USP3 Gene

HGNC Family	Ubiquitin-specific peptidases (USP)
Name	ubiquitin specific peptidase 3
Description	Enables deubiquitinase activity and histone binding activity. Involved in DNA repair and DNA repair-dependent chromatin remodeling. Located in several cellular components, including Flemming body; cytoplasmic ribonucleoprotein granule; and nucleoplasm. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nUSP3 was first characterized as a deubiquitinating enzyme that plays a crucial role in maintaining genome integrity. It removes monoubiquitin from histone H2A and H2B, modulating chromatin structure and facilitating an efficient DNA damage response. In particular, USP3 is essential for timely S phase progression and for the resolution of DNA double‐strand breaks, partly by deubiquitinating γH2AX and thereby contributing to the attenuation of damage‐induced signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in chromatin regulation, USP3 has emerged as a pivotal regulator in cancer biology by modulating the stability of numerous key proteins. USP3 promotes gastric cancer metastasis by remodeling ubiquitin conjugates, while in breast cancer it deubiquitinates and stabilizes the transcription factor KLF5 to drive cell proliferation. It also safeguards the levels of Cdc25A to ensure proper cell cycle progression and enhances the stability of oncogenic proteins such as MYCN. Moreover, USP3 functions in a competitive endogenous RNA network by modulating SMAD4 expression in colorectal cancer, and its expression can be indirectly upregulated via non‐coding RNAs such as lncRNA HOXA‐AS3 in glioblastoma as well as circRNAs in gastric cancer, thereby promoting tumor growth and metastasis. USP3 further contributes to tumorigenesis by stabilizing p53, Aurora A kinase, and the stem cell factor Oct4, and its deregulation is associated with poor prognostic outcomes in gastric cancer. USP3 has also been implicated in non‐small cell lung cancer (NSCLC), both in terms of enhancing proliferation and by promoting chemoresistance through ACOT7 deubiquitination, while in esophageal squamous cell carcinoma and osteosarcoma it stabilizes EPHA2 and Aurora A, thereby activating key signaling pathways that support malignant progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "19"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its oncogenic roles, USP3 is also involved in modulating other disease processes. In osteoarthritis, for example, enhanced expression of USP3 counteracts inflammatory signaling by deubiquitinating TRAF6, thereby suppressing NF‐κB activation and chondrocyte apoptosis. Collectively, recent reviews have underscored the multifaceted functions of USP3 in regulating protein turnover, cell cycle control, DNA repair, and signaling pathways across various physiological and pathological contexts, highlighting its potential as a therapeutic target."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Francesco Nicassio, Nadia Corrado, Joseph H A Vissers, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human USP3 is a chromatin modifier required for S phase progression and genome stability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cub.2007.10.034"}], "href": "https://doi.org/10.1016/j.cub.2007.10.034"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17980597"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17980597"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Nidhi Sharma, Qianzheng Zhu, Gulzar Wani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "USP3 counteracts RNF168 via deubiquitinating H2A and γH2AX at lysine 13 and 15."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/cc.26814"}], "href": "https://doi.org/10.4161/cc.26814"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24196443"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24196443"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xiaosheng Wu, Mengwei Liu, Huiqiong Zhu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "USP3 promotes breast cancer cell proliferation by deubiquitinating KLF5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA119.009102"}], "href": "https://doi.org/10.1074/jbc.RA119.009102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31624151"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31624151"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Soumyadip Das, Arun Pandian Chandrasekaran, Bharathi Suresh, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "LncRNA HOXA-AS3 promotes the malignancy of glioblastoma through regulating miR-455-5p/USP3 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.15788"}], "href": "https://doi.org/10.1111/jcmm.15788"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32918360"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32918360"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Xiaosheng Wu, Hao Wang, Danping Zhu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "USP3 stabilizes p53 protein through its deubiquitinase activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2017.08.036"}], "href": "https://doi.org/10.1016/j.bbrc.2017.08.036"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28807825"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28807825"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Qi Zhou, Zhonghua Xiao, Rong Zhou, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "USP3 promotes cisplatin resistance in non-small cell lung cancer cells by suppressing ACOT7-regulated ferroptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Anticancer Drugs (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/CAD.0000000000001562"}], "href": "https://doi.org/10.1097/CAD.0000000000001562"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38502867"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38502867"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Anan Li, Shijiang Wang, Jiangbo Nie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "USP3 promotes osteosarcoma progression via deubiquitinating EPHA2 and activating the PI3K/AKT signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-024-06624-7"}], "href": "https://doi.org/10.1038/s41419-024-06624-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38531846"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38531846"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Hongyan Zhang, Wenjing Liu, Yingying Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "USP3: Key deubiquitylation enzyme in human diseases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Sci (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cas.16178"}], "href": "https://doi.org/10.1111/cas.16178"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38651282"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38651282"}]}]}]}
Synonyms	SIH003
Proteins	UBP3_HUMAN
NCBI Gene ID	9960
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

USP3 has 10,519 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 117 datasets.

Click the + buttons to view associations for USP3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

USP3 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 USP3 gene relative to other tissues from the Allen Brain Atlas Adult Human 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 USP3 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 USP3 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 USP3 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 USP3 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 USP3 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 USP3 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 USP3 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 USP3 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 USP3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with USP3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with USP3 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 USP3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of USP3 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 USP3 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 USP3 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 USP3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing USP3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with USP3 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 USP3 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 USP3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with USP3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with USP3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with USP3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of USP3 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 USP3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with USP3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with USP3 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 USP3 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 USP3 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 USP3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with USP3 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 USP3 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 USP3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of USP3 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 USP3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with USP3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with USP3 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 USP3 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with USP3 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.