Reviewed, UniProtKB/Swiss-Prot Q8NHW3 (MAFA_HUMAN)

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
    Transcription factor RIPE3b1

Gene names

Name:

MAFA

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	352 AA.
Sequence status	Complete.
Protein existence	Evidence 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.4 Ref.6 Ref.7 Ref.8
Subunit structure	Binds DNA as a homodimer Probable. Interacts with NEUROD1, PCAF and PDX1. Ref.6 Ref.7
Subcellular location	Nucleus. Note: Detected in nuclei of pancreas islet beta cells By similarity. Ref.1 Ref.3
Induction	Up-regulated by glucose. Ref.1
Post-translational modification	Ubiquitinated, leading to its degradation by the proteasome. Ref.7 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 an ubiquitin/proteasome-dependent pathway. Ref.7 Ref.3 Ref.5
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
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	insulin secretion Inferred from direct assay. Source: UniProtKB nitric oxide mediated signal transduction Inferred from direct assay. Source: UniProtKB response to glucose stimulus Ref.1 Inferred from direct assay. Source: UniProtKB transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Ref.1 Inferred from direct assay. Source: UniProtKB
Molecular function	protein heterodimerization activity Ref.1 Non-traceable author statement. Source: UniProtKB protein homodimerization activity Ref.1 Traceable author statement. Source: UniProtKB sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro transcription factor activity Ref.1 Traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 352	352	Transcription factor MafA		PRO_0000320274
Regions
	Domain	281 – 302	22	Leucine-zipper
	DNA binding	253 – 279	27	Basic motif
	Compositional bias	74 – 86	13	Poly-Gly
	Compositional bias	147 – 219	73	His-rich
Amino acid modifications
	Modified residue	14	1	Phosphoserine; by MAPK1 Ref.3
	Modified residue	49	1	Phosphoserine; by GSK3 Ref.7
	Modified residue	53	1	Phosphothreonine; by GSK3 Ref.7
	Modified residue	57	1	Phosphothreonine; by GSK3 Ref.7
	Modified residue	61	1	Phosphoserine; by GSK3 Ref.7
	Modified residue	65	1	Phosphoserine; by MAPK1 Ref.3
Experimental info
	Mutagenesis	14	1	S → A: Abolishes transactivation activity; when associated with A-65. Ref.3
	Mutagenesis	49	1	S → A: Diminishes transcriptional activity and transforming activity and abolishes ubiquitination; when associated with A-53; A-57 and A-61. Ref.7
	Mutagenesis	53	1	T → A: Diminishes transcriptional activity and transforming activity and abolishes ubiquitination; when associates with A-49; A-57 and A-61. Ref.7
	Mutagenesis	57	1	T → A: Diminishes transcriptional activity and transforming activity and abolishes ubiquitination; when associates with A-49; A-53 and A-61. Ref.7
	Mutagenesis	61	1	S → A: Diminishes transcriptional activity and transforming activity and abolishes ubiquitination; when associated with A-49; A-53 and A-57. Ref.7
	Mutagenesis	65	1	S → A: Greatly reduces phosphorylation and reduces transcriptional activity; when associated with A-14. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q8NHW3-1 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: 55DD8A77FE5BA35C	FASTA	352	36,845
	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 HHHHHHHGGA GHGGGAGHHV RLEERFSDDQ LVSMSVRELN 250 260 270 280 290 300 RQLRGFSKEE VIRLKQKRRT LKNRGYAQSC RFKRVQQRHI LESEKCQLQS QVEQLKLEVG 310 320 330 340 350 RLAKERDLYK EKYEKLAGRG GPGSAGGAGF PREPSPPQAG PGGAKGTADF FL

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], 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: 12011435] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION.
[3]	"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: 11416124] [Abstract] Cited for: PHOSPHORYLATION AT SER-14 AND SER-65, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-14 AND SER-65.
[4]	"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: 15993959] [Abstract] Cited for: FUNCTION.
[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: FUNCTION, INTERACTION WITH NEUROD1 AND PDX1.
[7]	"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: 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.
[8]	"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
EMBL GenBank DDBJ	AB086960 Genomic DNA. Translation: BAC20389.1. AY083269 Genomic DNA. Translation: AAL89527.1.
IPI	IPI00169353.
UniGene	Hs.670866
3D structure databases
HSSP	HSSP built from PDB template 1K1V based on UniProtKB O54790.
SMR	Q8NHW3. Positions 226-266.
ModBase	Search...
Protein-protein interaction databases
STRING	Q8NHW3.
PTM databases
PhosphoSite	Q8NHW3.
Genome annotation databases
Ensembl	ENST00000333480; ENSP00000328364; ENSG00000182759; Homo sapiens. [Genome view]
UCSC	uc003yyc.1. human.
Organism-specific databases
GeneCards	GC08M144582.
HGNC	HGNC:23145. MAFA.
MIM	610303. gene.
PharmGKB	PA134963361.
GenAtlas	Search...
Phylogenomic databases
eggNOG	maNOG18913.
HOGENOM	HBG714605.
HOVERGEN	Q8NHW3.
InParanoid	Q8NHW3.
Gene expression databases
ArrayExpress	Q8NHW3.
Bgee	Q8NHW3.
CleanEx	HS_MAFA.
Genevestigator	Q8NHW3.
Family and domain databases
InterPro	IPR008917. Euk_TF_DNA_bd. 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
SOURCE	Search...

Entry information

Entry name

MAFA_HUMAN

Accession

Primary (citable) accession number: Q8NHW3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 26, 2008
Last sequence update:	October 1, 2002
Last modified:	January 19, 2010
This is version 47 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.