MAFA (gene)

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
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesMAFA, RIPE3b1, hMafA, MAF bZIP transcription factor A, INSDM
External IDsOMIM: 610303 MGI: 2673307 HomoloGene: 65867 GeneCards: MAFA
Orthologs
SpeciesHumanMouse
Entrez

389692

378435

Ensembl

ENSG00000182759

ENSMUSG00000047591

UniProt

Q8NHW3

Q8CF90

RefSeq (mRNA)

NM_201589

NM_194350

RefSeq (protein)

NP_963883

NP_919331

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

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]

References

  1. GRCh38: Ensembl release 89: ENSG00000182759 - Ensembl, May 2017
  2. 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. 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. 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. 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


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