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Q8NHW3 (MAFA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 90. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Transcription factor MafA
Alternative name(s):
Pancreatic beta-cell-specific transcriptional activator
Transcription factor RIPE3b1
V-maf musculoaponeurotic fibrosarcoma oncogene homolog A
Gene names
Name:MAFA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length353 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.2 Ref.5 Ref.7 Ref.8 Ref.9

Subunit structure

Binds DNA as a homodimer. Interacts with NEUROD1, PCAF and PDX1. Ref.7 Ref.8 Ref.10

Subcellular location

Nucleus. Note: Detected in nuclei of pancreas islet beta cells By similarity. Ref.1 Ref.4

Induction

Up-regulated by glucose. Ref.1

Post-translational modification

Ubiquitinated, leading to its degradation by the proteasome. Ref.8

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. Ref.4 Ref.6 Ref.8

Sequence similarities

Belongs to the bZIP family. Maf subfamily.

Contains 1 bZIP (basic-leucine zipper) domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 353353Transcription factor MafA
PRO_0000320274

Regions

Domain254 – 31764bZIP
Region254 – 27926Basic motif
Region260 – 27415Interaction with DNA
Region282 – 30322Leucine-zipper
Compositional bias74 – 8613Poly-Gly
Compositional bias147 – 22074His-rich

Amino acid modifications

Modified residue141Phosphoserine; by MAPK1 Ref.4
Modified residue491Phosphoserine; by GSK3 Ref.8
Modified residue531Phosphothreonine; by GSK3 Ref.8
Modified residue571Phosphothreonine; by GSK3 Ref.8
Modified residue611Phosphoserine; by GSK3 Ref.8
Modified residue651Phosphoserine; by MAPK1 Ref.4

Experimental info

Mutagenesis141S → A: Abolishes transactivation activity; when associated with A-65. Ref.4
Mutagenesis491S → A: Diminishes transcriptional activity and transforming activity and abolishes ubiquitination; when associated with A-53; A-57 and A-61. Ref.8
Mutagenesis531T → A: Diminishes transcriptional activity and transforming activity and abolishes ubiquitination; when associated with A-49; A-57 and A-61. Ref.8
Mutagenesis571T → A: Diminishes transcriptional activity and transforming activity and abolishes ubiquitination; when associated with A-49; A-53 and A-61. Ref.8
Mutagenesis611S → A: Diminishes transcriptional activity and transforming activity and abolishes ubiquitination; when associated with A-49; A-53 and A-57. Ref.8
Mutagenesis651S → A: Greatly reduces phosphorylation and reduces transcriptional activity; when associated with A-14. Ref.4
Sequence conflict1991Missing in BAC20389. Ref.1
Sequence conflict1991Missing in AAL89527. Ref.2

Secondary structure

........ 353
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q8NHW3 [UniParc].

Last modified May 18, 2010. Version 2.
Checksum: 38F732D4C959AD62

FASTA35336,982
        10         20         30         40         50         60 
MAAELAMGAE LPSSPLAIEY VNDFDLMKFE VKKEPPEAER FCHRLPPGSL SSTPLSTPCS 

        70         80         90        100        110        120 
SVPSSPSFCA PSPGTGGGGG AGGGGGSSQA GGAPGPPSGG PGAVGGTSGK PALEDLYWMS 

       130        140        150        160        170        180 
GYQHHLNPEA LNLTPEDAVE ALIGSGHHGA HHGAHHPAAA AAYEAFRGPG FAGGGGADDM 

       190        200        210        220        230        240 
GAGHHHGAHH AAHHHHAAHH HHHHHHHHGG AGHGGGAGHH VRLEERFSDD QLVSMSVREL 

       250        260        270        280        290        300 
NRQLRGFSKE EVIRLKQKRR TLKNRGYAQS CRFKRVQQRH ILESEKCQLQ SQVEQLKLEV 

       310        320        330        340        350 
GRLAKERDLY KEKYEKLAGR GGPGSAGGAG FPREPSPPQA GPGGAKGTAD FFL 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"MafA transcription factor is phosphorylated by p38 MAP kinase."
Sii-Felice K., Pouponnot C., Gillet S., Lecoin L., Girault J.-A., Eychene A., Felder-Schmittbuhl M.-P.
FEBS Lett. 579:3547-3554(2005) [PubMed] [Europe PMC] [Abstract]
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]"GSK-3-mediated phosphorylation enhances Maf-transforming activity."
Rocques N., Abou Zeid N., Sii-Felice K., Lecoin L., Felder-Schmittbuhl M.-P., Eychene A., Pouponnot C.
Mol. Cell 28:584-597(2007) [PubMed] [Europe PMC] [Abstract]
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]"A new MAFia in cancer."
Eychene A., Rocques N., Pouponnot C.
Nat. Rev. Cancer 8:683-693(2008) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB086960 Genomic DNA. Translation: BAC20389.1.
AY083269 Genomic DNA. Translation: AAL89527.1.
AC105118 Genomic DNA. No translation available.
CCDSCCDS34955.1.
RefSeqNP_963883.2. NM_201589.3.
UniGeneHs.521914.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4EOTX-ray2.86A/B226-318[»]
ProteinModelPortalQ8NHW3.
SMRQ8NHW3. Positions 226-317.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid133233. 5 interactions.
STRING9606.ENSP00000328364.

PTM databases

PhosphoSiteQ8NHW3.

Polymorphism databases

DMDM296435511.

Proteomic databases

PaxDbQ8NHW3.
PRIDEQ8NHW3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000333480; ENSP00000328364; ENSG00000182759.
GeneID389692.
KEGGhsa:389692.
UCSCuc003yyc.2. human.

Organism-specific databases

CTD389692.
GeneCardsGC08M144511.
HGNCHGNC:23145. MAFA.
MIM610303. gene.
neXtProtNX_Q8NHW3.
PharmGKBPA134963361.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG241084.
HOGENOMHOG000261683.
HOVERGENHBG000313.
InParanoidQ8NHW3.
KOK07595.
OMAQRHILES.
OrthoDBEOG7BGHMQ.
PhylomeDBQ8NHW3.
TreeFamTF325689.

Gene expression databases

BgeeQ8NHW3.
CleanExHS_MAFA.
GenevestigatorQ8NHW3.

Family and domain databases

Gene3D1.10.880.10. 1 hit.
InterProIPR004827. bZIP.
IPR004826. bZIP_Maf.
IPR013592. Maf_TF_N.
IPR028562. MafA.
IPR008917. TF_DNA-bd.
IPR024874. Transciption_factor_Maf.
[Graphical view]
PANTHERPTHR10129. PTHR10129. 1 hit.
PTHR10129:SF24. PTHR10129:SF24. 1 hit.
PfamPF03131. bZIP_Maf. 1 hit.
PF08383. Maf_N. 1 hit.
[Graphical view]
SMARTSM00338. BRLZ. 1 hit.
[Graphical view]
SUPFAMSSF47454. SSF47454. 1 hit.
PROSITEPS50217. BZIP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMAFA_(gene).
GenomeRNAi389692.
NextBio103038.
PROQ8NHW3.
SOURCESearch...

Entry information

Entry nameMAFA_HUMAN
AccessionPrimary (citable) accession number: Q8NHW3
Entry history
Integrated into UniProtKB/Swiss-Prot: February 26, 2008
Last sequence update: May 18, 2010
Last modified: July 9, 2014
This is version 90 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM