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ZBTB33 (zinc finger and BTB domain containing 33)

Written2010-11Michael R Dohn, Albert B Reynolds
Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)ZNF-kaiso
kaiso
WUGSC:H_DJ525N14.1
KAISO
ZNF348
Other alias
HGNC (Hugo) ZBTB33
LocusID (NCBI) 10009
Atlas_Id 43785
Location Xq24  [Link to chromosome band Xq24]
Location_base_pair Starts at 120250755 and ends at 120258396 bp from pter ( according to hg19-Feb_2009)  [Mapping ZBTB33.png]
Fusion genes
(updated 2016)
YWHAZ (8q22.3) / ZBTB33 (Xq24)ZBTB33 (Xq24) / ZBTB33 (Xq24)

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.

Protein

 
  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

Note
  
Entity 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 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 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 Vertebrate development
Note Injection of Xenopus laevis embryos with morpholinos targeting xKaiso leads to a developmental delay during gastrulation. Initially, Kaiso's 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 Kaiso's 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.
  

Bibliography

Cytoplasmic Kaiso is associated with poor prognosis in non-small cell lung cancer.
Dai SD, Wang Y, Miao Y, Zhao Y, Zhang Y, Jiang GY, Zhang PX, Yang ZQ, Wang EH.
BMC Cancer. 2009 Jun 9;9:178.
PMID 19508730
 
The catenin p120(ctn) interacts with Kaiso, a novel BTB/POZ domain zinc finger transcription factor.
Daniel JM, Reynolds AB.
Mol Cell Biol. 1999 May;19(5):3614-23.
PMID 10207085
 
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, Spring CM, Crawford HC, Reynolds AB, Baig A.
Nucleic Acids Res. 2002 Jul 1;30(13):2911-9.
PMID 12087177
 
Dancing in and out of the nucleus: p120(ctn) and the transcription factor Kaiso.
Daniel JM.
Biochim Biophys Acta. 2007 Jan;1773(1):59-68. Epub 2006 Sep 7. (REVIEW)
PMID 17050009
 
The human enhancer blocker CTC-binding factor interacts with the transcription factor Kaiso.
Defossez PA, Kelly KF, Filion GJ, Perez-Torrado R, Magdinier F, Menoni H, Nordgaard CL, Daniel JM, Gilson E.
J Biol Chem. 2005 Dec 30;280(52):43017-23. Epub 2005 Oct 17.
PMID 16230345
 
Kaiso regulates Znf131-mediated transcriptional activation.
Donaldson NS, Nordgaard CL, Pierre CC, Kelly KF, Robinson SC, Swystun L, Henriquez R, Graham M, Daniel JM.
Exp Cell Res. 2010 Jun 10;316(10):1692-705. Epub 2010 Mar 18.
PMID 20303951
 
Non-canonical Wnt signals are modulated by the Kaiso transcriptional repressor and p120-catenin.
Kim SW, Park JI, Spring CM, Sater AK, Ji H, Otchere AA, Daniel JM, McCrea PD.
Nat Cell Biol. 2004 Dec;6(12):1212-20. Epub 2004 Nov 14.
PMID 15543138
 
Kaiso contributes to DNA methylation-dependent silencing of tumor suppressor genes in colon cancer cell lines.
Lopes EC, Valls E, Figueroa ME, Mazur A, Meng FG, Chiosis G, Laird PW, Schreiber-Agus N, Greally JM, Prokhortchouk E, Melnick A.
Cancer Res. 2008 Sep 15;68(18):7258-63.
PMID 18794111
 
p120 and Kaiso regulate Helicobacter pylori-induced expression of matrix metalloproteinase-7.
Ogden SR, Wroblewski LE, Weydig C, Romero-Gallo J, O'Brien DP, Israel DA, Krishna US, Fingleton B, Reynolds AB, Wessler S, Peek RM Jr.
Mol Biol Cell. 2008 Oct;19(10):4110-21. Epub 2008 Jul 23.
PMID 18653469
 
Kaiso/p120-catenin and TCF/beta-catenin complexes coordinately regulate canonical Wnt gene targets.
Park JI, Kim SW, Lyons JP, Ji H, Nguyen TT, Cho K, Barton MC, Deroo T, Vleminckx K, Moon RT, McCrea PD.
Dev Cell. 2005 Jun;8(6):843-54.
PMID 15935774
 
Kaiso-deficient mice show resistance to intestinal cancer.
Prokhortchouk A, Sansom O, Selfridge J, Caballero IM, Salozhin S, Aithozhina D, Cerchietti L, Meng FG, Augenlicht LH, Mariadason JM, Hendrich B, Melnick A, Prokhortchouk E, Clarke A, Bird A.
Mol Cell Biol. 2006 Jan;26(1):199-208.
PMID 16354691
 
Regulation of the rapsyn promoter by kaiso and delta-catenin.
Rodova M, Kelly KF, VanSaun M, Daniel JM, Werle MJ.
Mol Cell Biol. 2004 Aug;24(16):7188-96.
PMID 15282317
 
Kaiso is a genome-wide repressor of transcription that is essential for amphibian development.
Ruzov A, Dunican DS, Prokhortchouk A, Pennings S, Stancheva I, Prokhortchouk E, Meehan RR.
Development. 2004 Dec;131(24):6185-94. Epub 2004 Nov 17.
PMID 15548582
 
The non-methylated DNA-binding function of Kaiso is not required in early Xenopus laevis development.
Ruzov A, Savitskaya E, Hackett JA, Reddington JP, Prokhortchouk A, Madej MJ, Chekanov N, Li M, Dunican DS, Prokhortchouk E, Pennings S, Meehan RR.
Development. 2009 Mar;136(5):729-38. Epub 2009 Jan 21.
PMID 19158185
 
The transcriptional repressor Kaiso localizes at the mitotic spindle and is a constituent of the pericentriolar material.
Soubry A, Staes K, Parthoens E, Noppen S, Stove C, Bogaert P, van Hengel J, van Roy F.
PLoS One. 2010 Feb 15;5(2):e9203.
PMID 120169156
 
Expression and nuclear location of the transcriptional repressor Kaiso is regulated by the tumor microenvironment.
Soubry A, van Hengel J, Parthoens E, Colpaert C, Van Marck E, Waltregny D, Reynolds AB, van Roy F.
Cancer Res. 2005 Mar 15;65(6):2224-33.
PMID 15781635
 
The catenin p120ctn inhibits Kaiso-mediated transcriptional repression of the beta-catenin/TCF target gene matrilysin.
Spring CM, Kelly KF, O'Kelly I, Graham M, Crawford HC, Daniel JM.
Exp Cell Res. 2005 May 1;305(2):253-65.
PMID 15817151
 
N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso.
Yoon HG, Chan DW, Reynolds AB, Qin J, Wong J.
Mol Cell. 2003 Sep;12(3):723-34.
PMID 14527417
 

Citation

This paper should be referenced as such :
Dohn, MR ; Reynolds, AB
ZBTB33 (zinc finger, BTB domain containing 33)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(7):605-607.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/ZBTB33ID43785chXq24.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(9;17)(p13;p12) PAX5/NCOR1


External links

Nomenclature
HGNC (Hugo)ZBTB33   16682
Cards
AtlasZBTB33ID43785chXq24
Entrez_Gene (NCBI)ZBTB33  10009  zinc finger and BTB domain containing 33
AliasesZNF-kaiso; ZNF348
GeneCards (Weizmann)ZBTB33
Ensembl hg19 (Hinxton)ENSG00000177485 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000177485 [Gene_View]  chrX:120250755-120258396 [Contig_View]  ZBTB33 [Vega]
ICGC DataPortalENSG00000177485
TCGA cBioPortalZBTB33
AceView (NCBI)ZBTB33
Genatlas (Paris)ZBTB33
WikiGenes10009
SOURCE (Princeton)ZBTB33
Genetics Home Reference (NIH)ZBTB33
Genomic and cartography
GoldenPath hg38 (UCSC)ZBTB33  -     chrX:120250755-120258396 +  Xq24   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)ZBTB33  -     Xq24   [Description]    (hg19-Feb_2009)
EnsemblZBTB33 - Xq24 [CytoView hg19]  ZBTB33 - Xq24 [CytoView hg38]
Mapping of homologs : NCBIZBTB33 [Mapview hg19]  ZBTB33 [Mapview hg38]
OMIM300329   
Gene and transcription
Genbank (Entrez)AK092998 AK094230 AK312321 AL833604 AL833856
RefSeq transcript (Entrez)NM_001184742 NM_006777
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)ZBTB33
Cluster EST : UnigeneHs.143604 [ NCBI ]
CGAP (NCI)Hs.143604
Alternative Splicing GalleryENSG00000177485
Gene ExpressionZBTB33 [ NCBI-GEO ]   ZBTB33 [ EBI - ARRAY_EXPRESS ]   ZBTB33 [ SEEK ]   ZBTB33 [ MEM ]
Gene Expression Viewer (FireBrowse)ZBTB33 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)10009
GTEX Portal (Tissue expression)ZBTB33
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ86T24   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ86T24  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ86T24
Splice isoforms : SwissVarQ86T24
PhosPhoSitePlusQ86T24
Domaine pattern : Prosite (Expaxy)BTB (PS50097)    ZINC_FINGER_C2H2_1 (PS00028)    ZINC_FINGER_C2H2_2 (PS50157)   
Domains : Interpro (EBI)BTB/POZ_dom    SKP1/BTB/POZ    Znf_C2H2    Znf_C2H2-like    Znf_C2H2/integrase_DNA-bd   
Domain families : Pfam (Sanger)BTB (PF00651)   
Domain families : Pfam (NCBI)pfam00651   
Domain families : Smart (EMBL)BTB (SM00225)  ZnF_C2H2 (SM00355)  
Conserved Domain (NCBI)ZBTB33
DMDM Disease mutations10009
Blocks (Seattle)ZBTB33
PDB (SRS)2LT7    3FKC    3M4T    3M8V    4F6M    4F6N   
PDB (PDBSum)2LT7    3FKC    3M4T    3M8V    4F6M    4F6N   
PDB (IMB)2LT7    3FKC    3M4T    3M8V    4F6M    4F6N   
PDB (RSDB)2LT7    3FKC    3M4T    3M8V    4F6M    4F6N   
Structural Biology KnowledgeBase2LT7    3FKC    3M4T    3M8V    4F6M    4F6N   
SCOP (Structural Classification of Proteins)2LT7    3FKC    3M4T    3M8V    4F6M    4F6N   
CATH (Classification of proteins structures)2LT7    3FKC    3M4T    3M8V    4F6M    4F6N   
SuperfamilyQ86T24
Human Protein AtlasENSG00000177485
Peptide AtlasQ86T24
HPRD02269
IPIIPI00465140   
Protein Interaction databases
DIP (DOE-UCLA)Q86T24
IntAct (EBI)Q86T24
FunCoupENSG00000177485
BioGRIDZBTB33
STRING (EMBL)ZBTB33
ZODIACZBTB33
Ontologies - Pathways
QuickGOQ86T24
Ontology : AmiGOprotein binding  nucleus  nucleoplasm  nucleolus  cytosol  plasma membrane  transcription, DNA-templated  methyl-CpG binding  Wnt signaling pathway  intracellular signal transduction  sequence-specific DNA binding  negative regulation of transcription, DNA-templated  negative regulation of transcription, DNA-templated  metal ion binding  
Ontology : EGO-EBIprotein binding  nucleus  nucleoplasm  nucleolus  cytosol  plasma membrane  transcription, DNA-templated  methyl-CpG binding  Wnt signaling pathway  intracellular signal transduction  sequence-specific DNA binding  negative regulation of transcription, DNA-templated  negative regulation of transcription, DNA-templated  metal ion binding  
NDEx NetworkZBTB33
Atlas of Cancer Signalling NetworkZBTB33
Wikipedia pathwaysZBTB33
Orthology - Evolution
OrthoDB10009
GeneTree (enSembl)ENSG00000177485
Phylogenetic Trees/Animal Genes : TreeFamZBTB33
HOVERGENQ86T24
HOGENOMQ86T24
Homologs : HomoloGeneZBTB33
Homology/Alignments : Family Browser (UCSC)ZBTB33
Gene fusions - Rearrangements
Fusion : MitelmanYWHAZ/ZBTB33 [8q22.3/Xq24]  [t(X;8)(q24;q22)]  
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerZBTB33 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)ZBTB33
dbVarZBTB33
ClinVarZBTB33
1000_GenomesZBTB33 
Exome Variant ServerZBTB33
ExAC (Exome Aggregation Consortium)ZBTB33 (select the gene name)
Genetic variants : HAPMAP10009
Genomic Variants (DGV)ZBTB33 [DGVbeta]
DECIPHERZBTB33 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisZBTB33 
Mutations
ICGC Data PortalZBTB33 
TCGA Data PortalZBTB33 
Broad Tumor PortalZBTB33
OASIS PortalZBTB33 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICZBTB33  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDZBTB33
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)X-chromosome gene database
BioMutasearch ZBTB33
DgiDB (Drug Gene Interaction Database)ZBTB33
DoCM (Curated mutations)ZBTB33 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)ZBTB33 (select a term)
intoGenZBTB33
NCG5 (London)ZBTB33
Cancer3DZBTB33(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM300329   
Orphanet
MedgenZBTB33
Genetic Testing Registry ZBTB33
NextProtQ86T24 [Medical]
TSGene10009
GENETestsZBTB33
Target ValidationZBTB33
Huge Navigator ZBTB33 [HugePedia]
snp3D : Map Gene to Disease10009
BioCentury BCIQZBTB33
ClinGenZBTB33
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD10009
Chemical/Pharm GKB GenePA134928604
Clinical trialZBTB33
Miscellaneous
canSAR (ICR)ZBTB33 (select the gene name)
Probes
Litterature
PubMed63 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineZBTB33
EVEXZBTB33
GoPubMedZBTB33
iHOPZBTB33
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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