The Function of UHRF1
Multidomain protein that acts as a key epigenetic regulator by bridging DNA methylation and chromatin modification. Specifically recognizes and binds hemimethylated DNA at replication forks via its YDG domain and recruits DNMT1 methyltransferase to ensure faithful propagation of the DNA methylation patterns through DNA replication. In addition to its role in maintenance of DNA methylation, also plays a key role in chromatin modification: through its tudor-like regions and PHD-type zinc fingers, specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3) and unmethylated at 'Arg-2' (H3R2me0), respectively, and recruits chromatin proteins. Enriched in pericentric heterochromatin where it recruits different chromatin modifiers required for this chromatin replication. Also localizes to euchromatic regions where it negatively regulates transcription possibly by impacting DNA methylation and histone modifications. Has E3 ubiquitin-protein ligase activity by mediating the ubiquitination of target proteins such as histone H3 and PML. It is still unclear how E3 ubiquitin-protein ligase activity is related to its role in chromatin in vivo. May be involved in DNA repair.
Protein names
Recommended name:
E3 ubiquitin-protein ligase UHRF1Alternative name(s):
Inverted CCAAT box-binding protein of 90 kDaNuclear protein 95
Nuclear zinc finger protein Np95
HuNp95
hNp95
RING finger protein 106
Transcription factor ICBP90
Ubiquitin-like PHD and RING finger domain-containing protein 1
hUHRF1
Ubiquitin-like-containing PHD and RING finger domains protein 1
- RS34232444 (UHRF1) ??
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Top Gene-Substance Interactions
Substances That Increase UHRF1
| Substances | Interaction | Organism | Category |
Substances That Decrease UHRF1
| Substances | Interaction | Organism | Category |
Conditions with Increased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Conditions with Decreased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Technical
The following transcription factors affect gene expression:
Tissue specificity:
Expressed in thymus, bone marrow, testis, lung and heart. Overexpressed in breast cancer.
Induction:
Up-regulated in proliferating cells, and down-regulated in quiescent cells. Down-regulated upon adriamycin-induced DNA damage, in a p53/TP53 and CDKN1A-dependent way. Induced by E2F1 transcription factor.
Developmental stage:
Expressed in fetal thymus, liver and kidney.
Molecular Function:
- Core Promoter Proximal Region Sequence-Specific Dna Binding
- Hemi-Methylated Dna-Binding
- Histone Binding
- Identical Protein Binding
- Ligase Activity
- Methylated Histone Binding
- Methyl-Cpg Binding
- Nucleosomal Histone Binding
- Transcription Factor Activity, Sequence-Specific Dna Binding
- Ubiquitin Protein Ligase Activity
- Ubiquitin-Protein Transferase Activity
- Zinc Ion Binding
Biological Processes:
- Cell Cycle
- Cell Proliferation
- Dna Repair
- Histone Monoubiquitination
- Histone Ubiquitination
- Maintenance Of Dna Methylation
- Negative Regulation Of Transcription From Rna Polymerase Ii Promoter
- Positive Regulation Of Cellular Protein Metabolic Process
- Positive Regulation Of Dna Topoisomerase (Atp-Hydrolyzing) Activity
- Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
- Protein Autoubiquitination
- Protein Ubiquitination Involved In Ubiquitin-Dependent Protein Catabolic Process
- Regulation Of Methylation-Dependent Chromatin Silencing
- Transcription, Dna-Templated