UBR1
Ubiquitin Protein Ligase E3 Component N-Recognin 1
Gene Information Card
| Symbol | UBR1 |
|---|---|
| Full Name | Ubiquitin Protein Ligase E3 Component N-Recognin 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 15q15.2 |
| NCBI Gene ID | 197131 ncbi.nlm.nih.gov/gene/197131 |
| Ensembl ID | ENSG00000137807 |
| UniProt ID | Q8IWV8 |
| OMIM ID | 605981 |
| HGNC ID | 16808 |
| Aliases | JBS, N-recognin-1, E3 ubiquitin-protein ligase UBR1 |
Description
The UBR1 gene encodes a component of the N-end rule pathway, a ubiquitin-dependent proteolytic system that targets proteins with destabilizing N-terminal residues for degradation. UBR1 functions as an E3 ubiquitin ligase that recognizes specific N-terminal amino acids (type 1 and type 2) and mediates ubiquitination and subsequent proteasomal degradation. Mutations in UBR1 cause Johanson-Blizzard syndrome, a rare autosomal recessive disorder characterized by exocrine pancreatic insufficiency, nasal wing hypoplasia, intellectual disability, and other congenital anomalies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Johanson-Blizzard syndrome | Loss-of-function mutations in UBR1 impair N-end rule pathway-mediated protein degradation, leading to abnormal development and function of exocrine pancreas, nasal structures, and other tissues. | ClinVar, OMIM |
| Pancreatic insufficiency | UBR1 deficiency disrupts normal acinar cell homeostasis, resulting in exocrine pancreatic insufficiency. | OMIM, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 34.2 | High |
| Testis | 18.5 | Medium |
| Kidney | 12.1 | Medium |
| Liver | 9.8 | Medium |
| Brain | 5.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical adenocarcinoma |
| HEK 293 | 12.8 | Embryonic kidney |
| HepG2 | 10.5 | Hepatocellular carcinoma |
| K562 | 7.1 | Leukemia |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2935C>T (p.Arg979*) | Nonsense | Rare | Loss of function; truncation of UBR1 protein |
| c.1669C>T (p.Arg557*) | Nonsense | Rare | Loss of function; premature stop codon |
| c.2782G>A (p.Gly928Arg) | Missense | Rare | Likely loss of function; disrupts substrate recognition |
Mutation functional classification
Loss of Function (LOF)
Most reported UBR1 mutations are loss-of-function, leading to reduced or absent E3 ubiquitin ligase activity and impaired N-end rule pathway.
Gain of Function (GOF)
No gain-of-function mutations have been reported for UBR1.
Dominant Negative (DN)
No dominant-negative mutations have been described for UBR1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• N-end rule pathway (R-HSA-983168)
• Ubiquitin-mediated proteolysis (KEGG hsa04120)
Protein Summary
UBR1 is a 2033-amino acid E3 ubiquitin ligase that recognizes N-terminal destabilizing residues (type 1: basic; type 2: bulky hydrophobic) and mediates ubiquitination of target proteins. It contains a UBR box, a RING finger domain, and multiple substrate-binding domains. The protein is predominantly cytoplasmic and plays a critical role in protein quality control and cellular homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| UBR1 Knockout HEK293T Cell Line | EDJ-KQ101 | Human | 197131 | Details Get a Quote |
| UBR1 Knockout HEK293 Cell Line | EDJ-KQ11592 | Human | 197131 | Details Get a Quote |
| UBR1 Knockout A-549 Cell Line | EDJ-KQ39929 | Human | 197131 | Details Get a Quote |
| UBR1 Knockout HCT 116 Cell Line | EDJ-KQ39930 | Human | 197131 | Details Get a Quote |
| UBR1 Knockout HeLa Cell Line | EDJ-KQ39931 | Human | 197131 | Details Get a Quote |
