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Q8NHW3

- MAFA_HUMAN

UniProt

Q8NHW3 - MAFA_HUMAN

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Protein

Transcription factor MafA

Gene

MAFA

Organism
Homo sapiens (Human)
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 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
Complete GO annotation...

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
Complete GO annotation...

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 MAPK11 Publication
Modified residuei49 – 491Phosphoserine; by GSK31 Publication
Modified residuei53 – 531Phosphothreonine; by GSK31 Publication
Modified residuei57 – 571Phosphothreonine; by GSK31 Publication
Modified residuei61 – 611Phosphoserine; by GSK31 Publication
Modified residuei65 – 651Phosphoserine; by MAPK11 Publication

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.
ExpressionAtlasiQ8NHW3. baseline.
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.
GeneTreeiENSGT00550000074549.
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

        10         20         30         40         50
MAAELAMGAE LPSSPLAIEY VNDFDLMKFE VKKEPPEAER FCHRLPPGSL
60 70 80 90 100
SSTPLSTPCS SVPSSPSFCA PSPGTGGGGG AGGGGGSSQA GGAPGPPSGG
110 120 130 140 150
PGAVGGTSGK PALEDLYWMS GYQHHLNPEA LNLTPEDAVE ALIGSGHHGA
160 170 180 190 200
HHGAHHPAAA AAYEAFRGPG FAGGGGADDM GAGHHHGAHH AAHHHHAAHH
210 220 230 240 250
HHHHHHHHGG AGHGGGAGHH VRLEERFSDD QLVSMSVREL NRQLRGFSKE
260 270 280 290 300
EVIRLKQKRR TLKNRGYAQS CRFKRVQQRH ILESEKCQLQ SQVEQLKLEV
310 320 330 340 350
GRLAKERDLY KEKYEKLAGR GGPGSAGGAG FPREPSPPQA GPGGAKGTAD

FFL
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.
GeneTreei ENSGT00550000074549.
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.
ExpressionAtlasi Q8NHW3. baseline.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 93 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