Q8NHW3 (MAFA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

MAFA

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	353 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.5 Ref.7 Ref.8 Ref.9
Subunit structure	Binds DNA as a homodimer Probable. Interacts with NEUROD1, PCAF and PDX1. Ref.7 Ref.8
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 an ubiquitin/proteasome-dependent pathway. Ref.4 Ref.6 Ref.8
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 Reference proteome
Gene Ontology (GO)
Biological process	insulin secretion Inferred from direct assay. Source: BHF-UCL nitric oxide mediated signal transduction Inferred from direct assay. Source: BHF-UCL response to glucose stimulus Inferred from direct assay Ref.1. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from direct assay Ref.1. Source: UniProtKB
Molecular function	protein heterodimerization activity Non-traceable author statement Ref.1. Source: UniProtKB protein homodimerization activity Traceable author statement Ref.1. Source: UniProtKB sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 353	353	Transcription factor MafA		PRO_0000320274
Regions
	Domain	282 – 303	22	Leucine-zipper
	DNA binding	254 – 280	27	Basic motif By similarity
	Compositional bias	74 – 86	13	Poly-Gly
	Compositional bias	147 – 220	74	His-rich
Amino acid modifications
	Modified residue	14	1	Phosphoserine; by MAPK1 Ref.4
	Modified residue	49	1	Phosphoserine; by GSK3 Ref.8
	Modified residue	53	1	Phosphothreonine; by GSK3 Ref.8
	Modified residue	57	1	Phosphothreonine; by GSK3 Ref.8
	Modified residue	61	1	Phosphoserine; by GSK3 Ref.8
	Modified residue	65	1	Phosphoserine; by MAPK1 Ref.4
Experimental info
	Mutagenesis	14	1	S → A: Abolishes transactivation activity; when associated with A-65. Ref.4
	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.8
	Mutagenesis	53	1	T → A: Diminishes transcriptional activity and transforming activity and abolishes ubiquitination; when associated with A-49; A-57 and A-61. Ref.8
	Mutagenesis	57	1	T → A: Diminishes transcriptional activity and transforming activity and abolishes ubiquitination; when associated with A-49; A-53 and A-61. Ref.8
	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.8
	Mutagenesis	65	1	S → A: Greatly reduces phosphorylation and reduces transcriptional activity; when associated with A-14. Ref.4
	Sequence conflict	199	1	Missing in BAC20389. Ref.1
	Sequence conflict	199	1	Missing in AAL89527. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q8NHW3 [UniParc]. Last modified May 18, 2010. Version 2. Checksum: 38F732D4C959AD62	FASTA	353	36,982
	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

References

	« Hide 'large scale' referencesShow '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: 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]	"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: 16421571] [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: 11416124] [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: 15993959] [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: 15963504] [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: 15665000] [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: 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.
[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
EMBL GenBank DDBJ	AB086960 Genomic DNA. Translation: BAC20389.1. AY083269 Genomic DNA. Translation: AAL89527.1. AC105118 Genomic DNA. No translation available.
IPI	IPI00169353.
RefSeq	NP_963883.2. NM_201589.3.
UniGene	Hs.521914.
3D structure databases
HSSP	HSSP built from PDB template 1K1V based on UniProtKB O54790.
ProteinModelPortal	Q8NHW3.
SMR	Q8NHW3. Positions 230-318.
ModBase	Search...
Protein-protein interaction databases
STRING	Q8NHW3.
PTM databases
PhosphoSite	Q8NHW3.
Polymorphism databases
DMDM	296435511.
Proteomic databases
PRIDE	Q8NHW3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000333480; ENSP00000328364; ENSG00000182759.
GeneID	389692.
KEGG	hsa:389692.
UCSC	uc003yyc.1. human.
Organism-specific databases
CTD	389692.
GeneCards	GC08M144511.
H-InvDB	HIX0034389.
HGNC	HGNC:23145. MAFA.
MIM	610303. gene.
neXtProt	NX_Q8NHW3.
PharmGKB	PA134963361.
GenAtlas	Search...
Phylogenomic databases
eggNOG	maNOG18913.
GeneTree	ENSGT00550000074549.
HOGENOM	HBG714605.
HOVERGEN	HBG000313.
InParanoid	Q8NHW3.
OMA	EKCTLQS.
OrthoDB	EOG4F1X44.
PhylomeDB	Q8NHW3.
Gene expression databases
ArrayExpress	Q8NHW3.
Bgee	Q8NHW3.
CleanEx	HS_MAFA.
Genevestigator	Q8NHW3.
Family and domain databases
InterPro	IPR004827. bZIP. IPR004826. bZIP_Maf. IPR008917. Euk_TF_DNA-bd. IPR013592. Maf_TF_N. IPR024874. Transciption_factor_Maf. [Graphical view]
Gene3D	G3DSA:1.10.880.10. G3DSA:1.10.880.10. 1 hit.
KO	K07595.
PANTHER	PTHR10129. PTHR10129. 1 hit.
Pfam	PF03131. bZIP_Maf. 1 hit. PF08383. Maf_N. 1 hit. [Graphical view]
SMART	SM00338. BRLZ. 1 hit. [Graphical view]
SUPFAM	SSF47454. Euk_transcr_DNA. 1 hit.
PROSITE	PS50217. BZIP. 1 hit. PS00036. BZIP_BASIC. False negative. [Graphical view]
ProtoNet	Search...
Other
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:	May 18, 2010
Last modified:	January 25, 2012
This is version 66 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.