InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: DDB2

Summary

InnateDB Protein

IDBP-42773.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

DDB2

Protein Name

damage-specific DNA binding protein 2, 48kDa

Synonyms

DDBB; UV-DDB2;

Species

Homo sapiens

Ensembl Protein

ENSP00000367866

InnateDB Gene

IDBG-42769 (DDB2)

Protein Structure

UniProt Annotation

Function

Required for DNA repair. Binds to DDB1 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 the substrate recognition module for the DCX (DDB1- CUL4-X-box) E3 ubiquitin-protein ligase complex DDB1-CUL4-ROC1 (also known as CUL4-DDB-ROC1 and CUL4-DDB-RBX1). The DDB1-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. The DDB1-CUL4-ROC1 complex also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. Isoform D1 and isoform D2 inhibit UV-damaged DNA repair. {ECO:0000269PubMed:10882109, ECO:0000269PubMed:11278856, ECO:0000269PubMed:11705987, ECO:0000269PubMed:12732143, ECO:0000269PubMed:12944386, ECO:0000269PubMed:14751237, ECO:0000269PubMed:15882621, ECO:0000269PubMed:16260596, ECO:0000269PubMed:16473935, ECO:0000269PubMed:16678110, ECO:0000269PubMed:18593899, ECO:0000269PubMed:9892649}.

Subcellular Localization

Nucleus {ECO:0000269PubMed:10777490, ECO:0000269PubMed:10777491, ECO:0000269PubMed:11705987, ECO:0000269PubMed:12944386, ECO:0000269PubMed:14751237, ECO:0000269PubMed:16473935, ECO:0000269PubMed:16713579, ECO:0000269PubMed:17635991, ECO:0000269PubMed:18593899}. Note=Accumulates at sites of DNA damage following UV irradiation.

Disease Associations

Xeroderma pigmentosum complementation group E (XP-E) [MIM:278740]: An autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. The skin develops marked freckling and other pigmentation abnormalities. XP-E patients show a mild phenotype with minimal or no neurologic features. {ECO:0000269PubMed:8798680}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Ubiquitously expressed; with highest levels in corneal endothelium and lowest levels in brain. Isoform D1 is highly expressed in brain and heart. Isoform D2, isoform D3 and isoform D4 are weakly expressed. {ECO:0000269PubMed:14751237}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 74 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	74 [view]
Protein-Protein	69 [view]
Protein-DNA	4 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003677	DNA binding
GO:0003684	damaged DNA binding
GO:0004842	ubiquitin-protein transferase activity
GO:0005515	protein binding

Biological Process

GO:0000209	protein polyubiquitination
GO:0000718	nucleotide-excision repair, DNA damage removal
GO:0006281	DNA repair
GO:0006289	nucleotide-excision repair
GO:0009411	response to UV
GO:0035518	histone H2A monoubiquitination
GO:0051865	protein autoubiquitination
GO:0070914	UV-damage excision repair