DDB2
DDB2 (DNA damage-binding protein 2) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as an oncogene driver, a tumour suppressor and a DNA repair gene, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Bladder & urothelial cancer, Skin cancer and Acute myeloid leukaemia.
Overview
Protein, which is both involved in DNA repair and protein ubiquitination, as part of the UV-DDB complex and DCX (DDB1-CUL4-X-box) complexes, respectively. Core component of the UV-DDB complex (UV-damaged DNA-binding protein complex), a complex that recognises UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches.
Open Targets scores its association with cancer at 0.65 (direct and indirect evidence; datatypes literature 0.96, genetic association 0.06, somatic mutation 0.84). IntOGen calls it a driver in 2 cohorts (1 activating, 1 loss-of-function), covering Acute Myeloid Leukaemia, Bladder Urothelial 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 · DDB2 (DNA damage-binding protein 2) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as an oncogene driver, a tumour suppressor and a DNA repair gene, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Bladder & urothelial cancer, Skin cancer and Acute myeloid leukaemia.
- 1 · What it is
DDB2 (DNA damage-binding protein 2) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as an oncogene driver, a tumour suppressor and a DNA repair gene, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Bladder & urothelial cancer, Skin cancer and Acute myeloid leukaemia.
- 2 · What goes wrong in cancer
Protein, which is both involved in DNA repair and protein ubiquitination, as part of the UV-DDB complex and DCX (DDB1-CUL4-X-box) complexes, respectively.
- 3 · How drugs use it
No product in this corpus aims at DDB2 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:2718 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q92466 (protein name, function text, keywords and locations (REST API)); Open Targets ENSG00000134574 (association with cancer (MONDO_0004992) 0.65; per-cancer scores at or above 0.5: skin cancer 0.51 (GraphQL API, CC0)); IntOGen DDB2 (driver in 2 cohorts (Act 1, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Protein, which is both involved in DNA repair and protein ubiquitination, as part of the UV-DDB complex and DCX (DDB1-CUL4-X-box) complexes, respectively. Core component of the UV-DDB complex (UV-damaged DNA-binding protein complex), a complex that recognises UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches. Also functions as the substrate recognition module for the DCX (DDB2-CUL4-X-box) E3 ubiquitin-protein ligase complex DDB2-CUL4-ROC1 (also known as CUL4-DDB-ROC1 and CUL4-DDB-RBX1). The DDB2-CUL4-ROC1 complex may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage. The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair. Location: Nucleus; Chromosome (UniProt). Locus 11p11.2 (HGNC).
- Bladder & urothelial cancer: IntOGen driver in 1 cohort (BLCA)
- Skin cancer: Open Targets association 0.51 with skin cancer (MONDO_0002898)
- Acute myeloid leukaemia: IntOGen driver in 1 cohort (AML)
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 1 cohort; IntOGen calls it a loss-of-function (LoF) driver in 1 cohort; UniProt keyword "DNA repair". 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:"DDB2" OR ABSTRACT:"DDB2" OR TITLE:"damage specific DNA binding protein 2" OR ABSTRACT:"damage specific DNA binding protein 2" OR TITLE:"DNA damage-binding protein 2" OR ABSTRACT:"DNA damage-binding protein 2" OR TITLE:"UV-DDB2" OR ABSTRACT:"UV-DDB2" OR TITLE:"FLJ34321" OR ABSTRACT:"FLJ34321") 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 DDB2, not a curated reading list.