Details for: DBX2

Gene ID: 440097

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: DBX2

Ensembl ID: ENSG00000185610

Description: developing brain homeobox 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • conventional dendritic cell CL0000990
    CSI 91.49
    rCSI 76.37%
    PRS 3.48
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 63.5
    rCSI 76.94%
    PRS 1.64
  • chondrocyte CL0000138
    CSI 49.48
    rCSI 78.7%
    PRS 0.98
  • suprabasal keratinocyte CL4033013
    CSI 45.98
    rCSI 75.05%
    PRS 0.96
  • melanocyte of skin CL1000458
    CSI 43.3
    rCSI 59.01%
    PRS 0.95
  • regulatory T cell CL0000815
    CSI 42.59
    rCSI 49.38%
    PRS 3.79
  • mast cell CL0000097
    CSI 32.85
    rCSI 70.92%
    PRS 6.26
  • basal cell of epidermis CL0002187
    CSI 13.45
    rCSI 23.84%
    PRS 1.46
  • helper T cell CL0000912
    CSI 8.31
    rCSI 11.75%
    PRS 1.62
  • cytotoxic T cell CL0000910
    CSI 7.64
    rCSI 43.8%
    PRS 1.7
  • pericyte CL0000669
    CSI 1.68
    rCSI 4.46%
    PRS 9.92
  • innate lymphoid cell CL0001065
    CSI -7.75
    rCSI -16%
    PRS 1.78
  • astrocyte of the cerebral cortex CL0002605
    CSI -44.77
    rCSI -100%
    PRS 0.68

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.

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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 [DBX2](/details-gene/440097), or developing brain homeobox 2, is a protein-coding gene located on chromosome 12q12 [Link](https://doi.org/10.1038/nature04569). Functionally, it is annotated as a DNA-binding transcription factor that localizes to the nucleus and chromatin, where it participates in the regulation of transcription ([GO:0006357](https://www.ebi.ac.uk/QuickGO/term/GO:0006357)). **Overall** expression data indicates that [DBX2](/details-gene/440097) is a highly significant gene in several distinct cell lineages. It shows the highest significance in immune cells, particularly [conventional dendritic cell](/details-cell/CL0000990) and various T cell subsets, as well as in cells of the skin and connective tissues, such as [chondrocyte](/details-cell/CL0000138) and [suprabasal keratinocyte](/details-cell/CL4033013), suggesting a pleiotropic role in both immunity and tissue homeostasis. ## Cellular Roles and Expression Landscape The expression profile of [DBX2](/details-gene/440097) reveals a specialized role across diverse tissues. **Overall**, its most significant expression is observed in [conventional dendritic cell](/details-cell/CL0000990) (CSI: 91.49), indicating it may be a key transcriptional regulator defining the identity or function of this critical antigen-presenting cell type. The gene is also highly significant across the adaptive immune system, with prominent roles in [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203) (CSI: 63.50) and [regulatory T cell](/details-cell/CL0000815) (CSI: 42.59), suggesting its involvement in T cell memory and immune suppression programs. Beyond the immune system, [DBX2](/details-gene/440097) demonstrates high significance in structural and epidermal cell types. These include [chondrocyte](/details-cell/CL0000138) (CSI: 49.48), [suprabasal keratinocyte](/details-cell/CL4033013) (CSI: 45.98), and [melanocyte of skin](/details-cell/CL1000458) (CSI: 43.30), pointing towards a functional role in cartilage maintenance and skin biology. Conversely, the gene shows very low significance in [astrocyte of the cerebral cortex](/details-cell/CL0002605) (CSI: -44.77). This is notable given the gene's name and suggests that its function may be specific to embryonic brain development rather than the maintenance of the adult central nervous system. Its low significance in [innate lymphoid cell](/details-cell/CL0001065) further refines its immunological role, pointing towards a specialization within the adaptive, rather than innate, lymphoid compartment. ## Pathways and Molecular Function Functionally, [DBX2](/details-gene/440097) is a transcription factor involved in regulating gene expression via RNA polymerase II ([GO:0006357](https://www.ebi.ac.uk/QuickGO/term/GO:0006357)). Its molecular activities include sequence-specific DNA binding ([GO:0000981](https://www.ebi.ac.uk/QuickGO/term/GO:0000981)) and protein binding ([GO:0005515](https://www.ebi.ac.uk/QuickGO/term/GO:0005515)), consistent with its role as a regulator that integrates into larger protein complexes on chromatin ([GO:0000785](https://www.ebi.ac.uk/QuickGO/term/GO:0000785)). This transcriptional regulatory function is the likely mechanism through which it exerts its influence on the diverse cell types where it is prominently expressed. For example, in [conventional dendritic cell](/details-cell/CL0000990), [DBX2](/details-gene/440097) may control the expression of genes essential for antigen processing and presentation, while in [keratinocyte](/details-cell/CL0000312), it could regulate differentiation pathways. ## Research Directions The diverse expression pattern of [DBX2](/details-gene/440097) across both the immune system and epidermal tissues raises several questions about its specific roles. The high significance in cell types central to immune activation and regulation suggests it may be a key node in controlling immune responses. **Proposed Hypotheses:** 1. Given its premier significance in [conventional dendritic cell](/details-cell/CL0000990), [DBX2](/details-gene/440097) acts as a master transcriptional regulator necessary for dendritic cell maturation and the subsequent activation of naive T cells. 2. The high significance of [DBX2](/details-gene/440097) in both [regulatory T cell](/details-cell/CL0000815) and cytotoxic/helper T cell lineages suggests it plays a context-dependent role in T cell fate, potentially regulating the balance between effector function and immune tolerance. 3. The gene's name ('developing brain homeobox 2') contrasts with its low expression in adult brain cells but high expression in epidermal cells. This suggests a functional repurposing, where [DBX2](/details-gene/440097) shifts from a neurodevelopmental role to one involved in skin homeostasis and repair in adults. **Suggested Experimental Approach:** To test the first hypothesis regarding the role of [DBX2](/details-gene/440097) in dendritic cell function, one could perform a loss-of-function study. Specifically, CRISPR-Cas9 could be used to knock out [DBX2](/details-gene/440097) in primary human monocytes, which would then be differentiated into dendritic cells. The maturation capacity of these knockout dendritic cells could be assessed by stimulating them with lipopolysaccharide (LPS) and measuring the expression of co-stimulatory markers (e.g., CD80, CD86, HLA-DR) by flow cytometry. A functional readout could be achieved through a mixed lymphocyte reaction, where the ability of knockout dendritic cells to stimulate proliferation in allogeneic T cells is quantified and compared to wild-type controls. **Therapeutic Potential:** As an intracellular transcription factor, [DBX2](/details-gene/440097) presents a challenging drug target for conventional biologics or small molecules. However, if its dysregulation is implicated in diseases like psoriasis (keratinocyte biology) or autoimmune disorders (dendritic and T cell biology), it could become an indirect therapeutic target. Strategies might focus on modulating upstream signaling pathways that control [DBX2](/details-gene/440097) expression or targeting its key downstream effector genes. At present, without a clear link to pathology, its direct therapeutic potential is limited, but it remains a gene of interest for understanding fundamental processes in immunology and dermatology.

Genular Protein ID: 2328439165

Symbol: DBX2_HUMAN

Name: Homeobox protein DBX2

UniProtKB Accession Codes:

Q6ZNG2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 1 GO 5 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 RefSeq 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 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: 16541075

Title: The finished DNA sequence of human chromosome 12.

PubMed ID: 16541075

DOI: 10.1038/nature04569

Sequence Information:

  • Length: 339
  • Mass: 36555
  • Checksum: 7E9CAD61C3DAEBEB
  • Sequence:
    • MLPSAVAAHA GAYWDVVASS ALLNLPAAPG FGNLGKSFLI ENLLRVGGAP TPRLQPPAPH 
DPATALATAG AQLRPLPASP VPLKLCPAAE QVSPAGAPYG TRWAFQVLSP SADSARLPGR 
APGDRDCTFQ PSAPAPSKPF LLSTPPFYSA CCGGSCRRPA SSTAFPREES MLPLLTQDSN 
SKARRGILRR AVFSEDQRKA LEKMFQKQKY ISKTDRKKLA INLGLKESQV KIWFQNRRMK 
WRNSKEKEVL SNRCIQEVGL QEDPLSRSAL GFPSPCPSIW DVPQQHSSPR WRENSPEPSE 
RLIQESSGAP PPEANSLQGA LYLCSEEEAG SKGVLTGAV