Details for: ZBTB2

Gene ID: 57621

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: ZBTB2

Ensembl ID: ENSG00000181472

Description: zinc finger and BTB domain containing 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

  • Dna-binding transcription repressor activity, rna polymerase ii-specific
    (GO:0001227)
  • Identical protein binding
    (GO:0042802)
  • Metal ion binding
    (GO:0046872)
  • Negative regulation of transcription by rna polymerase ii
    (GO:0000122)
  • Nucleoplasm
    (GO:0005654)
  • Protein binding
    (GO:0005515)
  • Regulation of cytokine production
    (GO:0001817)
  • Regulation of immune system process
    (GO:0002682)
  • Rna polymerase ii cis-regulatory region sequence-specific dna binding
    (GO:0000978)
  • Sequence-specific double-stranded dna binding
    (GO:1990837)

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • group 3 innate lymphoid cell CL0001071
    CSI 3.38
    rCSI 2.54%
    PRS 95.3
  • neural crest cell CL0011012
    CSI 3.13
    rCSI 2.47%
    PRS 87.76
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 3.05
    rCSI 2.06%
    PRS 98.64
  • early lymphoid progenitor CL0000936
    CSI 2.97
    rCSI 2.61%
    PRS 95.67
  • keratinocyte CL0000312
    CSI 2.7
    rCSI 2.26%
    PRS 92.91
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 2.61
    rCSI 2.66%
    PRS 96.7
  • endothelial cell of lymphatic vessel CL0002138
    CSI 2.17
    rCSI 4.3%
    PRS 93.7
  • extravillous trophoblast CL0008036
    CSI 2.1
    rCSI 2.59%
    PRS 91.88
  • CD14-positive monocyte CL0001054
    CSI 2.09
    rCSI 2.61%
    PRS 97.23
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.09
    rCSI 1.61%
    PRS 95.67
  • activated CD8-positive, alpha-beta T cell, human CL0001049
    CSI 1.79
    rCSI 3.06%
    PRS 97.2
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.72
    rCSI 2.09%
    PRS 75.61
  • CD8-positive, CD28-negative, alpha-beta regulatory T cell CL0000920
    CSI 1.64
    rCSI 3.26%
    PRS 97.42
  • innate lymphoid cell CL0001065
    CSI 1.49
    rCSI 3.08%
    PRS 87.7
  • helper T cell CL0000912
    CSI 1.43
    rCSI 2.02%
    PRS 88.96

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [ZBTB2](/details-gene/57621), or Zinc Finger and BTB Domain Containing 2, is a protein-coding gene located on chromosome 6q25.1. The encoded protein is a transcription factor characterized by its zinc finger and BTB (Broad-Complex, Tramtrack and Bric-a-brac) domains. Functionally, it is annotated as a DNA-binding transcription repressor, playing roles in the negative regulation of transcription and the modulation of immune system processes ([GO:0002682](https://www.ebi.ac.uk/QuickGO/term/GO:0002682)). **Overall**, expression data reveals its significance in a diverse set of cell types, with a particular prominence in lymphoid lineages, including [group 3 innate lymphoid cell](/details-cell/CL0001071) and various T cell subsets, as well as in developmental cell types like [neural crest cell](/details-cell/CL0011012), suggesting a key role in both hematopoiesis and broader developmental programs. ## Cellular Roles and Expression Landscape The expression profile of [ZBTB2](/details-gene/57621) indicates a significant role across multiple, distinct cellular contexts. **Overall**, its highest significance is observed in immune cells, particularly those of the lymphoid lineage. It is a key marker for [group 3 innate lymphoid cell](/details-cell/CL0001071) (CSI: 3.38), [central memory CD8-positive, alpha-beta T cell](/details-cell/CL0000907) (CSI: 3.05), and developing lymphocytes such as [early lymphoid progenitor](/details-cell/CL0000936) (CSI: 2.97) and [double-positive, alpha-beta thymocyte](/details-cell/CL0000809) (CSI: 2.61). This pattern suggests a fundamental function in lymphoid cell development, lineage maintenance, and the establishment of immunological memory. Beyond the lymphoid compartment, [ZBTB2](/details-gene/57621) is also highly significant in myeloid cells, including [CD14-positive monocyte](/details-cell/CL0001054) (CSI: 2.09) and [CD14-low, CD16-positive monocyte](/details-cell/CL0002396) (CSI: 2.09), indicating its involvement may extend to innate immune functions. Interestingly, [ZBTB2](/details-gene/57621) also shows high significance in several non-hematopoietic cell types. Its prominence in [neural crest cell](/details-cell/CL0011012) (CSI: 3.13) and [keratinocyte](/details-cell/CL0000312) (CSI: 2.70) points towards a broader role in embryonic development and epithelial biology, potentially regulating differentiation or proliferation programs in these tissues. The gene's initial characterization was part of large-scale cDNA sequencing projects ([Link](https://doi.org/10.1038/ng1285), [Link](https://doi.org/10.1093/dnares/7.2.143)). ## Pathways and Molecular Function [ZBTB2](/details-gene/57621) is a nuclear protein ([GO:0005654](https://www.ebi.ac.uk/QuickGO/term/GO:0005654)) that functions primarily as a sequence-specific, DNA-binding transcriptional repressor ([GO:0001227](https://www.ebi.ac.uk/QuickGO/term/GO:0001227), [GO:1990837](https://www.ebi.ac.uk/QuickGO/term/GO:1990837)). This core molecular function underpins its involvement in the [negative regulation of transcription by rna polymerase ii](/details-go/GO0000122) ([GO:0000122](https://www.ebi.ac.uk/QuickGO/term/GO:0000122)). This repressor activity is consistent with its annotated roles in biological processes such as the [regulation of immune system process](/details-go/GO0002682) ([GO:0002682](https://www.ebi.ac.uk/QuickGO/term/GO:0002682)) and the [regulation of cytokine production](/details-go/GO0001817) ([GO:0001817](https://www.ebi.ac.uk/QuickGO/term/GO:0001817)). The high significance of [ZBTB2](/details-gene/57621) in various lymphoid cells suggests it may act to suppress specific gene expression programs, thereby controlling cellular differentiation, activation, or lineage commitment. The protein is also known to engage in [protein binding](/details-go/GO0005515) ([GO:0005515](https://www.ebi.ac.uk/QuickGO/term/GO:0005515)) and can be a substrate for post-translational modifications like SUMOylation, which may regulate its activity in response to cellular stress ([Link](https://doi.org/10.1016/j.celrep.2015.02.033), [Link](https://doi.org/10.1038/nsmb.3366)). ## Research Directions The expression profile and functional annotation of [ZBTB2](/details-gene/57621) provide a foundation for several testable hypotheses regarding its role in immunity and development. **Proposed Hypotheses:** 1. Given its high significance in [early lymphoid progenitor](/details-cell/CL0000936) and [group 3 innate lymphoid cell](/details-cell/CL0001071), [ZBTB2](/details-gene/57621) may act as a key lineage-determining factor that represses genes associated with alternative lymphoid fates (e.g., ILC1, ILC2) to promote commitment to the ILC3 lineage. 2. The high significance of [ZBTB2](/details-gene/57621) in [central memory CD8-positive, alpha-beta T cell](/details-cell/CL0000907) suggests that it may function to maintain T cell memory by repressing genes involved in terminal differentiation and effector function, thereby preserving a quiescent, long-lived state. 3. Its notable expression in [neural crest cell](/details-cell/CL0011012) suggests [ZBTB2](/details-gene/57621) may regulate the epithelial-to-mesenchymal transition (EMT) or cell migration during embryonic development by repressing key adhesion or signaling molecules. **Experimental Approach:** To test the first hypothesis regarding its role in ILC3 lineage commitment, one could employ a loss-of-function study. Specifically, CRISPR-Cas9 could be used to knock out [ZBTB2](/details-gene/57621) in primary human hematopoietic stem and progenitor cells (HSPCs). These modified HSPCs would then be cultured *in vitro* under conditions that promote ILC differentiation. The resulting cell populations could be analyzed by single-cell RNA sequencing (scRNA-seq) and flow cytometry to determine if the loss of [ZBTB2](/details-gene/57621) skews differentiation away from the ILC3 fate and towards other ILC or lymphoid lineages, and to identify the specific gene networks it regulates. **Therapeutic Potential:** As an intracellular transcription factor, [ZBTB2](/details-gene/57621) is not a suitable target for conventional antibody-based therapies. However, its role as a transcriptional repressor in key immune cell subsets suggests it could be a target for small molecule inhibitors. If its activity contributes to immune evasion or the maintenance of malignant cells in certain leukemias or lymphomas, developing drugs that disrupt its DNA-binding activity or its interaction with co-repressor complexes could represent a viable therapeutic strategy. Such an approach would require a deep understanding of its specific downstream targets and its precise role in the pathology of interest.

Genular Protein ID: 4061933406

Symbol: ZBTB2_HUMAN

Name: Zinc finger and BTB domain-containing protein 2

UniProtKB Accession Codes:

Q8N680 A8K7C7 Q5SZ81 Q9P245

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEMBL 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 1 GO 9 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 3 SMART 2 STRING 1 SUPFAM 2 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 10819331

Title: Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.

PubMed ID: 10819331

DOI: 10.1093/dnares/7.2.143

PubMed ID: 17525332

Title: ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.

PubMed ID: 17525332

DOI: 10.1126/science.1140321

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 25218447

Title: Uncovering global SUMOylation signaling networks in a site-specific manner.

PubMed ID: 25218447

DOI: 10.1038/nsmb.2890

PubMed ID: 25772364

Title: SUMO-2 orchestrates chromatin modifiers in response to DNA damage.

PubMed ID: 25772364

DOI: 10.1016/j.celrep.2015.02.033

PubMed ID: 25755297

Title: System-wide analysis of SUMOylation dynamics in response to replication stress reveals novel small ubiquitin-like modified target proteins and acceptor lysines relevant for genome stability.

PubMed ID: 25755297

DOI: 10.1074/mcp.o114.044792

PubMed ID: 28112733

Title: Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.

PubMed ID: 28112733

DOI: 10.1038/nsmb.3366

Sequence Information:

  • Length: 514
  • Mass: 57337
  • Checksum: 2087A104CCA3DD85
  • Sequence:
    • MDLANHGLIL LQQLNAQREF GFLCDCTVAI GDVYFKAHKS VLASFSNYFK MLFVHQTSEC 
VRLKPTDIQP DIFSYLLHLM YTGKMAPQLI DPVRLEQGIK FLHAYPLIQE ASLASQGAFS 
HPDQVFPLAS SLYGIQIADH QLRQATKIAS APEKLGRDPR PQTSRISQEQ VPEASQLSQL 
TSNLAQVNRT NMTPSDPLQT SLSPELVSTP VPPPPPGEET NLEASSSDEQ PASLTIAHVK 
PSIMKRNGSF PKYYACHLCG RRFTLRSSLR EHLQIHTGVP FTSSQQGESR VPLTLCSNAA 
DLGKDAMEVP EAGMISDSEL QHISDSPIID GQQQSETPPP SDIADIDNLE QADQEREVKR 
RKYECTICGR KFIQKSHWRE HMYIHTGKPF KCSTCDKSFC RANQAARHVC LNQSIDTYTM 
VDKQTLELCT FEEGSQMDNM LVQTNKPYKC NLCDKTFSTP NEVVKHSCQN QNSDVFALDE 
GRSILLGSGD SEVTEPDHPV LASIKKEQET VLLD