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Aliases | MAFA , RIPE3b1, hMafA, MAF bZIP transcription factor A, INSDM | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 610303; MGI: 2673307; HomoloGene: 65867; GeneCards: MAFA; OMA:MAFA - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Transcription factor MafA is a protein that in humans is encoded by the MAFA gene. [5] It is a member of the Maf family of transcription factors. [6]
MAFA is phosphorylated sequentially on four serine/threonine residues by GSK-3 kinase. [7] These phosphorylations activate MAFA transcription and trigger its degradation in the proteasome. Altering these post-translationnal modifications leads to severe pathological consequences. Mutation of these residues is perinatally lethal in mice, [8] and mutation of the Ser64Phe priming site was reported to induce familial diabetes mellitus and insulinomatosis in humans. [9]
An in vivo study on mice proved MafA binds to the promoter in an insulin gene to regulate insulin transcription in response to serum glucose levels. [10] MafA is a β cell-specific activator, which differentiates it from other transcription factors involved with insulin gene expression. [11] It helps regulate the β cells involved with insulin secretion primarily by maintaining β cell metabolism. [12] The amount of MafA in the β cells is regulated by levels of glucose and oxidative stress. [6]
MafA (gene) has been shown to interact with NEUROD1 [13] and Pdx1. [13] MafA works with Pdx1 to activate the insulin gene. [6]
In addition to its expression in pancreatic ßcells, MAFA is also expressed in specific subsets of excitatory and inhibitory neurons. In the peripheric nervous system, it is expressed in touch mechanoreceptors. [14] [15] In the central nervous system, Mafa is expressed in sensory neurons in the spinal cord and trigeminal nucleus, as well as in the olfactory bulb. It is also present in ventral inhibitory neurons of the spinal cord (Renshaw cells) and in brainstem inhibitory neurons controlling mouse neonatal apneas. [8]
Insulin is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (INS) gene. It is the main anabolic hormone of the body. It regulates the metabolism of carbohydrates, fats, and protein by promoting the absorption of glucose from the blood into cells of the liver, fat, and skeletal muscles. In these tissues the absorbed glucose is converted into either glycogen, via glycogenesis, or fats (triglycerides), via lipogenesis; in the liver, glucose is converted into both. Glucose production and secretion by the liver are strongly inhibited by high concentrations of insulin in the blood. Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is thus an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules in the cells. Low insulin in the blood has the opposite effect, promoting widespread catabolism, especially of reserve body fat.
Mothers against decapentaplegic homolog 2, also known as SMAD family member 2 or SMAD2, is a protein that in humans is encoded by the SMAD2 gene. MAD homolog 2 belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways.
Protein c-Fos is a proto-oncogene that is the human homolog of the retroviral oncogene v-fos. It is encoded in humans by the FOS gene. It was first discovered in rat fibroblasts as the transforming gene of the FBJ MSV. It is a part of a bigger Fos family of transcription factors which includes c-Fos, FosB, Fra-1 and Fra-2. It has been mapped to chromosome region 14q21→q31. c-Fos encodes a 62 kDa protein, which forms heterodimer with c-jun, resulting in the formation of AP-1 complex which binds DNA at AP-1 specific sites at the promoter and enhancer regions of target genes and converts extracellular signals into changes of gene expression. It plays an important role in many cellular functions and has been found to be overexpressed in a variety of cancers.
Mitogen-activated protein kinase 8 is a ubiquitous enzyme that in humans is encoded by the MAPK8 gene.
AKT2, also known as RAC-beta serine/threonine-protein kinase, is an enzyme that in humans is encoded by the AKT2 gene. It influences metabolite storage as part of the insulin signal transduction pathway.
PDX1, also known as insulin promoter factor 1, is a transcription factor in the ParaHox gene cluster. In vertebrates, Pdx1 is necessary for pancreatic development, including β-cell maturation, and duodenal differentiation. In humans this protein is encoded by the PDX1 gene, which was formerly known as IPF1. The gene was originally identified in the clawed frog Xenopus laevis and is present widely across the evolutionary diversity of bilaterian animals, although it has been lost in evolution in arthropods and nematodes. Despite the gene name being Pdx1, there is no Pdx2 gene in most animals; single-copy Pdx1 orthologs have been identified in all mammals. Coelacanth and cartilaginous fish are, so far, the only vertebrates shown to have two Pdx genes, Pdx1 and Pdx2.
Neurogenic differentiation 1 (Neurod1), also called β2, is a transcription factor of the NeuroD-type. It is encoded by the human gene NEUROD1.
Nuclear respiratory factor 1, also known as Nrf1, Nrf-1, NRF1 and NRF-1, encodes a protein that homodimerizes and functions as a transcription factor which activates the expression of some key metabolic genes regulating cellular growth and nuclear genes required for respiration, heme biosynthesis, and mitochondrial DNA transcription and replication. The protein has also been associated with the regulation of neurite outgrowth. Alternate transcriptional splice variants, which encode the same protein, have been characterized. Additional variants encoding different protein isoforms have been described but they have not been fully characterized. Confusion has occurred in bibliographic databases due to the shared symbol of NRF1 for this gene and for "nuclear factor -like 1" which has an official symbol of NFE2L1.
C-jun-amino-terminal kinase-interacting protein 1 is an enzyme that in humans is encoded by the MAPK8IP1 gene.
Calcium/calmodulin-dependent protein kinase type IV is an enzyme that in humans is encoded by the CAMK4 gene.
RAC-gamma serine/threonine-protein kinase is an enzyme that in humans is encoded by the AKT3 gene.
5'-AMP-activated protein kinase subunit beta-1 is an enzyme that in humans is encoded by the PRKAB1 gene.
Eukaryotic translation initiation factor 2 subunit 2 (eIF2β) is a protein that in humans is encoded by the EIF2S2 gene.
Transcription factor NF-E2 45 kDa subunit is a protein that in humans is encoded by the NFE2 gene.
Nuclear transcription factor Y subunit gamma is a protein that in humans is encoded by the NFYC gene.
LIM homeobox transcription factor 1, alpha, also known as LMX1A, is a protein which in humans is encoded by the LMX1A gene.
MODY 1 or HNF4A-MODY is a form of maturity onset diabetes of the young.
Neurogenin-3 (NGN3) is a protein that in humans is encoded by the Neurog3 gene.
Hepatocyte nuclear factor 3-gamma (HNF-3G), also known as forkhead box protein A3 (FOXA3) or transcription factor 3G (TCF-3G) is a protein that in humans is encoded by the FOXA3 gene.
Krüppel-like factor 15 is a protein that in humans is encoded by the KLF15 gene in the Krüppel-like factor family. Its former designation KKLF stands for kidney-enriched Krüppel-like factor.