MAFA (gene)

Last updated
MAFA
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases MAFA , RIPE3b1, hMafA, MAF bZIP transcription factor A, INSDM
External IDs OMIM: 610303; MGI: 2673307; HomoloGene: 65867; GeneCards: MAFA; OMA:MAFA - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_201589

NM_194350

RefSeq (protein)

NP_963883

NP_919331

Location (UCSC) Chr 8: 143.42 – 143.43 Mb Chr 15: 75.62 – 75.62 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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]

Contents

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]

MAFA assists in insulin regulation

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]

Interactions

MafA (gene) has been shown to interact with NEUROD1 [13] and Pdx1. [13] MafA works with Pdx1 to activate the insulin gene. [6]

MAFA in neurons

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]

Related Research Articles

<span class="mw-page-title-main">Insulin</span> Peptide hormone

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<span class="mw-page-title-main">Mothers against decapentaplegic homolog 2</span> Protein found in humans

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<span class="mw-page-title-main">Protein c-Fos</span> Mammalian protein found in Homo sapiens

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.

<span class="mw-page-title-main">MAPK8</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase 8 is a ubiquitous enzyme that in humans is encoded by the MAPK8 gene.

<span class="mw-page-title-main">AKT2</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">PDX1</span> A protein involved in the pancreas and duodenum differentiation

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.

<span class="mw-page-title-main">NEUROD1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">NRF1</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">MAPK8IP1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">CAMK4</span> Protein-coding gene in humans

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<span class="mw-page-title-main">AKT3</span> Protein-coding gene in the species Homo sapiens

RAC-gamma serine/threonine-protein kinase is an enzyme that in humans is encoded by the AKT3 gene.

<span class="mw-page-title-main">PRKAB1</span> Protein-coding gene in the species Homo sapiens

5'-AMP-activated protein kinase subunit beta-1 is an enzyme that in humans is encoded by the PRKAB1 gene.

<span class="mw-page-title-main">EIF2S2</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">NFE2</span> Protein-coding gene in the species Homo sapiens

Transcription factor NF-E2 45 kDa subunit is a protein that in humans is encoded by the NFE2 gene.

<span class="mw-page-title-main">NFYC</span> Protein-coding gene in the species Homo sapiens

Nuclear transcription factor Y subunit gamma is a protein that in humans is encoded by the NFYC gene.

<span class="mw-page-title-main">LMX1A</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">MODY 1</span> Medical condition

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<span class="mw-page-title-main">Neurogenin-3</span> Mammalian protein found in Homo sapiens

Neurogenin-3 (NGN3) is a protein that in humans is encoded by the Neurog3 gene.

<span class="mw-page-title-main">FOXA3</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">KLF15</span> Protein-coding gene in the species Homo sapiens

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.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000182759 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000047591 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: MAFA v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (avian)".
  6. 1 2 3 Aramata; Han (2007). "Roles and Regulation of Transcription Factor MafA in Islet β-cells". Endocr. J. 54 (5): 659–66. doi: 10.1507/endocrj.kr-101 . PMID   17785922.
  7. Rocques, Nathalie; Abou Zeid, Nancy; Sii-Felice, Karine; Lecoin, Laure; Felder-Schmittbuhl, Marie-Paule; Eychène, Alain; Pouponnot, Celio (November 2007). "GSK-3-Mediated Phosphorylation Enhances Maf-Transforming Activity". Molecular Cell. 28 (4): 584–597. doi: 10.1016/j.molcel.2007.11.009 . PMID   18042454.
  8. 1 2 Lecoin, Laure; Dempsey, Bowen; Garancher, Alexandra; Bourane, Steeve; Ruffault, Pierre-Louis; Morin-Surun, Marie-Pierre; Rocques, Nathalie; Goulding, Martyn; Eychène, Alain; Pouponnot, Celio; Fortin, Gilles; Champagnat, Jean (June 2022). "Mafa-dependent GABAergic activity promotes mouse neonatal apneas". Nature Communications. 13 (1): 3284. Bibcode:2022NatCo..13.3284L. doi:10.1038/s41467-022-30825-3. ISSN   2041-1723. PMC   9174494 . PMID   35672398.
  9. Iacovazzo, Donato; Flanagan, Sarah E.; Walker, Emily; Quezado, Rosana; de Sousa Barros, Fernando Antonio; Caswell, Richard; Johnson, Matthew B.; Wakeling, Matthew; Brändle, Michael; Guo, Min; Dang, Mary N.; Gabrovska, Plamena; Niederle, Bruno; Christ, Emanuel; Jenni, Stefan (30 January 2018). "MAFA missense mutation causes familial insulinomatosis and diabetes mellitus". Proceedings of the National Academy of Sciences. 115 (5): 1027–1032. Bibcode:2018PNAS..115.1027I. doi: 10.1073/pnas.1712262115 . ISSN   0027-8424. PMC   5798333 . PMID   29339498.
  10. Zhang; Moriguchi (2005). "MafA Is a Key Regulator of Glucose-Stimulated Insulin Secretion". Mol. Cell. Biol. 25 (12): 4969–4976. doi:10.1128/MCB.25.12.4969-4976.2005. PMC   1140590 . PMID   15923615.
  11. Matsuoka; Artner (March 2004). "The MafA transcription factor appears to be responsible for tissue-specific expression of insulin". Proc. Natl. Acad. Sci. U.S.A. 101 (9): 2930–3. Bibcode:2004PNAS..101.2930M. doi: 10.1073/pnas.0306233101 . PMC   365722 . PMID   14973194.
  12. Wang; Kataoka (2007). "MAFA controls genes implicated in insulin biosynthesis and secretion". Diabetologia. 50 (2): 348–58. doi:10.1007/s00125-006-0490-2. PMC   2196442 . PMID   17149590.
  13. 1 2 Zhao, Li; Guo Min; Matsuoka Taka-Aki; Hagman Derek K; Parazzoli Susan D; Poitout Vincent; Stein Roland (March 2005). "The islet beta cell-enriched MafA activator is a key regulator of insulin gene transcription". J. Biol. Chem. 280 (12): 11887–94. doi: 10.1074/jbc.M409475200 . ISSN   0021-9258. PMID   15665000.
  14. Bourane, Steeve; Garces, Alain; Venteo, Stephanie; Pattyn, Alexandre; Hubert, Thomas; Fichard, Agnes; Puech, Sylvie; Boukhaddaoui, Hassan; Baudet, Christel; Takahashi, Satoru; Valmier, Jean; Carroll, Patrick (December 2009). "Low-Threshold Mechanoreceptor Subtypes Selectively Express MafA and Are Specified by Ret Signaling". Neuron. 64 (6): 857–870. doi: 10.1016/j.neuron.2009.12.004 . PMID   20064392. S2CID   14370290.
  15. Lecoin, Laure; Rocques, Nathalie; El-Yakoubi, Warif; Achour, Sarrah Ben; Larcher, Magalie; Pouponnot, Celio; Eychène, Alain (2010). "MafA transcription factor identifies the early ret-expressing sensory neurons". Developmental Neurobiology. 70 (7): 485–497. doi:10.1002/dneu.20790. PMID   20213756. S2CID   421285.

Further reading