Reviewed, UniProtKB/Swiss-Prot O75444 (MAF_HUMAN)

Names and origin

Protein names

Recommended name:
    Transcription factor Maf
Alternative name(s):
    Proto-oncogene c-maf
      Short name=C-Maf
    V-maf musculoaponeurotic fibrosarcoma oncogene homolog

Gene names

Name:

MAF

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	373 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. Involved in embryonic lens fiber cell development. Recruits the transcriptional coactivators CREBBP and/or EP300 to crystallin promoters leading to up-regulation of crystallin gene during lens fiber cell differentiation. Activates the expression of IL4 in T helper 2 (Th2) cells. Increases T cell susceptibility to apoptosis by interacting with MYB and decreasing BCL2 expression. Together with PAX6, transactivates strongly the glucagon gene promoter through the G1 element. Activates transcription of the CD13 proximal promoter in endothelial cells. Represses transcription of the CD13 promoter in early stages of myelopoiesis by affecting the ETS1 and MYB cooperative interaction. Involved in the initial chondrocyte terminal differentiation and the disappearance of hypertrophic chondrocytes during endochondral bone development. Binds to the sequence 5'-[GT]G[GC]N[GT]NCTCAGNN-3' in the L7 promoter. Binds to the T-MARE (Maf response element) sites of lens-specific alpha- and beta-crystallin gene promoters. Binds element G1 on the glucagon promoter. Binds an AT-rich region adjacent to the TGC motif (atypical Maf response element) in the CD13 proximal promoter in endothelial cells By similarity. When overexpressed, represses anti-oxidant reponse element (ARE)-mediated transcription. Involved either as an oncogene or as a tumor suppressor, depending on the cell context. Binds to the ARE sites of detoxifying enzyme gene promoters.
Subunit structure	Homodimer or heterodimer with other bHLH-Zip transcription factors. Binds DNA as a homodimer or as a heterodimer. Heterotetramer of two MAF and two USF2. Interacts with PAX6; the interaction is direct. Interacts with MYB; interaction take place weakly in normal T cells and increases in T cells following stimulation through the TCR engagement. Interacts with MYB; the ternary complexe formed with MYB and the CD13 promoter is regulated in response to differentiating signals. Interacts with USF2; the interaction inhibits its DNA-binding activity on the L7 promoter. Interacts with CREBBP, EP300 and ETS1 By similarity.
Subcellular location	Nucleus By similarity.
Tissue specificity	Expressed in endothelial cells. Ref.10
Induction	Up-regulated with tert-butyl hydroquinone (t-BHQ). Ref.4
Post-translational modification	Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is triggered by glucocorticoids. Ref.8 Phosphorylated by GSK3 and MAPK13 on serine and threonine residues Probable. The posphorylation status can serve to either stimulate or inhibit transcription.
Involvement in disease	A chromosomal aberration involving MAF is found in some forms of multiple myeloma (MM). Translocation t(14;16)(q32.3;q23) with an IgH locus. Defects in MAF are the cause of juvenile-onset pulverulent cataract [MIM:610202]. Cataract is a partial or complete ocular opacity that affects the crystalline lens or its capsule, leading to impaired vision or blindness. Ref.13 Defects in MAF are the cause of congenital cerulean cataract 4 (CCA4) [MIM:610202]. CCA4 is a form of autosomal dominant congenital cataract (ADCC). Cerulean cataracts have peripheral bluish and white opacifications in concentric layers with occasional central lesions arranged radially. Although the opacities may be observed during fetal development and childhood, usually visual acuity is only mildly reduced until adulthood, when lens extraction is generally necessary. Ref.14
Sequence similarities	Belongs to the bZIP family. Maf subfamily. Contains 1 bZIP domain.

Ontologies

Keywords
Biological process	Cell cycle Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Chromosomal rearrangement
Disease	Cataract Disease mutation Proto-oncogene
Ligand	DNA-binding
Molecular function	Activator Anti-oncogene Oncogene Repressor
PTM	Ubl conjugation
Gene Ontology (GO)
Biological process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of cell cycle Inferred from electronic annotation. Source: UniProtKB-KW transcription from RNA polymerase II promoter Ref.1 Traceable author statement. Source: ProtInc
Cellular component	chromatin Ref.1 Traceable author statement. Source: ProtInc nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	RNA polymerase II transcription factor activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 2 (identifier: O75444-2)

Also known as: Short;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 1 (identifier: O75444-1)

Also known as: Long;

The sequence of this isoform differs from the canonical sequence as follows:
     373-373: M → ITEPTRKLEPSVGYATFWKPQHRVLTSVFTK

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 373	373	Transcription factor Maf		PRO_0000076491
Regions
	Domain	316 – 337	22	Leucine-zipper
	DNA binding	288 – 314	27	Basic motif Ref.4
	Region	126 – 373	248	Represses ARE-mediated transcription
	Compositional bias	126 – 254	129	Gly-rich
	Compositional bias	132 – 252	121	Ala-rich
	Compositional bias	180 – 194	15	His-rich
Natural variations
	Alternative sequence	373	1	M → ITEPTRKLEPSVGYATFWKP QHRVLTSVFTK in isoform 1.		VSP_000583
	Natural variant	288	1	R → P in juvenile-onset pulverulent cataract. Ref.13		VAR_029369
	Natural variant	297	1	K → R in CCA4. Ref.14		VAR_029370

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 (Short) [UniParc]. Last modified February 10, 2009. Version 2. Checksum: 566C2BC3E4A62762	FASTA	373	38,492
	10 20 30 40 50 60 MASELAMSNS DLPTSPLAME YVNDFDLMKF EVKKEPVETD RIISQCGRLI AGGSLSSTPM 70 80 90 100 110 120 STPCSSVPPS PSFSAPSPGS GSEQKAHLED YYWMTGYPQQ LNPEALGFSP EDAVEALISN 130 140 150 160 170 180 SHQLQGGFDG YARGAQQLAA AAGAGAGASL GGSGEEMGPA AAVVSAVIAA AAAQSGAGPH 190 200 210 220 230 240 YHHHHHHAAG HHHHPTAGAP GAAGSAAASA GGAGGAGGGG PASAGGGGGG GGGGGGGGAA 250 260 270 280 290 300 GAGGALHPHH AAGGLHFDDR FSDEQLVTMS VRELNRQLRG VSKEEVIRLK QKRRTLKNRG 310 320 330 340 350 360 YAQSCRFKRV QQRHVLESEK NQLLQQVDHL KQEISRLVRE RDAYKEKYEK LVSSGFRENG 370 SSSDNPSSPE FFM
	Isoform 1 (Long). Checksum: 263D2FF2AF8DFB5B	FASTA	403	41,961
	10 20 30 40 50 60 MASELAMSNS DLPTSPLAME YVNDFDLMKF EVKKEPVETD RIISQCGRLI AGGSLSSTPM 70 80 90 100 110 120 STPCSSVPPS PSFSAPSPGS GSEQKAHLED YYWMTGYPQQ LNPEALGFSP EDAVEALISN 130 140 150 160 170 180 SHQLQGGFDG YARGAQQLAA AAGAGAGASL GGSGEEMGPA AAVVSAVIAA AAAQSGAGPH 190 200 210 220 230 240 YHHHHHHAAG HHHHPTAGAP GAAGSAAASA GGAGGAGGGG PASAGGGGGG GGGGGGGGAA 250 260 270 280 290 300 GAGGALHPHH AAGGLHFDDR FSDEQLVTMS VRELNRQLRG VSKEEVIRLK QKRRTLKNRG 310 320 330 340 350 360 YAQSCRFKRV QQRHVLESEK NQLLQQVDHL KQEISRLVRE RDAYKEKYEK LVSSGFRENG 370 380 390 400 SSSDNPSSPE FFITEPTRKL EPSVGYATFW KPQHRVLTSV FTK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Frequent dysregulation of the c-maf proto-oncogene at 16q23 by translocation to an Ig locus in multiple myeloma." Chesi M., Bergsagel P.L., Shonukan O.O., Martelli M.L., Brents L.A., Chen T., Schrock E., Ried T., Kuehl W.M. Blood 91:4457-4463(1998) [PubMed: 9616139] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), ALTERNATIVE SPLICING.
[2]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed: 15616553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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] (ISOFORM 2). Tissue: Placenta.
[4]	"c-Maf negatively regulates ARE-mediated detoxifying enzyme genes expression and anti-oxidant induction." Dhakshinamoorthy S., Jaiswal A.K. Oncogene 21:5301-5312(2002) [PubMed: 12149651] [Abstract] Cited for: FUNCTION, SUBUNIT, INDUCTION, DNA-BINDING,.
[5]	"Overexpression of c-maf is a frequent oncogenic event in multiple myeloma that promotes proliferation and pathological interactions with bone marrow stroma." Hurt E.M., Wiestner A., Rosenwald A., Shaffer A.L., Campo E., Grogan T., Bergsagel P.L., Kuehl W.M., Staudt L.M. Cancer Cell 5:191-199(2004) [PubMed: 14998494] [Abstract] Cited for: FUNCTION.
[6]	"Integration of high-resolution array comparative genomic hybridization analysis of chromosome 16q with expression array data refines common regions of loss at 16q23-qter and identifies underlying candidate tumor suppressor genes in prostate cancer." Watson J.E., Doggett N.A., Albertson D.G., Andaya A., Chinnaiyan A., van Dekken H., Ginzinger D., Haqq C., James K., Kamkar S., Kowbel D., Pinkel D., Schmitt L., Simko J.P., Volik S., Weinberg V.K., Paris P.L., Collins C. Oncogene 23:3487-3494(2004) [PubMed: 15007382] [Abstract] Cited for: FUNCTION.
[7]	"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.
[8]	"A chemical biology screen identifies glucocorticoids that regulate c-maf expression by increasing its proteasomal degradation through up-regulation of ubiquitin." Mao X., Stewart A.K., Hurren R., Datti A., Zhu X., Zhu Y., Shi C., Lee K., Tiedemann R., Eberhard Y., Trudel S., Liang S., Corey S.J., Gillis L.C., Barber D.L., Wrana J.L., Ezzat S., Schimmer A.D. Blood 110:4047-4054(2007) [PubMed: 17875808] [Abstract] Cited for: UBIQUITINATION.
[9]	"Cell context reveals a dual role for Maf in oncogenesis." Pouponnot C., Sii-Felice K., Hmitou I., Rocques N., Lecoin L., Druillennec S., Felder-Schmittbuhl M.-P., Eychene A. Oncogene 25:1299-1310(2006) [PubMed: 16247450] [Abstract] Cited for: FUNCTION.
[10]	"CD13/APN transcription is regulated by the proto-oncogene c-Maf via an atypical response element." Mahoney K.M., Petrovic N., Schacke W., Shapiro L.H. Gene 403:178-187(2007) [PubMed: 17897790] [Abstract] Cited for: TISSUE SPECIFICITY.
[11]	"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.
[12]	"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.
[13]	"Domain disruption and mutation of the bZIP transcription factor, MAF, associated with cataract, ocular anterior segment dysgenesis and coloboma." Jamieson R.V., Perveen R., Kerr B., Carette M., Yardley J., Heon E., Wirth M.G., van Heyningen V., Donnai D., Munier F., Black G.C. Hum. Mol. Genet. 11:33-42(2002) [PubMed: 11772997] [Abstract] Cited for: VARIANT JUVENILE-ONSET PULVERULENT CATARACT PRO-288.
[14]	"A novel mutation in the DNA-binding domain of MAF at 16q23.1 associated with autosomal dominant 'cerulean cataract' in an Indian family." Vanita V., Singh D., Robinson P.N., Sperling K., Singh J.R. Am. J. Med. Genet. A 140:558-566(2006) [PubMed: 16470690] [Abstract] Cited for: VARIANT CCA4 ARG-297.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF055376 mRNA. Translation: AAC27037.1. AF055377 mRNA. Translation: AAC27038.1. AF055378 Genomic DNA. Translation: AAC27039.1. AC009159 Genomic DNA. No translation available. BC081542 mRNA. Translation: AAH81542.1.
IPI	IPI00022438. IPI00219060.
RefSeq	NP_001026974.1. NP_005351.2.
UniGene	Hs.709603
3D structure databases
HSSP	HSSP built from PDB template 1K1V based on UniProtKB O54790.
ModBase	Search...
PTM databases
PhosphoSite	O75444.
Genome annotation databases
Ensembl	ENSG00000178573. Homo sapiens. [Contig view]
GeneID	4094.
Organism-specific databases
GeneCards	GC16M078185.
H-InvDB	HIX0038539.
HGNC	HGNC:6776. MAF.
HPA	CAB010296.
MIM	177075. gene. 610202. phenotype.
Orphanet	98989. Cataract, cerulean. 98984. Cataract, pulverulent. 91492. Non-syndromic congenital cataract.
PharmGKB	PA30534.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O75444.
HOVERGEN	O75444.
OMA	O75444. NGFRENG.
Enzyme and pathway databases
Pathway_Interaction_DB	nfat_tfpathway. Calcineurin-regulated NFAT-dependent transcription in lymphocytes.
Gene expression databases
ArrayExpress	O75444.
Bgee	O75444.
CleanEx	HS_MAF.
GermOnline	ENSG00000178573. Homo sapiens.
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	16054.
SOURCE	Search...

Entry information

Entry name

MAF_HUMAN

Accession

Primary (citable) accession number: O75444
Secondary accession number(s): Q66I47, Q9UP93

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 11, 2002
Last sequence update:	February 10, 2009
Last modified:	June 16, 2009
This is version 69 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)