Atlas of Genetics and Cytogenetics in Oncology and Haematology

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MAFA (v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (avian))

Written2009-03Celio Pouponnot, Alain Eychène
Institut Curie, CNRS UMR 146, F-91405 Orsay, France

(Note : for Links provided by Atlas : click)


Alias (NCBI)RIPE3b1
HGNC Alias symbRIPE3b1
HGNC Previous namev-maf avian musculoaponeurotic fibrosarcoma oncogene homolog A
LocusID (NCBI) 389692
Atlas_Id 41235
Location 8q24.3  [Link to chromosome band 8q24]
Location_base_pair Starts at 143428064 and ends at 143430732 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping MAFA.png]
Local_order C8orf51, RHPN1, MAFA, ZC3H3, GSDMD
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)


Note The MAFA open reading frame is encoded by a unique exon. The entire genomic organization and the putative existence of non-coding exons remain unknown.
Transcription MAFA displays a restricted expression pattern. It is notably expressed in pancreas (in beta-cells) and lens.
Pseudogene Unknown.


Note Maf oncoproteins are b-ZIP transcription factors that belong to the AP-1 super-family, which notably includes JUN and FOS. The Maf family contains seven members, which can be subdivided into two groups; the large and small Maf proteins. While the small Maf proteins, MAFF, MAFG and MAFK, are essentially composed of a b-Zip domain, the large Maf proteins, MAFA/L-MAF, MAFB, MAF/c-MAF and NRL contain an additional amino-terminal transactivation domain. MAFA was initially cloned in quail and chicken species and named MAFA and L-MAF, respectively. More recently, mammalian MAFA was cloned and identified as an essential component of the RIPE3b1 complex, which binds the insulin promoter.
  Schematic representation of the MAFA protein structure. Critical residues involved in post-translational modifications are indicated by the color code. The kinases responsible for S14 and S65 phosphorylation in MAFA remain to be identified. GSK-3 phosphorylates the transactivation domain of MAFA, thereby inducing its ubiquitination and proteasome-dependent degradation. This is linked to an increase in MAFA transactivation. These phosphorylations are required for MAFA transforming activity. In contrast, sumoylation of MAFA transactivation domain decreases its transactivation activity.
Description MAFA, like all large Maf proteins, contains an amino-terminal transactivation domain and a carboxy-terminal b-ZIP DNA binding domain. Large Maf proteins stimulate transcription of their target genes through their binding to two types of palindromic sequences called TRE- or CRE- type MARE (Maf Responsive Element) (TGCTGAC(G)TCAGCA). The leucine zipper domain allows the formation of homo- or hetero- dimers, an absolute pre-requisite for DNA binding. As homodimers, these proteins recognize palindromic sequences, with the basic domain contacting DNA directly. Among the AP-1 family, the Maf proteins are defined by the presence of an additional homologous domain, called the Extended Homology Region (EHR) or ancillary domain, which also contacts DNA. Consequently, they recognize a longer palindromic sequence than other AP-1 family members. The MARE sequence is composed of a TRE or CRE core contacted by the basic domain and a TGC flanking sequence, which is recognized by the EHR domain. While the TGC motif is crucial for Maf binding, the TRE/CRE core can be more degenerate. MAFA transactivation activity and stability is regulated by post-translational modifications (phosphorylation, ubiquitylation and sumoylation) mostly occuring on the transactivation domain. GSK-3 was identified as the major protein kinase regulating MAFA activity and oncogenic properties.
Expression Endogenous MAFA protein is detected and phosphorylated in pancreatic beta cells.
Localisation Nucleus.
Function During development, Maf proteins are involved early in specification and later in terminal differentiation. MAFA is involved in the regulation of insulin gene expression in pancreatic beta cells. Accordingly, MAFA ablation in mice leads to diabetes.
Besides their roles during development, large Maf proteins, MAFA, MAFB, and MAF/c-MAF are also involved in oncogenesis.
Homology MAFB and MAF/c-MAF are the closest MAFA homologs. The MAFA entire protein sequence shares 52%, 48% and 40% identity with those of MAFB, MAF/c-MAF and NRL, respectively. MAFA DNA binding domain (EHR + b-ZIP) shares 82%, 83%, 64% and 55-60% identity with those of MAFB, MAF/c-MAF, NRL and small MAFs, respectively. MAFA and JUN share 30% sequence identity in their b-ZIP domain (20% identity in their entire sequence).

Implicated in

Entity Multiple myeloma
Hybrid/Mutated Gene Two cases reported translocations of MAFA to the immunoglobulin heavy-chain (IgH) locus, juxtaposing the MAFA gene with the strong enhancers of the IgH locus (meeting report, accurate description lacking).
Oncogenesis Large Maf proteins, MAFA, MAFB, and MAF/c-MAF are bona fide oncogenes as demonstrated in tissue culture, animal models and in human cancers. MAFA displays the strongest transforming activity, in vitro. In human, MAF/c-MAF, MAFB and MAFA genes are translocated to the immunoglobulin heavy chain (IgH) locus in 8-10% of multiple myelomas. MAFA translocations are present in less than 1% of multiple myelomas. MAF/C-MAF overexpression plays a causative role in multiple myeloma by promoting proliferation and pathological interactions with bone marrow stroma.
The transforming activity of Maf proteins is context dependent and they can occasionally display tumor suppressor-like activity in specific cellular settings. Their transforming activity relies on overexpression and does not require an activating mutation (no activating mutation has been identified to be associated with human cancers). It is regulated by post-translational modifications, notably phosphorylation.


Phosphorylation of MafA is essential for its transcriptional and biological properties.
Benkhelifa S, Provot S, Nabais E, Eychene A, Calothy G, Felder-Schmittbuhl MP.
Mol Cell Biol. 2001 Jul;21(14):4441-52.
PMID 11416124
Genetic events in the pathogenesis of multiple myeloma.
Chng WJ, Glebov O, Bergsagel PL, Kuehl WM.
Best Pract Res Clin Haematol. 2007 Dec;20(4):571-96. (REVIEW).
PMID 18070707
A new MAFia in cancer.
Eychene A, Rocques N, Pouponnot C.
Nat Rev Cancer. 2008 Sep;8(9):683-93. (REVIEW).
PMID 19143053
MafA stability in pancreatic beta cells is regulated by glucose and is dependent on its constitutive phosphorylation at multiple sites by glycogen synthase kinase 3.
Han SI, Aramata S, Yasuda K, Kataoka K.
Mol Cell Biol. 2007 Oct;27(19):6593-605. Epub 2007 Aug 6.
PMID 17682063
Identification of three novel chromosomal translocation partners involving the immunoglobulin loci in newly diagnosed myeloma and human myeloma cell lines.
Hanamura I, Iida S, Ueda R, Kuehl M, Cullraro C, Bergsagel L, Sawyer J, Barlogie B, Shaughnessy Jr J.
Blood (ASH Annual Meeting Abstracts) 2005; 106:1552.
MafA is a glucose-regulated and pancreatic beta-cell-specific transcriptional activator for the insulin gene.
Kataoka K, Han SI, Shioda S, Hirai M, Nishizawa M, Handa H.
J Biol Chem. 2002 Dec 20;277(51):49903-10. Epub 2002 Oct 3.
PMID 12368292
Members of the large Maf transcription family regulate insulin gene transcription in islet beta cells.
Matsuoka TA, Zhao L, Artner I, Jarrett HW, Friedman D, Means A, Stein R.
Mol Cell Biol. 2003 Sep;23(17):6049-62.
PMID 12917329
MafA has strong cell transforming ability but is a weak transactivator.
Nishizawa M, Kataoka K, Vogt PK.
Oncogene. 2003 Sep 11;22(39):7882-90.
PMID 12970735
Induction of lens differentiation by activation of a bZIP transcription factor, L-Maf.
Ogino H, Yasuda K.
Science. 1998 Apr 3;280(5360):115-8.
PMID 9525857
Identification of beta-cell-specific insulin gene transcription factor RIPE3b1 as mammalian MafA.
Olbrot M, Rud J, Moss LG, Sharma A.
Proc Natl Acad Sci U S A. 2002 May 14;99(10):6737-42.
PMID 12011435
Cell context reveals a dual role for Maf in oncogenesis.
Pouponnot C, Sii-Felice K, Hmitou I, Rocques N, Lecoin L, Druillennec S, Felder-Schmittbuhl MP, Eychene A.
Oncogene. 2006 Mar 2;25(9):1299-310.
PMID 16247450
GSK-3-mediated phosphorylation enhances Maf-transforming activity.
Rocques N, Abou Zeid N, Sii-Felice K, Lecoin L, Felder-Schmittbuhl MP, Eychene A, Pouponnot C.
Mol Cell. 2007 Nov 30;28(4):584-97.
PMID 18042454
Sumoylation regulates the transcriptional activity of MafA in pancreatic beta cells.
Shao C, Cobb MH.
J Biol Chem. 2009 Jan 30;284(5):3117-24. Epub 2008 Nov 22.
PMID 19029092
MafA transcription factor is phosphorylated by p38 MAP kinase.
Sii-Felice K, Pouponnot C, Gillet S, Lecoin L, Girault JA, Eychene A, Felder-Schmittbuhl MP.
FEBS Lett. 2005 Jul 4;579(17):3547-54.
PMID 15963504
MafA is a key regulator of glucose-stimulated insulin secretion.
Zhang C, Moriguchi T, Kajihara M, Esaki R, Harada A, Shimohata H, Oishi H, Hamada M, Morito N, Hasegawa K, Kudo T, Engel JD, Yamamoto M, Takahashi S.
Mol Cell Biol. 2005 Jun;25(12):4969-76.
PMID 15923615


This paper should be referenced as such :
Pouponnot, C ; Eychöne, A
MAFA (v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (avian))
Atlas Genet Cytogenet Oncol Haematol. 2010;14(3):235-237.
Free journal version : [ pdf ]   [ DOI ]

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 2 ]
  t(14;16)(q32;q23) IGH/MAF
t(14;20)(q32;q12) IGH/MAFB in Plasma Cell Myeloma

External links

HGNC (Hugo)MAFA   23145
Entrez_Gene (NCBI)MAFA    MAF bZIP transcription factor A
AliasesINSDM; RIPE3b1; hMafA
GeneCards (Weizmann)MAFA
Ensembl hg19 (Hinxton)ENSG00000182759 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000182759 [Gene_View]  ENSG00000182759 [Sequence]  chr8:143428064-143430732 [Contig_View]  MAFA [Vega]
ICGC DataPortalENSG00000182759
Genatlas (Paris)MAFA
SOURCE (Princeton)MAFA
Genetics Home Reference (NIH)MAFA
Genomic and cartography
GoldenPath hg38 (UCSC)MAFA  -     chr8:143428064-143430732 -  8q24.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)MAFA  -     8q24.3   [Description]    (hg19-Feb_2009)
GoldenPathMAFA - 8q24.3 [CytoView hg19]  MAFA - 8q24.3 [CytoView hg38]
genome Data Viewer NCBIMAFA [Mapview hg19]  
OMIM147630   610303   
Gene and transcription
Genbank (Entrez)-
RefSeq transcript (Entrez)NM_201589
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)MAFA
Alternative Splicing GalleryENSG00000182759
Gene ExpressionMAFA [ NCBI-GEO ]   MAFA [ EBI - ARRAY_EXPRESS ]   MAFA [ SEEK ]   MAFA [ MEM ]
Gene Expression Viewer (FireBrowse)MAFA [ Firebrowse - Broad ]
GenevisibleExpression of MAFA in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)389692
GTEX Portal (Tissue expression)MAFA
Human Protein AtlasENSG00000182759-MAFA [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ8NHW3   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ8NHW3  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ8NHW3
Splice isoforms : SwissVarQ8NHW3
Domaine pattern : Prosite (Expaxy)BZIP (PS50217)   
Domains : Interpro (EBI)bZIP    bZIP_Maf    Maf_TF_N    MafA    TF_DNA-bd_sf    Transcription_factor_Maf_fam   
Domain families : Pfam (Sanger)bZIP_Maf (PF03131)    Maf_N (PF08383)   
Domain families : Pfam (NCBI)pfam03131    pfam08383   
Domain families : Smart (EMBL)BRLZ (SM00338)  
Conserved Domain (NCBI)MAFA
Blocks (Seattle)MAFA
PDB Europe4EOT   
Structural Biology KnowledgeBase4EOT   
SCOP (Structural Classification of Proteins)4EOT   
CATH (Classification of proteins structures)4EOT   
Human Protein Atlas [tissue]ENSG00000182759-MAFA [tissue]
Peptide AtlasQ8NHW3
Protein Interaction databases
IntAct (EBI)Q8NHW3
Ontologies - Pathways
Ontology : AmiGO"nuclear chromatin  RNA polymerase II proximal promoter sequence-specific DNA binding  DNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription activator activity, RNA polymerase II-specific  DNA binding  DNA-binding transcription factor activity  DNA-binding transcription factor activity  nucleus  nucleus  regulation of transcription, DNA-templated  nitric oxide mediated signal transduction  response to glucose  insulin secretion  host cell nucleus  sequence-specific DNA binding  positive regulation of transcription by RNA polymerase II"  
Ontology : EGO-EBI"nuclear chromatin  RNA polymerase II proximal promoter sequence-specific DNA binding  DNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription activator activity, RNA polymerase II-specific  DNA binding  DNA-binding transcription factor activity  DNA-binding transcription factor activity  nucleus  nucleus  regulation of transcription, DNA-templated  nitric oxide mediated signal transduction  response to glucose  insulin secretion  host cell nucleus  sequence-specific DNA binding  positive regulation of transcription by RNA polymerase II"  
Pathways : KEGGType II diabetes mellitus    Maturity onset diabetes of the young   
REACTOMEQ8NHW3 [protein]
REACTOME PathwaysR-HSA-210745 [pathway]   
NDEx NetworkMAFA
Atlas of Cancer Signalling NetworkMAFA
Wikipedia pathwaysMAFA
Orthology - Evolution
GeneTree (enSembl)ENSG00000182759
Phylogenetic Trees/Animal Genes : TreeFamMAFA
Homologs : HomoloGeneMAFA
Homology/Alignments : Family Browser (UCSC)MAFA
Gene fusions - Rearrangements
Fusion : QuiverMAFA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerMAFA [hg38]
Exome Variant ServerMAFA
GNOMAD BrowserENSG00000182759
Varsome BrowserMAFA
Genomic Variants (DGV)MAFA [DGVbeta]
DECIPHERMAFA [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisMAFA 
ICGC Data PortalMAFA 
TCGA Data PortalMAFA 
Broad Tumor PortalMAFA
OASIS PortalMAFA [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICMAFA  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DMAFA
Mutations and Diseases : HGMDMAFA
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch MAFA
DgiDB (Drug Gene Interaction Database)MAFA
DoCM (Curated mutations)MAFA (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)MAFA (select a term)
NCG6 (London) select MAFA
Cancer3DMAFA(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM147630    610303   
Genetic Testing Registry MAFA
NextProtQ8NHW3 [Medical]
Target ValidationMAFA
Huge Navigator MAFA [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTD
Pharm GKB GenePA134963361
Pharm GKB PathwaysPA153627758   PA165985892   
Clinical trialMAFA
canSAR (ICR)MAFA (select the gene name)
DataMed IndexMAFA
PubMed42 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Feb 19 17:54:08 CET 2021

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