The MAFA open reading frame is encoded by a unique exon. The entire genomic organization and the putative existence of non-coding exons remain unknown.

MAFA displays a restricted expression pattern. It is notably expressed in pancreas (in beta-cells) and lens.

Unknown.

Maf oncoproteins are b-ZIP transcription factors that belong to the AP-1 super-family, which notably includes JUN and FOS. The Maf family contains seven members, which can be subdivided into two groups; the large and small Maf proteins. While the small Maf proteins, MAFF, MAFG and MAFK, are essentially composed of a b-Zip domain, the large Maf proteins, MAFA/L-MAF, MAFB, MAF/c-MAF and NRL contain an additional amino-terminal transactivation domain. MAFA was initially cloned in quail and chicken species and named MAFA and L-MAF, respectively. More recently, mammalian MAFA was cloned and identified as an essential component of the RIPE3b1 complex, which binds the insulin promoter.

MAFA, like all large Maf proteins, contains an amino-terminal transactivation domain and a carboxy-terminal b-ZIP DNA binding domain. Large Maf proteins stimulate transcription of their target genes through their binding to two types of palindromic sequences called TRE- or CRE- type MARE (Maf Responsive Element) (TGCTGAC(G)TCAGCA). The leucine zipper domain allows the formation of homo- or hetero- dimers, an absolute pre-requisite for DNA binding. As homodimers, these proteins recognize palindromic sequences, with the basic domain contacting DNA directly. Among the AP-1 family, the Maf proteins are defined by the presence of an additional homologous domain, called the Extended Homology Region (EHR) or ancillary domain, which also contacts DNA. Consequently, they recognize a longer palindromic sequence than other AP-1 family members. The MARE sequence is composed of a TRE or CRE core contacted by the basic domain and a TGC flanking sequence, which is recognized by the EHR domain. While the TGC motif is crucial for Maf binding, the TRE/CRE core can be more degenerate. MAFA transactivation activity and stability is regulated by post-translational modifications (phosphorylation, ubiquitylation and sumoylation) mostly occuring on the transactivation domain. GSK-3 was identified as the major protein kinase regulating MAFA activity and oncogenic properties.

Endogenous MAFA protein is detected and phosphorylated in pancreatic beta cells.

Nucleus.

During development, Maf proteins are involved early in specification and later in terminal differentiation. MAFA is involved in the regulation of insulin gene expression in pancreatic beta cells. Accordingly, MAFA ablation in mice leads to diabetes.
Besides their roles during development, large Maf proteins, MAFA, MAFB, and MAF/c-MAF are also involved in oncogenesis.

MAFB and MAF/c-MAF are the closest MAFA homologs. The MAFA entire protein sequence shares 52%, 48% and 40% identity with those of MAFB, MAF/c-MAF and NRL, respectively. MAFA DNA binding domain (EHR + b-ZIP) shares 82%, 83%, 64% and 55-60% identity with those of MAFB, MAF/c-MAF, NRL and small MAFs, respectively. MAFA and JUN share 30% sequence identity in their b-ZIP domain (20% identity in their entire sequence).