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O75444 (MAF_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Transcription factor Maf
Alternative name(s):
Proto-oncogene c-Maf
V-maf musculoaponeurotic fibrosarcoma oncogene homolog
Gene names
Name:MAF
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length373 AA.
Sequence statusComplete.
Protein existenceEvidence 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 response 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. Ref.4 Ref.5 Ref.6 Ref.9 Ref.12

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 takes place weakly in normal T-cells and increases in T-cells following stimulation through the TCR engagement. Interacts with MYB; the ternary complex 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. Ref.4

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 phosphorylation status can serve to either stimulate or inhibit transcription. Ref.7 Ref.11

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.

Cataract 21, multiple types (CTRCT21) [MIM:610202]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT21 includes cerulean and pulverulent cataracts. Cerulean cataracts are characterized by peripheral bluish and white opacifications organized in concentric layers with occasional central lesions arranged radially. The opacities are observed in the superficial layers of the fetal nucleus as well as the adult nucleus of the lens. Involvement is usually bilateral. Visual acuity is only mildly reduced in childhood. In adulthood, the opacifications may progress, making lens extraction necessary. Histologically the lesions are described as fusiform cavities between lens fibers which contain a deeply staining granular material. Although the lesions may take on various colors, a dull blue is the most common appearance and is responsible for the designation cerulean cataract. Pulverulent cataracts are characterized by a dust-like, 'pulverised' appearance of the opacities which can be found in any part of the lens. In some cases cataract is associated with microcornea without any other systemic anomaly or dysmorphism. Microcornea is defined by a corneal diameter inferior to 10 mm in both meridians in an otherwise normal eye.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13 Ref.14

Sequence similarities

Belongs to the bZIP family. Maf subfamily.

Contains 1 bZIP (basic-leucine zipper) domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
Chromosomal rearrangement
   DiseaseCataract
Disease mutation
Proto-oncogene
Tumor suppressor
   LigandDNA-binding
   Molecular functionActivator
Repressor
   PTMUbl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell development

Inferred from electronic annotation. Source: Ensembl

cytokine production

Inferred from electronic annotation. Source: Ensembl

inner ear development

Inferred from electronic annotation. Source: Ensembl

lens fiber cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

regulation of chondrocyte differentiation

Inferred from electronic annotation. Source: Ensembl

transcription from RNA polymerase II promoter

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentchromatin

Traceable author statement Ref.1. Source: ProtInc

cytoplasm

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionsequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 373373Transcription factor Maf
PRO_0000076491

Regions

Domain288 – 35164bZIP
Region126 – 373248Represses ARE-mediated transcription
Region288 – 31326Basic motif By similarity
Region316 – 33722Leucine-zipper By similarity
Compositional bias126 – 254129Gly-rich
Compositional bias132 – 252121Ala-rich
Compositional bias180 – 19415His-rich

Natural variations

Alternative sequence3731M → ITEPTRKLEPSVGYATFWKP QHRVLTSVFTK in isoform 1.
VSP_000583
Natural variant2881R → P in CTRCT21. Ref.13
VAR_029369
Natural variant2971K → R in CTRCT21. Ref.14
VAR_029370

Sequences

Sequence LengthMass (Da)Tools
Isoform 2 (Short) [UniParc].

Last modified February 10, 2009. Version 2.
Checksum: 566C2BC3E4A62762

FASTA37338,492
        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 

« Hide

Isoform 1 (Long) [UniParc].

Checksum: 263D2FF2AF8DFB5B
Show »

FASTA40341,961

References

« Hide '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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION.
[12]"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.
[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] [Europe PMC] [Abstract]
Cited for: VARIANT CTRCT21 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] [Europe PMC] [Abstract]
Cited for: VARIANT CTRCT21 ARG-297.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS10928.1. [O75444-1]
CCDS42198.1. [O75444-2]
RefSeqNP_001026974.1. NM_001031804.2. [O75444-2]
NP_005351.2. NM_005360.4. [O75444-1]
UniGeneHs.134859.

3D structure databases

ProteinModelPortalO75444.
SMRO75444. Positions 260-351.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110269. 22 interactions.
IntActO75444. 2 interactions.
STRING9606.ENSP00000327048.

PTM databases

PhosphoSiteO75444.

Proteomic databases

PaxDbO75444.
PRIDEO75444.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000326043; ENSP00000327048; ENSG00000178573. [O75444-1]
ENST00000393350; ENSP00000377019; ENSG00000178573. [O75444-2]
GeneID4094.
KEGGhsa:4094.
UCSCuc002ffm.3. human. [O75444-1]
uc002ffn.3. human. [O75444-2]

Organism-specific databases

CTD4094.
GeneCardsGC16M079627.
H-InvDBHIX0173268.
HGNCHGNC:6776. MAF.
HPACAB010296.
HPA028289.
MIM177075. gene.
610202. phenotype.
neXtProtNX_O75444.
Orphanet1377. Cataract-microcornea syndrome.
98989. Cerulean cataract.
98984. Pulverulent cataract.
PharmGKBPA30534.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG241084.
HOGENOMHOG000261683.
HOVERGENHBG000313.
InParanoidO75444.
KOK09035.
OMAISNGFRE.
PhylomeDBO75444.
TreeFamTF325689.

Enzyme and pathway databases

SignaLinkO75444.

Gene expression databases

ArrayExpressO75444.
BgeeO75444.
CleanExHS_MAF.
GenevestigatorO75444.

Family and domain databases

Gene3D1.10.880.10. 1 hit.
InterProIPR004827. bZIP.
IPR004826. bZIP_Maf.
IPR013592. Maf_TF_N.
IPR028573. MafF.
IPR008917. TF_DNA-bd.
IPR024874. Transciption_factor_Maf.
[Graphical view]
PANTHERPTHR10129. PTHR10129. 1 hit.
PTHR10129:SF9. PTHR10129:SF9. 1 hit.
PfamPF03131. bZIP_Maf. 1 hit.
PF08383. Maf_N. 1 hit.
[Graphical view]
SMARTSM00338. BRLZ. 1 hit.
[Graphical view]
SUPFAMSSF47454. SSF47454. 1 hit.
PROSITEPS50217. BZIP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMAF_(gene).
GenomeRNAi4094.
NextBio16054.
PROO75444.
SOURCESearch...

Entry information

Entry nameMAF_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 125 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM