O75444 (MAF_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified October 16, 2013. Version 118. History...
Names and origin
|Protein names||Recommended name:|
Transcription factor Maf
V-maf musculoaponeurotic fibrosarcoma oncogene homolog
|Organism||Homo sapiens (Human) [Reference proteome]|
|Taxonomic identifier||9606 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo|
|Sequence length||373 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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
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
Nucleus By similarity.
Expressed in endothelial cells. Ref.10
Up-regulated with tert-butyl hydroquinone (t-BHQ). Ref.4
Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is triggered by glucocorticoids. Ref.8
|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.
Contains 1 bZIP (basic-leucine zipper) domain.
|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|
|Chain||1 – 373||373||Transcription factor Maf||PRO_0000076491|
|Domain||288 – 351||64||bZIP|
|Region||126 – 373||248||Represses ARE-mediated transcription|
|Region||288 – 313||26||Basic motif By similarity|
|Region||316 – 337||22||Leucine-zipper By similarity|
|Compositional bias||126 – 254||129||Gly-rich|
|Compositional bias||132 – 252||121||Ala-rich|
|Compositional bias||180 – 194||15||His-rich|
|Alternative sequence||373||1||M → ITEPTRKLEPSVGYATFWKP QHRVLTSVFTK in isoform 1.||VSP_000583|
|Natural variant||288||1||R → P in CTRCT21. Ref.13||VAR_029369|
|Natural variant||297||1||K → R in CTRCT21. Ref.14||VAR_029370|
|||"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.
|||"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. Pennacchio L.A.
Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
|||"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).
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.|
|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.
|RefSeq||NP_001026974.1. NM_001031804.2. |
3D structure databases
|SMR||O75444. Positions 260-351. |
Protein-protein interaction databases
|IntAct||O75444. 2 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENST00000326043; ENSP00000327048; ENSG00000178573. |
ENST00000393350; ENSP00000377019; ENSG00000178573.
|UCSC||uc002ffm.3. human. |
|HGNC||HGNC:6776. MAF. |
|MIM||177075. gene. |
|Orphanet||1377. Cataract-microcornea syndrome. |
98989. Cerulean cataract.
98984. Pulverulent cataract.
Enzyme and pathway databases
Gene expression databases
Family and domain databases
|Gene3D||1.10.880.10. 1 hit. |
|InterPro||IPR004827. bZIP. |
|PANTHER||PTHR10129. PTHR10129. 1 hit. |
|Pfam||PF03131. bZIP_Maf. 1 hit. |
PF08383. Maf_N. 1 hit.
|SMART||SM00338. BRLZ. 1 hit. |
|SUPFAM||SSF47454. SSF47454. 1 hit. |
|PROSITE||PS50217. BZIP. 1 hit. |
PS00036. BZIP_BASIC. False negative.
|Accession||Primary (citable) accession number: O75444|
Secondary accession number(s): Q66I47, Q9UP93
|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.|
|Human chromosome 16|
Human chromosome 16: entries, gene names and cross-references to MIM
|Human entries with polymorphisms or disease mutations|
List of human entries with polymorphisms or disease mutations
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
|Human polymorphisms and disease mutations|
Index of human polymorphisms and disease mutations
Index of protein domains and families