Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

UHRF1 (Q96T88) - Overview - Molecular Target Synopsis

Protein


UHRF1, E3 ubiquitin-protein ligase UHRF1
Enzyme Classification 2.3.2.27
UniProt Q96T88

Also Known as UHRF1_HUMAN, UHRF1, ICBP90, NP95, RNF106

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. Interacts with DNMT3A and DNMT3B (By similarity). Interacts with DNMT1; the interaction is direct. Interacts with USP7; leading to its deubiquitination. Interacts with histone H3. Interacts with HDAC1, but not with HDAC2. Interacts with UHRF1BP1. Interacts with PML. Interacts with EHMT2. Binds hemimethylated CpG containing oligonucleotides.

5YYA
CRYSTAL STRUCTURE OF TANDEM TUDOR DOMAIN OF HUMAN UHRF1
RCSB/PDB
Inspect Structure
See all 3D Structures for UHRF1

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
806Q96T88-2
793Q96T88-1

Sub-cellular localization


UniProt: UHRF1 is active in the following subcellular-locations: nucleus.
GO terms: UHRF1 is active in the following subcellular-locations: euchromatin, heterochromatin, nuclear chromatin, nuclear heterochromatin, nuclear matrix, nucleus, replication fork.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project UHRF1 has gain in 0 cell-lines, loss in 0 cell-lines and no signal in 0 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: CCRF_CEM, MOLT_4, SR

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: SUP-B15, NALM-6, G61

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, HSMM, IMR-90

(see details)

3D Structures


For UHRF1 there are:
29 structures (48 chains) solved
3 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


UHRF1 has been screened with 110 compounds (122 bioactivities). (see details)