ZFHX3 (AT-binding transcription factor 1)

2003-10-01   Nadine Van Roy , Frank Speleman 

Center for Medical Genetics, Ghent University Hospital, 1K5, De Pintelaan 185, B-9000 Gent, Belgium

Identity

HGNC
LOCATION
16q22.2
IMAGE
Atlas Image
LEGEND
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
LOCUSID
ALIAS
ATBF1,ATBT,C16orf47,ZFH-3,ZNF927
FUSION GENES

DNA/RNA

Description

10 exons, DNA size: 261.32 kb.

Transcription

two isoforms ATBF1-A and ATBF1-B, due to alternative promotor usage combined with alternative splicing, mRNA-size: 11893 bp.

Proteins

Description

3703 amino acids; 404 kDa; four homeodomains and 23 zinc fingers including 1 pseudo zinc finger motif, one DEAD and one DEAH box, a RNA and an ATP binding site, two large RS domains and multiple phosphorylation sites.

Expression

Embryonic and neonatal brain.

Localisation

nuclear

Function

Transcription factor that binds to the AT-rich core sequence of the enhancer element of the AFP gene and downregulates AFP gene expression, possibly involved in neuronal differentiation (ATBF1-A).

Homology

mouse atbf1, drosophila zfh2 and C. Elegans ZC 123.3

Mutations

Somatic

Amplification, in one early neural crest derived cell line SJNB-12 under the form of extrachromosomally double minutes, non-syntenic co-amplification with MYC.
Absence of ATBF1 expression in alpha-fetoprotein expressing gastric cancer cell lines, lack of ATBF1 expression not due to mutation, deletion or translocation but to strong repression at the transcriptional level.

Implicated in

Disease
Early neural crest derived cell line (SJNB-12).
Prognosis
unknown
Cytogenetics
Several structural and numerical chromosomal aberrations and presence of extrachromosomally double minutes and homogenously staining regions, presence of a reciprocal unbalanced t(8;16)(q24.3;q22.3).
Oncogenesis
Amplification in one neural crest derived cell line (SJNB-12), non-syntenic co-amplification with MYC.
Disease
Alpha-fetoprotein producing gastric cancer cell lines (GCIY and Ist-I).
Prognosis
poor (very malignant and highly metastatic cancer)
Oncogenesis
Alpha-fetoprotein producing cancer cell lines show absence of ATBF1 expression, lack of ATBF1 expression not due to deletion mutation or translocation but to strong repression at the transcriptional level.

Bibliography

Pubmed IDLast YearTitleAuthors
113122612001Positive and negative regulation of myogenic differentiation of C2C12 cells by isoforms of the multiple homeodomain zinc finger transcription factor ATBF1.Berry FB et al
90347131997Regulation and activities of alpha-fetoprotein.Chen H et al
129260162003ATBF1-A protein, but not ATBF1-B, is preferentially expressed in developing rat brain.Ishii Y et al
103188671999Myb-interacting protein, ATBF1, represses transcriptional activity of Myb oncoprotein.Kaspar P et al
106235802000AT motif binding factor 1-A (ATBF1-A) negatively regulates transcription of the aminopeptidase N gene in the crypt-villus axis of small intestine.Kataoka H et al
113140202001Alpha-fetoprotein producing gastric cancer lacks transcription factor ATBF1.Kataoka H et al
108557932000Characterization of trinucleotide- and tandem repeat-containing transcripts obtained from human spinal cord cDNA library by high-density filter hybridization.Kaushik N et al
117552052001DNA/RNA-dependent ATPase activity is associated with ATBF1, a multiple homeodomain-zinc finger protein.Kawaguchi M et al
118120772002Expression of homeobox genes in cervical cancer.Li H et al
75929261995Cloning and characterization of an ATBF1 isoform that expresses in a neuronal differentiation-dependent manner.Miura Y et al
17193791991A human alpha-fetoprotein enhancer-binding protein, ATBF1, contains four homeodomains and seventeen zinc fingers.Morinaga T et al
117869622002Regulation of the alpha-fetoprotein gene by the isoforms of ATBF1 transcription factor in human hepatoma.Ninomiya T et al
110044892000Cloning and characterization of a novel RNA-binding protein SRL300 with RS domains.Sawada Y et al
85888961995Automated fluorescent dye-terminator sequencing of G+C-rich tracts with the aid of dimethyl sulfoxide.Scheidl TM et al
88278891996[ZFH/ATBF1 gene family: transcription factors containing both homeo- and zinc finger-domains].Tamaoki T et al
115502802001Combined M-FISH and CGH analysis allows comprehensive description of genetic alterations in neuroblastoma cell lines.Van Roy N et al
90137921996Developmental changes in expression of the ATBF1 transcription factor gene.Watanabe M et al
86664091995Assignment of the human ATBF1 transcription factor gene to chromosome 16q22.3-q23.1.Yamada K et al
75072061994ATBF1, a multiple-homeodomain zinc finger protein, selectively down-regulates AT-rich elements of the human alpha-fetoprotein gene.Yasuda H et al

Other Information

Locus ID:

NCBI: 463
MIM: 104155
HGNC: 777
Ensembl: ENSG00000140836

Variants:

dbSNP: 463
ClinVar: 463
TCGA: ENSG00000140836
COSMIC: ZFHX3

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000140836ENST00000268489Q15911
ENSG00000140836ENST00000397992Q15911
ENSG00000140836ENST00000641206Q15911

Expression (GTEx)

0
5
10
15
20
25
30
35

Pathways

PathwaySourceExternal ID
Signaling pathways regulating pluripotency of stem cellsKEGGhsa04550
Signaling pathways regulating pluripotency of stem cellsKEGGko04550

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
195974912009A sequence variant in ZFHX3 on 16q22 associates with atrial fibrillation and ischemic stroke.172
195974912009A sequence variant in ZFHX3 on 16q22 associates with atrial fibrillation and ischemic stroke.172
195974922009Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry.162
195974922009Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry.162
230426602012Genetic heritability of ischemic stroke and the contribution of previously reported candidate gene and genomewide associations.97
191320872009A genome-wide association study identifies novel and functionally related susceptibility Loci for Kawasaki disease.84
157505932005Frequent somatic mutations of the transcription factor ATBF1 in human prostate cancer.66
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
202019262010Human variation in alcohol response is influenced by variation in neuronal signaling genes.45
211076082011Significant association of SNP rs2106261 in the ZFHX3 gene with atrial fibrillation in a Chinese Han GeneID population.28

Citation

Nadine Van Roy ; Frank Speleman

ZFHX3 (AT-binding transcription factor 1)

Atlas Genet Cytogenet Oncol Haematol. 2003-10-01

Online version: http://atlasgeneticsoncology.org/gene/357/zfhx3