Maf transcription factors form a distinct family of the basic leucine zipper (bZip) transcription factors. The Maf family is divided into two subclasses, large Mafs (c-maf, mafB, and mafA/L-maf, nrl) and small Mafs (MafF, MafK and MafG). Both subclasses contain leucine-zipper motifs, which allow homodimerisation as well as heterodimerisation with a variety of other bZip proteins. In contrast to the small Mafs, the large Maf proteins contain a transactivator domain in their amino terminus []. The small Maf proteins might contribute to oncogenic processes by participating in antioxidant responses, while large Maf proteins have been directly implicated in carcinogenesis []. This entry represents MafA. MafA plays a critical role in the regulation of crystalline genes and lens development [, ]. It also binds the insulin enhancer element RIPE3b and regulates the insulin gene transcription [, , ].
GLI-similar (Glis) 1-3 proteins constitute a subfamily of the Krüppel-like zinc finger transcription factors that are closely related to the Gli family. They play key roles in the regulation of a number of physiological processes and have been implicated in several pathologies. Glis1-3 share a highly homologous zinc finger domain (ZFD) containing five Cys2-His2-type zinc finger (ZF) motifs with members of the Gli and Zic family [].Glis3 has repressor and activation functions []and is involved in pancreatic beta cell generation and insulin gene expression []. Glis3 deficient mice have decreased expression of several key transcription factors required for the endocrine development of the pancreas, such as Neurogenin3, NeuroD1, MafA and Pdx1 [, ]. Mutations in human glis3 cause a rare disease known as diabetes mellitus, neonatal, with congenital hypothyroidism (NDH) []. The glis3 gene has been identified as a susceptibility locus for the risk of type 1 and 2 diabetes [].
This entry represents a C-type lectin-like domain (CTLD) of the type found in natural killer cell receptors (NKRs), including proteins similar to oxidized low density lipoprotein (OxLDL) receptor (LOX-1), CD94, CD69, NKG2-A and -D, osteoclast inhibitory lectin (OCIL), dendritic cell-associated C-type lectin-1 (dectin-1), human myeloid inhibitory C-type lectin-like receptor (MICL), mast cell-associated functional antigen (MAFA), killer cell lectin-like receptors: subfamily F, member 1 (KLRF1) and subfamily B, member 1 (KLRB1), and lys49 receptors. CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins [].NKRs are variously associated with activation or inhibition of natural killer (NK) cells. Activating NKRs stimulate cytolysis by NK cells of virally infected or transformed cells; inhibitory NKRs block cytolysis upon recognition of markers of healthy self cells. Most Lys49 receptors are inhibitory; some are stimulatory. OCIL inhibits NK cell function via binding to the receptor NKRP1D. Murine OCIL in addition to inhibiting NK cell function inhibits osteoclast differentiation []. MAFA clusters with the type I Fc epsilon receptor (FcepsilonRI) and inhibits the mast cells secretory response to FcepsilonRI stimulus [, ]. CD72 is a regulator of B cell receptor signaling []. NKG2D is an activating receptor for stress-induced antigens; human NKG2D ligands include the stress induced MHC-I homologs, MICA, MICB, and ULBP family of glycoproteins. Several NKRs have a carbohydrate-binding capacity which is not mediated through calcium ions (e.g. OCIL binds a range of high molecular weight sulfated glycosaminoglycans including dextran sulfate, fucoidan, and gamma-carrageenan sugars) []. Dectin-1 binds fungal beta-glucans and is involved in the innate immune responses to fungal pathogens [, ]. MAFA binds saccharides having terminal alpha-D mannose residues in a calcium-dependent manner. LOX-1 is the major receptor for OxLDL in endothelial cells and thought to play a role in the pathology of atherosclerosis []. Some NKRs exist as homodimers (e.g.Lys49, NKG2D, CD69, LOX-1) and some as heterodimers (e.g. CD94/NKG2A). Dectin-1 can function as a monomer in vitro.
