Tbio DDB1 DNA damage-binding protein 1

Protein Summary

Description

Required for DNA repair. Binds to DDB2 to form the UV-damaged DNA-binding protein complex (the UV-DDB complex). The UV-DDB complex may recognize 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 appears to function as a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1. DCX(DDB2) (also known as DDB1-CUL4-ROC1, CUL4-DDB-ROC1 and CUL4-DDB-RBX1) 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. DCX(DDB2) also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication. DCX(ERCC8) (the CSA complex) plays a role in transcription-coupled repair (TCR). May also play a role in ubiquitination of CDKN1B/p27kip when associated with CUL4 and SKP2. The protein encoded by this gene is the large subunit (p127) of the heterodimeric DNA damage-binding (DDB) complex while another protein (p48) forms the small subunit. This protein complex functions in nucleotide-excision repair and binds to DNA following UV damage. Defective activity of this complex causes the repair defect in patients with xeroderma pigmentosum complementation group E (XPE) - an autosomal recessive disorder characterized by photosensitivity and early onset of carcinomas. However, it remains for mutation analysis to demonstrate whether the defect in XPE patients is in this gene or the gene encoding the small subunit. In addition, Best vitelliform mascular dystrophy is mapped to the same region as this gene on 11q, but no sequence alternations of this gene are demonstrated in Best disease patients. The protein encoded by this gene also functions as an adaptor molecule for the cullin 4 (CUL4) ubiquitin E3 ligase complex by facilitating the binding of substrates to this complex and the ubiquitination of proteins. [provided by RefSeq, May 2012]

Uniprot Accession IDs

• Q16531
• A6NG77
• B2R648
• B4DG00
• O15176
• Q13289
• Q58F96

Gene Name

• DDB1

Ensembl ID

• ENST00000301764
• ENSP00000301764
• ENSG00000167986

Symbol

• XAP1
• XPE
• DDBA
• XAP1
• XPCE
• XPE-BF
• UV-DDB1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
disease perturbation	1
virus perturbation	0.99
hub protein	0.98
protein complex	0.98
co-expressed gene	0.96

Protein Classes

PANTHER Classes

Protein / Nucleic Acid Binding / Rna Binding Protein / Mrna Processing Factor / Mrna Polyadenylation Factor / Dna Damage-binding Protein 1

Protein / Nucleic Acid Binding / Dna Binding Protein / Damaged Dna-binding Protein / Dna Damage-binding Protein 1

DTO Classes

Protein / Nucleic Acid Binding / Rna Binding Protein / Mrna Processing Factor / Mrna Polyadenylation Factor / Dna Damage-binding Protein 1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 322.54   (req: < 5)

Gene RIFs: 87   (req: <= 3)

Antibodies: 464   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 322.54   (req: >= 5)

Gene RIFs: 87   (req: > 3)

Antibodies: 464   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 33

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0