background:
Insulin gene expression is regulated by several islet-enriched transcription factors. However, MAFA is the only beta cell-specific activator. MAFA selectively induces endogenous insulin transcription in non-beta cells. MAFA was also first detected in the insulin-producing cells formed during the second and predominant phase of beta cell differentiation, and absent in the few insulin-positive cells found in Nkx6.1(-/-) pancreata, which lack the majority of second-phase beta cells. These results demonstrate that MAFA is a potent insulin activator that is likely to function downstream of Nkx6.1 during islet insulin-producing cell development.
Function:
Acts as a transcriptional factor. Specifically binds the insulin enhancer element RIPE3b. Cooperates synergistically with NEUROD1 and PDX1. Phosphorylation by GSK3 increases its transcriptional activity and is required for its oncogenic activity. Regulates the insulin gene transcription. Involved either as an oncogene or as a tumor suppressor, depending on the cell context.
Subunit:
Binds DNA as a homodimer. Interacts with PCAF. Interacts with NEUROD1 and PDX1.
Subcellular Location:
Nucleus. Note=Detected in nuclei of pancreas islet beta cells.
Tissue Specificity:
Selectively expressed in pancreatic beta but not in alpha cells (at protein level). Expressed in eyes and at low levels in thymus. Expressed in brain, lung, spleen and kidney. Expressed in embryo.
Post-translational modifications:
Ubiquitinated, leading to its degradation by the proteasome.
Phosphorylation by GSK3 requires prior phosphorylation of Ser-65 by another kinase. Phosphorylation proceeds then from Ser-61 to Thr-57, Thr-53 and Ser-49. GSK3-mediated phosphorylation increases its transcriptional activity through the recruitment of the coactivator PCAF, is required for its transforming activity and leads to its degradation through an ubiquitin/proteasome-dependent pathway. Ser-14 and Ser-65 appear to be the major phosphorylation sites. Phosphorylated by MAPK13 on serine and threonine residues (Probable).
Similarity:
Belongs to the bZIP family. Maf subfamily.
Contains 1 bZIP (basic-leucine zipper) domain.
Database links:
Entrez Gene: 389692 Human
Entrez Gene: 378435 Mouse
Entrez Gene: 366949 Rat
Omim: 610303 Human
SwissProt: Q8NHW3 Human
SwissProt: Q8CF90 Mouse
Unigene: 521914 Human
Unigene: 309589 Mouse
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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