Reviewed, UniProtKB/Swiss-Prot P54841 (MAFB_MOUSE)

Names and origin

Protein names

Recommended name:
    Transcription factor MafB
      Short name=Maf-B
Alternative name(s):
    V-maf musculoaponeurotic fibrosarcoma oncogene homolog B
    Transcription factor Maf-1
    Segmentation protein Kr
    Kreisler

Gene names

Name:	Mafb
Synonyms:	Krml, Maf1

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	323 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 activator or repressor. Plays a pivotal role in regulating lineage-specific hematopoiesis by repressing ETS1-mediated transcription of erythroid-specific genes in myeloid cells. Required for monocytic, macrophage, podocyte and islet beta cell differentiation. Involved in renal tubule survival and F4/80 maturation. Activates the insulin and glucagon promoters. Together with PAX6, transactivates weakly the glucagon gene promoter through the G1 element. SUMO modification controls its transcriptional activity and ability to specify macrophage fate. Binds element G1 on the glucagon promoter. Involved either as an oncogene or as a tumor suppressor, depending on the cell context. Ref.8 Ref.11 Ref.12 Ref.14 Ref.15 Ref.17 Ref.18
Subunit structure	Homodimer or heterodimer with other bHLH-Zip transcription factors. Forms homo- and heterodimers with FOS, FOSB and FOSL2, but not with JUN proteins (JUN, JUNB and JUND). Interacts with the intracellular cytoplasmic domain of LRP1 (LRPICD); the interaction results in a moderate reduction of MAFB transcriptional potential By similarity. Binds DNA as a homodimer or a heterodimer. Interacts with PAX6; the interaction is direct. Interacts with ETS1 and LRP1.
Subcellular location	Nucleus. Ref.10
Tissue specificity	Expressed in pancreatic alpha-cells (glucagon-positive cells), in podocytes of the kidney and macrophages (at protein level). Most abundant in kidney, gut, lung and brain. Ref.11 Ref.12 Ref.14
Developmental stage	Expressed in pancreatic alpha-cells at 10.5 dpc. Expressed in insulin and glucagon islet progenitor cells at 12 dpc onwards (at protein level). Detectable at 8.0 dpc (one somite) as a band in the caudal hindbrain and by 8.5 dpc (six to eight somites) as a sharp rostral edge coincident with the rhombomeres (r) 4 and 5 boundary and a diffuse caudal edge located midway through r6. Expressed in the lens epithelial cells at 10.5 to 14.5 dpc. Ref.11 Ref.14 Ref.7
Domain	The leucine-zipper domain is involved in the interaction with LRPICD.
Post-translational modification	Sumoylated. Sumoylation on Lys-32 and Lys-297 stimulates its transcriptional repression activity and promotes macrophage differentiation from myeloid progenitors. Ref.15
Disruption phenotype	Mice show a defect in frequency of respiratory rhythm with a fatal apnea at birth due to lack of neurons from the preBoetC region. They displayed renal dysgenesis with abnormal podocyte differentiation as well as tubular apoptosis. They show altered actin-dependent macrophage morphology. They show a reduced number of cells expressing insulin and glucagon. Ref.12 Ref.17 Ref.9 Ref.13 Ref.16
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 Repressor
PTM	Isopeptide bond Ubl conjugation
Gene Ontology (GO)
Biological process	brain segmentation Inferred from mutant phenotype. Source: MGI cell cycle Inferred from electronic annotation. Source: UniProtKB-KW inner ear morphogenesis Inferred from mutant phenotype. Source: MGI negative regulation of cell cycle Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay. Source: MGI respiratory gaseous exchange Ref.9 Inferred from mutant phenotype. Source: MGI rhombomere 5 development Inferred from mutant phenotype. Source: MGI rhombomere 6 development Inferred from mutant phenotype. Source: MGI segment specification Inferred from mutant phenotype. Source: MGI transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	transcription factor complex Inferred from direct assay. Source: MGI
Molecular function	protein binding Inferred from physical interaction. Source: MGI sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro 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 – 323	323	Transcription factor MafB		PRO_0000076495
Regions
	Domain	266 – 287	22	Leucine-zipper
	DNA binding	238 – 264	27	Basic motif Ref.11 Ref.14
	Compositional bias	131 – 143	13	Poly-His
	Compositional bias	158 – 167	10	Poly-His
Amino acid modifications
	Cross-link	32		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.15
	Cross-link	297		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.15
Experimental info
	Mutagenesis	32	1	K → R: Loss of SUMO modification, increases transactivation activity, increases macrophage differentiation and inhibits myeloid progenitor growth; when associated with R-297. Ref.15
	Mutagenesis	248	1	N → A: Reduces ability to activate insulin and glucagon gene expression. Ref.17
	Mutagenesis	248	1	N → S: Loss of transcriptional activity. Ref.17
	Mutagenesis	297	1	K → R: Loss of SUMO modification, increases transactivation activity, increases macrophage differentiation and inhibits myeloid progenitor growth; when associated with R-32. Ref.15
	Sequence conflict	275	1	Q → K in BAE32860. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P54841-1 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: D77AE07ABD9C2AD2	FASTA	323	35,809
	10 20 30 40 50 60 MAAELSMGQE LPTSPLAMEY VNDFDLLKFD VKKEPLGRAE RPGRPCTRLQ PAGSVSSTPL 70 80 90 100 110 120 STPCSSVPSS PSFSPTEPKT HLEDLYWMAS NYQQMNPEAL NLTPEDAVEA LIGSHPVPQP 130 140 150 160 170 180 LQSFDGFRSA HHHHHHHHPH PHHGYPGAGV THDDLGQHAH PHHHHHHQAS PPPSSAASPA 190 200 210 220 230 240 QQLPTSHPGP GPHATAAATA AGGNGSVEDR FSDDQLVSMS VRELNRHLRG FTKDEVIRLK 250 260 270 280 290 300 QKRRTLKNRG YAQSCRYKRV QQKHHLENEK TQLIQQVEQL KQEVSRLARE RDAYKVKCEK 310 320 LANSGFREAG STSDSPSSPE FFL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The mouse segmentation gene kr encodes a novel basic domain-leucine zipper transcription factor." Cordes S.P., Barsh G.S. Cell 79:1025-1034(1994) [PubMed: 8001130] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Molecular cloning and functional characterization of the mouse mafB gene." Huang K., Serria M.S., Nakabayashi H., Nishi S., Sakai M. Gene 242:419-426(2000) [PubMed: 10721736] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: 129/SvJ.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J and NOD. Tissue: Eye and Skin.
[4]	The mouse genome sequencing consortium Submitted (NOV-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[5]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N. Tissue: Liver and Mammary gland.
[7]	"Regulation of lens fiber cell differentiation by transcription factor c-Maf." Kawauchi S., Takahashi S., Nakajima O., Ogino H., Morita M., Nishizawa M., Yasuda K., Yamamoto M. J. Biol. Chem. 274:19254-19260(1999) [PubMed: 10383433] [Abstract] Cited for: DEVELOPMENTAL STAGE.
[8]	"MafB is an inducer of monocytic differentiation." Kelly L.M., Englmeier U., Lafon I., Sieweke M.H., Graf T. EMBO J. 19:1987-1997(2000) [PubMed: 10790365] [Abstract] Cited for: FUNCTION, INTERACTION WITH ETS1.
[9]	"MafB deficiency causes defective respiratory rhythmogenesis and fatal central apnea at birth." Blanchi B., Kelly L.M., Viemari J.-C., Lafon I., Burnet H., Bevengut M., Tillmanns S., Daniel L., Graf T., Hilaire G., Sieweke M.H. Nat. Neurosci. 6:1091-1100(2003) [PubMed: 14513037] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[10]	"Low-density lipoprotein receptor-related protein interacts with MafB, a regulator of hindbrain development." Petersen H.H., Hilpert J., Jacobsen C., Lauwers A., Roebroek A.J.M., Willnow T.E. FEBS Lett. 565:23-27(2004) [PubMed: 15135046] [Abstract] Cited for: INTERACTION WITH LRP1, SUBCELLULAR LOCATION.
[11]	"MafB: an activator of the glucagon gene expressed in developing islet alpha- and beta-cells." Artner I., Le Lay J., Hang Y., Elghazi L., Schisler J.C., Henderson E., Sosa-Pineda B., Stein R. Diabetes 55:297-304(2006) [PubMed: 16443760] [Abstract] Cited for: FUNCTION, DNA-BINDING, DEVELOPMENTAL STAGE, TISSUE SPECIFICITY.
[12]	"MafB is essential for renal development and F4/80 expression in macrophages." Moriguchi T., Hamada M., Morito N., Terunuma T., Hasegawa K., Zhang C., Yokomizo T., Esaki R., Kuroda E., Yoh K., Kudo T., Nagata M., Greaves D.R., Engel J.D., Yamamoto M., Takahashi S. Mol. Cell. Biol. 26:5715-5727(2006) [PubMed: 16847325] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
[13]	"Development of macrophages with altered actin organization in the absence of MafB." Aziz A., Vanhille L., Mohideen P., Kelly L.M., Otto C., Bakri Y., Mossadegh N., Sarrazin S., Sieweke M.H. Mol. Cell. Biol. 26:6808-6818(2006) [PubMed: 16943423] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[14]	"Pax-6 and c-Maf functionally interact with the alpha-cell-specific DNA element G1 in vivo to promote glucagon gene expression." Gosmain Y., Avril I., Mamin A., Philippe J. J. Biol. Chem. 282:35024-35034(2007) [PubMed: 17901057] [Abstract] Cited for: FUNCTION, SUBUNIT, INTERACTION WITH PAX6, DNA-BINDING, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[15]	"SUMO modification regulates MafB-driven macrophage differentiation by enabling Myb-dependent transcriptional repression." Tillmanns S., Otto C., Jaffray E., Du Roure C., Bakri Y., Vanhille L., Sarrazin S., Hay R.T., Sieweke M.H. Mol. Cell. Biol. 27:5554-5564(2007) [PubMed: 17548468] [Abstract] Cited for: FUNCTION, SUMOYLATION AT LYS-32 AND LYS-297, MUTAGENESIS OF LYS-32 AND LYS-297.
[16]	"MafB is required for islet beta cell maturation." Artner I., Blanchi B., Raum J.C., Guo M., Kaneko T., Cordes S., Sieweke M., Stein R. Proc. Natl. Acad. Sci. U.S.A. 104:3853-3858(2007) [PubMed: 17360442] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[17]	"Preferential reduction of beta cells derived from Pax6-MafB pathway in MafB deficient mice." Nishimura W., Rowan S., Salameh T., Maas R.L., Bonner-Weir S., Sell S.M., Sharma A. Dev. Biol. 314:443-456(2008) [PubMed: 18199433] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF ASN-248, DISRUPTION PHENOTYPE.
[18]	"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	L36435 mRNA. Translation: AAA65689.1. AF180338 Genomic DNA. Translation: AAD56221.1. AK132425 mRNA. Translation: BAE21161.1. AK143209 mRNA. Translation: BAE25306.1. AK154830 mRNA. Translation: BAE32860.1. AL591665 Genomic DNA. Translation: CAM21248.1. CH466551 Genomic DNA. Translation: EDL06288.1. BC016434 mRNA. Translation: AAH16434.1. BC038256 mRNA. Translation: AAH38256.1.
IPI	IPI00109981.
PIR	I49529.
RefSeq	NP_034788.1.
UniGene	Mm.330745
3D structure databases
HSSP	HSSP built from PDB template 1K1V based on UniProtKB O54790.
ModBase	Search...
PTM databases
PhosphoSite	P54841.
Genome annotation databases
Ensembl	ENSMUSG00000074622. Mus musculus. [Contig view]
GeneID	16658.
KEGG	mmu:16658.
Organism-specific databases
MGI	MGI:104555. Mafb.
Phylogenomic databases
HOGENOM	P54841.
HOVERGEN	P54841.
OMA	P54841. HHGYPGA.
Gene expression databases
ArrayExpress	P54841.
Bgee	P54841.
CleanEx	MM_MAF1.
GermOnline	ENSMUSG00000074622. Mus musculus.
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	290353.
SOURCE	Search...

Entry information

Entry name

MAFB_MOUSE

Accession

Primary (citable) accession number: P54841
Secondary accession number(s): Q3U3C8, Q3UPT9

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	July 7, 2009
This is version 76 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)