Affinage

UHRF2

E3 ubiquitin-protein ligase UHRF2 · UniProt Q96PU4

Length
802 aa
Mass
90.0 kDa
Annotated
2026-06-10
48 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

UHRF2 is a multi-domain nuclear E3 ubiquitin ligase and epigenetic reader that integrates histone and DNA modification signals at chromatin to govern DNA methylation dynamics, the cell cycle, and DNA damage responses (PMID:22064703, PMID:21598301, PMID:34111398). It engages chromatin through a tandem Tudor domain that binds H3K9me2/3, an SRA domain that reads DNA modifications, and a PHD finger, with heterochromatin enrichment driven principally by H3K9me recognition (PMID:22064703, PMID:21598301); structural work showed its SRA domain forms a dedicated pocket that hydrogen-bonds the 5-hydroxymethylcytosine hydroxyl group, conferring preferential 5hmC over 5mC binding (PMID:24813944), and in vivo it acts as a 5hmC reader without altering TET enzymatic activity (PMID:28115522, PMID:28402695). Recognition of hemi-methylated or hemi-hydroxymethylated DNA allosterically activates its RING-dependent ubiquitin ligase activity (PMID:29506131), and 5hmC-stimulated UHRF2 catalyzes non-proteolytic K33-linked polyubiquitination of XRCC1, which recruits RAD23B and TDG to drive TDG-BER-dependent active DNA demethylation at promoters and enhancers during neuronal commitment (PMID:34111398). Despite interacting with DNMT1/3a/3b and G9a, UHRF2 cannot bind DNMT1 in an S-phase-dependent manner or maintain global methylation, and its physiological roles are locus-specific: knockout mice retain global methylation but lose brain 5hmC and locus-specific 5mC and develop seizures (PMID:22064703, PMID:21598301, PMID:28115522, PMID:28402695), while in primordial germ cells UHRF2 protects retrotransposon methylation and restrains precocious germline demethylation (PMID:40783491). Beyond methylation, UHRF2 regulates the cell cycle by ubiquitinating cyclins D1/E1 and p21 and controlling CDK-inhibitor levels (PMID:22673569, PMID:29923055, PMID:38752903), cooperates with UHRF1 to retain FANCD2 at interstrand crosslinks and promote its monoubiquitination (PMID:30335751), and is required for UV-induced ATR activation via its TTD domain (PMID:33848395). It additionally functions as a SUMO E3 ligase and chromatin co-regulator—SUMOylating TCF4 to sustain Wnt signaling, stabilizing TIP60 to modulate histone acetylation, and forming a complex with HDAC1 that, via atypical K29-linked ubiquitination, silences type I interferon genes during viral infection (PMID:23404503, PMID:27743347, PMID:32372448, PMID:42212328).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2011 High

    Established how UHRF2 is targeted to chromatin, answering whether it reads histone and DNA marks like its paralog and why it nonetheless cannot substitute for UHRF1.

    Evidence Binding assays, Co-IP, live-cell imaging and FRAP with domain mutants in cells, including Uhrf1-null mouse ES cells

    PMID:21598301 PMID:22064703

    Open questions at the time
    • Did not define the catalytic output of chromatin engagement
    • Structural basis of mark recognition not resolved at this stage
  2. 2014 High

    Defined the molecular basis for UHRF2's selective recognition of 5hmC, distinguishing its reader specificity from 5mC binding.

    Evidence X-ray crystallography of SRA-5hmC DNA complex with binding assays and mutagenesis

    PMID:24813944

    Open questions at the time
    • Did not connect 5hmC reading to a catalytic or cellular output
    • In vivo relevance of the pocket not tested here
  3. 2012 Medium

    Identified UHRF2 as an E3 ubiquitin ligase acting on cell cycle regulators, linking it to G1 control.

    Evidence In vivo and in vitro ubiquitination assays with cell cycle analysis

    PMID:22673569

    Open questions at the time
    • Ubiquitin chain linkage and degradation outcome not characterized
    • Reported in a synthesis paper rather than fully primary form
  4. 2013 High

    Revealed that UHRF2 possesses SUMO E3 activity distinct from its ubiquitin ligase function, broadening its enzymatic repertoire.

    Evidence In vitro and in vivo SUMOylation assays with domain deletion mapping on ZNF131

    PMID:23404503

    Open questions at the time
    • Biological consequence of ZNF131 SUMOylation unresolved
    • Domain requirements for SUMO vs ubiquitin activity not structurally explained
  5. 2013 Medium

    Placed UHRF2 in the E2F1 apoptotic program and at DNA damage sites, implicating it in damage signaling.

    Evidence shRNA screen, ChIP, Co-IP, reporter and apoptosis assays; laser microirradiation with domain mutants and γH2AX readouts

    PMID:23833190 PMID:24134842

    Open questions at the time
    • Direct enzymatic targets at damage sites not identified
    • Mechanism linking recruitment to H2AX phosphorylation unresolved
  6. 2016 Medium

    Identified protein partners and chromatin-modifying complexes that direct UHRF2 to specific loci and let it modulate histone acetylation and EMT/Wnt programs.

    Evidence Co-IP, ChIP-seq/ChIP-qPCR, IP-MS and ubiquitination assays across multiple cell systems (ZNF618, TIP60/HDAC1, TCF7L2)

    PMID:27114453 PMID:27129234 PMID:27743347

    Open questions at the time
    • Causal hierarchy between locus targeting and transcriptional output unclear
    • TIP60 stabilization mechanism not structurally defined
  7. 2017 High

    Used genetic and structural approaches to establish UHRF2 as a 5hmC reader in vivo and a PCNA-interacting protein, while clarifying its locus-specific (not global) role in methylation.

    Evidence Knockout mice with 5hmC/5mC dot-blot and bisulfite sequencing; PCNA-PIP box crystal structure with mutagenesis

    PMID:28115522 PMID:28402695 PMID:28951215

    Open questions at the time
    • Causal mechanism by which UHRF2 maintains locus-specific 5mC unresolved at this stage
    • Functional role of PCNA interaction in vivo untested
  8. 2018 High

    Demonstrated allosteric control of UHRF2 ligase activity by DNA hydroxymethylation and a cooperative role in interstrand crosslink repair, connecting its reader and catalytic functions.

    Evidence Reconstituted in vitro E3 assays with modified DNA and nucleosomes; live imaging, Co-IP and FANCD2 monoubiquitination assays

    PMID:29506131 PMID:29923055 PMID:30335751

    Open questions at the time
    • Why UHRF2 is unproductive on mononucleosomes despite allosteric activation not resolved
    • In vivo substrate of allosteric activation not yet defined here
  9. 2021 High

    Resolved the central mechanism linking 5hmC reading to active DNA demethylation, identifying XRCC1 K33 ubiquitination as the catalytic output, and added ATR activation and CDK2-mediated regulation of UHRF2.

    Evidence In vitro linkage-specific ubiquitination, Co-IP, MS, integrative epigenomics in Uhrf2-KO ES cells; CoIP/phospho-western for ATR; phospho-site mutagenesis for CDK2/S643

    PMID:33848395 PMID:33876395 PMID:34111398 PMID:34766381 PMID:36690646

    Open questions at the time
    • Generality of the XRCC1-RAD23B-TDG axis beyond neuronal commitment untested
    • Structural mechanism of allosteric activation still not solved
  10. 2020 High

    Linked UHRF2 SUMO ligase activity to oncogenic Wnt signaling through TCF4 stabilization in vivo.

    Evidence Co-IP, SUMOylation assays, ApcMin knockout mice and organoid assays

    PMID:32372448

    Open questions at the time
    • SUMO chain architecture on TCF4 not defined
    • Relationship to UHRF2 ubiquitin activity in the same cells unclear
  11. 2023 High

    Extended UHRF2 function to metabolic and autophagy control, showing a hepatocyte requirement for suppressing cholesterol biosynthesis during liver regeneration.

    Evidence Hepatocyte-specific knockout with partial hepatectomy and bile acid scavenger rescue, Co-IP; Co-IP and xenograft for PARP1/PRDX1

    PMID:37253089 PMID:37356603

    Open questions at the time
    • Direct chromatin targets of UHRF2 in cholesterol gene suppression not mapped
    • PARP1/PRDX1 interactions rest on single Co-IPs without mechanistic depth
  12. 2024 Medium

    Defined UHRF2's own cell-cycle-coupled expression and a negative-feedback circuit controlling cyclin and CDK-inhibitor levels.

    Evidence CRISPR/Cas9 knockout, cell synchronization, flow cytometry, CDK1 inhibitor treatment

    PMID:38752903

    Open questions at the time
    • Direct ubiquitination of each cyclin/inhibitor not all reconstituted
    • Mechanism of self-transcriptional repression undefined
  13. 2025 High

    Established a germline-specific role for UHRF2 in protecting retrotransposon methylation, distinct from its somatic functions.

    Evidence Knockout mouse model with whole-genome bisulfite sequencing, RNA-seq and fertility assays

    PMID:40783491

    Open questions at the time
    • Molecular mechanism conferring resistance to germline demethylation not defined
    • Whether the XRCC1 ubiquitination axis operates in PGCs untested
  14. 2026 Medium

    Connected UHRF2 to innate immune control, showing it stabilizes HDAC1 via atypical K29 ubiquitination to silence type I interferon genes.

    Evidence Co-IP, linkage-specific ubiquitination assays, ChIP, H4K12la analysis and Uhrf2-KO mice with viral challenge

    PMID:42212328

    Open questions at the time
    • Direct demonstration of K29 chain assembly geometry absent
    • How TBK1 nuclear translocation recruits UHRF2 not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unifying structural model explaining how chromatin-bound UHRF2 selects among ubiquitin (K33, K29) and SUMO outputs on different substrates remains undefined.
  • No structure of full-length UHRF2 bound to chromatin with E2/SUMO machinery
  • Determinants of linkage specificity across substrates unknown
  • Reconciliation of allosteric activation with nucleosome unproductivity unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0003677 DNA binding 3 GO:0016874 ligase activity 3 GO:0042393 histone binding 3 GO:0016740 transferase activity 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005654 nucleoplasm 4 GO:0005634 nucleus 3 GO:0000228 nuclear chromosome 2
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-73894 DNA Repair 4 R-HSA-1640170 Cell Cycle 3 R-HSA-4839726 Chromatin organization 3 R-HSA-1266738 Developmental Biology 2 R-HSA-162582 Signal Transduction 2 R-HSA-168256 Immune System 1
Partners
ATRFANCD2HDAC1TCF4TIP60UHRF1XRCC1ZNF618
Complex memberships
BER complex (XRCC1-RAD23B-TDG)FA core complex (with UHRF1 and FANCD2)UHRF2-HDAC1 complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 UHRF2 binds preferentially to methylated histone H3 lysine 9 (H3K9me2/3) through its conserved tandem Tudor domain, and to hemi-methylated DNA through its SRA domain. Both activities are required for its enrichment at pericentric heterochromatin. Binding assays, co-immunoprecipitation, fluorescence localization experiments in cells Cell research High 21598301 22064703
2011 UHRF2 interacts with DNMT1, DNMT3a, DNMT3b, and G9a by co-immunoprecipitation, but unlike UHRF1, UHRF2 does not interact with DNMT1 in an S phase-dependent manner and cannot recruit DNMT1 to replication foci, explaining why UHRF2 cannot rescue DNA methylation defects in Uhrf1-null ES cells. Co-immunoprecipitation, cell synchronization, fluorescence microscopy in Uhrf1-null mouse embryonic stem cells Cell research High 21598301 22064703
2011 UHRF2 heterochromatin localization depends primarily on its H3K9me-binding activity (tandem Tudor domain) and to a lesser extent on its methylated DNA-binding activity (SRA domain), as shown by FRAP analyses and domain mutants. FRAP, domain mutagenesis, fluorescence localization in live cells Journal of cellular biochemistry Medium 21598301
2014 Crystal structure of UHRF2-SRA domain in complex with 5-hydroxymethylcytosine (5hmC)-containing DNA revealed that a phenylalanine residue forms an optimal 5hmC binding pocket and a hydrogen bond between the hydroxyl group of 5hmC and the SRA domain is critical for preferential binding over 5mC. X-ray crystallography, in vitro binding assays, site-directed mutagenesis Molecular cell High 24813944
2012 UHRF2 (NIRF) acts as an E3 ubiquitin ligase that ubiquitinates cyclins D1 and E1, thereby inducing G1 cell cycle arrest. Ubiquitination assays in vivo and in vitro, cell cycle analysis FEBS letters Medium 22673569
2013 UHRF2 acts as a SUMO E3 ligase for zinc finger protein 131 (ZNF131), enhancing ZNF131 SUMOylation but not ubiquitination. The SUMO E3 activity requires the SRA and NLS-containing region domains, whereas the RING domain (critical for ubiquitin E3 activity) is dispensable for SUMOylation. SUMOylation assays in vivo and in vitro, domain deletion/mutagenesis analysis The Journal of biological chemistry High 23404503
2013 UHRF2 is a direct transcriptional target of E2F1 and physically interacts with E2F1 protein; UHRF2 is required for E2F1-induced apoptosis and for E2F1 transcription of apoptotic regulators. shRNA screen, ChIP, Co-immunoprecipitation, reporter assays, apoptosis assays The Journal of biological chemistry Medium 23833190
2013 UHRF2 is recruited to sites of DNA damage (by laser microirradiation), and the TTD, PHD, and SRA domains are required for this recruitment. Depletion of UHRF2 suppresses DNA damage-induced H2AX phosphorylation and impairs DNA damage repair in vascular smooth muscle cells. Laser microirradiation, live-cell fluorescence imaging, domain mutant analysis, siRNA knockdown, γH2AX immunofluorescence Biochemical and biophysical research communications Medium 24134842
2016 ZNF618 specifically interacts with UHRF2 (but not UHRF1) and regulates UHRF2 chromatin localization to 5hmC-enriched genomic loci in vivo. ZNF618 chromatin binding is independent of its interaction with UHRF2 and is mediated through its first two zinc fingers. Co-immunoprecipitation, ChIP-seq, co-localization experiments, domain mutant analysis The Journal of biological chemistry Medium 27129234
2016 UHRF2 interacts with TIP60 acetyltransferase and HDAC1 by co-immunoprecipitation. UHRF2 stabilizes TIP60 via ubiquitination through its RING domain, thereby regulating H3K9ac and H3K14ac levels. Co-immunoprecipitation, ubiquitination assays, western blot, histone modification analysis Protein & cell Medium 27743347
2016 UHRF2 overexpression acts as a transcriptional co-regulator of EMT transcription factors; UHRF2 binds to the CDH1 promoter (by ChIP-qPCR) and interacts with TCF7L2 and chromatin remodeling/histone modification complexes (by IP-MS). ChIP-seq, ChIP-qPCR, IP-MS, proteome profiling, cell invasion assays Molecular & cellular proteomics Medium 27114453
2016 UHRF2 interacts with H3K9ac through its PHD finger domain, as shown by co-immunoprecipitation and domain deletion experiments, and decreases H3K9ac expression in HCC cells. Co-immunoprecipitation, immunofluorescence, domain deletion analysis, western blot International journal of molecular medicine Low 28004105
2017 Crystal structure of UHRF2 PCNA-interacting protein (PIP) box peptide in complex with PCNA revealed the molecular basis for UHRF2-PCNA interaction via a canonical PIP-box motif (residues 784-800). Mutagenesis experiments validated the structural findings. X-ray crystallography, site-directed mutagenesis, structural analysis Biochemical and biophysical research communications High 28951215
2017 Uhrf2 knockout mice show no global DNA methylation change but exhibit decreased 5hmC levels specifically in brain (cortex and hippocampus), and UHRF2 binds 5hmC in cells without affecting TET1 enzymatic activity, supporting UHRF2 as a 5hmC reader in vivo. Knockout mouse model, dot-blot for 5hmC/5mC, gene expression profiling, in vivo binding assays The Journal of biological chemistry High 28115522 28402695
2017 Uhrf2 knockout mice develop spontaneous seizures and show decreased 5mC levels at specific genomic loci in brain, without global DNA methylation changes, demonstrating a locus-specific role for UHRF2 in 5mC maintenance in brain distinct from UHRF1. Knockout mouse model, bisulfite sequencing, EEG recording, locus-specific methylation analysis Epigenetics High 28402695
2018 Comparative biochemical analysis revealed that UHRF2 has divergent DNA binding properties from UHRF1: both hemi-methylated and hemi-hydroxymethylated DNA allosterically stimulate UHRF2 ubiquitin ligase activity toward histone H3 peptide substrates (first example of an E3 ligase allosterically regulated by DNA hydroxymethylation), but UHRF2 is not a productive histone E3 ligase toward purified mononucleosomes, suggesting a conformational constraint when bound to chromatin. Recombinant protein biochemistry, in vitro E3 ubiquitin ligase assays with DNA oligonucleotides, binding assays, mononucleosome substrates Nucleic acids research High 29506131
2018 UHRF2 cooperates with UHRF1 to ensure recruitment of FANCD2 to interstrand crosslinks (ICLs). UHRF2 is recruited to ICLs within seconds, forms direct protein-protein interactions with UHRF1 and FANCD2, and stimulates monoubiquitination of FANCD2 by retaining it on chromatin for the FA core complex. Live-cell imaging (rapid recruitment assay), Co-immunoprecipitation, chromatin fractionation, FANCD2 monoubiquitination assays, siRNA knockdown PLoS genetics High 30335751
2018 UHRF2 ubiquitinates p21 via its RING domain, leading to p21 degradation and shortened p21 half-life, which promotes DNA damage response in HEK293 cells. Co-immunoprecipitation, ubiquitination assay, cycloheximide chase, immunofluorescence Biotechnology letters Medium 29923055
2020 UHRF2 directly interacts with and SUMOylates TCF4 (a Wnt pathway transcription factor), stabilizing TCF4 protein and sustaining hyperactive Wnt/β-catenin signaling in intestinal tumor cells. Co-immunoprecipitation, SUMOylation assays, genetic knockout mice on ApcMin background, organoid formation assays International journal of cancer High 32372448
2021 UHRF2 is allosterically activated by 5hmC and catalyzes K33-linked polyubiquitination of XRCC1. This non-proteolytic ubiquitination promotes XRCC1 interaction with RAD23B (via its ubiquitin-binding domain), which recruits TDG into the BER complex to complete active DNA demethylation. In mouse embryonic stem cells, Uhrf2 ablation impedes DNA demethylation at active promoters and poised-to-active enhancers during neuronal commitment. In vitro ubiquitination assays, Co-immunoprecipitation, mass spectrometry, integrative epigenomic analysis (ChIP-seq, bisulfite-seq), Uhrf2 knockout mouse ES cells, neuronal differentiation assay Molecular cell High 34111398
2021 UHRF2 physically interacts with ATR through its TTD domain in a DNA damage-dependent manner. UHRF2 depletion impairs phosphorylation of ATR at threonine 1989 (required for UV-induced ATR activation), indicating UHRF2 is required for ATR activation after UV irradiation. Co-immunoprecipitation, domain mutant analysis, phospho-specific western blot, siRNA knockdown, UV irradiation Genes to cells Medium 33848395
2021 UHRF2 TTD domain has modestly higher affinity for the H3 tail than the PHD domain (opposite to UHRF1 where PHD is primary contributor). Aromatic residues in UHRF2 TTD contribute to both selectivity and affinity for H3K9me3, whereas the PHD contains a distinct asparagine that lowers binding affinity. TTD and PHD cooperate in H3 tail binding. Fluorescence polarization binding assays, isothermal titration calorimetry, domain mutagenesis, thermal shift assays Proteins Medium 34766381
2021 UHRF2 binds CDK2 directly and is phosphorylated at serine 643 by CDK2 (promoted by the HBx-ETS1-CDK2 axis in HBV-associated HCC), which blocks UHRF2's E3 ubiquitin ligase activity and promotes DHX9 protein stability by preventing its ubiquitination. Co-immunoprecipitation, ubiquitination assays, phosphorylation-site mutagenesis (S643), western blot in HBV-positive HCC cells Hepatology international / Cell death discovery Medium 33876395 36690646
2023 UHRF2 interacts with chromatin remodeling proteins (Co-IP in hepatocytes) and suppresses the expression of cholesterol biosynthesis genes in an FGFR-dependent manner. Hepatocyte-specific Uhrf2 knockout leads to cholesterol and bile acid accumulation during liver regeneration, causing liver necrosis that is rescued by bile acid scavenger treatment. Hepatocyte-specific Uhrf2 knockout, partial hepatectomy model, Co-immunoprecipitation, gene expression analysis, bile acid scavenger rescue Science signaling High 37253089
2023 UHRF2 binds autophagy-related protein PARP1 (by Co-IP) and upregulates PARP1 protein level, promoting autophagy in HCC cells. PRDX1 also binds UHRF2 and upregulates its protein expression. Co-immunoprecipitation, western blot, electron microscopy, immunofluorescence, in vivo xenograft Cellular signalling Low 37356603
2024 UHRF2 protein accumulates in early G1 phase following serum stimulation from quiescence or after mitotic exit (where it is degraded during G2/M in a CDK1-dependent manner). UHRF2 controls cyclin and CDK inhibitor levels and represses its own transcription in a negative-feedback loop. CRISPR/Cas9 deletion of UHRF2 causes elevated cyclin levels and elevated p27KIP1, reducing retinoblastoma phosphorylation and prolonging each cell cycle phase. CRISPR/Cas9 knockout, cell synchronization, flow cytometry, western blot, CDK1-specific inhibitor treatment Cell cycle Medium 38752903
2025 UHRF2 is required for resistance to DNA methylation reprogramming at retrotransposons in primordial germ cells (PGCs). Uhrf2 knockout PGCs show loss of retrotransposon DNA methylation and precocious demethylation of germline genes, leading to meiotic gene overexpression in females, impaired oocyte development, female-specific reduced fertility, and incomplete remethylation of retrotransposons during spermatogenesis. This function in the germline is distinct from somatic cells. Knockout mouse model, whole-genome bisulfite sequencing, RNA-seq, fertility assays Nature communications High 40783491
2026 During viral infection, nuclear-translocated TBK1 is hijacked by UHRF2 at IFN-I gene loci. UHRF2 physically interacts with HDAC1 and catalyzes atypical K29-linked polyubiquitination of HDAC1, stabilizing it. The UHRF2-HDAC1 complex erases H4K12 lactylation at IFN-I loci, silencing type I interferon transcription. IFN-I signaling feedback transiently downregulates UHRF2 expression to allow initial antiviral response. Co-immunoprecipitation, ubiquitination assays (linkage-specific), ChIP, H4K12la chromatin analysis, Uhrf2 knockout mouse model with viral challenge International journal of biological sciences Medium 42212328

Source papers

Stage 0 corpus · 48 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 S phase-dependent interaction with DNMT1 dictates the role of UHRF1 but not UHRF2 in DNA methylation maintenance. Cell research 112 22064703
2014 Structural basis for hydroxymethylcytosine recognition by the SRA domain of UHRF2. Molecular cell 90 24813944
2011 Cooperative DNA and histone binding by Uhrf2 links the two major repressive epigenetic pathways. Journal of cellular biochemistry 64 21598301
1983 Genes for cytochrome c oxidase subunit I, URF2, and three tRNAs in Drosophila mitochondrial DNA. Nucleic acids research 55 6314262
2017 The 5-Hydroxymethylcytosine (5hmC) Reader UHRF2 Is Required for Normal Levels of 5hmC in Mouse Adult Brain and Spatial Learning and Memory. The Journal of biological chemistry 43 28115522
2012 NIRF/UHRF2 occupies a central position in the cell cycle network and allows coupling with the epigenetic landscape. FEBS letters 37 22673569
1984 Mitochondrial DNA of Chlamydomonas reinhardtii: the DNA sequence of a region showing homology with mammalian URF2. Current genetics 34 24173513
1985 Sequence homologies among mitochondrial DNA-coded URF2, URF4 and URF5. FEBS letters 33 4029400
2016 Multidimensional Proteomics Reveals a Role of UHRF2 in the Regulation of Epithelial-Mesenchymal Transition (EMT). Molecular & cellular proteomics : MCP 30 27114453
2018 Comparative biochemical analysis of UHRF proteins reveals molecular mechanisms that uncouple UHRF2 from DNA methylation maintenance. Nucleic acids research 28 29506131
2013 The nuclear protein UHRF2 is a direct target of the transcription factor E2F1 in the induction of apoptosis. The Journal of biological chemistry 28 23833190
2020 UHRF2 promotes intestinal tumorigenesis through stabilization of TCF4 mediated Wnt/β-catenin signaling. International journal of cancer 25 32372448
2021 UHRF2 commissions the completion of DNA demethylation through allosteric activation by 5hmC and K33-linked ubiquitination of XRCC1. Molecular cell 24 34111398
2016 Loss of UHRF2 expression is associated with human neoplasia, promoter hypermethylation, decreased 5-hydroxymethylcytosine, and high proliferative activity. Oncotarget 23 27738314
2018 Identification of UHRF2 as a novel DNA interstrand crosslink sensor protein. PLoS genetics 19 30335751
2013 UHRF2, a ubiquitin E3 ligase, acts as a small ubiquitin-like modifier E3 ligase for zinc finger protein 131. The Journal of biological chemistry 19 23404503
2021 MiR-196a promotes the proliferation and migration of esophageal cancer via the UHRF2/TET2 axis. Molecular and cellular biochemistry 18 34826027
2017 Overexpression of UHRF2 in intrahepatic cholangiocarcinoma and its clinical significance. OncoTargets and therapy 18 29270024
2016 E3 ligase UHRF2 stabilizes the acetyltransferase TIP60 and regulates H3K9ac and H3K14ac via RING finger domain. Protein & cell 18 27743347
2018 Identification of UHRF2 as a Negative Regulator of Epithelial-Mesenchymal Transition and Its Clinical Significance in Esophageal Squamous Cell Carcinoma. Oncology 17 29909415
2016 Zinc Finger Protein 618 Regulates the Function of UHRF2 (Ubiquitin-like with PHD and Ring Finger Domains 2) as a Specific 5-Hydroxymethylcytosine Reader. The Journal of biological chemistry 17 27129234
2013 Uhrf2 is important for DNA damage response in vascular smooth muscle cells. Biochemical and biophysical research communications 17 24134842
2017 UHRF2 regulates local 5-methylcytosine and suppresses spontaneous seizures. Epigenetics 15 28402695
2018 Loss of UHRF2 Is Associated With Non-small Cell Lung Carcinoma Progression. Journal of Cancer 14 30210621
2023 Phosphorylation of UHRF2 affects malignant phenotypes of HCC and HBV replication by blocking DHX9 ubiquitylation. Cell death discovery 13 36690646
2012 UHRF2 mRNA expression is low in malignant glioma but silencing inhibits the growth of U251 glioma cells in vitro. Asian Pacific journal of cancer prevention : APJCP 13 23244124
2023 UHRF2 promotes the malignancy of hepatocellular carcinoma by PARP1 mediated autophagy. Cellular signalling 11 37356603
2016 UHRF2 decreases H3K9ac expression by interacting with it through the PHD and SRA/YDG domain in HepG2 hepatocellular carcinoma cells. International journal of molecular medicine 11 28004105
2021 UHRF2 promotes Hepatocellular Carcinoma Progression by Upregulating ErbB3/Ras/Raf Signaling Pathway. International journal of medical sciences 10 34400880
2018 UHRF2 promotes DNA damage response by decreasing p21 via RING finger domain. Biotechnology letters 10 29923055
2017 Structure insights into the molecular mechanism of the interaction between UHRF2 and PCNA. Biochemical and biophysical research communications 9 28951215
2021 HBx promotes hepatocarcinogenesis by enhancing phosphorylation and blocking ubiquitinylation of UHRF2. Hepatology international 8 33876395
2023 The ubiquitin ligase Uhrf2 is a master regulator of cholesterol biosynthesis and is essential for liver regeneration. Science signaling 7 37253089
2021 IGF2BP1/UHRF2 Axis Mediated by miR-98-5p to Promote the Proliferation of and Inhibit the Apoptosis of Esophageal Squamous Cell Carcinoma. Annals of clinical and laboratory science 7 34162562
2022 Quantification of Global DNA Hydroxymethylation Level Using UHRF2 SRA-Luciferase Based on Bioluminescence Resonance Energy Transfer. Analytical chemistry 6 35657260
2021 Molecular investigation of the tandem Tudor domain and plant homeodomain histone binding domains of the epigenetic regulator UHRF2. Proteins 6 34766381
2024 E3 Ubiquitin Ligase Uhrf2 Knockout Reveals a Critical Role in Social Behavior and Synaptic Plasticity in the Hippocampus. International journal of molecular sciences 5 38338822
2021 UV-induced activation of ATR is mediated by UHRF2. Genes to cells : devoted to molecular & cellular mechanisms 5 33848395
2017 Uhrf2 deletion impairs the formation of hippocampus-dependent memory by changing the structure of the dentate gyrus. Brain structure & function 5 28900727
2024 UHRF2 accumulates in early G1-phase after serum stimulation or mitotic exit to extend G1 and total cell cycle length. Cell cycle (Georgetown, Tex.) 3 38752903
2023 Impaired Repopulating Ability of Uhrf2-/- Hematopoietic Progenitor Cells in Mice. Genes 3 37628583
2012 UHRF2, another E3 ubiquitin ligase for p53. Biochemical and biophysical research communications 3 22902639
2025 UHRF2 mediates resistance to DNA methylation reprogramming in primordial germ cells. Nature communications 1 40783491
2025 PCNP promotes hepatocellular carcinoma progression by upregulating UHRF2 to activate ErbB3/Ras/Raf pathway. Scientific reports 1 41271959
2026 UHRF2 related to sumoylation : assessment of its role in immune suppression and therapeutic potential in colorectal cancer. BMC cancer 0 41761142
2026 Platycodin D Overcomes Cisplatin Resistance in Gastric Cancer by Inducing Ferroptosis through TLK1-Dependent UHRF2/DNMT3A/ALOX15 Pathway. Chinese journal of integrative medicine 0 42149324
2026 E3 ligase UHRF2 hijacks nuclear TBK1 to epigenetically repress type I interferons expression. International journal of biological sciences 0 42212328
2025 Identification and functional regulation of two alternative splicing isoforms of the Uhrf2 gene in Miichthysmiiuy. Developmental and comparative immunology 0 40074104

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