ZBTB33

Summary

ZBTB33 (zinc finger and BTB domain containing 33, HGNC:16682) is a protein-coding gene on chromosome Xq24, encoding Transcriptional regulator Kaiso (Q86T24). Transcriptional regulator with bimodal DNA-binding specificity.

This gene encodes a transcriptional regulator with bimodal DNA-binding specificity, which binds to methylated CGCG and also to the non-methylated consensus KAISO-binding site TCCTGCNA. The protein contains an N-terminal POZ/BTB domain and 3 C-terminal zinc finger motifs. It recruits the N-CoR repressor complex to promote histone deacetylation and the formation of repressive chromatin structures in target gene promoters. It may contribute to the repression of target genes of the Wnt signaling pathway, and may also activate transcription of a subset of target genes by the recruitment of catenin delta-2 (CTNND2). Its interaction with catenin delta-1 (CTNND1) inhibits binding to both methylated and non-methylated DNA. It also interacts directly with the nuclear import receptor Importin-α2 (also known as karyopherin alpha2 or RAG cohort 1), which may mediate nuclear import of this protein. Alternatively spliced transcript variants encoding the same protein have been identified.

Source: NCBI Gene 10009 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total
• Druggable target: yes
• Transcription factor: yes — 11 downstream targets (CollecTRI)
• MANE Select transcript: NM_001184742

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16682
Approved symbol	ZBTB33
Name	zinc finger and BTB domain containing 33
Location	Xq24
Locus type	gene with protein product
Status	Approved
Aliases	ZNF-kaiso, kaiso, WUGSC:H_DJ525N14.1, KAISO, ZNF348
Ensembl gene	ENSG00000177485
Ensembl biotype	protein_coding
OMIM	300329
Entrez	10009

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000326624, ENST00000557385, ENST00000861559, ENST00000924911

RefSeq mRNA: 2 — MANE Select: NM_001184742 NM_001184742, NM_006777

CCDS: CCDS14596

Canonical transcript exons

ENST00000557385 — 3 exons

Exon	Start	End
ENSE00002509495	120253414	120258398
ENSE00002592551	120252669	120252770
ENSE00002615800	120250812	120250977

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 98.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.9458 / max 151.9586, expressed in 1793 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197419	14.0233	1783
197418	0.7384	451
197421	0.6669	363
197420	0.5172	309

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.30	gold quality
upper leg skin	UBERON:0004262	96.31	gold quality
endothelial cell	CL:0000115	96.01	gold quality
skin of hip	UBERON:0001554	95.73	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.47	gold quality
gingival epithelium	UBERON:0001949	95.34	gold quality
gingiva	UBERON:0001828	95.15	gold quality
esophagus squamous epithelium	UBERON:0006920	94.37	gold quality
epithelium of nasopharynx	UBERON:0001951	93.87	gold quality
oocyte	CL:0000023	93.49	gold quality
corpus epididymis	UBERON:0004359	93.39	gold quality
bronchial epithelial cell	CL:0002328	93.36	gold quality
middle temporal gyrus	UBERON:0002771	92.87	gold quality
trabecular bone tissue	UBERON:0002483	92.74	gold quality
palpebral conjunctiva	UBERON:0001812	92.69	gold quality
germinal epithelium of ovary	UBERON:0001304	91.96	gold quality
ganglionic eminence	UBERON:0004023	91.94	gold quality
mammary duct	UBERON:0001765	91.93	gold quality
mammalian vulva	UBERON:0000997	91.69	gold quality
parotid gland	UBERON:0001831	91.34	gold quality
visceral pleura	UBERON:0002401	91.16	gold quality
caput epididymis	UBERON:0004358	90.89	gold quality
parietal pleura	UBERON:0002400	90.60	gold quality
tibia	UBERON:0000979	90.32	gold quality
penis	UBERON:0000989	90.21	gold quality
ventricular zone	UBERON:0003053	90.21	gold quality
entorhinal cortex	UBERON:0002728	89.99	gold quality
oral cavity	UBERON:0000167	89.84	gold quality
amniotic fluid	UBERON:0000173	89.14	gold quality
nipple	UBERON:0002030	89.13	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.81

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

11 targets.

Target	Regulation
CBFA2T3
CCND1	Unknown
CDH1
CDKN1B
CDKN2A
CTNND1
EGF
MMP1
MMP7	Unknown
MUC1
RB1

JASPAR motifs

Motif	Name	Family
MA0527.1	ZBTB33	Other factors with up to three adjacent zinc fingers
MA0527.2	ZBTB33	Other factors with up to three adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:23693142

miRNA regulators (miRDB)

151 targeting ZBTB33, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-570-3P	99.96	72.41	4910
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-539-5P	99.93	70.30	2855

Literature-anchored findings (GeneRIF, showing 40)

• differential expression of p120(ctn) and Kaiso mRNA was observed in human coronary artery endothelial cells depending on how laminar shear stress was applied in relation to the wounding process (PMID:14699141)
• Kaiso translocates to the nucleus to regulate transcription of genes with diverse roles in cell growth and development (PMID:15564377)
• Data imply an unexpected influence of the microenvironment on Kaiso expression and localizationin colorectal adenocarcinoma. (PMID:15781635)
• Kaiso associates with the matrilysin promoter in vivo. (PMID:15817151)
• KAISO binds specifically to the methylated, but not the unmethylated, sequence in the first exon of the tyrosine hydroxylase [TH]gene and thus may play an important role in modulating human TH gene expresison. (PMID:15953356)
• the Kaiso-CTCF interaction negatively regulates CTCF insulator activity (PMID:16230345)
• Our study suggests that this gene is not implicated in the RTT molecular pathogenesis (PMID:16530985)
• p120 and Kaiso regulate Helicobacter pylori-induced expression of matrix metalloproteinase-7 (PMID:18653469)
• Kaiso represses methylated tumor suppressor genes and can bind in a methylation-dependent manner to the CDKN2A in human colon cancer cell lines. Kaiso depletion induced tumor suppressor gene expression without affecting DNA methylation levels. (PMID:18794111)
• Kaiso plays some specific role in centrosome assembly and function, which is not restricted to mitosis (PMID:19502788)
• Data suggest cytoplasmic Kaiso expression is associated with poor prognosis of NSCLC and various subcellular localizations of Kaiso may play differential biological roles in NSCLC. (PMID:19508730)
• Data strongly imply that Kaiso’s function as a transcriptional regulator might be linked to the control of the cell cycle and to cell proliferation in cancer. (PMID:20169156)
• In endothelial cells, p120ctn has a transcription repression function through regulation of Kaiso, possibly as a cofactor with the transcription factor. (PMID:20382170)
• Bifunctional role of domain zinc fingers of methyl-DNA-binding protein Kaiso (PMID:20586187)
• Increased delta-catenin expression is critical for maintenance of the malignant phenotype of lung cancer, making delta-catenin a candidate target protein for future cancer therapeutics. (PMID:21070476)
• when released from E-cadherin by Wnt3a-stimulated phosphorylation, p120-catenin controls the activity of Kaiso, enhancing its binding to repressed promoters and relieving its inhibition of the beta-catenin-Tcf-4 transcriptional complex. (PMID:21670201)
• Results suggest that p120ctn isoforms 1 and 3 up-regulate cyclin D1, and thereby cyclin E, resulting in the promotion of cell proliferation and cell cycle progression in lung cancer cells. (PMID:22276175)
• Data show that Kaiso requires all three zinc fingers plus adjacent protein regions for DNA recognition. (PMID:22300642)
• Selective activation of p120ctn-Kaiso signaling to unlock contact inhibition of ARPE-19 cells without epithelial-mesenchymal transition. (PMID:22590627)
• nuclear Kaiso is common in clinically aggressive ductal breast cancer, while cytoplasmic Kaiso and a p120-mediated relief of Kaiso-dependent transcriptional repression characterize invasive lobular carcinoma (ILC). (PMID:22662240)
• High cytoplasmic kaiso expression is associated with thymoma. (PMID:22833212)
• Molecular basis for recognition of methylated and specific DNA sequences by the zinc finger protein Kaiso (PMID:22949637)
• These findings establish a defined oncogenic role of Kaiso in promoting the progression of prostate cancer. (PMID:22974583)
• Kaiso represses the cell cycle gene cyclin D1 via sequence-specific and methyl-CpG-dependent mechanism. (PMID:23226276)
• presence of MTG16 in this complex, and its contributions to transcriptional repression both required Kaiso binding to its binding site on DNA, establishing MTG16-Kaiso binding as functionally relevant in Kaiso-dependent transcriptional repression (PMID:23251453)
• Transcription factor Kaiso does not interact with hydroxymethylated DNA within CTGCNA sequence context (PMID:23888785)
• The optimized knockdown with p120 and Kaiso siRNAs further expands the size of HCEC monolayers without endothelial mesenchymal transition (EMT) via selective activation of p120/Kaiso signaling that requires the RhoA-ROCK-noncanonical BMP-NFkB signaling. (PMID:24474278)
• Data indicate that Kaiso protein participates in the regulation of beta-catenin mRNA expression by interacting with p120-catenin in the lung cancer cell lines. (PMID:24498333)
• Nuclear localization of Kaiso promotes the poorly differentiated phenotype and EMT in infiltrating ductal carcinomas. (PMID:24570268)
• KAISO is a regulator of p53-mediated transcription of CDKN1A and apoptotic genes (PMID:25288747)
• NF-kappaB response element, located close to the p53RE#1, mediates APAF1 transcriptional repression by affecting interaction between KAISO and p53 (PMID:26183023)
• GR is a putative target gene of Kaiso. (PMID:26424557)
• Kaiso modulates HIF1A gene expression by binding to the methylated HIF1A promoter in a region proximal to the autoregulatory HIF-1 binding site, primarily during hypoxia. (PMID:26514431)
• Kaiso high expression correlated with invasion of prostate cancer. (PMID:26734997)
• Results show that Kaiso binding to unmethylated Kaiso binding site in the human ICR1 is necessary for ICR1 methylation maintenance and affects transcription rates of the lncRNA H19. (PMID:27152123)
• Suggest a role for Kaiso in the progression of pancreatic ductal adenocarcinomas, involving the epithelial mesenchymal transformation markers, E-cadherin and Zeb1. (PMID:27424525)
• extracellular microenvironment signals regulate RhoH and Kaiso to modulate actin-cytoskeleton structure and transcriptional activity during T cell migration (PMID:27574848)
• a novel mechanism by which ZBTB33 mediates the cyclin D1/cyclin E1/RB1/E2F pathway, controlling passage through the G1 restriction point and accelerating cancer cell proliferation. (PMID:27694442)
• A role for Kaiso in the proliferation. (PMID:28333150)
• Kaiso promotes Jagged-1 expression, which may have implications in Notch-mediated colon cancer progression (PMID:28637464)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	zbtb33	ENSDARG00000071467
mus_musculus	Zbtb33	ENSMUSG00000048047
rattus_norvegicus	Zbtb33	ENSRNOG00000028899

Paralogs (28): ZNF280C (ENSG00000056277), ZBTB25 (ENSG00000089775), PRDM13 (ENSG00000112238), BCL6 (ENSG00000113916), FEZF1 (ENSG00000128610), ZBTB46 (ENSG00000130584), PRDM12 (ENSG00000130711), ZNF280D (ENSG00000137871), NACC2 (ENSG00000148411), FEZF2 (ENSG00000153266), ZBTB7B (ENSG00000160685), NACC1 (ENSG00000160877), BCL6B (ENSG00000161940), GFI1 (ENSG00000162676), GFI1B (ENSG00000165702), ZBTB49 (ENSG00000168826), ZNF280A (ENSG00000169548), ZNF581 (ENSG00000171425), ZNF524 (ENSG00000171443), ZBTB26 (ENSG00000171448), ZBTB21 (ENSG00000173276), ZNF683 (ENSG00000176083), ZBTB3 (ENSG00000185670), ZBTB6 (ENSG00000186130), ZBTB14 (ENSG00000198081), ZBTB12 (ENSG00000204366), ZNF580 (ENSG00000213015), ZNF280B (ENSG00000275004)

Protein

Protein identifiers

Transcriptional regulator Kaiso — Q86T24 (reviewed: Q86T24)

Alternative names: Zinc finger and BTB domain-containing protein 33

All UniProt accessions (1): Q86T24

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional regulator with bimodal DNA-binding specificity. Binds to methylated CpG dinucleotides in the consensus sequence 5’-CGCG-3’ and also binds to the non-methylated consensus sequence 5’-CTGCNA-3’ also known as the consensus kaiso binding site (KBS). Recruits the N-CoR repressor complex to promote histone deacetylation and the formation of repressive chromatin structures in target gene promoters. May contribute to the repression of target genes of the Wnt signaling pathway. May also activate transcription of a subset of target genes by the recruitment of CTNND2. Represses expression of MMP7 in conjunction with transcriptional corepressors CBFA2T3, CBFA2T2 and RUNX1T1.

Subunit / interactions. Self-associates. Interacts with CTNND2. Interacts with CTNND1, and this interaction inhibits binding to both methylated and non-methylated DNA. Interacts with NCOR1. Interacts with KPNA2/RCH1, which may mediate nuclear import of this protein. Interacts with CBFA2T3.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed in vascular endothelium.

Induction. Induced in vascular endothelium by wounding. This effect is potentiated by prior laminar shear stress, which enhances wound closure.

RefSeq proteins (2): NP_001171671, NP_006768 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050457	ZnFinger_BTB_dom_contain	Family

Pfam: PF00651

UniProt features (62 total): cross-link 14, strand 12, helix 11, region of interest 7, sequence conflict 5, turn 4, zinc finger region 3, chain 1, domain 1, short sequence motif 1, compositionally biased region 1, modified residue 1, mutagenesis site 1

Structure

Experimental structures (PDB)

19 structures.

PDB	Method	Resolution (Å)
6DFB	X-RAY DIFFRACTION	1.66
3FKC	X-RAY DIFFRACTION	1.7
6DF5	X-RAY DIFFRACTION	1.82
6DFC	X-RAY DIFFRACTION	1.85
6DFA	X-RAY DIFFRACTION	1.91
5VMY	X-RAY DIFFRACTION	2
3M4T	X-RAY DIFFRACTION	2.05
5VMX	X-RAY DIFFRACTION	2.05
6V8U	X-RAY DIFFRACTION	2.1
5VMV	X-RAY DIFFRACTION	2.31
5VMZ	X-RAY DIFFRACTION	2.32
6DF9	X-RAY DIFFRACTION	2.32
5VMU	X-RAY DIFFRACTION	2.35
5VMW	X-RAY DIFFRACTION	2.4
4F6M	X-RAY DIFFRACTION	2.4
6DF8	X-RAY DIFFRACTION	2.54
3M8V	X-RAY DIFFRACTION	2.7
4F6N	X-RAY DIFFRACTION	2.8
2LT7	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86T24-F1	55.90	0.24

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (15): 251, 151, 153, 390, 407, 414, 449, 465, 474, 479, 539, 570, 582, 611, 618

Mutagenesis-validated functional residues (1):

Position	Phenotype
552	abrogates both sequence-specific and methylation-dependent dna-binding.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9764725	Negative Regulation of CDH1 Gene Transcription

MSigDB gene sets: 176 (showing top): MORF_BRCA1, BROWNE_HCMV_INFECTION_16HR_UP, TGACCTY_ERR1_Q2, TACAATC_MIR508, MODULE_308, CAGCTG_AP4_Q5, PUJANA_CHEK2_PCC_NETWORK, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, GOBP_CYTOKINE_PRODUCTION, PID_AJDISS_2PATHWAY, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, RYTTCCTG_ETS2_B, HAN_SATB1_TARGETS_DN, MORF_ATF2, ACEVEDO_LIVER_CANCER_UP

GO Biological Process (6): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of cytokine production (GO:0001817), regulation of immune system process (GO:0002682), Wnt signaling pathway (GO:0016055), intracellular signal transduction (GO:0035556), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (10): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), zinc ion binding (GO:0008270), methyl-CpG binding (GO:0008327), sequence-specific DNA binding (GO:0043565), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (7): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Regulation of CDH1 Gene Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
intracellular anatomical structure	2
sequence-specific DNA binding	2
nuclear lumen	2
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
cytokine production	1
regulation of gene expression	1
regulation of multicellular organismal process	1
immune system process	1
regulation of biological process	1
cell surface receptor signaling pathway	1
signal transduction	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
transition metal ion binding	1
nucleotide binding	1
DNA binding	1
double-stranded DNA binding	1
nucleic acid binding	1
binding	1
cation binding	1
chromosome	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1636 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZBTB33	CTNND1	O60716	998
ZBTB33	NCOR1	O75376	922
ZBTB33	CTNND2	Q9UQB3	922
ZBTB33	RAPSN	Q13702	814
ZBTB33	MBD4	O95243	745
ZBTB33	CTCF	P49711	701
ZBTB33	NCOR2	Q9Y618	692
ZBTB33	MECP2	P51608	653
ZBTB33	CTNNB1	P35222	627
ZBTB33	ZBTB4	Q9P1Z0	615
ZBTB33	UHRF2	Q96PU4	614
ZBTB33	PKP4	Q99569	589
ZBTB33	HDAC1	Q13547	584
ZBTB33	ZFP57	Q9NU63	582
ZBTB33	MGMT	P16455	579
ZBTB33	DACT1	Q9NYF0	579

IntAct

81 interactions, top by confidence:

A	B	Type	Score
ZBTB33	TRIML2	psi-mi:“MI:0915”(physical association)	0.800
TUBG1	TUBG1	psi-mi:“MI:2364”(proximity)	0.760
PFDN4	PFDN6	psi-mi:“MI:0914”(association)	0.730
FBXL17	BACH1	psi-mi:“MI:0914”(association)	0.730
KLHL22	TMEM223	psi-mi:“MI:0914”(association)	0.640
ENPP6	SCAMP1	psi-mi:“MI:0914”(association)	0.640
ZNF576	ZBED1	psi-mi:“MI:0914”(association)	0.640
CAMKK2	OBSL1	psi-mi:“MI:0914”(association)	0.640
CTNND1	ZBTB33	psi-mi:“MI:0915”(physical association)	0.560
ZBTB33	NUDT22	psi-mi:“MI:0915”(physical association)	0.560
SUMO2	ZBTB33	psi-mi:“MI:0915”(physical association)	0.560
GSDMD	ZBTB33	psi-mi:“MI:0915”(physical association)	0.560
GYS1	ZBTB33	psi-mi:“MI:0915”(physical association)	0.560
SUMO3	ZBTB33	psi-mi:“MI:0915”(physical association)	0.560
WWOX	DVL2	psi-mi:“MI:0914”(association)	0.560
FOXP3	FOXP2	psi-mi:“MI:0914”(association)	0.530
VWCE	ZNF316	psi-mi:“MI:0914”(association)	0.530
DEFA5	NUDT19	psi-mi:“MI:0914”(association)	0.530
XAGE1A	THAP12	psi-mi:“MI:0914”(association)	0.530
TRIML2	SRGAP2	psi-mi:“MI:0914”(association)	0.530
PIP	TBKBP1	psi-mi:“MI:0914”(association)	0.530

BioGRID (193): ZBTB33 (Affinity Capture-MS), ZBTB33 (Reconstituted Complex), ZBTB33 (Affinity Capture-MS), ZBTB33 (Affinity Capture-MS), ZBTB33 (Affinity Capture-MS), ZBTB33 (Affinity Capture-MS), ZBTB33 (Affinity Capture-MS), ZBTB33 (Affinity Capture-MS), ZBTB33 (Affinity Capture-MS), TP53 (Affinity Capture-Western), KAT5 (Affinity Capture-Western), EP300 (Affinity Capture-Western), ZBTB33 (Affinity Capture-Western), ZBTB33 (Affinity Capture-Western), TP53 (Co-localization)

ESM2 similar proteins: A0A1L8H0H2, A0JN51, A4QNP0, F8VPJ6, O13186, O46567, O57415, O70477, O94842, P09775, P15257, P22361, P28324, P32519, P36197, P37275, P50534, P55347, P59759, P79686, Q05041, Q07243, Q0P5K4, Q14872, Q15723, Q2HJ84, Q2KHR2, Q3UH06, Q5R6A9, Q5W1J6, Q60542, Q60775, Q61321, Q62947, Q64318, Q6DJL0, Q6IRR0, Q6XLJ0, Q86T24, Q8AYC1

Diamond homologs: A0JMG1, A0JN76, A1L2U9, A1YEX3, A1YPR0, B1WAZ8, B1WBS3, B1WBU4, B2RXF5, O14867, O15062, O15156, O35260, O43167, O43298, O43791, O43829, P0DMR5, P0DMR6, P10074, P24278, P97302, P97303, Q08376, Q0IH98, Q0IJ29, Q0VCJ6, Q0VCW1, Q13105, Q14526, Q1H9T6, Q1L8W0, Q2M2N2, Q3B725, Q3B7N9, Q3SWU4, Q3ZB90, Q562B4, Q5BL35, Q5EXX3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CTNND1	down-regulates	ZBTB33

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 94 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
protein sumoylation	5	18.8×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

336 predictions. Top by Δscore:

Variant	Effect	Δscore
X:120250974:GCAG:G	donor_gain	1.0000
X:120250975:CAGGT:C	donor_loss	1.0000
X:120250976:AGGTG:A	donor_loss	1.0000
X:120250977:GGT:G	donor_loss	1.0000
X:120250978:G:GG	donor_gain	1.0000
X:120250978:GTGA:G	donor_loss	1.0000
X:120250979:T:A	donor_loss	0.9900
X:120253409:TAAA:T	acceptor_loss	0.9900
X:120253411:AAGG:A	acceptor_loss	0.9900
X:120253412:A:AC	acceptor_loss	0.9900
X:120253412:A:AG	acceptor_gain	0.9900
X:120253413:G:GG	acceptor_gain	0.9900
X:120253413:GGC:G	acceptor_gain	0.9900
X:120253410:AAAG:A	acceptor_gain	0.9800
X:120253413:GGCAT:G	acceptor_gain	0.9800
X:120253410:A:AG	acceptor_gain	0.9700
X:120250898:G:T	donor_gain	0.9600
X:120253412:AG:A	acceptor_gain	0.9600
X:120253413:GG:G	acceptor_gain	0.9600
X:120253411:A:G	acceptor_gain	0.9500
X:120250971:G:T	donor_gain	0.9400
X:120253413:GGCA:G	acceptor_gain	0.9400
X:120250898:G:GT	donor_gain	0.9300
X:120250971:G:GT	donor_gain	0.9300
X:120253411:AAG:A	acceptor_gain	0.9300
X:120250973:AGCAG:A	donor_gain	0.9200
X:120250974:GCAGG:G	donor_gain	0.9200
X:120252663:T:G	acceptor_gain	0.9000
X:120253580:C:G	donor_gain	0.9000
X:120254840:TATGA:T	donor_gain	0.9000

AlphaMissense

4443 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:120254901:T:C	C496R	1.000
X:120254902:G:A	C496Y	1.000
X:120254903:T:G	C496W	1.000
X:120254910:T:A	C499S	1.000
X:120254910:T:C	C499R	1.000
X:120254911:G:A	C499Y	1.000
X:120254911:G:C	C499S	1.000
X:120254912:C:G	C499W	1.000
X:120254948:A:C	R511S	1.000
X:120254948:A:T	R511S	1.000
X:120254985:T:C	C524R	1.000
X:120254995:G:A	C527Y	1.000
X:120254996:T:G	C527W	1.000
X:120255006:T:C	F531L	1.000
X:120255007:T:C	F531S	1.000
X:120255008:T:A	F531L	1.000
X:120255008:T:G	F531L	1.000
X:120255025:G:C	R537P	1.000
X:120255069:T:C	C552R	1.000
X:120254911:G:T	C499F	0.999
X:120254928:T:C	C505R	0.999
X:120254930:T:G	C505W	0.999
X:120254937:A:C	S508R	0.999
X:120254939:C:A	S508R	0.999
X:120254939:C:G	S508R	0.999
X:120254941:T:C	L509S	0.999
X:120254947:G:C	R511T	0.999
X:120254947:G:T	R511I	0.999
X:120254949:C:G	H512D	0.999
X:120254951:T:A	H512Q	0.999

dbSNP variants (sampled 300 via entrez): RS1000278739 (X:120252114 C>T), RS1000415724 (X:120252665 A>G), RS1000725191 (X:120255428 T>G), RS1001363018 (X:120249860 C>T), RS1001416851 (X:120250525 G>A), RS1004621012 (X:120258677 T>C), RS1004993482 (X:120255574 T>C), RS1005313013 (X:120251113 T>G), RS1005588850 (X:120250629 G>A), RS1007628357 (X:120248957 C>A,T), RS1010503134 (X:120251649 G>A), RS1011474251 (X:120249724 C>A,G,T), RS1016958856 (X:120253239 A>G), RS1017357957 (X:120252908 C>T), RS1017929227 (X:120251114 T>C)

Disease associations

OMIM: gene MIM:300329 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5069376 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
Tetrachlorodibenzodioxin	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
deoxynivalenol	increases expression	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
coumarin	decreases phosphorylation	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
jinfukang	decreases expression	1
Arsenic Trioxide	decreases methylation	1
Acetaminophen	decreases expression	1
Ethanol	increases abundance, affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Gasoline	decreases expression, increases abundance, affects cotreatment	1
Polycyclic Aromatic Hydrocarbons	decreases expression, increases abundance, affects cotreatment	1
Silver	decreases expression	1
Urethane	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Particulate Matter	affects cotreatment, decreases expression, increases abundance	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5059509	Binding	Proteomics fold change data (SUDHL4 cells, 1h)	Data for DCP probe CCT369260

Cellosaurus cell lines

7 cell lines: 3 embryonic stem cell, 3 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A8A2	SEES3-1V human ZBTB33, clone1	Embryonic stem cell	Male
CVCL_A8A3	SEES3-1V human ZBTB33, clone2	Embryonic stem cell	Male
CVCL_A8A4	SEES3-1V human ZBTB33, clone3	Embryonic stem cell	Male
CVCL_D7FZ	Ubigene 22Rv1 ZBTB33 KO	Cancer cell line	Male
CVCL_TY54	HAP1 ZBTB33 (-) 1	Cancer cell line	Male
CVCL_TY55	HAP1 ZBTB33 (-) 2	Cancer cell line	Male
CVCL_XV91	HEK293 eGFP-ZBTB33	Transformed cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.