MAFA | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | MAFA , RIPE3b1, hMafA, MAF bZIP transcription factor A, INSDM | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 610303 MGI: 2673307 HomoloGene: 65867 GeneCards: MAFA | ||||||||||||||||||||||||||||||||||||||||||||||||||
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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]
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.
SMAD family member 6, also known as SMAD6, is a protein that in humans is encoded by the SMAD6 gene.
JAK1 is a human tyrosine kinase protein essential for signaling for certain type I and type II cytokines. It interacts with the common gamma chain (γc) of type I cytokine receptors, to elicit signals from the IL-2 receptor family, the IL-4 receptor family, the gp130 receptor family. It is also important for transducing a signal by type I (IFN-α/β) and type II (IFN-γ) interferons, and members of the IL-10 family via type II cytokine receptors. Jak1 plays a critical role in initiating responses to multiple major cytokine receptor families. Loss of Jak1 is lethal in neonatal mice, possibly due to difficulties suckling. Expression of JAK1 in cancer cells enables individual cells to contract, potentially allowing them to escape their tumor and metastasize to other parts of the body.
Mitogen-activated protein kinase 8 is a ubiquitous enzyme that in humans is encoded by the MAPK8 gene.
Dual specificity mitogen-activated protein kinase kinase 2 is an enzyme that in humans is encoded by the MAP2K2 gene. It is more commonly known as MEK2, but has many alternative names including CFC4, MKK2, MAPKK2 and PRKMK2.
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.
Eukaryotic translation initiation factor 2 subunit 2 (eIF2β) is a protein that in humans is encoded by the EIF2S2 gene.
Transcription factor Maf also known as proto-oncogene c-Maf or V-maf musculoaponeurotic fibrosarcoma oncogene homolog is a transcription factor that in humans is encoded by the MAF gene.
Peroxisome proliferator-activated receptor gamma coactivator 1-beta is a protein that in humans is encoded by the PPARGC1B gene.
Transcription factor NF-E2 45 kDa subunit is a protein that in humans is encoded by the NFE2 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 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.
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.
Small Maf proteins are basic region leucine zipper-type transcription factors that can bind to DNA and regulate gene regulation. There are three small Maf (sMaf) proteins, namely MafF, MafG, and MafK, in vertebrates. HUGO Gene Nomenclature Committee (HGNC)-approved gene names of MAFF, MAFG and MAFK are “v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog F, G, and K”, respectively.