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Symbol UHRF1 contributors: mct/npt/pgu - updated : 24-05-2016
HGNC name ubiquitin-like with PHD and ring finger domains 1
HGNC id 12556
Location 19p13.3      Physical location : 4.909.509 - 4.962.164
Synonym name
  • ubiquitin-like, containing PHD and RING finger domains, 1
  • transcription factor ICBP90
  • inverted CCAAT box-binding protein of 90 kDa
  • RING finger protein 106
  • nuclear zinc finger protein Np95
  • CCAAT-box binding protein
  • Synonym symbol(s) NP95, ICBP90, FLJ21925, RNF106, MGC138707
    TYPE functioning gene
    STRUCTURE 52.66 kb     18 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   transcription factor
    text structure
  • SP1 binding sites
  • in intron1 two E2F-1-binding motifs
  • MAPPING cloned Y linked N status provisional
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    17 - 3922 89.7 793 - 2006 17067204
    16 - 4086 91 806 - 2006 17067204
    - - 4339 - 793 - 2006 17067204
    - - 3927 - 793 - 2006 17067204
    - - 3901 - 793 - 2006 17067204
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   moderately
    Lymphoid/Immunelymph node   highly
     thymus   highly
    Reproductivemale systemprostate  moderately
    Respiratorylung   moderately
    Skin/Tegumentskin   highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier liningepidermisstratum basalehighly
    cell lineage
    cell lines
    at STAGE
    physiological period fetal
    Text thymus, liver, bone marrow
  • N-terminal ubiquitin-like domain partially overlapped by a leucine zipper domain
  • a central zinc finger of the PHD finger type, contributing to the opening and/or stabilization of dense chromocenter structures to support the recruitment of modifying enzymes, like HDAC and DNMT1, required for the replication and formation of pericentromeric heterochromatin , and crucial for recruitment of DNMT1 to DNA replication sites and for maintenance of DNA methylation in mammalian cells
  • conserved SRA (SET- and RING finger-associated) domain, involved in recognition of hemimethylated DNA
  • a tandem Tudor domain and a PHD finger, tethered by a 17-AA linker, and has been implicated to link histone modifications and DNA methylation
  • a C-terminal zinc finger of the ring finger type, involved in chromatin modification function with the ability to recruit EME1 following replication-associated DNA damage
  • two nuclear localization signals
  • phosphorylation sites for several kinases
  • a consensus Rb binding sequence
  • a methyl DNA binding domain, the SRA (SET and RING Associated)
  • domain, which shows strong preferential binding to hemimethylated
    CG sites, the physiological substrate for DNMT1
    interspecies homolog to C.elegans F01e11.1
    intraspecies paralog to UHRF2
  • ubiquitin family
  • CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
  • enriched in pericentric heterochromatin of interphase nuclei, and this localization is dependent on H3K9 methylation
  • endogenous N-methylpurine DNA glycosylase (MPG) and UHRF1 were co-localized in the nucleoplasm
  • basic FUNCTION
  • functions to maintain CpG DNA methylation patterns through DNA replication by co-localizing with the DNA methyltransferase DNMT1 at chromatin
  • involved in the regulation of topoisomerase 2 alpha gene expression
  • RNA polymerase 2 transcription factor
  • nuclear protein binding to the TOP2A gene promoter and involved in DNA replication (expression is cell cycle regulated in normal cells but stably high throughout cell cycle in various cancer cell lines)
  • involved in cell proliferation by way of methylation-mediated regulation of certain genes
  • required for maintenance of CG DNA methylation,
  • and is required for the stable association of DNMT1 with chromatin
  • facilitate the optimal processing of DNA damage, consistent with previously described models and studies of chromatin remodeling during DNA repair
  • being an E3 ligase important for the maintenance of global and local DNA methylation
  • acting as a key factor for DNMT1 maintenance methylation through recognition of a fundamental unit of epigenetic inheritance, mCpG
  • required for proper heterochromatin formation in mammalian cells
  • histone-binding protein expressed only in proliferating cells
  • may serve as a focal point of transcriptional regulation mediated by EHMT2 and other chromatin modification enzymes
  • may play a role in the DNA methylation profile inheritance as well as in the histone code inheritance
  • crucial cofactor for maintenance of DNA methylation by DNMT1, is endowed with E3 ubiquitin ligase activity
  • both DNMT1 and UHRF1 coprecipitate with ubiquitin specific peptidase 7 (USP7), a de-ubiquitinating enzyme
  • required for cell cycle progression and epigenetic regulation
  • links epigenetic regulation with DNA replication
  • specifically binds to hemi-methylated DNA through its SRA and has an essential role in maintenance of DNA methylation by recruiting Dnmt1 to hemi-methylated DNA sites
  • its ability to repress its direct target gene expression is dependent on PHD(UHRF1) binding to unmodified H3R2
  • UHRF2 and UHRF1 are not functionally redundant in DNA methylation maintenance, revealing the cell-cycle-dependent interaction between UHRF1 and DNMT1 as a key regulatory mechanism targeting DNMT1 for DNA methylation
  • UHRF1 is emerging as a cofactor that coordinates the epigenetic silencing of tumor suppressor genes
  • is required for growth and maintenance of the transformed phenotype in prostate cancer cells
  • UHRF1 controls DNA methylation at the promoters of tumour suppressor genes in prostate cancer cells
  • UHRF1 along with EZH2 coordinate epigenetic silencing of tumour suppressor genes in prostate tumours
  • plays an important role in DNA CpG methylation, heterochromatin function and gene expression
  • is protected by USP7 during G1 and S phases of the cell cycle
  • mediates cross-talk between H3K9 methylation and DNA methylation at the level of DNA methylation maintenance
  • UHRF1 is a critical negative regulator of KAT5, suggesting that UHRF1-mediated effects on TP53 may contribute, at least in part, to its role in tumorigenesis
  • UHRF1-dependent histone H3 ubiquitylation has a prerequisite role in the maintenance DNA methylation
  • plays a major role in the inheritance of some epigenetic marks from mother cells to daughter cells due to its particular structural domains
  • essential regulator of DNA methylation that is highly expressed in many cancers
  • CELLULAR PROCESS nucleotide, transcription, regulation
    a component
  • KAT5, UHRF1, HDAC1 and DNMT1 are present in the same macro-molecular complex and are partners for the epigenetic code inheritance
    small molecule
  • binds to an inverted CCAAT box in the promoter of topoisomerase II-alpha (TOP2A)
  • methyl K9 H3-specific binding protein
  • MUS81/EME1 is recruited to replication centers following DNA damage, through interaction with UHRF1
  • recruits HDAC and DNMT1 to pericentromeric heterochromatin
  • associating with DNMT1 (with DNMT1 together play a crucial role in gene expression and more generally in the epigenetic code inheritance)
  • Binds DNMT1 through SET and RING finger-associated (SRA) domain
  • interacting with KAT5 (acts at different levels of KAT5 activity by recruiting KAT5 to chromatin and by modulating its levels)
  • USP7 is an interaction partner of DNMT1 and UHRF1
  • ZFP57 and its cofactor TRIM28 are associated with DNMTs and hemimethylated DNA-binding UHRF1
  • UHRF1 is required for DNA methylation maintenance by targeting DNMT1 to DNA replication foci, presumably through its unique hemi-methylated DNA-binding activity and interaction with DNMT1
  • negatively regulates PPARG and is associated with a higher proliferative, clonogenic and migration potential
  • relationship between UHRF1 and PPARG may have a relevant role in colorectal cancer progression
  • UHRF1 might interact with SUV39H1 and, through this interaction, direct the recruitment of SUV39H1 to gene promoters
  • USP7 interacts with UHRF1 (both physical interaction and catalytic activity of USP7 are necessary for UHRF1 ubiquitylation and stability regulation)
  • UHRF1 promotes the turnover of PML protein
  • UHRF1 interacts with KAT5 and induces degradation-independent ubiquitination of KAT5
  • DNMT1 directly interacts with the SET and RING finger-associated (SRA) domain of UHRF1 to facilitate accession of the catalytic center to hemi-methylated DNA
  • essential for maintenance DNA methylation by DNA methyltransferase 1 (DNMT1) (interaction with UHRF1 increased the specificity of DNMT1 for methylation of hemimethylated CpG sites)
  • UHRF1-dependent epigenetic silencing of CDKN1A was required for the maintenance of gut immunological homeostasis (PMUID: 24777532)
  • interaction of PARP1 with the E3 ubiquitin ligase UHRF1 that influences two UHRF1-regulated cellular processes
  • direct recruitment of UHRF1 by the replication machinery via DNA ligase 1 (LIG1)
  • ZNF479 induced the expression of DNMT1, UHRF1, and mixed-lineage leukemia (MLL) complex proteins (ASH2L and Menin), and increased tri-methylated histone H3 (H3K4me3) levels, but suppressed H3K4 (H3K4me2) di-methylation
  • cell & other
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in high-grade breast carcinomas
    tumoral     --over  
    in cervical and prostate cancers, in pancreatic adenocarcinomas, rhabdomyosarcomas and gliomas
    tumoral     --over  
    is potentially a mechanism underlying DNA hypomethylation in cancer cells and senescence is a primary means of restricting tumorigenesis due to epigenetic disruption
    Variant & Polymorphism
    Candidate gene
  • appears as an important prognostic biomarker for prostate cancer
  • Therapy target
    targeting UHRF1 to restore PML-mediated tumor suppression represents a promising, novel, anticancer strategy