DTX3L Gene

HGNC Family	Zinc fingers
Name	deltex 3 like, E3 ubiquitin ligase
Description	Enables several functions, including STAT family protein binding activity; histone H4K91 ubiquitin ligase activity; and protein ADP-ribosyltransferase-substrate adaptor activity. Involved in several processes, including positive regulation of protein localization; protein ubiquitination; and regulation of macromolecule metabolic process. Located in several cellular components, including early endosome; lysosome; and nucleoplasm. Part of protein-containing complex. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DTX3L is a versatile E3 ubiquitin ligase that participates in several fundamental cellular processes by targeting key proteins for ubiquitin modification. In immune‐competent cells, DTX3L forms a complex with PARP9 to modulate interferon signaling: it enhances interferon‐stimulated gene expression through histone ubiquitination and promotes the degradation of viral proteases, thereby contributing to a dual layer of host antiviral defense."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In various tumor models, DTX3L engages in oncogenic signaling. For instance, in metastatic prostate cancer and glioma, DTX3L complexes with mono‐ADP‐ribosyltransferases (ARTD8/ARTD9) to drive proliferation, chemoresistance, and cell migration while repressing tumor suppressors such as IRF1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In addition, DTX3L regulates intracellular protein trafficking; upon receptor activation, it localizes to early endosomes and interacts with other E3 ligases to modulate the ubiquitination status of ESCRT components, thereby influencing lysosomal sorting of targets like CXCR4."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Furthermore, DTX3L heterodimerizes with DTX1 to form a functional Notch E3 ligase that downregulates NOTCH1 activity, a process that is critical for lymphatic endothelial sprouting in response to shear stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In the context of the DNA damage response, DTX3L, as a component of the BAL1-BBAP complex, is implicated in histone modification events that facilitate the recruitment of repair mediators such as 53BP1 and BRCA1, thereby contributing indirectly to genomic stability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Nuclear receptor signaling is also influenced by DTX3L; ADP-ribosylation of the androgen receptor by PARP7 promotes the subsequent recruitment of the DTX3L/PARP9 complex, which in turn fine-tunes the transcriptional activity of a subset of androgen-responsive genes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Additionally, expression of DTX3L is inducible by inflammatory cytokines such as interferon-γ in certain lymphomas, linking its activity to immune regulation and the development of chemoresistance"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", while in multiple myeloma its upregulation correlates with enhanced cell adhesion and subsequent resistance to chemotherapy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Finally, proteomic analyses have identified DTX3L on the plasma membranes of vascular endothelial cells, suggesting that it may also contribute to endothelial cell function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Collectively, these observations position DTX3L as a key integrator of ubiquitin-dependent signaling pathways that govern antiviral defenses, receptor trafficking, DNA repair, and oncogenic processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yong Zhang, Dailing Mao, William T Roswit, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni.3279"}], "href": "https://doi.org/10.1038/ni.3279"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26479788"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26479788"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lilian Cristina Russo, Rebeka Tomasin, Isaac Araújo Matos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The SARS-CoV-2 Nsp3 macrodomain reverses PARP9/DTX3L-dependent ADP-ribosylation induced by interferon signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbc.2021.101041"}], "href": "https://doi.org/10.1016/j.jbc.2021.101041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34358560"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34358560"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Samia B Bachmann, Sandra C Frommel, Rosalba Camicia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DTX3L and ARTD9 inhibit IRF1 expression and mediate in cooperation with ARTD8 survival and proliferation of metastatic prostate cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1476-4598-13-125"}], "href": "https://doi.org/10.1186/1476-4598-13-125"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24886089"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24886089"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Peng Xu, Xuelei Tao, Chengjin Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DTX3L is upregulated in glioma and is associated with glioma progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Med (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijmm.2017.3023"}], "href": "https://doi.org/10.3892/ijmm.2017.3023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28627634"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28627634"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Justine Holleman, Adriano Marchese "}, {"type": "b", "children": [{"type": "t", "text": "The ubiquitin ligase deltex-3l regulates endosomal sorting of the G protein-coupled receptor CXCR4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E13-10-0612"}], "href": "https://doi.org/10.1091/mbc.E13-10-0612"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24790097"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24790097"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Dongwon Choi, Eunkyung Park, Eunson Jung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Laminar flow downregulates Notch activity to promote lymphatic sprouting."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI87442"}], "href": "https://doi.org/10.1172/JCI87442"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28263185"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28263185"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Qingsheng Yan, Rong Xu, Liya Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BAL1 and its partner E3 ligase, BBAP, link Poly(ADP-ribose) activation, ubiquitylation, and double-strand DNA repair independent of ATM, MDC1, and RNF8."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00990-12"}], "href": "https://doi.org/10.1128/MCB.00990-12"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23230272"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23230272"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Chun-Song Yang, Kasey Jividen, Teddy Kamata, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Androgen signaling uses a writer and a reader of ADP-ribosylation to regulate protein complex assembly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-021-23055-6"}], "href": "https://doi.org/10.1038/s41467-021-23055-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33976187"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33976187"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Teddy Kamata, Chun-Song Yang, Bryce M Paschal "}, {"type": "b", "children": [{"type": "t", "text": "PARP7 mono-ADP-ribosylates the agonist conformation of the androgen receptor in the nucleus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BCJ20210378"}], "href": "https://doi.org/10.1042/BCJ20210378"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34264286"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34264286"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Przemyslaw Juszczynski, Jeffery L Kutok, Cheng Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BAL1 and BBAP are regulated by a gamma interferon-responsive bidirectional promoter and are overexpressed in diffuse large B-cell lymphomas with a prominent inflammatory infiltrate."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.02351-05"}], "href": "https://doi.org/10.1128/MCB.02351-05"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16809771"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16809771"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Yaodong Shen, Yuxiang Sun, Linlin Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effects of DTX3L on the cell proliferation, adhesion, and drug resistance of multiple myeloma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tumour Biol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/1010428317703941"}], "href": "https://doi.org/10.1177/1010428317703941"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28653881"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28653881"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Stefan Tenzer, Petra Leidinger, Christina Backes, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Integrated quantitative proteomic and transcriptomic analysis of lung tumor and control tissue: a lung cancer showcase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.7562"}], "href": "https://doi.org/10.18632/oncotarget.7562"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26930711"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26930711"}]}]}]}
Synonyms	RNF143, BBAP
Proteins	DTX3L_HUMAN
NCBI Gene ID	151636
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

DTX3L has 5,802 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 111 datasets.

Click the + buttons to view associations for DTX3L from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

DTX3L Gene

Functional Associations

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

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by DTX3L gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of DTX3L 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 DTX3L 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 DTX3L 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 DTX3L 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 DTX3L 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 DTX3L gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of DTX3L gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of DTX3L 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 DTX3L gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with DTX3L protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with DTX3L gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of DTX3L gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of DTX3L gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of DTX3L gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing DTX3L protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing DTX3L protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing DTX3L protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing DTX3L protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with DTX3L 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 DTX3L 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 DTX3L gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with DTX3L gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with DTX3L gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with DTX3L gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of DTX3L protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by DTX3L gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with DTX3L 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 DTX3L 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 DTX3L gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with DTX3L 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 DTX3L 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 DTX3L gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of DTX3L 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 DTX3L from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with DTX3L 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 DTX3L from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of DTX3L gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of DTX3L gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Kinase Perturbations	kinase perturbations changing expression of DTX3L gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.