregulate target genes.

Expression of MAFG is widespread across human tissues, and MafG participates in roles related to development, cellular differentiation, and the oxidative stress response. In experimental models, MafG-related pathways influence responses to oxidative and electrophilic stress, linking MafG activity to disease contexts where redox balance is disrupted, including neurodegenerative conditions and cancer, depending on Nrf2 signaling status.

Genetics and evolution: MAFG is conserved across vertebrates. MafG interacts with a range of bZIP transcription factors, illustrating its function as a flexible regulator of gene expression in processes such as oxidative stress response, metabolism, and development.