UBR5
UBR5 (E3 ubiquitin-protein ligase UBR5) is an enzyme. The public catalogues list it as an oncogene driver, a tumour suppressor, a biomarker and a DNA repair gene, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Gastric & gastro-oesophageal junction cancer, Breast cancer, Renal cell carcinoma and 5 more.
Overview
E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm and nucleus. Mainly acts as a ubiquitin chain elongator that extends pre-ubiquitinated substrates. Component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilising according to the N-end rule, leading to their degradation.
CIViC holds 1 clinical evidence item and 0 assertions across 1 variant. Open Targets scores its association with cancer at 0.70 (direct and indirect evidence; datatypes literature 0.98, genetic association 0.27, somatic mutation 0.88). IntOGen calls it a driver in 7 cohorts (2 activating, 5 loss-of-function), covering Acute Myeloid Leukaemia, Invasive Breast Carcinoma, Chromophobe Renal Cell Carcinoma, Cutaneous Squamous Cell Carcinoma, Melanoma, Stomach Adenocarcinoma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · UBR5 (E3 ubiquitin-protein ligase UBR5) is an enzyme. The public catalogues list it as an oncogene driver, a tumour suppressor, a biomarker and a DNA repair gene, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Gastric & gastro-oesophageal junction cancer, Breast cancer, Renal cell carcinoma and 5 more.
- 1 · What it is
UBR5 (E3 ubiquitin-protein ligase UBR5) is an enzyme. The public catalogues list it as an oncogene driver, a tumour suppressor, a biomarker and a DNA repair gene, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Gastric & gastro-oesophageal junction cancer, Breast cancer, Renal cell carcinoma and 5 more.
- 2 · What goes wrong in cancer
E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm and nucleus. Mainly acts as a ubiquitin chain elongator that extends pre-ubiquitinated substrates.
- 3 · How drugs use it
No product in this corpus aims at UBR5 yet. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
External identifiers
Sources: HGNC HGNC:16806 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt O95071 (protein name, function text, keywords and locations (REST API)); CIViC gene UBR5 (1 evidence items, 0 assertions, 1 variants; diseases: Mantle Cell Lymphoma (GraphQL API, CC0)); Open Targets ENSG00000104517 (association with cancer (MONDO_0004992) 0.70; per-cancer scores at or above 0.5: colorectal cancer 0.55, gastric cancer 0.57, ovarian cancer 0.51, melanoma 0.59, non-Hodgkin lymphoma 0.52, skin cancer 0.57 (GraphQL API, CC0)); IntOGen UBR5 (driver in 7 cohorts (Act 2, LoF 5); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm and nucleus. Mainly acts as a ubiquitin chain elongator that extends pre-ubiquitinated substrates. Component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilising according to the N-end rule, leading to their degradation. Recognises type-1 N-degrons, containing positively charged amino acids (Arg, Lys and His). Together with UBR4, part of a cytoplasm protein quality control pathway that prevents protein aggregation by catalysing assembly of heterotypic 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on aggregated proteins, leading to substrate recognition by the segregase p97/VCP and degradation by the proteasome: UBR5 is probably branching multiple 'Lys-48'-linked chains of substrates initially modified with mixed conjugates by UBR4. Together with ITCH, catalyses 'Lys-48'-/'Lys-63'-branched ubiquitination of TXNIP, leading to its degradation: UBR5 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by ITCH. Location: Nucleus; Cytoplasm (UniProt). Locus 8q22.3 (HGNC).
- Gastric & gastro-oesophageal junction cancer: Open Targets association 0.57 with gastric cancer (MONDO_0001056); IntOGen driver in 2 cohorts (STAD)
- Breast cancer: Open Targets association 0.57 with breast cancer (MONDO_0007254); IntOGen driver in 1 cohort (BRCA)
- Renal cell carcinoma: IntOGen driver in 1 cohort (CHRCC)
- Skin cancer: Open Targets association 0.57 with skin cancer (MONDO_0002898)
- Colorectal cancer: Open Targets association 0.55 with colorectal cancer (MONDO_0005575)
- Non-Hodgkin lymphoma: Open Targets association 0.52 with non-Hodgkin lymphoma (MONDO_0018908)
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it an activating (Act) driver in 2 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 5 cohorts; CIViC holds 1 clinical evidence items on its variants; UniProt keyword "DNA repair". Evidence tier "clinical-evidence" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"UBR5" OR ABSTRACT:"UBR5" OR TITLE:"ubiquitin protein ligase E3 component n-recognin 5" OR ABSTRACT:"ubiquitin protein ligase E3 component n-recognin 5" OR TITLE:"E3 ubiquitin-protein ligase UBR5" OR ABSTRACT:"E3 ubiquitin-protein ligase UBR5" OR TITLE:"DD5" OR ABSTRACT:"DD5" OR TITLE:"KIAA0896" OR ABSTRACT:"KIAA0896" OR TITLE:"EDD1" OR ABSTRACT:"EDD1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about UBR5, not a curated reading list.
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