UBR2: E3 Ubiquitin-Protein Ligase UBR2
A key component of the N-end rule pathway involved in protein degradation, cell cycle regulation, and spermatogenesis.
Gene Information Card
| Symbol | UBR2 |
|---|---|
| Full Name | Ubiquitin Protein Ligase E3 Component N-Recognin 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 6p21.1 |
| NCBI Gene ID | 23304 ncbi.nlm.nih.gov/gene/23304 |
| Ensembl ID | ENSG00000112210 |
| UniProt ID | Q8IWV8 |
| OMIM ID | 609137 |
| HGNC ID | 16860 |
| Aliases | C6orf133, dJ392M17.1, UBR2-AS1 |
Description
UBR2 encodes an E3 ubiquitin-protein ligase that is a component of the N-end rule pathway. This pathway targets proteins for degradation based on their N-terminal residue. UBR2 recognizes type 1 (basic) and type 2 (bulky hydrophobic) N-terminal residues and mediates ubiquitination of substrates, playing critical roles in spermatogenesis, chromosome stability, and regulation of apoptosis. The gene is located on chromosome 6p21.1 and is expressed in multiple tissues, with highest levels in testis and brain.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Male infertility (azoospermia) | UBR2 deficiency disrupts meiotic progression and spermatogenesis, leading to germ cell apoptosis. | OMIM 609137; mouse models show impaired spermatogenesis. |
| Cancer (potential tumor suppressor) | UBR2 regulates p53 stability via N-end rule; loss may contribute to tumorigenesis. | COSMIC; NCBI GeneRIFs. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 38.5 | High |
| Brain (cerebellum) | 12.3 | Medium |
| Heart | 8.1 | Medium |
| Liver | 4.2 | Low |
| Kidney | 6.7 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | Embryonic kidney cells; moderate expression |
| HeLa | 9.8 | Cervical carcinoma; moderate expression |
| K562 | 5.1 | Leukemia; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2152C>T (p.Arg718Trp) | Missense | <0.01% | Unknown effect; rare variant in population databases |
| c.1234delG | Frameshift | <0.001% | Predicted loss of function; associated with spermatogenic failure |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations in UBR2 are predicted to cause loss of E3 ligase activity, impairing N-end rule degradation and leading to accumulation of substrates such as caspase-2 and p53.
Gain of Function (GOF)
No gain-of-function mutations have been reported for UBR2.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for UBR2.
View complete mutation data：
Gene Ontology (GO)
Pathways
• N-end rule pathway (R-HSA-983168)
• Ubiquitin-mediated proteolysis (KEGG hsa04120)
• p53 signaling pathway (KEGG hsa04115)
Protein Summary
UBR2 is a 1755-amino acid E3 ubiquitin-protein ligase that belongs to the UBR box family. It contains a UBR box domain responsible for recognizing N-terminal degrons, a RING finger domain for ubiquitin transfer, and an autoregulatory domain. The protein localizes to both the cytoplasm and nucleus. It ubiquitinates substrates such as p53, caspase-2, and RGS4, targeting them for proteasomal degradation. UBR2 is essential for male meiosis and chromosome synapsis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| UBR2 Knockout HEK293T Cell Line | EDJ-KQ220 | Human | 23304 | Details Get a Quote |
| UBR2 Knockout HEK293 Cell Line | EDJ-KQ7950 | Human | 23304 | Details Get a Quote |
| UBR2 Knockout A-549 Cell Line | EDJ-KQ33622 | Human | 23304 | Details Get a Quote |
| UBR2 Knockout HCT 116 Cell Line | EDJ-KQ33623 | Human | 23304 | Details Get a Quote |
| UBR2 Knockout HeLa Cell Line | EDJ-KQ33624 | Human | 23304 | Details Get a Quote |
