ZBTB33 (zinc finger and BTB domain containing 33)
2010-11-01 Michael R Dohn , Albert B Reynolds AffiliationDepartment of Cancer Biology, Vanderbilt University, Nashville, TN, USA
Identity
HGNC
LOCATION
Xq24
LOCUSID
ALIAS
ZNF-kaiso,ZNF348
FUSION GENES
DNA/RNA
ZBTB33/Kaiso genomic sequence (7.64 Kb) is composed of three exons (green). The coding region (red) is within exon 3.
Description
DNA consists of three exons, the third of which contains the coding region.
Transcription
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.
Pseudogene
None.
Proteins
ZBTB33/Kaiso contains an N-terminal POZ/BTB domain (green), two acidic regions (blue), and three C-terminal zinc finger domains (red).
Description
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.
Expression
Kaiso is ubiquitously expressed.
Localisation
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.
Function
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.
Homology
Mus musculus - Zbtb33; Rattus norvegicus - Zbtb33; Xenopus laevis - zbtb33; Danio rerio - zbtb33; Pan troglodytes - ZBTB33; Bos Taurus - ZBTB33; Gallus gallus - ZBTB33.
Mutations
Note
None reported.
Implicated in
Entity name
Lung cancer
Note
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
Note
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
Note
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
Note
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.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 19508730 | 2009 | Cytoplasmic Kaiso is associated with poor prognosis in non-small cell lung cancer. | Dai SD et al |
| 10207085 | 1999 | The catenin p120(ctn) interacts with Kaiso, a novel BTB/POZ domain zinc finger transcription factor. | Daniel JM et al |
| 12087177 | 2002 | The 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 |
| 17050009 | 2007 | Dancing in and out of the nucleus: p120(ctn) and the transcription factor Kaiso. | Daniel JM et al |
| 16230345 | 2005 | The human enhancer blocker CTC-binding factor interacts with the transcription factor Kaiso. | Defossez PA et al |
| 20303951 | 2010 | Kaiso regulates Znf131-mediated transcriptional activation. | Donaldson NS et al |
| 15543138 | 2004 | Non-canonical Wnt signals are modulated by the Kaiso transcriptional repressor and p120-catenin. | Kim SW et al |
| 18794111 | 2008 | Kaiso contributes to DNA methylation-dependent silencing of tumor suppressor genes in colon cancer cell lines. | Lopes EC et al |
| 18653469 | 2008 | p120 and Kaiso regulate Helicobacter pylori-induced expression of matrix metalloproteinase-7. | Ogden SR et al |
| 15935774 | 2005 | Kaiso/p120-catenin and TCF/beta-catenin complexes coordinately regulate canonical Wnt gene targets. | Park JI et al |
| 16354691 | 2006 | Kaiso-deficient mice show resistance to intestinal cancer. | Prokhortchouk A et al |
| 15282317 | 2004 | Regulation of the rapsyn promoter by kaiso and delta-catenin. | Rodova M et al |
| 15548582 | 2004 | Kaiso is a genome-wide repressor of transcription that is essential for amphibian development. | Ruzov A et al |
| 19158185 | 2009 | The non-methylated DNA-binding function of Kaiso is not required in early Xenopus laevis development. | Ruzov A et al |
| 15781635 | 2005 | Expression and nuclear location of the transcriptional repressor Kaiso is regulated by the tumor microenvironment. | Soubry A et al |
| 15817151 | 2005 | The catenin p120ctn inhibits Kaiso-mediated transcriptional repression of the beta-catenin/TCF target gene matrilysin. | Spring CM et al |
| 14527417 | 2003 | N-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
Variants:
dbSNP: 10009
ClinVar: 10009
TCGA: ENSG00000177485
COSMIC: ZBTB33
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000177485 | ENST00000326624 | Q86T24 |
| ENSG00000177485 | ENST00000557385 | Q86T24 |
Expression (GTEx)
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 35851744 | 2022 | Kaiso phosphorylation at threonine 606 leads to its accumulation in the cytoplasm, reducing its transcriptional repression of the tumour suppressor CDH1. | 0 |
| 36115941 | 2022 | Expressional variations of Kaiso: an association with pathological characteristics and field cancerization of OSCC. | 1 |
| 35851744 | 2022 | Kaiso phosphorylation at threonine 606 leads to its accumulation in the cytoplasm, reducing its transcriptional repression of the tumour suppressor CDH1. | 0 |
| 36115941 | 2022 | Expressional variations of Kaiso: an association with pathological characteristics and field cancerization of OSCC. | 1 |
| 32352758 | 2020 | A Conformational Switch in the Zinc Finger Protein Kaiso Mediates Differential Readout of Specific and Methylated DNA Sequences. | 5 |
| 32352758 | 2020 | A Conformational Switch in the Zinc Finger Protein Kaiso Mediates Differential Readout of Specific and Methylated DNA Sequences. | 5 |
| 30858547 | 2019 | Kaiso is required for MTG16-dependent effects on colitis-associated carcinoma. | 7 |
| 31199830 | 2019 | Kaiso-induced intestinal inflammation is preceded by diminished E-cadherin expression and intestinal integrity. | 4 |
| 31296660 | 2019 | Temporal and differential regulation of KAISO-controlled transcription by phosphorylated and acetylated p53 highlights a crucial regulatory role of apoptosis. | 3 |
| 30858547 | 2019 | Kaiso is required for MTG16-dependent effects on colitis-associated carcinoma. | 7 |
| 31199830 | 2019 | Kaiso-induced intestinal inflammation is preceded by diminished E-cadherin expression and intestinal integrity. | 4 |
| 31296660 | 2019 | Temporal and differential regulation of KAISO-controlled transcription by phosphorylated and acetylated p53 highlights a crucial regulatory role of apoptosis. | 3 |
| 27574848 | 2018 | RhoH participates in a multi-protein complex with the zinc finger protein kaiso that regulates both cytoskeletal structures and chemokine-induced T cells. | 8 |
| 28800784 | 2018 | Upregulation of MicroRNA-4262 Targets Kaiso (ZBTB33) to Inhibit the Proliferation and EMT of Cervical Cancer Cells. | 7 |
| 29472715 | 2018 | DeSUMOylation switches Kaiso from activator to repressor upon hyperosmotic stress. | 10 |
Citation
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/gene-fusions/gene-fusions-explorer/submit-meetings/deep-insight-explorer/
