Reviewed, UniProtKB/Swiss-Prot Q8CF90 (MAFA_MOUSE)

Names and origin

Protein names

Recommended name:
    Transcription factor MafA
Alternative name(s):
    V-maf musculoaponeurotic fibrosarcoma oncogene homolog A
    Pancreatic beta-cell-specific transcriptional activator

Gene names

Name:

Mafa

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	359 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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.
Subunit structure	Binds DNA as a homodimer By similarity. Interacts with PCAF By similarity. Interacts with NEUROD1 and PDX1.
Subcellular location	Nucleus. Note: Detected in nuclei of pancreas islet beta cells. Ref.4
Tissue specificity	Selectively expressed in pancreatic beta but not in alpha cells (at protein lvel). Expressed in eyes and at low levels in thymus. Expressed in brain, lung, spleen and kidney. Expressed in embryo. Ref.1 Ref.2 Ref.3
Developmental stage	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. Ref.2 Ref.3
Post-translational modification	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 an 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.
Disruption phenotype	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. Ref.7
Sequence similarities	Belongs to the bZIP family. Maf subfamily. Contains 1 bZIP domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Disease	Proto-oncogene Tumor suppressor
Ligand	DNA-binding
Molecular function	Activator
PTM	Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Biological process	positive regulation of transcription from RNA polymerase II promoter Ref.4 Inferred from direct assay. Source: MGI response to glucose stimulus Inferred from sequence or structural similarity. Source: UniProtKB transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Ref.1 Ref.4 Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro transcription activator activity Ref.1 Inferred from direct assay. Source: MGI transcription factor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 359	359	Transcription factor MafA		PRO_0000320275
Regions
	Domain	288 – 309	22	Leucine-zipper
	DNA binding	260 – 286	27	Basic motif
	Compositional bias	74 – 83	10	Poly-Gly
	Compositional bias	145 – 226	82	His-rich
Amino acid modifications
	Modified residue	14	1	Phosphoserine; by MAPK1 By similarity
	Modified residue	49	1	Phosphoserine; by GSK3 By similarity
	Modified residue	53	1	Phosphothreonine; by GSK3 By similarity
	Modified residue	57	1	Phosphothreonine; by GSK3 By similarity
	Modified residue	61	1	Phosphoserine; by GSK3 By similarity
	Modified residue	65	1	Phosphoserine; by MAPK1 By similarity
Experimental info
	Mutagenesis	14	1	S → A: Reduces phosphorylation. Ref.8
	Mutagenesis	65	1	S → A: Reduces phosphorylation. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Q8CF90-1 [UniParc]. Last modified March 1, 2003. Version 1. Checksum: B10BC396218AB8A5	FASTA	359	37,576
	10 20 30 40 50 60 MAAELAMGAE LPSSPLAIEY VNDFDLMKFE VKKEPPEAER FCHRLPPGSL SSTPLSTPCS 70 80 90 100 110 120 SVPSSPSFCA PSPGTGGGAG GGGSAAQAGG APGPPSGGPG TVGGASGKAV LEDLYWMSGY 130 140 150 160 170 180 QHHLNPEALN LTPEDAVEAL IGSGHHGAHH GAHHPAAAAA YEAFRGQSFA GGGGADDMGA 190 200 210 220 230 240 GHHHGAHHTA HHHHSAHHHH HHHHHHGGSG HHGGGAGHGG GGAGHHVRLE ERFSDDQLVS 250 260 270 280 290 300 MSVRELNRQL RGFSKEEVIR LKQKRRTLKN RGYAQSCRFK RVQQRHILES EKCQLQSQVE 310 320 330 340 350 QLKLEVGRLA KERDLYKEKY EKLAGRGGPG GAGGAGFPRE PSPAQAGPGA AKGAPDFFL

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: 12368292] [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: 12011435] [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: 14680841] [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: 12917329] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[5]	"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: 15963504] [Abstract] 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: 15665000] [Abstract] Cited for: INTERACTION WITH NEUROD1 AND PDX1.
[7]	"MafA is a key regulator of glucose-stimulated insulin secretion." Zhang C., Moriguchi T., Kajihara M., Esaki R., Harada A., Shimohata H., Oishi H., Hamada M., Morito N., Hasegawa K., Kudo T., Engel J.D., Yamamoto M., Takahashi S. Mol. Cell. Biol. 25:4969-4976(2005) [PubMed: 15923615] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[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: 18042454] [Abstract] Cited for: PHOSPHORYLATION AT SER-14 AND SER-65, MUTAGENESIS OF SER-14 AND SER-65.
[9]	"A new MAFia in cancer." Eychene A., Rocques N., Pouponnot C. Nat. Rev. Cancer 8:683-693(2008) [PubMed: 19143053] [Abstract] Cited for: REVIEW, FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB086961 Genomic DNA. Translation: BAC20390.1.
IPI	IPI00229250.
RefSeq	NP_919331.1.
UniGene	Mm.309589
3D structure databases
HSSP	HSSP built from PDB template 1K1V based on UniProtKB O54790.
ModBase	Search...
Protein-protein interaction databases
STRING	Q8CF90.
PTM databases
PhosphoSite	Q8CF90.
Proteomic databases
PRIDE	Q8CF90.
Genome annotation databases
Ensembl	ENSMUST00000062002; ENSMUSP00000054226; ENSMUSG00000047591; Mus musculus. [Genome view]
GeneID	378435.
KEGG	mmu:378435.
UCSC	uc007whe.1. mouse.
Organism-specific databases
CTD	378435.
MGI	MGI:2673307. Mafa.
Phylogenomic databases
HOGENOM	Q8CF90.
HOVERGEN	Q8CF90.
OMA	QLEDLYW.
Gene expression databases
Bgee	Q8CF90.
Genevestigator	Q8CF90.
Family and domain databases
InterPro	IPR013592. Maf_TF_N. IPR004827. TF_bZIP. IPR004826. TF_Maf. [Graphical view]
Pfam	PF03131. bZIP_Maf. 1 hit. PF08383. Maf_N. 1 hit. [Graphical view]
SMART	SM00338. BRLZ. 1 hit. [Graphical view]
PROSITE	PS50217. BZIP. 1 hit. PS00036. BZIP_BASIC. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	400973.
SOURCE	Search...

Entry information

Entry name

MAFA_MOUSE

Accession

Primary (citable) accession number: Q8CF90

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 26, 2008
Last sequence update:	March 1, 2003
Last modified:	November 3, 2009
This is version 46 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)