UBE2D3 Gene

HGNC Family	Ubiquitin-conjugating enzymes E2 (UBE2)
Name	ubiquitin-conjugating enzyme E2D 3
Description	The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. This enzyme functions in the ubiquitination of the tumor-suppressor protein p53, which is induced by an E3 ubiquitin-protein ligase. [provided by RefSeq, Jan 2017]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nUBE2D3 is a versatile ubiquitin‐conjugating enzyme that plays key roles in innate immune signaling and the maintenance of genomic stability. In the context of viral infection, UBE2D3 partners with the E3 ligase Riplet to catalyze the polyubiquitination of RIG‑I, thereby triggering MAVS aggregation and subsequent type I interferon production."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, UBE2D family members contribute to efficient DNA double‑strand break repair; in this setting, UBE2Ds act together with the nuclear E3 ligase RNF138 to promote CtIP ubiquitination and facilitate homologous recombination."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, UBE2D3 has been implicated in the regulation of telomerase activity: in human breast cancer MCF‑7 cells, UBE2D3 interacts with hTERT such that its down‑regulation leads to an accumulation of hTERT and cyclin D1, thereby affecting cell cycle progression and radiosensitivity"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", whereas in esophageal squamous carcinoma cells overexpression of UBE2D3 promotes the proteasomal degradation of hTERT, shortens telomeres, and adjusts cell‑cycle dynamics to enhance radiosensitivity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in immunity and genomic maintenance, UBE2D3 regulates key aspects of cellular trafficking and protein quality control. In neurons, UBE2D3 cooperates with the E3 ligase Nedd4‑2 to mediate Lys(63)‑linked polyubiquitination of the dopamine transporter, thereby controlling its endocytosis and turnover."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Quantitative proteomics studies have further revealed that UBE2D3 directly ubiquitinates ribosomal proteins RPS10 and RPS20, implicating it in ribosome‑associated quality control mechanisms and autophagic protein turnover."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRegulation of UBE2D3 itself is subject to evolutionary and post‑translational fine‑tuning. Comparative analyses have uncovered that a unique serine residue (S138) acquired in amniotes creates a phosphorylation site that destabilizes UBE2D3 and modulates its ubiquitin‑transfer activity, thereby affecting the ubiquitination landscape for developmental and signaling proteins."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, interactions with regulatory proteins such as Otub1 further illustrate the complex control of UBE2D3 activity; monoubiquitination of Otub1 by UBE2D3 is crucial for inhibiting UBE2D3’s own activity in pathways governing p53 stability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yuheng Shi, Bofeng Yuan, Wenting Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ube2D3 and Ube2N are essential for RIG-I-mediated MAVS aggregation in antiviral innate immunity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms15138"}], "href": "https://doi.org/10.1038/ncomms15138"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28469175"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28469175"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Christine K Schmidt, Yaron Galanty, Matylda Sczaniecka-Clift, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Systematic E2 screening reveals a UBE2D-RNF138-CtIP axis promoting DNA repair."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb3260"}], "href": "https://doi.org/10.1038/ncb3260"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26502057"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26502057"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Wenbo Wang, Lei Yang, Liu Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of UBE2D3 expression attenuates radiosensitivity of MCF-7 human breast cancer cells by increasing hTERT expression and activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0064660"}], "href": "https://doi.org/10.1371/journal.pone.0064660"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23741361"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23741361"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xiaojia Gao, Wenbo Wang, Hui Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "UBE2D3 gene overexpression increases radiosensitivity of EC109 esophageal cancer cells in vitro and in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.8869"}], "href": "https://doi.org/10.18632/oncotarget.8869"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27105523"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27105523"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Arnau Vina-Vilaseca, Alexander Sorkin "}, {"type": "b", "children": [{"type": "t", "text": "Lysine 63-linked polyubiquitination of the dopamine transporter requires WW3 and WW4 domains of Nedd4-2 and UBE2D ubiquitin-conjugating enzymes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.058990"}], "href": "https://doi.org/10.1074/jbc.M109.058990"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20051513"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20051513"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Zeliha Yalçin, Daniëlle Koot, Karel Bezstarosti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ubiquitinome Profiling Reveals in Vivo UBE2D3 Targets and Implicates UBE2D3 in Protein Quality Control."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Proteomics (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mcpro.2023.100548"}], "href": "https://doi.org/10.1016/j.mcpro.2023.100548"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37059365"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37059365"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Monica Roman-Trufero, Constance M Ito, Conrado Pedebos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evolution of an Amniote-Specific Mechanism for Modulating Ubiquitin Signaling via Phosphoregulation of the E2 Enzyme UBE2D3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Evol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/molbev/msaa060"}], "href": "https://doi.org/10.1093/molbev/msaa060"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32145025"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32145025"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yuhuang Li, Xiao-Xin Sun, Johannes Elferich, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Monoubiquitination is critical for ovarian tumor domain-containing ubiquitin aldehyde binding protein 1 (Otub1) to suppress UbcH5 enzyme and stabilize p53 protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.533109"}], "href": "https://doi.org/10.1074/jbc.M113.533109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24403071"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24403071"}]}]}]}
Synonyms	E2(17)KB3, UBCH5C
Proteins	UB2D3_HUMAN
NCBI Gene ID	7323
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

UBE2D3 has 7,309 functional associations with biological entities spanning 9 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, sequence feature) extracted from 119 datasets.

Click the + buttons to view associations for UBE2D3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

UBE2D3 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 UBE2D3 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 UBE2D3 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 UBE2D3 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of UBE2D3 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 UBE2D3 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 UBE2D3 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 UBE2D3 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 UBE2D3 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 UBE2D3 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of UBE2D3 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 UBE2D3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with UBE2D3 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 UBE2D3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of UBE2D3 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 UBE2D3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of UBE2D3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing UBE2D3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing UBE2D3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with UBE2D3 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 UBE2D3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing UBE2D3 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of UBE2D3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with UBE2D3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with UBE2D3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with UBE2D3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with UBE2D3 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 UBE2D3 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with UBE2D3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with UBE2D3 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 UBE2D3 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 UBE2D3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with UBE2D3 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 UBE2D3 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 UBE2D3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of UBE2D3 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 UBE2D3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with UBE2D3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with UBE2D3 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of UBE2D3 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with UBE2D3 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.