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FLASH GENE
Symbol UHRF1 contributors: mct/npt/pgu - updated : 24-05-2014
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
    EC.number 6.3.2.19
    DNA
    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
    Physical map
    CREB3L3 19p13.3 cAMP responsive element binding protein 3-like 3 SIRT6 19p13.3 sirtuin (silent mating type information regulation 2 homolog) 6 (S. cerevisiae) KIAA1981 EBI3 19p13.3 Epstein-Barr virus induced gene 3 FLJ10374 19p13.3 hypothetical protein FLJ10374 SHD 19p13.3 src homology 2 domain-containing transforming protein D MGC23244 19p13.3 hypothetical protein MGC23244 FSD1 19p13.3 fibronectin type 3 and SPRY (spla, ryanodine) domain containing (with coiled-coil motif) 1 STAP2 19p13.3 signal-transducing adaptor protein-2 FLJ14981 19p13.3 hypothetical protein FLJ14981 SH3GL1 19p13.3 SH3-domain GRB2-like 1 CHAF1A 19p13.3 chromatin assembly factor 1, subunit A (p150) UBXD1 19p13 UBX domain containing 1 MGC2641 19p13.3 hepatoma-derived growth factor-related protein 2 FLJ20700 19p13.3 hypothetical protein FLJ20700 LOC388495 19 similar to Calphotin CG4795-PA LRG SEMA6B 19p13.3 sema domain, transmembrane domain (TM), and cytoplasmic domain, (semaphorin) 6B MGC17791 19p13.3 hypothetical protein MGC17791 C19orf10 19p13.3 chromosome 19 open reading frame 10 DPP9 19p13.3 dipeptidylpeptidase 9 PGSF1 19p13.3 pituitary gland specific factor 1a FEM1A 19p13.3 fem-1 homolog a (C.elegans) TRIF 19p13.3 fem-1 homolog a (C.elegans) TIP47 LOC342959 19p13.3 similar to Hypothetical protein CBG18249 UHRF1 19p13.3 ubiquitin-like, containing PHD and RING finger domains, 1 KIAA0876 PTPRS 19p13.3 protein tyrosine phosphatase, receptor type, S LOC388496 19 LOC388496 LOC148066 19p13.3 zinc and ring finger 4
    RNA
    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
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    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
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier liningepidermisstratum basalehighly
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text thymus, liver, bone marrow
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • 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
    HOMOLOGY
    interspecies homolog to C.elegans F01e11.1
    Homologene
    FAMILY
  • ubiquitin family
  • CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome,euchromosome
    intracellular,nucleus,chromatin/chromosome,heterochromosome
    text
  • enriched in pericentric heterochromatin of interphase nuclei, and this localization is dependent on H3K9 methylation
  • 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
  • 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-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 (pMID: 24134914)
  • essential regulator of DNA methylation that is highly expressed in many cancers
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • KAT5, UHRF1, HDAC1 and DNMT1 are present in the same macro-molecular complex and are partners for the epigenetic code inheritance
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • 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
  • 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
  • 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
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    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
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    targeting UHRF1 to restore PML-mediated tumor suppression represents a promising, novel, anticancer strategy
    ANIMAL & CELL MODELS