DDB2
entrez
1643
canonical
uniprot
Q92466
canonical
ensembl
ENSG00000134574
resolver
ensp
ENSP00000256996
resolver
ensp
ENSP00000367863
resolver
ensp
ENSP00000367864
resolver
ensp
ENSP00000367866
resolver
ensp
ENSP00000637723
resolver
genesymbol
DDB2
resolver
hgnc
HGNC:2718
resolver
uniprot
B2R875
resolver
uniprot
Q76E54
resolver
uniprot
Q76E55
resolver
uniprot
Q76E56
resolver
uniprot
Q76E57
resolver
uniprot_entry
DDB2_HUMAN
resolver
uniprot_sec
B2R875
resolver
uniprot_sec
Q76E54
resolver
uniprot_sec
Q76E55
resolver
uniprot_sec
Q76E56
resolver
uniprot_sec
Q76E57
resolver
amino_acid_sequence
MAPKKRPETQKTSEIVLRPRNKRSRSPLELEPEAKKLCAKGSGPSRRCDSDCLWVGLAGPQILPPCRSIVRTLHQHKLGRASWPSVQQGLQQSFLHTLDSYRILQKAAPFDRRATSLAWHPTHPSTVAVGSKGGDIMLWNFGIKDKPTFIKGIGAGGSITGLKFNPLNTNQFYASSMEGTTRLQDFKGNILRVFASSDTINIWFCSLDVSASSRMVVTGDNVGNVILLNMDGKELWNLRMHKKKVTHVALNPCCDWFLATASVDQTVKIWDLRQVRGKASFLYSLPHRHPVNAACFSPDGARLLTTDQKSEIRVYSASQWDCPLGLIPHPHRHFQHLTPIKAAWHPRYNLIVVGRYPDPNFKSCTPYELRTIDVFDGNSGKMMCQLYDPESSGISSLNEFNPMGDTLASAMGYHILIWSQEEARTRK
uniprot
proteins
disease_involvement
DISEASE: 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:0000269|PubMed:8798680}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: 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 (PubMed:10882109, PubMed:11278856, PubMed:11705987, PubMed:12732143, PubMed:15882621, PubMed:16473935, PubMed:18593899, PubMed:32789493, PubMed:9892649). Core component of the UV-DDB complex (UV-damaged DNA-binding protein complex), a complex that recognizes UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair (PubMed:10882109, PubMed:11278856, PubMed:11705987, PubMed:12944386, PubMed:14751237, PubMed:16260596, PubMed:32789493). The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches (PubMed:10882109, PubMed:11278856, PubMed:11705987, PubMed:12944386, PubMed:16260596). 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) (PubMed:12732143, PubMed:15882621, PubMed:16473935, PubMed:18593899, PubMed:26572825). The DDB2-CUL4-ROC1 complex may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage (PubMed:16473935, PubMed:16678110). The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair (PubMed:16473935, PubMed:16678110). The DDB2-CUL4-ROC1 complex also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER (PubMed:15882621). The DDB2-CUL4-ROC1 complex also ubiquitinates KAT7/HBO1 in response to DNA damage, leading to its degradation: recognizes KAT7/HBO1 following phosphorylation by ATR (PubMed:26572825). {ECO:0000269|PubMed:10882109, ECO:0000269|PubMed:11278856, ECO:0000269|PubMed:11705987, ECO:0000269|PubMed:12732143, ECO:0000269|PubMed:12944386, ECO:0000269|PubMed:14751237, ECO:0000269|PubMed:15882621, ECO:0000269|PubMed:16260596, ECO:0000269|PubMed:16473935, ECO:0000269|PubMed:16678110, ECO:0000269|PubMed:18593899, ECO:0000269|PubMed:26572825, ECO:0000269|PubMed:32789493, ECO:0000269|PubMed:9892649}.; FUNCTION: [Isoform D1]: Inhibits UV-damaged DNA repair. {ECO:0000269|PubMed:14751237}.; FUNCTION: [Isoform D2]: Inhibits UV-damaged DNA repair. {ECO:0000269|PubMed:14751237}.
uniprot
proteins
mass_dalton
47864
uniprot
proteins
mutagenesis
MUTAGEN 35; /note="K->R: Decreased acetylation levels."; /evidence="ECO:0000269|PubMed:32789493"; MUTAGEN 40; /note="K->R: Does not affect acetylation levels."; /evidence="ECO:0000269|PubMed:32789493"; MUTAGEN 77; /note="K->R: Decreased acetylation levels."; /evidence="ECO:0000269|PubMed:32789493"; MUTAGEN 258; /note="L->A: Impairs interaction with DDB1."; /evidence="ECO:0000269|PubMed:17079684"; MUTAGEN 262; /note="S->A: Impairs interaction with DDB1."; /evidence="ECO:0000269|PubMed:17079684"; MUTAGEN 264; /note="D->A: Impairs interaction with DDB1."; /evidence="ECO:0000269|PubMed:17079684"; MUTAGEN 269; /note="I->A: Impairs interaction with DDB1."; /evidence="ECO:0000269|PubMed:17079684"; MUTAGEN 270; /note="W->A: Impairs interaction with DDB1."; /evidence="ECO:0000269|PubMed:17079684"; MUTAGEN 272; /note="L->A: Impairs interaction with DDB1."; /evidence="ECO:0000269|PubMed:17079684"; MUTAGEN 273; /note="R->A: Impairs interaction with DDB1."; /evidence="ECO:0000269|PubMed:17079684"; MUTAGEN 350; /note="L->P: Impairs interaction with DDB1."; /evidence="ECO:0000269|PubMed:16949367
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination.
uniprot
proteins
post_translational_modification
PTM: Phosphorylation by ABL1 negatively regulate UV-DDB activity. {ECO:0000250|UniProtKB:Q99J79}.; PTM: Ubiquitinated by CUL4A in response to UV irradiation. Ubiquitination appears to both impair DNA-binding and promotes ubiquitin-dependent proteolysis. Degradation of DDB2 at sites of DNA damage may be a prerequisite for their recognition by XPC and subsequent repair. CUL4A-mediated degradation appears to be promoted by ABL1. {ECO:0000269|PubMed:23159851}.; PTM: Ubiquitinated, leading to proteasomal degradation, and deubiquitinated by USP24. Deubiquitinated by USP44; leading to its stabilization on DNA lesions (By similarity). {ECO:0000250|UniProtKB:Q99J79, ECO:0000269|PubMed:23159851}.; PTM: Acetylated (PubMed:32789493). Deacetylation by SIRT6 in response to UV stress facilitates nucleotide excision repair pathway (the NER pathway) transduction (PubMed:32789493). {ECO:0000269|PubMed:32789493}.
uniprot
proteins
protein_family
WD repeat DDB2/WDR76 family
uniprot
proteins
pubmed
10777490
uniprot
proteins
pubmed
10777491
uniprot
proteins
pubmed
10882109
uniprot
proteins
pubmed
11278856
uniprot
proteins
pubmed
11673459
uniprot
proteins
pubmed
11705987
uniprot
proteins
pubmed
12732143
uniprot
proteins
pubmed
12944386
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14751237
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15882621
uniprot
proteins
pubmed
16223728
uniprot
proteins
pubmed
16260596
uniprot
proteins
pubmed
16473935
uniprot
proteins
pubmed
16527807
uniprot
proteins
pubmed
16678110
uniprot
proteins
pubmed
16713579
uniprot
proteins
pubmed
16949367
uniprot
proteins
pubmed
16964240
uniprot
proteins
pubmed
17041588
uniprot
proteins
pubmed
17079684
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17635991
uniprot
proteins
pubmed
18593899
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19109893
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19966799
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22822215
uniprot
proteins
pubmed
23159851
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
26572825
uniprot
proteins
pubmed
32789493
uniprot
proteins
pubmed
8530102
uniprot
proteins
pubmed
8798680
uniprot
proteins
pubmed
9632823
uniprot
proteins
pubmed
9892649
uniprot
proteins
sequence_length
427
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10777490, ECO:0000269|PubMed:10777491, ECO:0000269|PubMed:11705987, ECO:0000269|PubMed:12944386, ECO:0000269|PubMed:14751237, ECO:0000269|PubMed:16473935, ECO:0000269|PubMed:16713579, ECO:0000269|PubMed:17635991, ECO:0000269|PubMed:18593899}. Chromosome {ECO:0000269|PubMed:32789493}. Note=Accumulates at sites of DNA damage following UV irradiation. {ECO:0000269|PubMed:32789493}.
uniprot
proteins