DTL Gene

HGNC Family	DDB1 and CUL4 associated factors (DCAF), WD repeat domain containing (WDR)
Name	denticleless E3 ubiquitin protein ligase homolog (Drosophila)
Description	Contributes to ubiquitin-protein transferase activity. Involved in several processes, including protein ubiquitination; regulation of G2/M transition of mitotic cell cycle; and translesion synthesis. Located in centrosome; cytosol; and nuclear lumen. Part of Cul4A-RING E3 ubiquitin ligase complex and Cul4B-RING E3 ubiquitin ligase complex. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DTL (also known as CDT2 or L2DTL) is a key substrate‐recruiting component of the CRL4 (Cul4–DDB1) E3 ubiquitin ligase complex that is essential for maintaining genomic integrity and proper cell cycle progression. By binding to proliferating cell nuclear antigen (PCNA) through a specialized PIP degron, DTL targets critical regulatory proteins—including the replication licensing factor CDT1, the cyclin‐dependent kinase inhibitor p21, and chromatin modifiers such as SET8—for ubiquitylation and proteasomal degradation during S phase and following DNA damage."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": " This regulated proteolysis prevents unscheduled origin firing and re‐replication, thereby ensuring robust checkpoint control and proper DNA repair.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, modulation of DTL by microRNAs (such as miR‑215 and miR‑30a‑5p) has been shown to induce cell cycle arrest via p53 and p21 accumulation, underscoring its role in promoting cell proliferation and its oncogenic potential in various cancers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In cancer cells, overexpression or deregulated activity of DTL contributes to enhanced proliferation, defective cell cycle checkpoints, and chemoresistance.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, DTL/ CDT2 serves as an indispensable regulator of ubiquitin‐mediated proteolysis that coordinates the timely degradation of proteins controlling DNA replication, cell cycle checkpoints, and chromatin structure. Through these actions, DTL preserves genome stability under normal conditions and its dysregulation is closely linked to tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}, {"type": "fg_f", "ref": "6"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Bo Song, Yuan Wang, Matthew A Titmus, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular mechanism of chemoresistance by miR-215 in osteosarcoma and colon cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1476-4598-9-96"}], "href": "https://doi.org/10.1186/1476-4598-9-96"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20433742"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20433742"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Leigh Ann Higa, Damon Banks, Min Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "L2DTL/CDT2 interacts with the CUL4/DDB1 complex and PCNA and regulates CDT1 proteolysis in response to DNA damage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/cc.5.15.3149"}], "href": "https://doi.org/10.4161/cc.5.15.3149"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16861906"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16861906"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Christopher L Sansam, Jennifer L Shepard, Kevin Lai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DTL/CDT2 is essential for both CDT1 regulation and the early G2/M checkpoint."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.1482106"}], "href": "https://doi.org/10.1101/gad.1482106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17085480"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17085480"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Damon Banks, Min Wu, Leigh Ann Higa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "L2DTL/CDT2 and PCNA interact with p53 and regulate p53 polyubiquitination and protein stability through MDM2 and CUL4A/DDB1 complexes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/cc.5.15.3150"}], "href": "https://doi.org/10.4161/cc.5.15.3150"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16861890"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16861890"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Alexander Baraniskin, Karin Birkenkamp-Demtroder, Abdelouahid Maghnouj, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-30a-5p suppresses tumor growth in colon carcinoma by targeting DTL."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/bgs020"}], "href": "https://doi.org/10.1093/carcin/bgs020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22287560"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22287560"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Mihriban Karaayvaz, Timothy Pal, Bo Song, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prognostic significance of miR-215 in colon cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Colorectal Cancer (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.clcc.2011.06.002"}], "href": "https://doi.org/10.1016/j.clcc.2011.06.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21752725"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21752725"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "T Ueki, T Nishidate, J H Park, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of elevated expression of multiple cell-cycle regulator, DTL/RAMP (denticleless/RA-regulated nuclear matrix associated protein), in the growth of breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2008.186"}], "href": "https://doi.org/10.1038/onc.2008.186"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18542055"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18542055"}]}]}]}
Synonyms	DCAF2, CDT2, L2DTL
Proteins	DTL_HUMAN
NCBI Gene ID	51514
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

DTL has 10,647 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 116 datasets.

Click the + buttons to view associations for DTL from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

DTL Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of DTL gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of DTL gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of DTL gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of DTL gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of DTL gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of DTL gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of DTL gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of DTL gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of DTL gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of DTL gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of DTL gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of DTL gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of DTL gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of DTL gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing DTL protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of DTL gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing DTL protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing DTL protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing DTL protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing DTL protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with DTL protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with DTL protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of DTL gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with DTL gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with DTL gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with DTL gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with DTL gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of DTL protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with DTL gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with DTL gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with DTL gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with DTL gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at DTL gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of DTL gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of DTL gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing DTL from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with DTL gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of DTL gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with DTL gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing DTL from the GeneSigDB Published Gene Signatures dataset.