Details for: POU3F2

Gene ID: 5454

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: POU3F2

Ensembl ID: ENSG00000184486

Description: POU class 3 homeobox 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • progenitor cell CL0011026
    CSI 18.53
    rCSI 39.41%
    PRS 86.96
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 7.63
    rCSI 8.81%
    PRS 86
  • forebrain radial glial cell CL0013000
    CSI 6.79
    rCSI 21.77%
    PRS 92.53
  • glioblast CL0000030
    CSI 5.94
    rCSI 9.48%
    PRS 86.26
  • ependymal cell CL0000065
    CSI 5.66
    rCSI 11.49%
    PRS 77.24
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 5.38
    rCSI 15.88%
    PRS 92.36
  • Bergmann glial cell CL0000644
    CSI 5.15
    rCSI 7.05%
    PRS 86.47
  • radial glial cell CL0000681
    CSI 4.88
    rCSI 6.78%
    PRS 91.13
  • glutamatergic neuron CL0000679
    CSI 4.87
    rCSI 10.01%
    PRS 82.6
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 4.68
    rCSI 6%
    PRS 89.5
  • interneuron CL0000099
    CSI 4.01
    rCSI 8.05%
    PRS 87.73
  • inhibitory interneuron CL0000498
    CSI 3.08
    rCSI 7.11%
    PRS 85.21
  • epithelial cell CL0000066
    CSI 3.04
    rCSI 4.67%
    PRS 81.69
  • midbrain dopaminergic neuron CL2000097
    CSI 2.57
    rCSI 16.45%
    PRS 87.16
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.79
    rCSI 4.01%
    PRS 82.23
  • neural progenitor cell CL0011020
    CSI 1.73
    rCSI 7.6%
    PRS 83.25
  • macroglial cell CL0000126
    CSI 1.68
    rCSI 4.31%
    PRS 89.5
  • neural cell CL0002319
    CSI 1.51
    rCSI 5.69%
    PRS 80.15
  • Cajal-Retzius cell CL0000695
    CSI 1.42
    rCSI 11.13%
    PRS 93.66
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.41
    rCSI 3.44%
    PRS 79.92

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 [POU3F2](/details-gene/5454), also known as POU class 3 homeobox 2 or Brn-2, is a protein-coding gene located on chromosome 6q16.1. It encodes a POU domain-containing transcription factor that plays a crucial role in nervous system development and cell fate determination. As a sequence-specific DNA binding protein, [POU3F2](/details-gene/5454) is integral to processes such as neuron differentiation, myelination, and cerebral cortex development. Its expression is highly specific to the developing nervous system, with profound significance in [progenitor cell](/details-cell/CL0011026) populations and various neuronal and glial subtypes. Clinically, it is associated with neurodevelopmental processes and has been implicated in the tumorigenesis of neuroectodermal cancers like melanoma ([Link](https://pubmed.ncbi.nlm.nih.gov/7651733/)) and glioblastoma, as suggested by its high expression in [glioblast](/details-cell/CL0000030) cells. The gene is associated with an OMIM entry of [600494](https://omim.org/entry/600494). ## Cellular Roles and Expression Landscape The expression profile of [POU3F2](/details-gene/5454) firmly establishes it as a key regulator within the central nervous system, particularly during development. **Overall**, the gene exhibits its most profound significance in neural precursors, highlighted by its exceptionally high Cell Significance Index (CSI) in [progenitor cell](/details-cell/CL0011026) (CSI: 18.53). This suggests a foundational role in maintaining the identity or directing the fate of these early-stage cells. Its importance extends to more committed neural lineages, including [neuroblast (sensu Nematoda and Protostomia)](/details-cell/CL0000338), [forebrain radial glial cell](/details-cell/CL0013000), and [neuroblast (sensu Vertebrata)](/details-cell/CL0000031). Furthermore, [POU3F2](/details-gene/5454) is a significant marker for a spectrum of mature and developing neurons and glia. It shows high significance in both excitatory and inhibitory neurons, such as [glutamatergic neuron](/details-cell/CL0000679) and [cerebral cortex GABAergic interneuron](/details-cell/CL0010011). Its role in glial cell identity is supported by its expression in specialized glia like [Bergmann glial cell](/details-cell/CL0000644) and [astrocyte of the cerebral cortex](/details-cell/CL0002605). Notably, the gene's high CSI in [glioblast](/details-cell/CL0000030) (CSI: 5.94) points towards a potential role in the pathology of brain tumors, possibly by driving a progenitor-like state. The collective expression pattern indicates that [POU3F2](/details-gene/5454) is a critical transcription factor for establishing and maintaining the identity of a wide array of cell types of neuroectodermal origin. ## Pathways and Molecular Function The molecular functions and biological pathways associated with [POU3F2](/details-gene/5454) are highly consistent with its observed cellular expression pattern. As a transcription factor, its primary molecular functions involve direct interaction with DNA, including '[Dna-binding transcription factor activity, rna polymerase ii-specific](/details-cell/GO:0000981)' and '[Rna polymerase ii cis-regulatory region sequence-specific dna binding](/details-cell/GO:0000978)'. It operates within the '[Nucleoplasm](/details-cell/GO:0005654)' as part of the cellular machinery that controls gene expression. The biological processes it regulates are predominantly linked to neurogenesis. It is annotated in critical developmental events such as '[Nervous system development](/details-cell/GO:0007399)', '[Neuron differentiation](/details-cell/GO:0030182)', '[Neuron fate commitment](/details-cell/GO:0048663)', and '[Cerebral cortex radially oriented cell migration](/details-cell/GO:0021799)'. This functional profile aligns perfectly with its high expression in neural progenitors and developing neurons. The Reactome pathway annotations further solidify this role, placing it within the broader context of '[Developmental biology](/details-cell/R-HSA-1266738)' and more specifically within '[Nervous system development](/details-cell/R-HSA-9675108)'. Beyond the central nervous system, [POU3F2](/details-gene/5454) is also involved in '[Myelination in peripheral nervous system](/details-cell/GO:0022011)' and '[Mitf-m-regulated melanocyte development](/details-cell/R-HSA-9730414)', consistent with research that connects it to both Schwann cell and melanocyte biology ([Link](https://pubmed.ncbi.nlm.nih.gov/7651733/)). ## Research Directions The specific expression pattern and established functions of [POU3F2](/details-gene/5454) suggest several avenues for future investigation, particularly regarding its role in development and disease. **Proposed Hypotheses:** 1. Given its paramount CSI in [progenitor cell](/details-cell/CL0011026) and its role in '[Neuron fate commitment](/details-cell/GO:0048663)', it is hypothesized that [POU3F2](/details-gene/5454) functions as a master regulator that orchestrates the transition from a multipotent progenitor state to a committed neuronal or glial lineage. Its precise expression level may act as a rheostat, where high levels maintain progenitor identity and gradual downregulation permits terminal differentiation. 2. The high significance of [POU3F2](/details-gene/5454) in [glioblast](/details-cell/CL0000030), combined with its known role in melanoma tumorigenesis ([Link](https://pubmed.ncbi.nlm.nih.gov/7651733/)), suggests that its aberrant reactivation or sustained expression is a key driver of malignancy in neuroectodermal cancers. It may contribute to tumor progression by enforcing a de-differentiated, stem-like phenotype that confers properties of self-renewal and therapeutic resistance. **Experimental Approach:** To test the second hypothesis, a compelling experiment would involve the targeted depletion of [POU3F2](/details-gene/5454) in patient-derived glioblastoma stem cell (GSC) lines. Using a CRISPR-Cas9 knockout or shRNA-mediated knockdown system, one could assess the impact on GSC self-renewal and tumorigenicity. Key readouts would include in vitro neurosphere formation assays to measure self-renewal capacity and in vivo orthotopic xenograft models in immunocompromised mice to evaluate tumor initiation and growth. Concurrently, RNA-sequencing of the [POU3F2](/details-gene/5454)-depleted GSCs would reveal the downstream transcriptional networks it regulates, identifying pathways critical for maintaining the malignant state. **Therapeutic Potential:** As an intracellular transcription factor, [POU3F2](/details-gene/5454) represents a challenging drug target for traditional small molecule inhibitors. However, its specific and high expression in tumors like glioblastoma makes it an attractive candidate for therapeutic **inhibition**. Novel therapeutic modalities could be explored, such as antisense oligonucleotides (ASOs) or targeted protein degraders (e.g., PROTACs) designed to specifically reduce [POU3F2](/details-gene/5454) protein levels within cancer cells. Such a strategy could potentially reverse the progenitor-like state of tumor cells, rendering them more susceptible to conventional therapies like radiation and chemotherapy.

Genular Protein ID: 4046760082

Symbol: PO3F2_HUMAN

Name: POU domain, class 3, transcription factor 2

UniProtKB Accession Codes:

P20265 Q14960 Q86V54 Q9UJL0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEMBL 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 1 GO 30 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 8 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PIR 1 PIRSF 1 PRINTS 1 PRO 1 PROSITE 5 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 Pumba 1 RNAct 1 Reactome 3 RefSeq 1 SASBDB 1 SIGNOR 1 SMART 2 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: 8441633

Title: cDNA cloning of human N-Oct3, a nervous-system specific POU domain transcription factor binding to the octamer DNA motif.

PubMed ID: 8441633

DOI: 10.1093/nar/21.2.253

PubMed ID: 7651733

Title: The brn-2 gene regulates the melanocytic phenotype and tumorigenic potential of human melanoma cells.

PubMed ID: 7651733

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: 2739723

Title: Expression of a large family of POU-domain regulatory genes in mammalian brain development.

PubMed ID: 2739723

DOI: 10.1038/340035a0

PubMed ID: 10332029

Title: PQBP-1, a novel polyglutamine tract binding protein, inhibits transcription activation by Brn-2 and affects cell survival.

PubMed ID: 10332029

DOI: 10.1093/hmg/8.6.977

PubMed ID: 19413330

Title: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.

PubMed ID: 19413330

DOI: 10.1021/ac9004309

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

Sequence Information:

  • Length: 443
  • Mass: 46893
  • Checksum: D470360894D788C6
  • Sequence:
    • MATAASNHYS LLTSSASIVH AEPPGGMQQG AGGYREAQSL VQGDYGALQS NGHPLSHAHQ 
WITALSHGGG GGGGGGGGGG GGGGGGGGDG SPWSTSPLGQ PDIKPSVVVQ QGGRGDELHG 
PGALQQQHQQ QQQQQQQQQQ QQQQQQQQQR PPHLVHHAAN HHPGPGAWRS AAAAAHLPPS 
MGASNGGLLY SQPSFTVNGM LGAGGQPAGL HHHGLRDAHD EPHHADHHPH PHSHPHQQPP 
PPPPPQGPPG HPGAHHDPHS DEDTPTSDDL EQFAKQFKQR RIKLGFTQAD VGLALGTLYG 
NVFSQTTICR FEALQLSFKN MCKLKPLLNK WLEEADSSSG SPTSIDKIAA QGRKRKKRTS 
IEVSVKGALE SHFLKCPKPS AQEITSLADS LQLEKEVVRV WFCNRRQKEK RMTPPGGTLP 
GAEDVYGGSR DTPPHHGVQT PVQ