ZBTB33 (zinc finger and BTB domain containing 33)

2010-11-01   Michael R Dohn , Albert B Reynolds 

Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA




Atlas Image
ZBTB33/Kaiso genomic sequence (7.64 Kb) is composed of three exons (green). The coding region (red) is within exon 3.


DNA consists of three exons, the third of which contains the coding region.


Transcription of this gene produces transcript variants 1 (5324 bp) and 2 (5225 bp) that encode the same protein. Variant 2 lacks exon 2 in the 5 UTR.




Atlas Image
ZBTB33/Kaiso contains an N-terminal POZ/BTB domain (green), two acidic regions (blue), and three C-terminal zinc finger domains (red).


ZBTB33/Kaiso (hereafter Kaiso) is a member of the BTB/POZ (Broad complex, Tramtrak, Bric á brac/Pox virus and zinc finger)-zinc finger family of transcription factors. Kaiso was originally identified in a yeast two-hybrid screen as a binding partner for the Armadillo repeat domain protein p120-catenin (CTNND1) and has subsequently been found to also interact with the p120-catenin-related protein delta-catenin. The N-terminal POZ/BTB domain mediates Kaiso interactions with N-CoR, the CTC-binding factor (CTCF), and Znf131, as well as Kaiso homodimerization.


Kaiso is ubiquitously expressed.


In various mammalian cell lines Kaiso localizes nearly exclusively to the nucleus, but in normal and tumor tissues Kaiso is predominantly detected in the cytoplasm. During mitosis a pool of Kaiso localizes to microtubles and centrosomes.


Via its zinc finger domain, Kaiso binds DNA and functions as both a repressor and activator of transcription. Kaiso recognizes methylated CpG dinucleotides as well as a sequence-specific site (TCCTGCNA). While several genes are repressed by Kaiso (including matrilysin, siamois, c-Fos, cyclin-D1, c-Myc, Wnt11, MMP-7 and MTA2), rapsyn is the only reported gene to be activated by Kaiso.


Mus musculus - Zbtb33; Rattus norvegicus - Zbtb33; Xenopus laevis - zbtb33; Danio rerio - zbtb33; Pan troglodytes - ZBTB33; Bos Taurus - ZBTB33; Gallus gallus - ZBTB33.



None reported.

Implicated in

Entity name
Lung cancer
Immunohistochemical analysis of 294 cases of non-small cell lung cancer, including 50 cases of paired lymph node metastases, revealed a correlation of cytoplasmic Kaiso staining with poor prognosis, and shRNA-mediated knockdown of Kaiso enhances proliferative and invasive capabilities of several lung cancer cell lines.
Entity name
Colon cancer
Kaiso has been shown to repress expression of methylated tumor suppressor genes, and depletion of Kaiso sensitizes colon cancer cell lines to chemotherapy. Moreover, Kaiso is upregulated in intestinal tumors in mice, and a delayed onset of intestinal tumorigenesis is observed when Kaiso-null mice are crossed with the tumor-susceptible ApcMin/+ mice.
Entity name
Gastric cancer
A study of the Helicobacter pylori-induced inflammatory response, which, if persistent, increases the risk for gastric adenocarcinoma, revealed that H. pylori induces nuclear translocation of the Kaiso-binding partner p120-catenin. Nuclear p120-catenin then relieves Kaiso-mediated repression of MMP-7, which is often overexpressed in premalignant and malignant gastric lesions.
Entity name
Vertebrate development
Injection of Xenopus laevis embryos with morpholinos targeting xKaiso leads to a developmental delay during gastrulation. Initially, Kaisos roles in both general transcription repression and in regulation of canonical and non-canonical Wnt-signaling were thought to contribute to this phenotype, but subsequent studies determined that Kaisos main role in early Xenopus development is restricted to the maintenence of transcriptional silencing. However, disruption of the Kaiso gene in mice did not reveal any abnormalities in development or gene expression.


Pubmed IDLast YearTitleAuthors
195087302009Cytoplasmic Kaiso is associated with poor prognosis in non-small cell lung cancer.Dai SD et al
102070851999The catenin p120(ctn) interacts with Kaiso, a novel BTB/POZ domain zinc finger transcription factor.Daniel JM et al
120871772002The p120(ctn)-binding partner Kaiso is a bi-modal DNA-binding protein that recognizes both a sequence-specific consensus and methylated CpG dinucleotides.Daniel JM et al
170500092007Dancing in and out of the nucleus: p120(ctn) and the transcription factor Kaiso.Daniel JM et al
162303452005The human enhancer blocker CTC-binding factor interacts with the transcription factor Kaiso.Defossez PA et al
203039512010Kaiso regulates Znf131-mediated transcriptional activation.Donaldson NS et al
155431382004Non-canonical Wnt signals are modulated by the Kaiso transcriptional repressor and p120-catenin.Kim SW et al
187941112008Kaiso contributes to DNA methylation-dependent silencing of tumor suppressor genes in colon cancer cell lines.Lopes EC et al
186534692008p120 and Kaiso regulate Helicobacter pylori-induced expression of matrix metalloproteinase-7.Ogden SR et al
159357742005Kaiso/p120-catenin and TCF/beta-catenin complexes coordinately regulate canonical Wnt gene targets.Park JI et al
163546912006Kaiso-deficient mice show resistance to intestinal cancer.Prokhortchouk A et al
152823172004Regulation of the rapsyn promoter by kaiso and delta-catenin.Rodova M et al
155485822004Kaiso is a genome-wide repressor of transcription that is essential for amphibian development.Ruzov A et al
191581852009The non-methylated DNA-binding function of Kaiso is not required in early Xenopus laevis development.Ruzov A et al
157816352005Expression and nuclear location of the transcriptional repressor Kaiso is regulated by the tumor microenvironment.Soubry A et al
158171512005The catenin p120ctn inhibits Kaiso-mediated transcriptional repression of the beta-catenin/TCF target gene matrilysin.Spring CM et al
145274172003N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso.Yoon HG et al

Other Information

Locus ID:

NCBI: 10009
MIM: 300329
HGNC: 16682
Ensembl: ENSG00000177485


dbSNP: 10009
ClinVar: 10009
TCGA: ENSG00000177485


Gene IDTranscript IDUniprot

Expression (GTEx)


Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
158171512005The catenin p120ctn inhibits Kaiso-mediated transcriptional repression of the beta-catenin/TCF target gene matrilysin.57
229496372012Molecular basis for recognition of methylated and specific DNA sequences by the zinc finger protein Kaiso.51
187941112008Kaiso contributes to DNA methylation-dependent silencing of tumor suppressor genes in colon cancer cell lines.45
229745832012Nuclear Kaiso indicates aggressive prostate cancers and promotes migration and invasiveness of prostate cancer cells.32
162303452005The human enhancer blocker CTC-binding factor interacts with the transcription factor Kaiso.30
186534692008p120 and Kaiso regulate Helicobacter pylori-induced expression of matrix metalloproteinase-7.28
226622402012Nuclear Kaiso expression is associated with high grade and triple-negative invasive breast cancer.28
216702012011Wnt controls the transcriptional activity of Kaiso through CK1ε-dependent phosphorylation of p120-catenin.24
232262762012Kaiso represses the cell cycle gene cyclin D1 via sequence-specific and methyl-CpG-dependent mechanisms.23
252887472014KAISO, a critical regulator of p53-mediated transcription of CDKN1A and apoptotic genes.21


Michael R Dohn ; Albert B Reynolds

ZBTB33 (zinc finger and BTB domain containing 33)

Atlas Genet Cytogenet Oncol Haematol. 2010-11-01

Online version: http://atlasgeneticsoncology.org/gene/43785/zbtb33-(zinc-finger-and-btb-domain-containing-33)