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Q8CF90

- MAFA_MOUSE

UniProt

Q8CF90 - MAFA_MOUSE

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Protein

Transcription factor MafA

Gene

Mafa

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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
Complete GO annotation...

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
Complete GO annotation...

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

« Hide

        10         20         30         40         50
MAAELAMGAE LPSSPLAIEY VNDFDLMKFE VKKEPPEAER FCHRLPPGSL
60 70 80 90 100
SSTPLSTPCS SVPSSPSFCA PSPGTGGGAG GGGSAAQAGG APGPPSGGPG
110 120 130 140 150
TVGGASGKAV LEDLYWMSGY QHHLNPEALN LTPEDAVEAL IGSGHHGAHH
160 170 180 190 200
GAHHPAAAAA YEAFRGQSFA GGGGADDMGA GHHHGAHHTA HHHHSAHHHH
210 220 230 240 250
HHHHHHGGSG HHGGGAGHGG GGAGHHVRLE ERFSDDQLVS MSVRELNRQL
260 270 280 290 300
RGFSKEEVIR LKQKRRTLKN RGYAQSCRFK RVQQRHILES EKCQLQSQVE
310 320 330 340 350
QLKLEVGRLA KERDLYKEKY EKLAGRGGPG GAGGAGFPRE PSPAQAGPGA

AKGAPDFFL
Length:359
Mass (Da):37,576
Last modified:March 1, 2003 - v1
Checksum:iB10BC396218AB8A5
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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