sMaf

Small Maf proteins (sMaf) are a subgroup of the Maf transcription factor family found in vertebrates. In humans, the sMaf family comprises MafF, MafG, and MafK. They are basic leucine zipper (bZIP) transcription factors that lack strong transactivation domains, so their activity depends on dimerization and interaction with other factors.

sMaf proteins bind DNA as dimers to Maf recognition elements (MAREs). They can form homodimers, which often act as transcriptional repressors, or heterodimers with other transcription factors. A central role is as obligate partners for CNC transcription factors such as Nrf2 (NFE2L2), Nrf1 (NFE2L1), and Nrf3, enabling activation of antioxidant response element (ARE)-driven genes. This partnership coordinates cellular responses to oxidative stress and detoxification processes.

Biological and physiological implications of sMaf activity include regulation of genes involved in redox balance and phase II detoxification, such as NQO1 and HMOX1, as well as enzymes involved in glutathione biosynthesis. Beyond oxidative stress responses, sMafs participate in development, differentiation, and tissue-specific gene regulation, with roles observed in liver, kidney, brain, and hematopoietic contexts. Dysregulation of sMaf–CNC interactions has been implicated in various disease settings, including cancer and neurodegenerative conditions, highlighting their function as important modulators of transcriptional programs rather than standalone activators.

In research, sMafs are studied as cofactors that modulate ARE-dependent transcription and as components of broader transcriptional networks. Their activity reflects the balance between repressive homodimer formation and activating heterodimer formation with CNC factors, adapting gene expression to cellular stress and developmental cues.