Details for: DTX1

Gene ID: 1840

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: DTX1

Ensembl ID: ENSG00000135144

Description: deltex E3 ubiquitin ligase 1

Cell Significance Landscape

Associated with

Significant Cells

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

  • mature B cell CL0000785
    CSI 7.01
    rCSI 6.09%
    PRS 96.91
  • alpha-beta T cell CL0000789
    CSI 5.72
    rCSI 6.71%
    PRS 97.87
  • retina horizontal cell CL0000745
    CSI 5.5
    rCSI 8.38%
    PRS 89.55
  • ependymal cell CL0000065
    CSI 4.62
    rCSI 9.38%
    PRS 76.85
  • small pre-B-II cell CL0000954
    CSI 3.66
    rCSI 3.52%
    PRS 97.28
  • precursor B cell CL0000817
    CSI 3.53
    rCSI 3.09%
    PRS 95.31
  • naive B cell CL0000788
    CSI 3.47
    rCSI 2.98%
    PRS 95.37
  • pro-B cell CL0000826
    CSI 3.2
    rCSI 2.65%
    PRS 93.36
  • interneuron CL0000099
    CSI 3.05
    rCSI 6.13%
    PRS 87.36
  • immature B cell CL0000816
    CSI 3.03
    rCSI 2.25%
    PRS 96.86
  • periportal region hepatocyte CL0019026
    CSI 2.21
    rCSI 8.59%
    PRS 89.43
  • adipocyte CL0000136
    CSI 2.2
    rCSI 2.82%
    PRS 85.48
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.15
    rCSI 2.77%
    PRS 82.64
  • parietal epithelial cell CL1000452
    CSI 2.13
    rCSI 5.69%
    PRS 88.29
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.93
    rCSI 2.3%
    PRS 81.57
  • H1 horizontal cell CL0004217
    CSI 1.89
    rCSI 7.47%
    PRS 86.98
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.88
    rCSI 3.33%
    PRS 80.9
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.82
    rCSI 2.27%
    PRS 79.4
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.65
    rCSI 3.69%
    PRS 81.85
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.63
    rCSI 2.73%
    PRS 81.61
  • epicardial adipocyte CL1000309
    CSI 1.62
    rCSI 5.26%
    PRS 90.17
  • late pro-B cell CL0002048
    CSI 1.35
    rCSI 3.39%
    PRS 97.37
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.31
    rCSI 2.11%
    PRS 82.56
  • H2 horizontal cell CL0004218
    CSI 1.14
    rCSI 5.64%
    PRS 87.65
  • large pre-B-II cell CL0000957
    CSI 1.12
    rCSI 3.19%
    PRS 92.05
  • germinal center B cell CL0000844
    CSI 1.09
    rCSI 3.24%
    PRS 94.8
  • GABAergic neuron CL0000617
    CSI 0.94
    rCSI 3.15%
    PRS 80.73
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.83
    rCSI 2.01%
    PRS 79.45
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.76
    rCSI 2.38%
    PRS 84.46
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.68
    rCSI 2.58%
    PRS 81.79
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.51
    rCSI 1.83%
    PRS 79.73

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 [DTX1](/details-gene/1840) (deltex E3 ubiquitin ligase 1) is a protein-coding gene that functions as a key intracellular regulator of the Notch signaling pathway. It possesses E3 ubiquitin-protein ligase activity ([Link](https://doi.org/10.1074/jbc.m301157200)) and also acts as a transcriptional coactivator, mediating critical cell fate decisions. **Overall**, expression data reveals that [DTX1](/details-gene/1840) is a highly significant gene in the adaptive immune system, with its highest significance observed in [mature B cell](/details-cell/CL0000785)s and across various stages of B cell development, as well as in [alpha-beta T cell](/details-cell/CL0000789)s. Its role is particularly well-documented in directing lymphoid progenitors toward the B cell lineage by antagonizing Notch1 signaling ([Link](https://doi.org/10.1016/s1074-7613(02)00271-6)). Significant expression is also noted in specific neural populations, such as [retina horizontal cell](/details-cell/CL0000745)s, suggesting pleiotropic functions beyond immunology. Its clinical relevance is noted under OMIM entry [602582](https://omim.org/entry/602582). ## Cellular Roles and Expression Landscape The expression profile of [DTX1](/details-gene/1840) underscores its fundamental role in lymphocyte biology. **Overall**, the gene shows the highest significance in the B cell lineage, including [mature B cell](/details-cell/CL0000785) (CSI: 7.01), [small pre-B-II cell](/details-cell/CL0000954), [precursor B cell](/details-cell/CL0000817), [naive B cell](/details-cell/CL0000788), [pro-B cell](/details-cell/CL0000826), and [immature B cell](/details-cell/CL0000816). This pattern is consistent with its established role in antagonizing Notch signaling to promote B cell commitment and differentiation ([Link](https://doi.org/10.1016/s1074-7613(02)00271-6)). Beyond B cells, [DTX1](/details-gene/1840) is also highly significant in [alpha-beta T cell](/details-cell/CL0000789)s, indicating a broader function in adaptive immunity. Its involvement in the negative regulation of T cell differentiation further supports a role in fine-tuning T cell fate decisions. Interestingly, [DTX1](/details-gene/1840) also demonstrates notable significance in non-hematopoietic cells, particularly within the central nervous system. These include [retina horizontal cell](/details-cell/CL0000745)s, [ependymal cell](/details-cell/CL0000065)s, and specific subsets of [interneuron](/details-cell/CL0000099)s. This suggests that the regulatory functions of [DTX1](/details-gene/1840), likely through Notch modulation, are utilized in diverse developmental and homeostatic contexts, spanning both the immune and nervous systems. ## Pathways and Molecular Function The functional annotations for [DTX1](/details-gene/1840) converge on its dual role as an E3 ubiquitin ligase and a modulator of the Notch signaling pathway. Its molecular functions include [ubiquitin protein ligase activity](/details-go/GO:0061630), [protein binding](/details-go/GO:0005515), and direct [Notch binding](/details-go/GO:0005112). This is consistent with its participation in biological processes such as [protein ubiquitination](/details-go/GO:0016567) and the [regulation of notch signaling pathway](/details-go/GO:0008593). Reactome pathway analysis places [DTX1](/details-gene/1840) squarely within the Notch signaling cascade, including [Signaling by notch](/details-reactome/R-HSA-157118) and [Activated notch1 transmits signal to the nucleus](/details-reactome/R-HSA-2122948). The gene product acts within both the [cytoplasm](/details-go/GO:0005737) and [nucleoplasm](/details-go/GO:0005654), reflecting its ability to influence signaling events and subsequent transcriptional responses. Indeed, it is annotated with [transcription coactivator activity](/details-go/GO:0003713) and participates in [Dna-templated transcription](/details-go/GO:0006351), highlighting its role as a transcriptional regulator downstream of Notch receptor activation ([Link](https://doi.org/10.1074/jbc.m105245200)). This regulatory function is critical for its role in cell fate decisions, such as [T cell differentiation](/details-go/GO:0030217) and [glial cell differentiation](/details-go/GO:0010001). ## Research Directions Given the central role of [DTX1](/details-gene/1840) in lymphocyte development via Notch modulation, its dysregulation is a plausible contributor to hematological and immunological disorders. **Proposed Hypotheses:** 1. **Role in B-Cell Malignancies:** Given its function as a key decision-maker in B-cell lineage commitment, loss-of-function mutations or epigenetic silencing of [DTX1](/details-gene/1840) may contribute to the pathogenesis of certain B-cell leukemias or lymphomas by permitting uncontrolled Notch1 signaling, thereby blocking normal differentiation. 2. **Modulation of T-Cell Exhaustion:** The established role of [DTX1](/details-gene/1840) in the negative regulation of T-cell differentiation suggests it may be upregulated during chronic antigen stimulation to enforce a T-cell exhaustion phenotype. [DTX1](/details-gene/1840)-mediated ubiquitination could target key activators of T-cell function for degradation. **Experimental Approach:** To test the hypothesis that [DTX1](/details-gene/1840) modulates T-cell exhaustion (Hypothesis 2), a robust experimental plan could be implemented. A T-cell-specific conditional knockout mouse model for Dtx1 would be subjected to a chronic viral infection, such as with the Clone 13 strain of Lymphocytic Choriomeningitis Virus (LCMV). At late time points post-infection, virus-specific CD8+ T cells from knockout and wild-type mice would be isolated and analyzed. Key readouts would include: (i) multi-parameter flow cytometry to quantify expression of exhaustion markers (e.g., PD-1, LAG-3, TIM-3); (ii) intracellular cytokine staining and *in vivo* cytotoxicity assays to assess effector function; and (iii) RNA-sequencing of the sorted T cells to define the downstream transcriptional programs regulated by [DTX1](/details-gene/1840) in the context of exhaustion. **Therapeutic Potential:** [DTX1](/details-gene/1840) presents a compelling, albeit complex, therapeutic target. As an E3 ubiquitin ligase, it belongs to a class of enzymes that are amenable to small molecule inhibition or targeted degradation via technologies like PROTACs. If [DTX1](/details-gene/1840) is validated as a driver of T-cell exhaustion, its inhibition could serve as a novel immunotherapeutic strategy to reinvigorate anti-tumor or anti-viral T-cell responses, potentially acting synergistically with existing checkpoint inhibitors. Conversely, if loss-of-function is implicated in B-cell malignancies, strategies to restore its function or target the resulting aberrant downstream signaling could be explored. The high expression in multiple essential immune cell populations suggests that any systemic therapeutic approach would require careful evaluation to avoid unintended immunological consequences.

Genular Protein ID: 1210404130

Symbol: DTX1_HUMAN

Name: E3 ubiquitin-protein ligase DTX1

UniProtKB Accession Codes:

Q86Y01 O60630 Q9BS04

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CTD 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 3 Ensembl 2 GO 21 Gene3D 3 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 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 2 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 9590294

Title: Human deltex is a conserved regulator of Notch signalling.

PubMed ID: 9590294

DOI: 10.1038/ng0598-74

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: 11869684

Title: Deltex1 redirects lymphoid progenitors to the B cell lineage by antagonizing Notch1.

PubMed ID: 11869684

DOI: 10.1016/s1074-7613(02)00271-6

PubMed ID: 11564735

Title: Role of Deltex-1 as a transcriptional regulator downstream of the Notch receptor.

PubMed ID: 11564735

DOI: 10.1074/jbc.m105245200

PubMed ID: 12753744

Title: Notch2 is preferentially expressed in mature B cells and indispensable for marginal zone B lineage development.

PubMed ID: 12753744

DOI: 10.1016/s1074-7613(03)00111-0

PubMed ID: 12670957

Title: The BAL-binding protein BBAP and related Deltex family members exhibit ubiquitin-protein isopeptide ligase activity.

PubMed ID: 12670957

DOI: 10.1074/jbc.m301157200

PubMed ID: 17028573

Title: Itch/AIP4 mediates Deltex degradation through the formation of K29-linked polyubiquitin chains.

PubMed ID: 17028573

DOI: 10.1038/sj.embor.7400822

PubMed ID: 21124883

Title: The translation initiation factor 3f (eIF3f) exhibits a deubiquitinase activity regulating Notch activation.

PubMed ID: 21124883

DOI: 10.1371/journal.pbio.1000545

Sequence Information:

  • Length: 620
  • Mass: 67368
  • Checksum: 3BF3ECE46E25CCD4
  • Sequence:
    • MSRPGHGGLM PVNGLGFPPQ NVARVVVWEW LNEHSRWRPY TATVCHHIEN VLKEDARGSV 
VLGQVDAQLV PYIIDLQSMH QFRQDTGTMR PVRRNFYDPS SAPGKGIVWE WENDGGAWTA 
YDMDICITIQ NAYEKQHPWL DLSSLGFCYL IYFNSMSQMN RQTRRRRRLR RRLDLAYPLT 
VGSIPKSQSW PVGASSGQPC SCQQCLLVNS TRAASNAILA SQRRKAPPAP PLPPPPPPGG 
PPGALAVRPS ATFTGAALWA APAAGPAEPA PPPGAPPRSP GAPGGARTPG QNNLNRPGPQ 
RTTSVSARAS IPPGVPALPV KNLNGTGPVH PALAGMTGIL LCAAGLPVCL TRAPKPILHP 
PPVSKSDVKP VPGVPGVCRK TKKKHLKKSK NPEDVVRRYM QKVKNPPDED CTICMERLVT 
ASGYEGVLRH KGVRPELVGR LGRCGHMYHL LCLVAMYSNG NKDGSLQCPT CKAIYGEKTG 
TQPPGKMEFH LIPHSLPGFP DTQTIRIVYD IPTGIQGPEH PNPGKKFTAR GFPRHCYLPN 
NEKGRKVLRL LITAWERRLI FTIGTSNTTG ESDTVVWNEI HHKTEFGSNL TGHGYPDASY 
LDNVLAELTA QGVSEAAAKA