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Q8CF90

- MAFA_MOUSE

UniProt

Q8CF90 - MAFA_MOUSE

Protein

Transcription factor MafA

Gene

Mafa

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 90 (01 Oct 2014)
      Sequence version 1 (01 Mar 2003)
      Previous versions | rss
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    Functioni

    Acts as a transcriptional factor. Specifically binds the insulin enhancer element RIPE3b. Cooperates synergistically with NEUROD1 and PDX1. Phosphorylation by GSK3 increases its transcriptional activity and is required for its oncogenic activity By similarity. Regulates the insulin gene transcription. Involved either as an oncogene or as a tumor suppressor, depending on the cell context.By similarity3 Publications

    GO - Molecular functioni

    1. DNA binding Source: UniProtKB
    2. sequence-specific DNA binding Source: InterPro
    3. sequence-specific DNA binding transcription factor activity Source: InterPro

    GO - Biological processi

    1. insulin secretion Source: Ensembl
    2. nitric oxide mediated signal transduction Source: Ensembl
    3. positive regulation of transcription, DNA-templated Source: MGI
    4. positive regulation of transcription from RNA polymerase II promoter Source: MGI
    5. response to glucose Source: UniProtKB
    6. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Activator

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Transcription factor MafA
    Alternative name(s):
    Pancreatic beta-cell-specific transcriptional activator
    V-maf musculoaponeurotic fibrosarcoma oncogene homolog A
    Gene namesi
    Name:Mafa
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 15

    Organism-specific databases

    MGIiMGI:2673307. Mafa.

    Subcellular locationi

    Nucleus 1 PublicationPROSITE-ProRule annotation
    Note: Detected in nuclei of pancreas islet beta cells.

    GO - Cellular componenti

    1. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    Mice show a normal pancreatic morphology at birth, but after birth a reduction in the proportion of beta-cells with resulting impaired glucose tolerance and diabetes.1 Publication

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi14 – 141S → A: Reduces phosphorylation. 1 Publication
    Mutagenesisi65 – 651S → A: Reduces phosphorylation. 1 Publication

    Keywords - Diseasei

    Proto-oncogene, Tumor suppressor

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 359359Transcription factor MafAPRO_0000320275Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei14 – 141Phosphoserine; by MAPK1By similarity
    Modified residuei49 – 491Phosphoserine; by GSK3By similarity
    Modified residuei53 – 531Phosphothreonine; by GSK3By similarity
    Modified residuei57 – 571Phosphothreonine; by GSK3By similarity
    Modified residuei61 – 611Phosphoserine; by GSK3By similarity
    Modified residuei65 – 651Phosphoserine; by MAPK1By similarity

    Post-translational modificationi

    Ubiquitinated, leading to its degradation by the proteasome.By similarity
    Phosphorylation by GSK3 requires prior phosphorylation of Ser-65 by another kinase. Phosphorylation proceeds then from Ser-61 to Thr-57, Thr-53 and Ser-49. GSK3-mediated phosphorylation increases its transcriptional activity through the recruitment of the coactivator PCAF, is required for its transforming activity and leads to its degradation through a ubiquitin/proteasome-dependent pathway By similarity. Ser-14 and Ser-65 appear to be the major phosphorylation sites. Phosphorylated by MAPK13 on serine and threonine residues Probable.By similarityCurated

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiQ8CF90.
    PRIDEiQ8CF90.

    PTM databases

    PhosphoSiteiQ8CF90.

    Expressioni

    Tissue specificityi

    Selectively expressed in pancreatic beta but not in alpha cells (at protein level). Expressed in eyes and at low levels in thymus. Expressed in brain, lung, spleen and kidney. Expressed in embryo.3 Publications

    Developmental stagei

    Expressed on E14. During fetal period (12.5 dpc) detected in each formed somite and expression appears to be in the myotomal cells. Also expressed in the head neural tube and liver cells. Expressed at low levels some mesenchyme-like cells.2 Publications

    Gene expression databases

    BgeeiQ8CF90.
    GenevestigatoriQ8CF90.

    Interactioni

    Subunit structurei

    Binds DNA as a homodimer By similarity. Interacts with PCAF By similarity. Interacts with NEUROD1 and PDX1.By similarity1 Publication

    Protein-protein interaction databases

    BioGridi237545. 1 interaction.
    STRINGi10090.ENSMUSP00000054226.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8CF90.
    SMRiQ8CF90. Positions 232-323.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini260 – 32364bZIPPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni260 – 28526Basic motifAdd
    BLAST
    Regioni266 – 28015Interaction with DNABy similarityAdd
    BLAST
    Regioni288 – 30922Leucine-zipperAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi74 – 8310Poly-Gly
    Compositional biasi145 – 22682His-richAdd
    BLAST

    Sequence similaritiesi

    Belongs to the bZIP family. Maf subfamily.Curated
    Contains 1 bZIP (basic-leucine zipper) domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG241084.
    GeneTreeiENSGT00550000074549.
    HOGENOMiHOG000261683.
    HOVERGENiHBG000313.
    InParanoidiQ8CF90.
    KOiK07595.
    OMAiQRHILES.
    OrthoDBiEOG7BGHMQ.
    PhylomeDBiQ8CF90.
    TreeFamiTF325689.

    Family and domain databases

    Gene3Di1.10.880.10. 1 hit.
    InterProiIPR004827. bZIP.
    IPR004826. bZIP_Maf.
    IPR013592. Maf_TF_N.
    IPR028562. MafA.
    IPR008917. TF_DNA-bd.
    IPR024874. Transciption_factor_Maf.
    [Graphical view]
    PANTHERiPTHR10129. PTHR10129. 1 hit.
    PTHR10129:SF24. PTHR10129:SF24. 1 hit.
    PfamiPF03131. bZIP_Maf. 1 hit.
    PF08383. Maf_N. 1 hit.
    [Graphical view]
    SMARTiSM00338. BRLZ. 1 hit.
    [Graphical view]
    SUPFAMiSSF47454. SSF47454. 1 hit.
    PROSITEiPS50217. BZIP. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q8CF90-1 [UniParc]FASTAAdd to Basket

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    MAAELAMGAE LPSSPLAIEY VNDFDLMKFE VKKEPPEAER FCHRLPPGSL    50
    SSTPLSTPCS SVPSSPSFCA PSPGTGGGAG GGGSAAQAGG APGPPSGGPG 100
    TVGGASGKAV LEDLYWMSGY QHHLNPEALN LTPEDAVEAL IGSGHHGAHH 150
    GAHHPAAAAA YEAFRGQSFA GGGGADDMGA GHHHGAHHTA HHHHSAHHHH 200
    HHHHHHGGSG HHGGGAGHGG GGAGHHVRLE ERFSDDQLVS MSVRELNRQL 250
    RGFSKEEVIR LKQKRRTLKN RGYAQSCRFK RVQQRHILES EKCQLQSQVE 300
    QLKLEVGRLA KERDLYKEKY EKLAGRGGPG GAGGAGFPRE PSPAQAGPGA 350
    AKGAPDFFL 359
    Length:359
    Mass (Da):37,576
    Last modified:March 1, 2003 - v1
    Checksum:iB10BC396218AB8A5
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB086961 Genomic DNA. Translation: BAC20390.1.
    CCDSiCCDS27549.1.
    RefSeqiNP_919331.1. NM_194350.1.
    UniGeneiMm.309589.

    Genome annotation databases

    EnsembliENSMUST00000062002; ENSMUSP00000054226; ENSMUSG00000047591.
    GeneIDi378435.
    KEGGimmu:378435.
    UCSCiuc007whe.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB086961 Genomic DNA. Translation: BAC20390.1 .
    CCDSi CCDS27549.1.
    RefSeqi NP_919331.1. NM_194350.1.
    UniGenei Mm.309589.

    3D structure databases

    ProteinModelPortali Q8CF90.
    SMRi Q8CF90. Positions 232-323.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 237545. 1 interaction.
    STRINGi 10090.ENSMUSP00000054226.

    PTM databases

    PhosphoSitei Q8CF90.

    Proteomic databases

    PaxDbi Q8CF90.
    PRIDEi Q8CF90.

    Protocols and materials databases

    DNASUi 378435.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000062002 ; ENSMUSP00000054226 ; ENSMUSG00000047591 .
    GeneIDi 378435.
    KEGGi mmu:378435.
    UCSCi uc007whe.1. mouse.

    Organism-specific databases

    CTDi 389692.
    MGIi MGI:2673307. Mafa.

    Phylogenomic databases

    eggNOGi NOG241084.
    GeneTreei ENSGT00550000074549.
    HOGENOMi HOG000261683.
    HOVERGENi HBG000313.
    InParanoidi Q8CF90.
    KOi K07595.
    OMAi QRHILES.
    OrthoDBi EOG7BGHMQ.
    PhylomeDBi Q8CF90.
    TreeFami TF325689.

    Miscellaneous databases

    NextBioi 400973.
    PROi Q8CF90.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q8CF90.
    Genevestigatori Q8CF90.

    Family and domain databases

    Gene3Di 1.10.880.10. 1 hit.
    InterProi IPR004827. bZIP.
    IPR004826. bZIP_Maf.
    IPR013592. Maf_TF_N.
    IPR028562. MafA.
    IPR008917. TF_DNA-bd.
    IPR024874. Transciption_factor_Maf.
    [Graphical view ]
    PANTHERi PTHR10129. PTHR10129. 1 hit.
    PTHR10129:SF24. PTHR10129:SF24. 1 hit.
    Pfami PF03131. bZIP_Maf. 1 hit.
    PF08383. Maf_N. 1 hit.
    [Graphical view ]
    SMARTi SM00338. BRLZ. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47454. SSF47454. 1 hit.
    PROSITEi PS50217. BZIP. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "MafA is a glucose-regulated and pancreatic beta-cell-specific transcriptional activator for the insulin gene."
      Kataoka K., Han S.I., Shioda S., Hirai M., Nishizawa M., Handa H.
      J. Biol. Chem. 277:49903-49910(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY.
    2. "Identification of beta-cell-specific insulin gene transcription factor RIPE3b1 as mammalian MafA."
      Olbrot M., Rud J., Moss L.G., Sharma A.
      Proc. Natl. Acad. Sci. U.S.A. 99:6737-6742(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
    3. "Mouse MafA, homologue of zebrafish somite Maf 1, contributes to the specific transcriptional activity through the insulin promoter."
      Kajihara M., Sone H., Amemiya M., Katoh Y., Isogai M., Shimano H., Yamada N., Takahashi S.
      Biochem. Biophys. Res. Commun. 312:831-842(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
    4. "Members of the large Maf transcription family regulate insulin gene transcription in islet beta cells."
      Matsuoka T.A., Zhao L., Artner I., Jarrett H.W., Friedman D., Means A., Stein R.
      Mol. Cell. Biol. 23:6049-6062(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION.
    5. Cited for: PHOSPHORYLATION.
    6. "The islet beta cell-enriched MafA activator is a key regulator of insulin gene transcription."
      Zhao L., Guo M., Matsuoka T.A., Hagman D.K., Parazzoli S.D., Poitout V., Stein R.
      J. Biol. Chem. 280:11887-11894(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NEUROD1 AND PDX1.
    7. Cited for: DISRUPTION PHENOTYPE.
    8. Cited for: PHOSPHORYLATION AT SER-14 AND SER-65, MUTAGENESIS OF SER-14 AND SER-65.
    9. Cited for: REVIEW, FUNCTION.

    Entry informationi

    Entry nameiMAFA_MOUSE
    AccessioniPrimary (citable) accession number: Q8CF90
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 26, 2008
    Last sequence update: March 1, 2003
    Last modified: October 1, 2014
    This is version 90 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3