Details for: ZNF333

Gene ID: 84449

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: ZNF333

Ensembl ID: ENSG00000160961

Description: zinc finger protein 333

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 4.72
    rCSI 4.27%
    PRS 93.07
  • melanocyte CL0000148
    CSI 4.29
    rCSI 3.17%
    PRS 91.74
  • common myeloid progenitor CL0000049
    CSI 3.88
    rCSI 3.13%
    PRS 94.82
  • hepatic stellate cell CL0000632
    CSI 3.55
    rCSI 13.3%
    PRS 91.25
  • astrocyte of the cerebral cortex CL0002605
    CSI 3.54
    rCSI 7.95%
    PRS 84.9
  • Kupffer cell CL0000091
    CSI 3.22
    rCSI 7.37%
    PRS 94.9
  • interneuron CL0000099
    CSI 3.14
    rCSI 6.31%
    PRS 89.72
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.77
    rCSI 2.13%
    PRS 96.3
  • plasma cell CL0000786
    CSI 2.74
    rCSI 3.59%
    PRS 96.31
  • cerebellar granule cell CL0001031
    CSI 2.47
    rCSI 3.63%
    PRS 90.17
  • retinal bipolar neuron CL0000748
    CSI 2.38
    rCSI 4.46%
    PRS 87.86
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.33
    rCSI 2.9%
    PRS 82.59
  • Mueller cell CL0000636
    CSI 2.32
    rCSI 5.3%
    PRS 89.08
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.23
    rCSI 2.87%
    PRS 85.63
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 2.11
    rCSI 3.84%
    PRS 89.3
  • basal cell of epidermis CL0002187
    CSI 1.86
    rCSI 3.31%
    PRS 68.94
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.61
    rCSI 2.85%
    PRS 84.12
  • amacrine cell CL0000561
    CSI 1.43
    rCSI 4.14%
    PRS 87.63
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.41
    rCSI 1.7%
    PRS 76.86
  • cardiac neuron CL0010022
    CSI 1.33
    rCSI 4.24%
    PRS 93.11
  • glial cell CL0000125
    CSI 1.3
    rCSI 4.94%
    PRS 88.8
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.18
    rCSI 1.99%
    PRS 84.76
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.03
    rCSI 2.51%
    PRS 82.67
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.86
    rCSI 2.69%
    PRS 85.69
  • blood vessel smooth muscle cell CL0019018
    CSI 0.82
    rCSI 6.69%
    PRS 92.81
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.61
    rCSI 2.21%
    PRS 82.96
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.53
    rCSI 3.09%
    PRS 85.07

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)

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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 [ZNF333](/details-gene/84449) is a protein-coding gene located on chromosome 19p13.1 that encodes Zinc Finger Protein 333, a member of the Krüppel C2H2-type zinc-finger protein family [Link](https://doi.org/10.1016/s0167-4781(02)00397-4). Functional annotations classify [ZNF333](/details-gene/84449) as a nuclear DNA-binding transcription factor involved in the regulation of transcription by RNA polymerase II. Expression data indicates its significance across diverse and distinct cell lineages. **Overall**, it shows high significance in hematopoietic precursors, including [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) and [common myeloid progenitor](/details-cell/CL0000049), as well as in a wide array of cell types in the central nervous system, such as [astrocyte of the cerebral cortex](/details-cell/CL0002605) and [interneuron](/details-cell/CL0000099). This pattern suggests a fundamental role in regulating specific gene expression programs essential for the development or function of multiple, unrelated tissues. ## Cellular Roles and Expression Landscape The expression profile of [ZNF333](/details-gene/84449) highlights its importance in several key biological systems, rather than being restricted to a single tissue or lineage. * **Hematopoiesis:** The gene demonstrates a prominent role in early blood cell development, evidenced by its top-ranking significance score (CSI: 4.72) in [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) and high score in [common myeloid progenitor](/details-cell/CL0000049) (CSI: 3.88). Its activity is also noted in more differentiated immune cells like [CD14-low, CD16-positive monocyte](/details-cell/CL0002396) and terminally differentiated [plasma cell](/details-cell/CL0000786), suggesting a sustained role throughout myeloid and lymphoid development. * **Nervous System:** [ZNF333](/details-gene/84449) appears to be a significant transcriptional regulator within the central nervous system. It is highly expressed in both glial and neuronal populations, including [astrocyte of the cerebral cortex](/details-cell/CL0002605), various types of interneurons ([interneuron](/details-cell/CL0000099), [pvalb GABAergic cortical interneuron](/details-cell/CL4023018), [sst GABAergic cortical interneuron](/details-cell/CL4023017)), [cerebellar granule cell](/details-cell/CL0001031), and glial precursors like [differentiation-committed oligodendrocyte precursor](/details-cell/CL4023059). This broad yet specific expression pattern points towards a pleiotropic function in neural network maintenance, glial function, or neuronal differentiation. * **Specialized Cell Types:** Beyond these systems, [ZNF333](/details-gene/84449) is a significant marker in other specialized cells such as [melanocyte](/details-cell/CL0000148) (CSI: 4.29) and liver-resident cells like the [hepatic stellate cell](/details-cell/CL0000632) and [Kupffer cell](/details-cell/CL0000091). This suggests its function is adapted to control cell-specific transcriptional programs in a variety of contexts. ## Pathways and Molecular Function [ZNF333](/details-gene/84449) is a nuclear protein ([GO:0005634](https://www.ebi.ac.uk/QuickGO/term/GO:0005634)) whose primary molecular function is DNA-binding transcription factor activity specific to RNA polymerase II ([GO:0000981](https://www.ebi.ac.uk/QuickGO/term/GO:0000981)). Its structure, which includes zinc finger domains, facilitates sequence-specific binding to cis-regulatory regions of DNA ([GO:0000978](https://www.ebi.ac.uk/QuickGO/term/GO:0000978)), thereby controlling gene expression. This role is reflected in its involvement in fundamental biological processes such as the [Regulation of transcription by rna polymerase ii](https://www.ebi.ac.uk/QuickGO/term/GO:0006357). Consistent with these GO annotations, [ZNF333](/details-gene/84449) is a component of core transcriptional pathways cataloged by Reactome, including [Gene expression (transcription)](https://reactome.org/content/detail/R-HSA-74160) and [Rna polymerase ii transcription](https://reactome.org/content/detail/R-HSA-73857). The presence of a double KRAB (Krüppel-associated box) domain, a known transcriptional repression motif, suggests that [ZNF333](/details-gene/84449) likely functions as a transcriptional repressor [Link](https://doi.org/10.1016/s0167-4781(02)00397-4). This repressive activity is likely deployed in different cellular contexts to fine-tune gene expression programs critical for the identity and function of the diverse cell types in which it is expressed. ## Research Directions The widespread yet specific expression pattern of [ZNF333](/details-gene/84449) across hematopoietic and neural lineages provides a foundation for several compelling research avenues. **Proposed Hypotheses:** 1. Given its high significance in [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) and [common myeloid progenitor](/details-cell/CL0000049), [ZNF333](/details-gene/84449) may function as a key transcriptional repressor that enforces lineage fidelity during early hematopoiesis by silencing genes associated with alternative fates (e.g., lymphoid development). 2. In the central nervous system, the high expression of [ZNF333](/details-gene/84449) across mature neurons and glial cells suggests it may be involved in maintaining the terminally differentiated state by repressing developmental genes or genes associated with cellular plasticity and stress responses. **Experimental Approach:** To test the role of [ZNF333](/details-gene/84449) in hematopoietic lineage commitment (Hypothesis 1), a conditional knockout mouse model could be generated using a Cre-lox system with a hematopoietic stem cell-specific Cre driver (e.g., Vav1-iCre). Bone marrow progenitors from these mice could be isolated and their differentiation potential assessed using *in vitro* colony-forming unit (CFU) assays for erythroid, myeloid, and lymphoid lineages. Subsequent single-cell RNA sequencing (scRNA-seq) of the progenitor populations would reveal shifts in cell fate trajectories and identify derepressed target genes that may explain any observed lineage bias. **Therapeutic Potential:** As a transcription factor, [ZNF333](/details-gene/84449) is a challenging direct therapeutic target. However, if its dysregulation is linked to disease, such as leukemia or neurodevelopmental disorders, indirect strategies could be considered. For example, if its aberrant repressive activity drives a malignant phenotype, small molecules designed to disrupt its interaction with transcriptional corepressors could be developed. Conversely, if loss of function is pathogenic, identifying its critical downstream targets might reveal more druggable nodes in the affected pathways. Its potential as a target is entirely dependent on its future validation in a specific disease context.

Genular Protein ID: 1651315366

Symbol: ZN333_HUMAN

Name: Zinc finger protein 333

UniProtKB Accession Codes:

Q96JL9 Q6P2E6 Q86WS6 Q8TDL0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 2 ExpressionAtlas 1 GO 5 Gene3D 2 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 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 1 RefSeq 4 SMART 3 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12151103

Title: Characterization of ZNF333, a novel double KRAB domain containing zinc finger gene on human chromosome 19p13.1.

PubMed ID: 12151103

DOI: 10.1016/s0167-4781(02)00397-4

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

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: 11347906

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

PubMed ID: 11347906

DOI: 10.1093/dnares/8.2.85

Sequence Information:

  • Length: 665
  • Mass: 75544
  • Checksum: EE5ABF8468D8DD24
  • Sequence:
    • MESVTFEDVA VEFIQEWALL DSARRSLCKY RMLDQCRTLA SRGTPPCKPS CVSQLGQRAE 
PKATERGILR ATGVAWESQL KPEELPSMQD LLEEASSRDM QMGPGLFLRM QLVPSIEERE 
TPLTREDRPA LQEPPWSLGC TGLKAAMQIQ RVVIPVPTLG HRNPWVARDS AVPARDPAWL 
QEDKVEEEAM APGLPTACSQ EPVTFADVAV VFTPEEWVFL DSTQRSLYRD VMLENYRNLA 
SVADQLCKPN ALSYLEERGE QWTTDRGVLS DTCAEPQCQP QEAIPSQDTF TEILSIDVKG 
EQPQPGEKLY KYNELEKPFN SIEPLFQYQR IHAGEASCEC QEIRNSFFQS AHLIVPEKIR 
SGDKSYACNK CEKSFRYSSD LIRHEKTHTA EKCFDCQECG QAFKYSSNLR RHMRTHTGEK 
PFECSQCGKT FTRNFNLILH QRNHTGEKPY ECKDCGKAFN QPSSLRSHVR THTGEKPFEC 
SQCGKAFREH SSLKTHLRTH TREKPYECNQ CGKPFRTSTH LNVHKRIHTG EKLYECATCG 
QVLSRLSTLK SHMRTHTGEK PYVCQECGRA FSEPSSLRKH ARTHSGKKPY ACQECGRAFG 
QSSHLIVHVR THSAGRPYQC NQCEKAFRHS SSLTVHKRTH VGRETIRNGS LPLSMSHPYC 
GPLAN