UHRF1 (Ubiquitin Like With PHD And Ring Finger Domains 1)
Epigenetic regulator linking DNA methylation and histone modifications; implicated in cancer and developmental disorders.
Gene Information Card
| Symbol | UHRF1 |
|---|---|
| Full Name | Ubiquitin Like With PHD And Ring Finger Domains 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 19p13.3 |
| NCBI Gene ID | 29128 ncbi.nlm.nih.gov/gene/29128 |
| Ensembl ID | ENSG00000273547 |
| UniProt ID | Q96T88 |
| OMIM ID | 607990 |
| HGNC ID | 12556 |
| Aliases | ICBP90, Np95, RNF106, hNp95 |
Description
UHRF1 encodes a multi-domain protein that plays a central role in epigenetic inheritance. It recognizes hemi-methylated DNA via its SRA domain and interacts with histone H3K9me2/3, recruiting DNMT1 to maintain DNA methylation patterns during replication. UHRF1 also possesses E3 ubiquitin ligase activity, targeting histones and other proteins for ubiquitination, thereby influencing chromatin structure and gene expression. It is essential for cell proliferation and is frequently overexpressed in various cancers, making it a potential therapeutic target.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Overexpression of UHRF1 leads to aberrant DNA methylation and silencing of tumor suppressor genes, promoting tumorigenesis. | COSMIC, PubMed (e.g., PMID: 23455122) |
| Immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome | Mutations in UHRF1 are associated with ICF syndrome, characterized by DNA hypomethylation and immune defects. | OMIM, ClinVar |
| Developmental delay and intellectual disability | Pathogenic variants in UHRF1 have been reported in patients with neurodevelopmental disorders. | ClinVar, PubMed (e.g., PMID: 28973395) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.3 | High |
| Bone marrow | 8.7 | Medium |
| Lymph node | 7.9 | Medium |
| Spleen | 6.5 | Medium |
| Brain | 4.2 | Low |
| Liver | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical cancer cell line; high expression |
| K562 | 12.8 | Chronic myeloid leukemia; high expression |
| A549 | 9.4 | Lung carcinoma; moderate expression |
| MCF7 | 8.1 | Breast cancer; moderate expression |
| HepG2 | 5.6 | Hepatocellular carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg298Cys | Missense | Rare (ClinVar) | Impairs SRA domain binding to hemi-methylated DNA, leading to loss of function. |
| p.Arg298His | Missense | Rare (ClinVar) | Similar effect as Arg298Cys; associated with ICF syndrome. |
| p.Gly570Asp | Missense | Somatic (COSMIC) | Located in PHD domain; may affect histone binding. |
| p.Arg654* | Nonsense | Germline (ClinVar) | Truncating mutation causing loss of function; linked to neurodevelopmental disorder. |
Mutation functional classification
Loss of Function (LOF)
Mutations in the SRA domain (e.g., Arg298Cys) disrupt DNA methylation maintenance, leading to global hypomethylation and genomic instability.
Gain of Function (GOF)
Overexpression (not mutation) is common in cancers, leading to hypermethylation of tumor suppressors and oncogenic transformation.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with wild-type UHRF1 function in multimeric complexes.
View complete mutation data：
Gene Ontology (GO)
| • DNA binding | • Zinc ion binding |
| • Ubiquitin-protein transferase activity | • Histone binding |
| • Methylated histone binding | • Chromatin binding |
| • Nucleus | • Cytoplasm |
| • Regulation of DNA methylation | • Cell cycle |
| • DNA replication |
Pathways
• DNA methylation maintenance
• Histone ubiquitination
• Cell cycle regulation
• p53 signaling pathway
• Epigenetic regulation of gene expression
Protein Summary
UHRF1 is a 793-amino acid protein with multiple functional domains: an N-terminal ubiquitin-like domain (UBL), a tandem Tudor domain, a PHD finger, an SRA (SET and RING-associated) domain, and a RING finger domain. It acts as a key epigenetic reader that recognizes hemi-methylated CpG sites and histone H3K9me2/3, recruiting DNMT1 to maintain DNA methylation. Its E3 ligase activity ubiquitinates histone H3 and other substrates, facilitating chromatin compaction. UHRF1 is essential for cell proliferation and is overexpressed in many cancers, where it contributes to tumor suppressor silencing.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| UHRF1 Knockout HEK293 Cell Line | EDJ-KQ3622 | Human | 29128 | Details Get a Quote |
| UHRF1 Knockout A-549 Cell Line | EDJ-KQ25559 | Human | 29128 | Details Get a Quote |
| UHRF1 Knockout HCT 116 Cell Line | EDJ-KQ25560 | Human | 29128 | Details Get a Quote |
| UHRF1 Knockout HeLa Cell Line | EDJ-KQ25561 | Human | 29128 | Details Get a Quote |
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