MAFF (gene)

Last updated
MAFF
Identifiers
Aliases MAFF , U-MAF, hMafF, MAF bZIP transcription factor F
External IDs OMIM: 604877 MGI: 96910 HomoloGene: 7825 GeneCards: MAFF
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_152878
NM_001161572
NM_001161573
NM_001161574
NM_012323

Contents

NM_010755
NM_001304830
NM_001304831
NM_001304832

RefSeq (protein)

NP_001155044
NP_001155045
NP_001155046
NP_036455

NP_001291759
NP_001291760
NP_001291761
NP_034885

Location (UCSC) Chr 22: 38.2 – 38.22 Mb Chr 15: 79.23 – 79.24 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse
Structures of the Maf family proteins. W-F1.jpg
Structures of the Maf family proteins.

Transcription factor MafF is a bZip Maf transcription factor protein that in humans is encoded by the MAFF gene. [5] [6]

MafF is one of the small Maf proteins, which are basic region and leucine zipper (bZIP)-type transcription factors. The HUGO Gene Nomenclature Committee-approved gene name of MAFF is “v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog F”.

Discovery

MafF was first cloned and identified in chicken in 1993 as a member of the small Maf (sMaf) genes. [5] MAFF has been identified in many vertebrates, including humans. [6] There are three functionally redundant sMaf proteins in vertebrates, MafF, MafG, and MafK.

Structure

MafF has a bZIP structure that consists of a basic region for DNA binding and a leucine zipper structure for dimer formation. [5] Similar to other sMafs, MafF lacks any canonical transcriptional activation domains. [5]

Expression

MAFF is broadly but differentially expressed in various tissues. MAFF expression was detected in all 16 tissues examined by the human BodyMap Project, but relatively abundant in adipose, colon, lung, prostate and skeletal muscle tissues. [7] Human MAFF gene is induced by proinflammatory cytokines, interleukin 1 beta and tumor necrosis factor in myometrial cells. [8]

Function

Because of sequence similarity, no functional differences have been observed among the sMafs in terms of their bZIP structures. sMafs form homodimers by themselves and heterodimers with other specific bZIP transcription factors, such as CNC (cap 'n' collar) proteins [p45 NF-E2 (NFE2), Nrf1 (NFE2L1), Nrf2 (NFE2L2), and Nrf3 (NFE2L3)] [9] [10] [11] [12] and Bach proteins (BACH1 and BACH2). [13]

Target genes

sMafs regulate different target genes depending on their partners. For instance, the p45-NF-E2-sMaf heterodimer regulate genes responsible for platelet production. [9] [14] [15] Nrf2-sMaf heterodimer regulates a battery of cytoprotective genes, such as antioxidant/xenobiotic metabolizing enzyme genes. [11] [16] The Bach1-sMaf heterodimer regulates the heme oxygenase-1 gene. [13] In particular, it has been reported that MafF regulates the oxytocin receptor gene. [17] The contribution of individual sMafs to the transcriptional regulation of their target genes has not yet been well examined.

Disease linkage

Loss of sMafs results in disease-like phenotypes as summarized in table below. Mice lacking MafF are seemingly healthy under laboratory conditions. [18] However, mice lacking MafG exhibit mild neuronal phenotype and mild thrombocytopenia, [19] mice lacking Mafg and one allele of Mafk (Mafg−/−::Mafk+/−) exhibit progressive neuronal degeneration, thrombocytopenia and cataract, [20] [21] and mice lacking MafG and MafK (Mafg−/−::Mafk−/−) exhibit more severe neuronal degeneration and die in the perinatal stage. [22] Mice lacking MafF, MafG and MafK are embryonic lethal, demonstrating that MafF is indispensable for embryonic development. [23] Embryonic fibroblasts that are derived from Maff−/−::Mafg-/−::Mafk−/− mice fail to activate Nrf2-dependent cytoprotective genes in response to stress. [16]

GenotypeMouse Phenotype
MaffMafgMafk
−/−No apparent phenotype under laboratory conditions [18]
−/−Mild motor ataxia, mild thrombocytopenia [19]
−/−+/−Severe motor ataxia, progressive neuronal degeneration, severe thrombocytopenia, and cataract [20] [21]
−/−−/−More severe neuronal phenotypes, and perinatal lethal [22]
−/−+/−−/−No severe abnormality [23] (Fertile)
−/−−/−−/−Growth retardation, fetal liver hypoplasia, and lethal around embryonic day, 13.5 [23]
+/− (heterozygote), −/− (homozygote), blank (wild-type)

In addition, accumulating evidence suggests that as partners of CNC and Bach proteins, sMafs are involved in the onset and progression of various human diseases, including neurodegeneration, arteriosclerosis and cancer.

See also

Notes

Related Research Articles

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

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

The small heterodimer partner (SHP) also known as NR0B2 is a protein that in humans is encoded by the NR0B2 gene. SHP is a member of the nuclear receptor family of intracellular transcription factors. SHP is unusual for a nuclear receptor in that it lacks a DNA binding domain. Therefore, it is technically neither a transcription factor nor nuclear receptor but nevertheless it is still classified as such due to relatively high sequence homology with other nuclear receptor family members.

<span class="mw-page-title-main">NFE2L2</span> Human protein and coding gene

Nuclear factor erythroid 2-related factor 2 (NRF2), also known as nuclear factor erythroid-derived 2-like 2, is a transcription factor that in humans is encoded by the NFE2L2 gene. NRF2 is a basic leucine zipper (bZIP) protein that may regulate the expression of antioxidant proteins that protect against oxidative damage triggered by injury and inflammation, according to preliminary research. In vitro, NRF2 binds to antioxidant response elements (AREs) in the promoter regions of genes encoding cytoprotective proteins. NRF2 induces the expression of heme oxygenase 1 in vitro leading to an increase in phase II enzymes. NRF2 also inhibits the NLRP3 inflammasome.

<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">ATF4</span> Mammalian protein found in Homo sapiens

Activating transcription factor 4 , also known as ATF4, is a protein that in humans is encoded by the ATF4 gene.

<span class="mw-page-title-main">ATF6</span> Protein-coding gene in the species Homo sapiens

Activating transcription factor 6, also known as ATF6, is a protein that, in humans, is encoded by the ATF6 gene and is involved in the unfolded protein response.

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

GA-binding protein alpha chain is a protein that in humans is encoded by the GABPA gene.

<span class="mw-page-title-main">BACH1</span> Protein-coding gene in the species Homo sapiens

Transcription regulator protein BACH1 is a protein that in humans is encoded by the BACH1 gene.

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

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.

<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">MAFG</span> Protein-coding gene in the species Homo sapiens

Transcription factor MafG is a bZip Maf transcription factor protein that in humans is encoded by the MAFG gene.

<i>MAFB</i> (gene) Protein-coding gene in the species Homo sapiens

Transcription factor MafB also known as V-maf musculoaponeurotic fibrosarcoma oncogene homolog B is a protein that in humans is encoded by the MAFB gene. This gene maps to chromosome 20q11.2-q13.1, consists of a single exon and spans around 3 kb.

<span class="mw-page-title-main">NFE2L1</span> Protein-coding gene in the species Homo sapiens

Nuclear factor erythroid 2-related factor 1 (Nrf1) also known as nuclear factor erythroid-2-like 1 (NFE2L1) is a protein that in humans is encoded by the NFE2L1 gene. Since NFE2L1 is referred to as Nrf1, it is often confused with nuclear respiratory factor 1 (Nrf1).

<span class="mw-page-title-main">BACH2</span> Protein-coding gene in the species Homo sapiens

Transcription regulator protein BACH2 is a protein that in humans is encoded by the BACH2 gene. It contains a BTB/POZ domain at its N-terminus which forms a disulphide-linked dimer and a bZip_Maf domain at the C-terminus.

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

Transcription factor MafK is a bZip Maf transcription factor protein that in humans is encoded by the MAFK gene.

<span class="mw-page-title-main">NFE2L3</span> Protein-coding gene in the species Homo sapiens

Nuclear factor -like factor 3, also known as NFE2L3 or 'NRF3', is a transcription factor that in humans is encoded by the Nfe2l3 gene.

bZIP domain Protein domain

The Basic Leucine Zipper Domain is found in many DNA binding eukaryotic proteins. One part of the domain contains a region that mediates sequence specific DNA binding properties and the leucine zipper that is required to hold together (dimerize) two DNA binding regions. The DNA binding region comprises a number of basic amino acids such as arginine and lysine. Proteins containing this domain are transcription factors.

bZIP Maf

bZIP Maf is a domain found in Maf transcription factor proteins. It contains a leucine zipper (bZIP) domain, which mediates the transcription factor's dimerization and DNA binding properties. The Maf extended homology region (EHR) is present at the N-terminus of the protein. This region exists only within the Maf family and allows the family to recognize longer DNA motifs than other leucine zippers. These motifs are termed the Maf recognition element (MARE) and is 13 or 14 base pairs long. In particular, the two residues at the beginning of helix H2 are positioned to recognise the flanking region of the DNA. Small Maf proteins heterodimerize with Fos and may act as competitive repressors of the NF2-E2 transcription 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.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000185022 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000042622 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. 1 2 3 4 Fujiwara KT, Kataoka K, Nishizawa M (Sep 1993). "Two new members of the maf oncogene family, mafK and mafF, encode nuclear b-Zip proteins lacking putative trans-activator domain". Oncogene. 8 (9): 2371–80. PMID   8361754.
  6. 1 2 "Entrez Gene: MAFF v-maf musculoaponeurotic fibrosarcoma oncogene homolog F (avian)".
  7. Petryszak R, Burdett T, Fiorelli B, Fonseca NA, Gonzalez-Porta M, Hastings E, Huber W, Jupp S, Keays M, Kryvych N, McMurry J, Marioni JC, Malone J, Megy K, Rustici G, Tang AY, Taubert J, Williams E, Mannion O, Parkinson HE, Brazma A (Jan 2014). "Expression Atlas update--a database of gene and transcript expression from microarray- and sequencing-based functional genomics experiments". Nucleic Acids Research. 42 (Database issue): D926-32. doi:10.1093/nar/gkt1270. PMC   3964963 . PMID   24304889.
  8. Massrieh W, Derjuga A, Doualla-Bell F, Ku CY, Sanborn BM, Blank V (Apr 2006). "Regulation of the MAFF transcription factor by proinflammatory cytokines in myometrial cells". Biology of Reproduction. 74 (4): 699–705. doi: 10.1095/biolreprod.105.045450 . PMID   16371591. S2CID   11823930.
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  19. 1 2 Shavit JA, Motohashi H, Onodera K, Akasaka J, Yamamoto M, Engel JD (Jul 1998). "Impaired megakaryopoiesis and behavioral defects in mafG-null mutant mice". Genes & Development. 12 (14): 2164–74. doi:10.1101/gad.12.14.2164. PMC   317009 . PMID   9679061.
  20. 1 2 Katsuoka F, Motohashi H, Tamagawa Y, Kure S, Igarashi K, Engel JD, Yamamoto M (Feb 2003). "Small Maf compound mutants display central nervous system neuronal degeneration, aberrant transcription, and Bach protein mislocalization coincident with myoclonus and abnormal startle response". Molecular and Cellular Biology. 23 (4): 1163–74. doi:10.1128/mcb.23.4.1163-1174.2003. PMC   141134 . PMID   12556477.
  21. 1 2 Agrawal SA, Anand D, Siddam AD, Kakrana A, Dash S, Scheiblin DA, Dang CA, Terrell AM, Waters SM, Singh A, Motohashi H, Yamamoto M, Lachke SA (Jul 2015). "Compound mouse mutants of bZIP transcription factors Mafg and Mafk reveal a regulatory network of non-crystallin genes associated with cataract". Human Genetics. 134 (7): 717–35. doi:10.1007/s00439-015-1554-5. PMC   4486474 . PMID   25896808.
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  23. 1 2 3 Yamazaki H, Katsuoka F, Motohashi H, Engel JD, Yamamoto M (Feb 2012). "Embryonic lethality and fetal liver apoptosis in mice lacking all three small Maf proteins". Molecular and Cellular Biology. 32 (4): 808–16. doi:10.1128/MCB.06543-11. PMC   3272985 . PMID   22158967.

Further reading