MAZ (MYC Associated Zinc Finger Protein)

2017-11-01   Burcu Karakaya , Mesut Muyan 

Middle East Technical University, Department of Biological Sciences, ankaya 06800, Ankara, Turkey. burcu.karakaya@metu.edu.tr; mmuyan@metu.edu.tr

Identity

HGNC
LOCATION
16p11.2
IMAGE
Atlas Image
LEGEND
UCSC representation of the gene on chromosome 16. RefSeq sequence shows introns as lines, exons as boxes and encoding exons as thicker boxes. Retrieved from: http://genome.ucsc.edu on November 6, 2017.
LOCUSID
ALIAS
PUR1,Pur-1,SAF-1,SAF-2,SAF-3,ZF87,ZNF801,Zif87

Abstract

Myc-associated zinc finger protein (MAZ), also known as serum amyloid A-activating factor 1 (SAF1), Pur-1 or Zif87, is ubiquitously expressed in various tissues. MAZ is a transcription factor with six Cys2His2-type zinc finger motifs at the carboxyl-terminus that interact with a permutation of the GGGAGGG sequence motif present in GC-rich promoter regions of target genes, likely through DNA unfolding of G-quadruplex structures to modulate gene expressions. MAZ is also suggested to participate in transcription termination and polyadenylation. Deregulated expression of MAZ is reported to correlate with various tissue malignancies that include the breast, thyroid, hepatocellular and urothelial cancers.

DNA/RNA

Atlas Image
The human MAZ consists of six exons, the first five of which are encoding exons; total exon length is 4.57 kb (Song et al., 1998).

Description

The human MAZ contains six exons; the encoding sequence consists of 1431 bases (Song et al., 1998).

Transcription

The human gene encoding for MAZ is located on chromosome 16p11.2 and is transcribed as an mRNA of 2.7 kilobases (kb). The primary transcript encodes a 477 amino-acid long MAZ-1 protein with a 60-kDa molecular mass that contains six C2H2-type zinc-finger domains responsible for DNA binding. MAZ protein has two additional isoforms: MAZ-2 and MAZ-3. The MAZ-2 transcript is generated by an alternative splicing that results in the insertion of a new exon originating from the non-coding sequences of the intron 4. This transcript gives rise to the MAZ-2 isoform, which is a 493 amino-acids long protein with distinct carboxyl-terminus which contains two additional zinc-finger domains (Ray et al., 2002). The MAZ-2 isoform is reported to have a higher DNA-binding activity and to act as a negative regulator of MAZ-1 function (Ray et al., 2002). The MAZ-3 transcript is expressed at very low levels under normal physiological condition in various tissues, but is highly expressed during inflammation. The MAZ-3 transcript is transcribed from a distinct upstream promoter and is processed with alternative splicing. The MAZ-3 transcript is translated from a different starting codon that gives rise to the MAZ-3 isoform of 455 amino-acids (Ray et al., 2009).

Pseudogene

No reported pseudogenes are found.

Proteins

Atlas Image
Domains of MAZ are depicted with vertical colored lines; Blacks are Poly-Alanine repeats; Green is Poly-Proline tract; Red column is Poly-Glycine repeat. C2H2-type zinc finger domains of MAZ-1 are represented in dark blue-green vertical lines.

Description

The human MAZ protein contains three Poly alanine, one poly-proline and one poly-glycine domains (Song et al., 1998). Poly-alanine repeats considered to have role in cellular localization of the protein; the alteration in the intracellular distribution may contribute to diseases, including muscular dystrophy (OPMD) (Oma et al., 2004). Similarly, poly-glycine repeats are responsible in protein targeting (Uthayakumar et al., 2012). Poly-proline tracks, on the other hand, generates structures that are predicted to have important roles in protein-protein interactions (Williamson, 1994). The human MAZ-1 contains six C2H2-type zinc finger domains (Song et al., 1998), which are frequently occurring in proteins involved in transcriptional regulation.
Atlas Image
Expression and synthesis of MAZ in various cancerous tissues. Retrieved from: http://www.proteinatlas.org/ENSG00000103495-MAZ/cancer on November 2, 2017.

Expression

MAZ is expressed in the human heart, brain, lungs, liver, skeletal muscle, pancreas, and prostate (Jiao et al., 2013; Dudas et al., 2008). The synthesis of MAZ protein is observed to occur at high levels in breast, thyroid and urothelial cancers as well as in melanoma (Ugai et al., 2001)
Atlas Image
Immunofluorescent staining of human cell line MCF7. Retrieved from: http://www.proteinatlas.org/ENSG00000103495-MAZ/cell on November 2, 2017. Immunofluorescent staining of MCF7 cells derived from breast adenocarcinoma shows that MAZ localizes to the nucleus.

Localisation

MAZ is located in the nucleus (Jordan-Sciutto et al, 2000).

Function

MAZ as a transcription factor interacts with a permutation of the GGGAGGG sequence motif present in GC-rich promoter regions of target genes by unfolding of G-quadruplex structures of DNA (Cogoi et al., 2014) to activate or repress transcription. MAZ is also suggested to participate in transcription termination and polyadenylation. Several oncogenes, including MYC, HRAS, PPARG, TSG101, VEGFA, CAV1, PTHR1, NOS3, MYB, and hTER, are transcriptionally regulated by MAZ (Jun Song et al., 2001; Lee et al., 2016; Ray et al., 2002). Deregulated expression of MAZ appears to participate in the development and/or progress various tissue malignancies including the breast, thyroid, hepatocellular and urothelial cancers (Jiao et al., 2013; Dudas et al., 2008; Yu et al., 2017; Ray, 2011; Zhu et al., 2016)

Homology

The human MAZ protein is conserved 100% in chimpanzee (P.troglodytes), 98.4% in mouse (M.musculus), and 98.4% in rat (R.norvegicus); with conserved DNA of 99.8%, 93.2%, and 92.7%, respectively (Retrieved from: https://blast.ncbi.nlm.nih.gov/Blast.cgi. November 2, 2017).

Mutations

Note

Genetic mutations are not described for MAZ.

Implicated in

Entity name
Prostate cancer
Note
It was reported that the MAZ expression is higher in clinical prostate cancer (PCa) specimens than in benign prostatic hyperplasia (BPH) and adjacent normal tissues (Jiao et al., 2013). Moreover, the MAZ expression appears to be positively correlated with the expression of androgen receptor ( AR), which is critical for the initiation and development of androgen-dependent PCa (Jiao et al., 2013). Extending these findings, experimental studies in cell models derived from PCa indicated that MAZ is involved in the phenotypic manifestation of PCa cell models as siRNA knockdown of MAZ levels reduces cell proliferation, migration, and invasion through mechanisms involve the expression of AR (Jiao et al., 2013).
Entity name
Hepatocellular carcinoma
Note
The expression of MAZ was reported to be upregulated in the majority (78.94%) of hepatocellular carcinoma (HCC) samples compared to normal liver samples (Dudas et al., 2008). Experimental studies using cell lines derived from HCC further suggest that MAZ-mediated regulation of PROX1, which is a transcription factor critical for the expression of a number of genes involved in hepatic metabolic functions, contributes to the progression of HCC (Dudas et al., 2008).
Entity name
Breast cancer
Note
Based on data sets in Gene expression-based Outcome for Breast Cancer Online (GOBO, http://co.bmc.lu.se/gobo/), the expression of MAZ is found to be correlated with distant metastasis-free survival (DMFS) in basal-like breast cancer (BLBC) patients and that the under-expression of MAZ is involved in the metastatic spread of BLBC (Yu et al., 2017). Based on these finding, it was suggested that MAZ plays dual roles in basal-like breast cancer (BLBC): it suppresses cancer progression but promotes cellular proliferation (Yu et al., 2017). Experimental studies using model cell lines derived from breast cancer indeed suggest that MAZ promotes cell proliferation yet it suppresses the aggressiveness of BLBC by controlling the transition toward a more mesenchymal phenotype (Yu et al., 2017; Ray, 2011).
Entity name
Pancreatic carcinoma
Note
Based on samples from pancreatic carcinoma patients, it was reported that the expression of MAZ is significantly higher in PC tissue compared to the adjacent non-tumor tissues (Zhu et al., 2016). Moreover, it appears that the over-expression of MAZ is associated with poor prognosis of PC patients (Zhu et al., 2016).
Entity name
Hodgkins Disease and Paraneoplastic Cerebellar Dysfunction
Note
In neuronal cells, MAZ interacts with the Deleted in Colorectal Cancer product ( DCC), the receptor for NTN1 netrin-1 which plays a central role in axonal guidance and neuronal migration as well as survival during development. Analyses of sera from patients with HD and PCD Hodgkins disease and paraneoplastic cerebellar degeneration indicated that patient sera contain auto-antigens directed against the MAZ-DCC complex. Based on these observations, it was speculated that auto-antigens could interfere with neuronal function resulting in neuronal degeneration (Bataller and Wade, 2002).

Bibliography

Pubmed IDLast YearTitleAuthors
125098572003The MAZ protein is an autoantigen of Hodgkin's disease and paraneoplastic cerebellar dysfunction.Bataller L et al
15021571992MAZ, a zinc finger protein, binds to c-MYC and C2 gene sequences regulating transcriptional initiation and termination.Bossone SA et al
250131822014HRAS is silenced by two neighboring G-quadruplexes and activated by MAZ, a zinc-finger transcription factor with DNA unfolding property.Cogoi S et al
264711852015MiR-449a suppresses the epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma by multiple targets.Chen SP et al
184000942008Altered regulation of Prox1-gene-expression in liver tumors.Dudas J et al
79885631994MAZ-dependent termination between closely spaced human complement genes.Ashfield R et al
236091892013The prostate cancer-up-regulated Myc-associated zinc-finger protein (MAZ) modulates proliferation and metastasis through reciprocal regulation of androgen receptor.Jiao L et al
107272122000Fetal Alz-50 clone 1 (FAC1) protein interacts with the Myc-associated zinc finger protein (ZF87/MAZ) and alters its transcriptional activity.Jordan-Sciutto KL et al
164888872006A Prospero-related homeodomain protein is a novel co-regulator of hepatocyte nuclear factor 4alpha that regulates the cholesterol 7alpha-hydroxylase gene.Song KH et al
269024212016Akt phosphorylates myc-associated zinc finger protein (MAZ), releases P-MAZ from the p53 promoter, and activates p53 transcription.Lee WP et al
216659402011Control of VEGF expression in triple-negative breast carcinoma cells by suppression of SAF-1 transcription factor activity.Ray A et al
99336311999Activation of Sp1 and its functional co-operation with serum amyloid A-activating sequence binding factor in synoviocyte cells trigger synergistic action of interleukin-1 and interleukin-6 in serum amyloid A gene expression.Ray A et al
122709222002SAF-2, a splice variant of SAF-1, acts as a negative regulator of transcription.Ray BK et al
224153012012Myc-associated zinc finger protein (MAZ) is regulated by miR-125b and mediates VEGF-induced angiogenesis in glioblastoma.Smits M et al
112594062001Independent repression of a GC-rich housekeeping gene by Sp1 and MAZ involves the same cis-elements.Song J et al
113955152001Two consecutive zinc fingers in Sp1 and in MAZ are essential for interactions with cis-elements.Song J et al
115274122001Interaction of Myc-associated zinc finger protein with DCC, the product of a tumor-suppressor gene, during the neural differentiation of P19 EC cells.Ugai H et al
280082702016Overexpression and clinical significance of MYC-associated zinc finger protein in pancreatic carcinoma.Zhu X et al
254879552015MiR-449a exerts tumor-suppressive functions in human glioblastoma by targeting Myc-associated zinc-finger protein.Yao Y et al
103601751999Specific transcriptional pausing activates polyadenylation in a coupled in vitro system.Yonaha M et al
285779762017Dual function of MAZ mediated by FOXF2 in basal-like breast cancer: Promotion of proliferation and suppression of progression.Yu ZH et al
252015242015miR-34c regulates the permeability of blood-tumor barrier via MAZ-mediated expression changes of ZO-1, occludin, and claudin-5.Zhao L et al

Other Information

Locus ID:

NCBI: 4150
MIM: 600999
HGNC: 6914
Ensembl: ENSG00000103495

Variants:

dbSNP: 4150
ClinVar: 4150
TCGA: ENSG00000103495
COSMIC: MAZ

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000103495ENST00000219782P56270
ENSG00000103495ENST00000322945P56270
ENSG00000103495ENST00000545521P56270
ENSG00000103495ENST00000561855H3BRC5
ENSG00000103495ENST00000562337P56270
ENSG00000103495ENST00000562557I3L4Y2
ENSG00000103495ENST00000563012H3BQS2
ENSG00000103495ENST00000563402H3BTS8
ENSG00000103495ENST00000566906I3L4D3
ENSG00000103495ENST00000567444I3L2Z5
ENSG00000103495ENST00000568282I3L0M3
ENSG00000103495ENST00000568411H3BQI4
ENSG00000103495ENST00000568544H3BPU3
ENSG00000103495ENST00000569978I3L411
ENSG00000103495ENST00000616501A0A087WWR2

Expression (GTEx)

0
10
20
30
40
50
60

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
166484912006Pause sites promote transcriptional termination of mammalian RNA polymerase II.95
192425452009Association and mutation analyses of 16p11.2 autism candidate genes.35
254879552015MiR-449a exerts tumor-suppressive functions in human glioblastoma by targeting Myc-associated zinc-finger protein.21
236091892013The prostate cancer-up-regulated Myc-associated zinc-finger protein (MAZ) modulates proliferation and metastasis through reciprocal regulation of androgen receptor.19
179020472008MAZ drives tumor-specific expression of PPAR gamma 1 in breast cancer cells.18
155284672004Induction of the MMP-14 gene in macrophages of the atherosclerotic plaque: role of SAF-1 in the induction process.13
216659402011Control of VEGF expression in triple-negative breast carcinoma cells by suppression of SAF-1 transcription factor activity.13
252015242015miR-34c regulates the permeability of blood-tumor barrier via MAZ-mediated expression changes of ZO-1, occludin, and claudin-5.12
278611582016MYC associated zinc finger protein promotes the invasion and metastasis of hepatocellular carcinoma by inducing epithelial mesenchymal transition.12
254496832015Induction of Ras by SAF-1/MAZ through a feed-forward loop promotes angiogenesis in breast cancer.11

Citation

Burcu Karakaya ; Mesut Muyan

MAZ (MYC Associated Zinc Finger Protein)

Atlas Genet Cytogenet Oncol Haematol. 2017-11-01

Online version: http://atlasgeneticsoncology.org/gene/41307/maz