CUL3
CUL3 (Cullin-3) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Renal cell carcinoma, Non-small-cell lung cancer and Papillary renal cell carcinoma.
Overview
Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. BCR complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme.
CIViC holds 1 clinical evidence item and 0 assertions across 1 variant, naming Platinum Doublet. Open Targets scores its association with cancer at 0.55 (direct and indirect evidence; datatypes literature 0.95, animal model 0.56, genetic association 0.03, somatic mutation 0.71). IntOGen calls it a driver in 4 cohorts (1 activating, 3 loss-of-function), covering Lung Squamous Cell Carcinoma, Papillary Renal Cell Carcinoma, Renal Cell Carcinoma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · CUL3 (Cullin-3) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Renal cell carcinoma, Non-small-cell lung cancer and Papillary renal cell carcinoma.
- 1 · What it is
CUL3 (Cullin-3) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Renal cell carcinoma, Non-small-cell lung cancer and Papillary renal cell carcinoma.
- 2 · What goes wrong in cancer
Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins.
- 3 · How drugs use it
No product in this corpus aims at CUL3 yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
External identifiers
Sources: HGNC HGNC:2553 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q13618 (protein name, function text, keywords and locations (REST API)); CIViC gene CUL3 (1 evidence items, 0 assertions, 1 variants; diseases: Lung Non-small Cell Carcinoma (GraphQL API, CC0)); Open Targets ENSG00000036257 (association with cancer (MONDO_0004992) 0.55; (GraphQL API, CC0)); IntOGen CUL3 (driver in 4 cohorts (Act 1, LoF 3); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. BCR complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the BCR complex depends on the BTB domain-containing protein as the substrate recognition component. BCR(KLHL42) is involved in ubiquitination of KATNA1. Location: Nucleus; Golgi apparatus; Cell projection, cilium, flagellum; Cytoplasm, cytoskeleton, spindle (UniProt). Locus 2q36.2 (HGNC).
- Renal cell carcinoma: IntOGen driver in 2 cohorts (PRCC, RCC)
- Non-small-cell lung cancer: CIViC evidence names this disease; IntOGen driver in 2 cohorts (LUSC)
- Papillary renal cell carcinoma: IntOGen driver in 1 cohort (PRCC)
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: CIViC lists 1 therapies; IntOGen calls it an activating (Act) driver in 1 cohort; IntOGen calls it a loss-of-function (LoF) driver in 3 cohorts; CIViC holds 1 clinical evidence items on its variants. 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:"CUL3" OR ABSTRACT:"CUL3" OR TITLE:"cullin 3" OR ABSTRACT:"cullin 3" OR TITLE:"Cullin-3" OR ABSTRACT:"Cullin-3") 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 CUL3, not a curated reading list.
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