UHRF2 Gene

HGNC Family	Zinc fingers
Name	ubiquitin-like with PHD and ring finger domains 2, E3 ubiquitin protein ligase
Description	This gene encodes a nuclear protein which is involved in cell-cycle regulation. The encoded protein is a ubiquitin-ligase capable of ubiquinating PCNP (PEST-containing nuclear protein), and together they may play a role in tumorigenesis. The encoded protein contains an NIRF_N domain, a PHD finger, a set- and ring-associated (SRA) domain, and a RING finger domain and several of these domains have been shown to be essential for the regulation of cell proliferation. This protein may also have a role in intranuclear degradation of polyglutamine aggregates. Alternative splicing results in multiple transcript variants some of which are non-protein coding. [provided by RefSeq, Feb 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nUHRF2 is a multi‐domain nuclear protein that functions as both an epigenetic reader and an E3 ubiquitin ligase. Its SRA domain is uniquely adapted to recognize 5‑hydroxymethylcytosine (5hmC) by accommodating the hydroxymethyl group, thereby distinguishing it from 5‑methylcytosine. This binding specificity, along with cooperative interactions among its tandem domains, enables UHRF2 to preferentially associate with hemimethylated DNA and heterochromatin marks (e.g. H3K9me3), positioning it as a key regulator of active DNA demethylation and chromatin remodeling during cell differentiation and development."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its epigenetic functions, UHRF2 exerts critical control over cell cycle dynamics and proteostasis. Acting as an E3 ubiquitin ligase, it ubiquitinates a range of substrates—including cyclins D1 and E1—as well as other proteins involved in nuclear protein quality control. UHRF2 interacts with cell cycle regulators such as E2F1 to induce apoptosis and modulate the G1/S transition, and it participates in the clearance of aberrant polyglutamine protein aggregates. Moreover, its interaction with partners like PCNP and with base excision repair factors underscores its role as an intermodular hub linking the ubiquitin–proteasome system to cell cycle regulation and genome maintenance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAltered expression and deregulation of UHRF2 have been observed in various malignancies, where its role appears context dependent. In certain cancers—such as colorectal cancer, hepatocellular carcinoma, gliomas, and esophageal carcinoma—dysregulated UHRF2 (via overexpression, mislocalization, or epigenetic silencing) is associated with poor clinical outcomes. MicroRNAs (for example, let‑7a, miR‑196a, and miR‑98‑5p) have been shown to modulate UHRF2 levels and, consequently, affect targets such as TET2 and downstream signaling pathways. In addition, UHRF2 can interact with viral proteins (e.g. the hepatitis B virus core protein) and modulate histone acetylation states through interactions with chromatin regulators like TIP60 and HDAC1. These connections further influence pathways such as ErbB3/Ras/Raf and Wnt signaling, underscoring the multifaceted role of UHRF2 in tumor progression and cellular differentiation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "25"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nUHRF2 also contributes to genome stability by interfacing with DNA repair pathways. It becomes functionally integrated into the base excision repair (BER) machinery by catalyzing non‐proteolytic ubiquitination events that enhance the recruitment of repair factors such as XRCC1 and TDG, thus facilitating active DNA demethylation. Furthermore, through its interaction with ATR via its TTD domain and with the cell cycle regulator p21, UHRF2 plays an essential role in promoting proper checkpoint activation and repair responses following DNA damage induced by agents like ultraviolet light and hydroxyurea."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "26"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ting Zhou, Jun Xiong, Mingzhu Wang, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "HBx promotes hepatocarcinogenesis by enhancing phosphorylation and blocking ubiquitinylation of UHRF2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hepatol Int (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12072-021-10172-z"}], "href": "https://doi.org/10.1007/s12072-021-10172-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33876395"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33876395"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Yangyang Wang, Xinke Yan, Shengyuan Zeng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "UHRF2 promotes DNA damage response by decreasing p21 via RING finger domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biotechnol Lett (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10529-018-2577-5"}], "href": "https://doi.org/10.1007/s10529-018-2577-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29923055"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29923055"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Shunsuke Hanaki, Makoto Habara, Midori Shimada "}, {"type": "b", "children": [{"type": "t", "text": "UV-induced activation of ATR is mediated by UHRF2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Cells (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/gtc.12851"}], "href": "https://doi.org/10.1111/gtc.12851"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33848395"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33848395"}]}]}]}
Synonyms	RNF107, URF2, TDRD23
Proteins	UHRF2_HUMAN
NCBI Gene ID	115426
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

UHRF2 has 5,230 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 112 datasets.

Click the + buttons to view associations for UHRF2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

UHRF2 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 UHRF2 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 UHRF2 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 UHRF2 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 UHRF2 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 UHRF2 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 UHRF2 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 UHRF2 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 UHRF2 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 UHRF2 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 UHRF2 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 UHRF2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with UHRF2 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of UHRF2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of UHRF2 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 UHRF2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing UHRF2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing UHRF2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing UHRF2 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 UHRF2 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 UHRF2 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 UHRF2 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 UHRF2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with UHRF2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with UHRF2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with UHRF2 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 UHRF2 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 UHRF2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with UHRF2 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 UHRF2 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 UHRF2 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 UHRF2 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 UHRF2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with UHRF2 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 UHRF2 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 UHRF2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of UHRF2 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 UHRF2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with UHRF2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with UHRF2 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 UHRF2 from the GeneSigDB Published Gene Signatures dataset.