DDB2 Gene (Damage Specific DNA Binding Protein 2): Structure, Function, and Clinical Significance
A comprehensive overview of the DDB2 gene, its role in nucleotide excision repair, associated diseases, expression patterns, and mutation landscape.
Gene Information Card
| Symbol | DDB2 |
|---|---|
| Full Name | Damage Specific DNA Binding Protein 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q12.2 |
| NCBI Gene ID | 1643 ncbi.nlm.nih.gov/gene/1643 |
| Ensembl ID | ENSG00000134574 |
| UniProt ID | Q92466 |
| OMIM ID | 600811 |
| HGNC ID | 2718 |
| Aliases | XPE, DDB p48, UV-DDB2 |
Description
The DDB2 gene encodes the small subunit of the UV-damaged DNA-binding protein complex (UV-DDB). This complex is essential for global genomic nucleotide excision repair (GG-NER), recognizing UV-induced DNA lesions such as cyclobutane pyrimidine dimers and 6-4 photoproducts. DDB2 facilitates the recruitment of downstream repair factors and is critical for maintaining genomic stability. Mutations in DDB2 cause Xeroderma Pigmentosum Group E (XPE), a disorder characterized by extreme UV sensitivity and increased skin cancer risk.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Xeroderma Pigmentosum Group E (XPE) | Loss-of-function mutations in DDB2 impair the UV-DDB complex's ability to recognize DNA damage, leading to defective nucleotide excision repair and accumulation of mutations upon UV exposure. | ClinVar, OMIM (600811) |
| Cutaneous malignant melanoma (susceptibility) | Polymorphisms in DDB2 may modulate DNA repair capacity, increasing susceptibility to UV-induced melanoma. | COSMIC, literature (e.g., PMID: 23462293) |
| Basal cell carcinoma (susceptibility) | Reduced DDB2 expression or function compromises repair of UV-induced lesions, contributing to basal cell carcinoma development. | COSMIC, literature (e.g., PMID: 23462293) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 18.5 | Medium |
| Testis | 12.3 | Low |
| Lung | 10.1 | Low |
| Kidney | 9.8 | Low |
| Liver | 8.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical cancer cell line; moderate expression |
| A549 | 12.7 | Lung carcinoma; moderate expression |
| MCF7 | 11.9 | Breast cancer; moderate expression |
| HEK293 | 14.5 | Embryonic kidney; moderate expression |
| K562 | 9.3 | Leukemia; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.307C>T (p.Arg103Ter) | Nonsense | Rare (found in XPE patients) | Premature stop codon; loss of function |
| c.682C>T (p.Arg228Ter) | Nonsense | Rare (found in XPE patients) | Premature stop codon; loss of function |
| c.940C>T (p.Arg314Ter) | Nonsense | Rare (found in XPE patients) | Premature stop codon; loss of function |
| c.1A>G (p.Met1Val) | Missense | Rare (found in XPE patients) | Disrupts start codon; loss of function |
| c.1063G>A (p.Gly355Arg) | Missense | Rare (found in XPE patients) | Alters protein structure; reduced DNA binding |
Mutation functional classification
Loss of Function (LOF)
Most DDB2 mutations are loss-of-function, leading to defective UV-damage recognition and impaired NER, as seen in XPE.
Gain of Function (GOF)
No gain-of-function mutations have been reported for DDB2.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by forming non-functional heterodimers with DDB1, but this is not well established.
View complete mutation data：
Gene Ontology (GO)
| • DNA binding | • damaged DNA binding |
| • protein heterodimerization activity | • nucleotide-excision repair |
| • response to UV | • cell cycle arrest |
| • apoptotic process | • chromatin remodeling |
Pathways
• Nucleotide Excision Repair (NER) - Global Genomic Repair
• p53 signaling pathway (via DDB2 regulation)
• UV response and DNA damage checkpoint
Protein Summary
The DDB2 protein (p48) forms a heterodimeric complex with DDB1 (p127) to create the UV-DDB ubiquitin ligase complex. This complex recognizes UV-induced DNA lesions and recruits the XPC complex to initiate global genomic NER. DDB2 also participates in chromatin remodeling and ubiquitination of histones, facilitating DNA repair. The protein is regulated by p53 and is involved in cell cycle arrest and apoptosis after UV damage. Defects in DDB2 lead to XPE, characterized by photosensitivity and predisposition to skin cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DDB2 Knockout HEK293 Cell Line | EDJ-KQ2230 | Human | 1643 | Details Get a Quote |
| DDB2 Knockout HCT 116 Cell Line | EDJ-KQ21207 | Human | 1643 | Details Get a Quote |
| DDB2 Knockout A-549 Cell Line | EDJ-KQ22516 | Human | 1643 | Details Get a Quote |
| DDB2 Knockout HeLa Cell Line | EDJ-KQ22518 | Human | 1643 | Details Get a Quote |
