UBE4A Gene

HGNC Family	U-box domain containing (UBOX)
Name	ubiquitination factor E4A
Description	This gene encodes a member of the U-box ubiquitin ligase family. The encoded protein is involved in multiubiquitin chain assembly and plays a critical role in chromosome condensation and separation through the polyubiquitination of securin. Autoantibodies against the encoded protein may be markers for scleroderma and Crohn's disease. A pseudogene of this gene is located on the long arm of chromosome 3. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nUBE4A is a multifunctional U‐box–type ubiquitin ligase, originally identified as an E4 factor homologous to yeast Ufd2, with a tissue‐ and cell cycle–dependent expression profile that suggests roles extending beyond classical ubiquitination to include regulation of growth and differentiation in organs such as skeletal muscle, kidney, and liver."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Notably, UBE4A is rapidly recruited to sites of DNA double‐strand breaks where it enhances and sustains both K48‐ and K63–linked ubiquitin chains. This regulatory step is essential for guiding the timely arrival and proper organization of key repair proteins such as RAP80 and BRCA1, thereby ensuring end resection and favoring error‐free homologous recombination repair over more error-prone pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in the DNA damage response, UBE4A is critical for the faithful progression of mitosis. Loss or inhibition of its function results in defective polyubiquitination of substrates such as securin, leading to aberrant chromosome condensation, missegregation, and metaphase–anaphase arrest."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, UBE4A targets specific proteins involved in tumor progression; for example, it mediates the proteasomal degradation of the EMT inducer ILEI in prostate cancer cells and the RNA binding protein PCBP1 in thyroid cancer, thereby influencing cell migration, invasion, and overall tumor behavior."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent studies further highlight UBE4A’s involvement in oncogenic signaling networks. In colorectal cancer, stabilization of UBE4A mRNA by the RNA-binding protein PTBP3 leads to enhanced degradation of the tumor suppressor p53, promoting cell proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In parallel, UBE4A primes the transcription factor NRF1 for DDI2-mediated cleavage by extending its polyubiquitin chain length, a key step that activates NRF1 and drives the expression of proteasome subunits."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Collectively, these findings establish UBE4A as a versatile regulator of ubiquitin-dependent signaling pathways that are crucial for maintaining genomic integrity, proper cell cycle progression, and modulation of tumorigenic processes.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Gianmarco Contino, Francesca Amati, Sabina Pucci, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression analysis of the gene encoding for the U-box-type ubiquitin ligase UBE4A in human tissues."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2003.11.017"}], "href": "https://doi.org/10.1016/j.gene.2003.11.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15019985"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15019985"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ying Yang, Jian-qing Hou, Lu-yun Qu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Differential expression of USP2, USP14 and UBE4A between ovarian serous cystadenocarcinoma and adjacent normal tissues]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi (2007)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17553343"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17553343"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Keren Baranes-Bachar, Adva Levy-Barda, Judith Oehler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Ubiquitin E3/E4 Ligase UBE4A Adjusts Protein Ubiquitylation and Accumulation at Sites of DNA Damage, Facilitating Double-Strand Break Repair."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2018.02.002"}], "href": "https://doi.org/10.1016/j.molcel.2018.02.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29499138"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29499138"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Sarah Spinette, Christoph Lengauer, James A Mahoney, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ufd2, a novel autoantigen in scleroderma, regulates sister chromatid separation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2004)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15611659"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15611659"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yanan Sun, Xiaopeng Jia, Qiang Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The ubiquitin ligase UBE4A inhibits prostate cancer progression by targeting interleukin-like EMT inducer (ILEI)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "IUBMB Life (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/iub.1585"}], "href": "https://doi.org/10.1002/iub.1585"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27862841"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27862841"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ming-Peng Zhang, Wei-San Zhang, Jin Tan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Poly r(C) binding protein (PCBP) 1 expression is regulated by the E3 ligase UBE4A in thyroid carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biosci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BSR20170114"}], "href": "https://doi.org/10.1042/BSR20170114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28963376"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28963376"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Canbin Xie, Fei Long, Liang Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PTBP3 modulates P53 expression and promotes colorectal cancer cell proliferation by maintaining UBE4A mRNA stability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-022-04564-8"}], "href": "https://doi.org/10.1038/s41419-022-04564-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35136024"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35136024"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Xianyan Hu, Rong Zou, Zaihui Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "UBE4A catalyzes NRF1 ubiquitination and facilitates DDI2-mediated NRF1 cleavage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Gene Regul Mech (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbagrm.2023.194937"}], "href": "https://doi.org/10.1016/j.bbagrm.2023.194937"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37084817"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37084817"}]}]}]}
Synonyms	UFD2, UBOX2, E4
Proteins	UBE4A_HUMAN
NCBI Gene ID	9354
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

UBE4A has 6,082 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 119 datasets.

Click the + buttons to view associations for UBE4A from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

UBE4A 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 UBE4A 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 UBE4A 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 UBE4A 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 UBE4A 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 UBE4A 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 UBE4A 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 UBE4A 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 UBE4A 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 UBE4A 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 UBE4A gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of UBE4A 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 UBE4A gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with UBE4A protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with UBE4A 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 UBE4A gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of UBE4A 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 UBE4A 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 UBE4A 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 UBE4A gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing UBE4A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing UBE4A 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 UBE4A 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 UBE4A 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 UBE4A gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with UBE4A gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with UBE4A gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with UBE4A gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by UBE4A gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with UBE4A 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 UBE4A 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 UBE4A 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 UBE4A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with UBE4A 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 UBE4A 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 UBE4A gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of UBE4A 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 UBE4A from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of UBE4A gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with UBE4A 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 UBE4A from the GeneSigDB Published Gene Signatures dataset.