MafK

MafK is a protein encoded by the MAFK gene in humans and many vertebrates. It belongs to the small Maf (sMaf) subfamily of basic leucine zipper (bZIP) transcription factors. Like other sMafs, MafK lacks a strong transactivation domain and functions primarily as a dimerization partner for other transcription factors, enabling DNA binding and regulatory specificity.

In oxidative stress signaling, MafK commonly forms heterodimers with CNC family transcription factors, especially Nrf2, to activate genes containing antioxidant response elements (AREs). These ARE-driven genes include many detoxification and antioxidant enzymes that help shield cells from reactive oxygen species. In the absence of stress, MafK can also pair with Bach1 to repress ARE-driven transcription, providing a negative regulatory mechanism and contributing to the fine-tuning of the antioxidant response.

MafK is predominantly located in the nucleus, and its activity is influenced by the cellular redox state as well as the availability of Nrf2 and Bach1. Expression of MafK is widespread across tissues, reflecting its role in general cellular protection against oxidative stress.

Biological significance of MafK lies in its contribution to redox homeostasis, cytoprotection, and xenobiotic metabolism through its partner dimers. Dysregulation of MafK-containing dimers has been observed in contexts involving oxidative stress, including certain cancers and neurodegenerative conditions, though the effects are highly context-dependent.

Evolutionarily, MafK is part of the conserved Maf transcription factor family, with orthologs across vertebrates, reflecting its fundamental role in cellular stress responses. See also Nrf2, Bach1, ARE, and the broader Maf family.