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Q8NHW3

- MAFA_HUMAN

UniProt

Q8NHW3 - MAFA_HUMAN

Protein

Transcription factor MafA

Gene

MAFA

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 92 (01 Oct 2014)
      Sequence version 2 (18 May 2010)
      Previous versions | rss
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    Functioni

    Acts as a transcriptional factor. Specifically binds the insulin enhancer element RIPE3b and activates insulin gene expression. Cooperates synergistically with NEUROD1 and PDX1. Phosphorylation by GSK3 increases its transcriptional activity and is required for its oncogenic activity. Involved either as an oncogene or as a tumor suppressor, depending on the cell context.6 Publications

    GO - Molecular functioni

    1. DNA binding Source: UniProtKB
    2. protein heterodimerization activity Source: UniProtKB
    3. protein homodimerization activity Source: UniProtKB
    4. sequence-specific DNA binding Source: InterPro
    5. sequence-specific DNA binding transcription factor activity Source: UniProtKB

    GO - Biological processi

    1. insulin secretion Source: BHF-UCL
    2. nitric oxide mediated signal transduction Source: BHF-UCL
    3. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
    4. regulation of transcription, DNA-templated Source: UniProtKB
    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

    Enzyme and pathway databases

    ReactomeiREACT_13819. Regulation of gene expression in beta cells.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Transcription factor MafA
    Alternative name(s):
    Pancreatic beta-cell-specific transcriptional activator
    Transcription factor RIPE3b1
    V-maf musculoaponeurotic fibrosarcoma oncogene homolog A
    Gene namesi
    Name:MAFA
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 8

    Organism-specific databases

    HGNCiHGNC:23145. MAFA.

    Subcellular locationi

    Nucleus 2 PublicationsPROSITE-ProRule annotation
    Note: Detected in nuclei of pancreas islet beta cells.By similarity

    GO - Cellular componenti

    1. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi14 – 141S → A: Abolishes transactivation activity; when associated with A-65. 1 Publication
    Mutagenesisi49 – 491S → A: Diminishes transcriptional activity and transforming activity and abolishes ubiquitination; when associated with A-53; A-57 and A-61. 1 Publication
    Mutagenesisi53 – 531T → A: Diminishes transcriptional activity and transforming activity and abolishes ubiquitination; when associated with A-49; A-57 and A-61. 1 Publication
    Mutagenesisi57 – 571T → A: Diminishes transcriptional activity and transforming activity and abolishes ubiquitination; when associated with A-49; A-53 and A-61. 1 Publication
    Mutagenesisi61 – 611S → A: Diminishes transcriptional activity and transforming activity and abolishes ubiquitination; when associated with A-49; A-53 and A-57. 1 Publication
    Mutagenesisi65 – 651S → A: Greatly reduces phosphorylation and reduces transcriptional activity; when associated with A-14. 1 Publication

    Keywords - Diseasei

    Proto-oncogene, Tumor suppressor

    Organism-specific databases

    PharmGKBiPA134963361.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 353353Transcription factor MafAPRO_0000320274Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei14 – 141Phosphoserine; by MAPK12 Publications
    Modified residuei49 – 491Phosphoserine; by GSK32 Publications
    Modified residuei53 – 531Phosphothreonine; by GSK32 Publications
    Modified residuei57 – 571Phosphothreonine; by GSK32 Publications
    Modified residuei61 – 611Phosphoserine; by GSK32 Publications
    Modified residuei65 – 651Phosphoserine; by MAPK12 Publications

    Post-translational modificationi

    Ubiquitinated, leading to its degradation by the proteasome.1 Publication
    Ser-14 and Ser-65 appear to be the major phosphorylation sites. Phosphorylated by MAPK13 on serine and threonine residues Probable. 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.3 PublicationsCurated

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiQ8NHW3.
    PRIDEiQ8NHW3.

    PTM databases

    PhosphoSiteiQ8NHW3.

    Expressioni

    Inductioni

    Up-regulated by glucose.1 Publication

    Gene expression databases

    BgeeiQ8NHW3.
    CleanExiHS_MAFA.
    GenevestigatoriQ8NHW3.

    Interactioni

    Subunit structurei

    Binds DNA as a homodimer. Interacts with NEUROD1, PCAF and PDX1.3 Publications

    Protein-protein interaction databases

    BioGridi133233. 5 interactions.
    STRINGi9606.ENSP00000328364.

    Structurei

    Secondary structure

    1
    353
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi229 – 2346
    Helixi237 – 2437
    Turni244 – 2463
    Helixi249 – 31668

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4EOTX-ray2.86A/B226-318[»]
    ProteinModelPortaliQ8NHW3.
    SMRiQ8NHW3. Positions 226-317.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini254 – 31764bZIPPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni254 – 27926Basic motifAdd
    BLAST
    Regioni260 – 27415Interaction with DNAAdd
    BLAST
    Regioni282 – 30322Leucine-zipperAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi74 – 8613Poly-GlyAdd
    BLAST
    Compositional biasi147 – 22074His-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.
    HOGENOMiHOG000261683.
    HOVERGENiHBG000313.
    InParanoidiQ8NHW3.
    KOiK07595.
    OMAiQRHILES.
    OrthoDBiEOG7BGHMQ.
    PhylomeDBiQ8NHW3.
    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.

    Q8NHW3-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAAELAMGAE LPSSPLAIEY VNDFDLMKFE VKKEPPEAER FCHRLPPGSL    50
    SSTPLSTPCS SVPSSPSFCA PSPGTGGGGG AGGGGGSSQA GGAPGPPSGG 100
    PGAVGGTSGK PALEDLYWMS GYQHHLNPEA LNLTPEDAVE ALIGSGHHGA 150
    HHGAHHPAAA AAYEAFRGPG FAGGGGADDM GAGHHHGAHH AAHHHHAAHH 200
    HHHHHHHHGG AGHGGGAGHH VRLEERFSDD QLVSMSVREL NRQLRGFSKE 250
    EVIRLKQKRR TLKNRGYAQS CRFKRVQQRH ILESEKCQLQ SQVEQLKLEV 300
    GRLAKERDLY KEKYEKLAGR GGPGSAGGAG FPREPSPPQA GPGGAKGTAD 350
    FFL 353
    Length:353
    Mass (Da):36,982
    Last modified:May 18, 2010 - v2
    Checksum:i38F732D4C959AD62
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti199 – 1991Missing in BAC20389. (PubMed:12368292)Curated
    Sequence conflicti199 – 1991Missing in AAL89527. (PubMed:12011435)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB086960 Genomic DNA. Translation: BAC20389.1.
    AY083269 Genomic DNA. Translation: AAL89527.1.
    AC105118 Genomic DNA. No translation available.
    CCDSiCCDS34955.1.
    RefSeqiNP_963883.2. NM_201589.3.
    UniGeneiHs.521914.

    Genome annotation databases

    EnsembliENST00000333480; ENSP00000328364; ENSG00000182759.
    GeneIDi389692.
    KEGGihsa:389692.
    UCSCiuc003yyc.2. human.

    Polymorphism databases

    DMDMi296435511.

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB086960 Genomic DNA. Translation: BAC20389.1 .
    AY083269 Genomic DNA. Translation: AAL89527.1 .
    AC105118 Genomic DNA. No translation available.
    CCDSi CCDS34955.1.
    RefSeqi NP_963883.2. NM_201589.3.
    UniGenei Hs.521914.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4EOT X-ray 2.86 A/B 226-318 [» ]
    ProteinModelPortali Q8NHW3.
    SMRi Q8NHW3. Positions 226-317.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 133233. 5 interactions.
    STRINGi 9606.ENSP00000328364.

    PTM databases

    PhosphoSitei Q8NHW3.

    Polymorphism databases

    DMDMi 296435511.

    Proteomic databases

    PaxDbi Q8NHW3.
    PRIDEi Q8NHW3.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000333480 ; ENSP00000328364 ; ENSG00000182759 .
    GeneIDi 389692.
    KEGGi hsa:389692.
    UCSCi uc003yyc.2. human.

    Organism-specific databases

    CTDi 389692.
    GeneCardsi GC08M144511.
    HGNCi HGNC:23145. MAFA.
    MIMi 610303. gene.
    neXtProti NX_Q8NHW3.
    PharmGKBi PA134963361.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG241084.
    HOGENOMi HOG000261683.
    HOVERGENi HBG000313.
    InParanoidi Q8NHW3.
    KOi K07595.
    OMAi QRHILES.
    OrthoDBi EOG7BGHMQ.
    PhylomeDBi Q8NHW3.
    TreeFami TF325689.

    Enzyme and pathway databases

    Reactomei REACT_13819. Regulation of gene expression in beta cells.

    Miscellaneous databases

    GeneWikii MAFA_(gene).
    GenomeRNAii 389692.
    NextBioi 103038.
    PROi Q8NHW3.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q8NHW3.
    CleanExi HS_MAFA.
    Genevestigatori Q8NHW3.

    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], FUNCTION, SUBCELLULAR LOCATION, INDUCTION.
    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: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION.
    3. "DNA sequence and analysis of human chromosome 8."
      Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T.
      , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
      Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "Phosphorylation of MafA is essential for its transcriptional and biological properties."
      Benkhelifa S., Provot S., Nabais E., Eychene A., Calothy G., Felder-Schmittbuhl M.-P.
      Mol. Cell. Biol. 21:4441-4452(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-14 AND SER-65, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-14 AND SER-65.
    5. "Synergistic activation of the insulin gene promoter by the beta-cell enriched transcription factors MafA, Beta2, and Pdx1."
      Aramata S., Han S.I., Yasuda K., Kataoka K.
      Biochim. Biophys. Acta 1730:41-46(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    6. Cited for: PHOSPHORYLATION.
    7. "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: FUNCTION, INTERACTION WITH NEUROD1 AND PDX1.
    8. Cited for: FUNCTION, INTERACTION WITH PCAF, PHOSPHORYLATION AT SER-49; THR-53; THR-57 AND SER-61, MUTAGENESIS OF SER-49; THR-53; THR-57 AND SER-61, UBIQUITINATION.
    9. Cited for: REVIEW, FUNCTION.
    10. "A novel DNA binding mechanism for maf basic region-leucine zipper factors inferred from a MafA-DNA complex structure and binding specificities."
      Lu X., Guanga G.P., Wan C., Rose R.B.
      Biochemistry 51:9706-9717(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.86 ANGSTROMS) OF 226-318 IN COMPLEX WITH DNA, SUBUNIT, DNA-BINDING.

    Entry informationi

    Entry nameiMAFA_HUMAN
    AccessioniPrimary (citable) accession number: Q8NHW3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 26, 2008
    Last sequence update: May 18, 2010
    Last modified: October 1, 2014
    This is version 92 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 8
      Human chromosome 8: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3