RNF213
RNF213 (E3 ubiquitin-protein ligase RNF213) is an enzyme. The public catalogues list it as an oncogene driver, a tumour suppressor and a fusion partner, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Prostate cancer, Bladder & urothelial cancer, Renal cell carcinoma and 5 more.
Overview
Atypical E3 ubiquitin ligase that can catalyse ubiquitination of both proteins and lipids, and which is involved in various processes, such as lipid metabolism, angiogenesis and cell-autonomous immunity. Acts as a key immune sensor by catalysing ubiquitination of the lipid A moiety of bacterial lipopolysaccharide (LPS) via its RZ-type zinc-finger: restricts the proliferation of cytosolic bacteria, such as Salmonella, by generating the bacterial ubiquitin coat through the ubiquitination of LPS. Also acts indirectly by mediating the recruitment of the LUBAC complex, which conjugates linear polyubiquitin chains.
IntOGen calls it a driver in 11 cohorts (5 activating, 6 loss-of-function), covering Angiosarcoma, Bladder Urothelial Carcinoma, Renal Clear Cell Carcinoma, Cholangiocarcinoma, Oesophageal Adenocarcinoma, Glioblastoma Multiforme and others.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · RNF213 (E3 ubiquitin-protein ligase RNF213) is an enzyme. The public catalogues list it as an oncogene driver, a tumour suppressor and a fusion partner, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Prostate cancer, Bladder & urothelial cancer, Renal cell carcinoma and 5 more.
- 1 · What it is
RNF213 (E3 ubiquitin-protein ligase RNF213) is an enzyme. The public catalogues list it as an oncogene driver, a tumour suppressor and a fusion partner, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Prostate cancer, Bladder & urothelial cancer, Renal cell carcinoma and 5 more.
- 2 · What goes wrong in cancer
Atypical E3 ubiquitin ligase that can catalyse ubiquitination of both proteins and lipids, and which is involved in various processes, such as lipid metabolism, angiogenesis and cell-autonomous immunity.
- 3 · How drugs use it
No product in this corpus aims at RNF213 yet. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
External identifiers
Sources: HGNC HGNC:14539 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q63HN8 (protein name, function text, keywords and locations (REST API)); IntOGen RNF213 (driver in 11 cohorts (Act 5, LoF 6); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Atypical E3 ubiquitin ligase that can catalyse ubiquitination of both proteins and lipids, and which is involved in various processes, such as lipid metabolism, angiogenesis and cell-autonomous immunity. Acts as a key immune sensor by catalysing ubiquitination of the lipid A moiety of bacterial lipopolysaccharide (LPS) via its RZ-type zinc-finger: restricts the proliferation of cytosolic bacteria, such as Salmonella, by generating the bacterial ubiquitin coat through the ubiquitination of LPS. Also acts indirectly by mediating the recruitment of the LUBAC complex, which conjugates linear polyubiquitin chains. Ubiquitination of LPS triggers cell-autonomous immunity, such as antibacterial autophagy, leading to degradation of the microbial invader. Also functions as an intracellular sensor for ISGylated proteins: upon type I interferon stimulation, undergoes ISGylation and oligomerises on lipid droplets to form a binding platform for ISG15-modified substrate proteins, thereby acting as a broad-spectrum antimicrobial effector. Restricts intracellular bacterial pathogens, such as Listeria monocytogenes, in an ISG15-dependent manner by decorating the bacterial surface with ubiquitin to promote autophagic clearance. Location: Cytoplasm, cytosol; Lipid droplet (UniProt). Locus 17q25.3 (HGNC).
- Prostate cancer: IntOGen driver in 2 cohorts (PRAD)
- Bladder & urothelial cancer: IntOGen driver in 1 cohort (BLCA)
- Renal cell carcinoma: IntOGen driver in 1 cohort (CCRCC)
- Oesophageal cancer: IntOGen driver in 1 cohort (ESCA)
- Endometrial cancer: IntOGen driver in 1 cohort (UCEC)
- Angiosarcoma: IntOGen driver in 1 cohort (ANGS)
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 5 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 6 cohorts; UniProt disease notes describe a translocation or gene fusion involving the gene. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"RNF213" OR ABSTRACT:"RNF213" OR TITLE:"ring finger protein 213" OR ABSTRACT:"ring finger protein 213" OR TITLE:"E3 ubiquitin-protein ligase RNF213" OR ABSTRACT:"E3 ubiquitin-protein ligase RNF213" OR TITLE:"KIAA1554" OR ABSTRACT:"KIAA1554" OR TITLE:"NET57" OR ABSTRACT:"NET57" OR TITLE:"ALO17" OR ABSTRACT:"ALO17") 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 RNF213, not a curated reading list.
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