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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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. 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 an 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.

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	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	insulin secretion Inferred from direct assay PubMed 17941991. Source: BHF-UCL nitric oxide mediated signal transduction Inferred from direct assay PubMed 17941991. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara 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	DNA binding Inferred from direct assay Ref.1. Source: UniProtKB 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

254 – 317

64

bZIP

Region

254 – 279

26

Basic motif

Region

260 – 274

15

Interaction with DNA

Region

282 – 303

22

Leucine-zipper

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

Secondary structure

1

.

.

.

.

.

.

.

.

353

Helix Strand Turn

Details...

Helix

229 – 234

6

Helix

237 – 243

7

Turn

244 – 246

3

Helix

249 – 316

68

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] [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]	"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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4EOT	X-ray	2.86	A/B	226-318	[»]

ProteinModelPortal

Q8NHW3.

SMR

Q8NHW3. Positions 226-317.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000328364.

PTM databases

PhosphoSite

Q8NHW3.

Polymorphism databases

DMDM

296435511.

Proteomic databases

PaxDb

Q8NHW3.

PRIDE

Q8NHW3.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000333480; ENSP00000328364; ENSG00000182759.

GeneID

389692.

KEGG

hsa:389692.

UCSC

uc003yyc.2. human.

Organism-specific databases

CTD

389692.

GeneCards

GC08M144511.

HGNC

HGNC:23145. MAFA.

MIM

610303. gene.

neXtProt

NX_Q8NHW3.

PharmGKB

PA134963361.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG241084.

HOGENOM

HOG000261683.

HOVERGEN

HBG000313.

InParanoid

Q8NHW3.

KO

K07595.

OMA

VQQRHML.

OrthoDB

EOG4F1X44.

PhylomeDB

Q8NHW3.

Gene expression databases

ArrayExpress

Q8NHW3.

Bgee

Q8NHW3.

CleanEx

HS_MAFA.

Genevestigator

Q8NHW3.

Family and domain databases

Gene3D

1.10.880.10. 1 hit.

InterPro

IPR004827. bZIP.
IPR004826. bZIP_Maf.
IPR008917. Euk_TF_DNA-bd.
IPR013592. Maf_TF_N.
IPR024874. Transciption_factor_Maf.
[Graphical view]

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

GenomeRNAi

389692.

NextBio

103038.

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:	May 29, 2013
This is version 79 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.