Homo sapiens L. (human) [HSA]

FULL NAME: DNA damage-binding protein 2


DESCRIPTION:
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.

STRUCTURE SIMILARITY:
Contains 5 WD repeats.
Belongs to the WD repeat DDB2/WDR76 family.


POST-TRANSLATIONAL MODIFICATION:
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.
Phosphorylation by ABL1 negatively regulate UV-DDB activity (By similarity).


RELATED PATHWAY(S):
nucleotide excision repair (NER)


RELATED DISEASE(S):
xeroderma pigmentosum, complementation group E (XPE)


RELATED DAMAGE:
(6-4)PP
CPD
AP-site


Amino acids sequence

        10         20         30         40         50         60
MAPKKRPETQ KTSEIVLRPR NKRSRSPLEL EPEAKKLCAK GSGPSRRCDS DCLWVGLAGP
        70         80         90        100        110        120
QILPPCRSIV RTLHQHKLGR ASWPSVQQGL QQSFLHTLDS YRILQKAAPF DRRATSLAWH
       130        140        150        160        170        180
PTHPSTVAVG SKGGDIMLWN FGIKDKPTFI KGIGAGGSIT GLKFNPLNTN QFYASSMEGT
       190        200        210        220        230        240
TRLQDFKGNI LRVFASSDTI NIWFCSLDVS ASSRMVVTGD NVGNVILLNM DGKELWNLRM
       250        260        270        280        290        300
HKKKVTHVAL NPCCDWFLAT ASVDQTVKIW DLRQVRGKAS FLYSLPHRHP VNAACFSPDG
       310        320        330        340        350        360
ARLLTTDQKS EIRVYSASQW DCPLGLIPHP HRHFQHLTPI KAAWHPRYNL IVVGRYPDPN
       370        380        390        400        410        420
FKSCTPYELR TIDVFDGNSG KMMCQLYDPE SSGISSLNEF NPMGDTLASA MGYHILIWSQ

EEARTRK     

Encoded by DDB2 gene

FULL NAME: damage-specific DNA binding protein 2, 48kDa


OTHER NAME(S):
DDBB
FLJ34321
UV-DDB2


DESCRIPTION:
This gene encodes a protein that is necessary for the repair of ultraviolet light-damaged DNA. This protein is the smaller subunit of a heterodimeric protein complex that participates in nucleotide excision repair, and this complex mediates the ubiquitylation of histones H3 and H4, which facilitates the cellular response to DNA damage. This subunit appears to be required for DNA binding. Mutations in this gene cause xeroderma pigmentosum complementation group E, a recessive disease that is characterized by an increased sensitivity to UV light and a high predisposition for skin cancer development, in some cases accompanied by neurological abnormalities. [provided by RefSeq, Jul 2008]


Nucleic acid sequence

        10         20         30         40         50         60
atggctccca agaaacgccc agaaacccag aagacctccg agattgtatt acgccccagg
        70         80         90        100        110        120
aacaagagga gcaggagtcc cctggagctg gagcccgagg ccaagaagct ctgtgcgaag
       130        140        150        160        170        180
ggctccggtc ctagcagaag atgtgactca gactgcctct gggtggggct ggctggccca
       190        200        210        220        230        240
cagatcctgc caccatgccg cagcatcgtc aggaccctcc accagcataa gctgggcaga
       250        260        270        280        290        300
gcttcctggc catctgtcca gcaggggctc cagcagtcct ttttgcacac tctggattct
       310        320        330        340        350        360
taccggatat tacaaaaggc tgcccccttt gacaggaggg ctacatcctt ggcgtggcac
       370        380        390        400        410        420
ccaactcacc ccagcaccgt ggctgtgggt tccaaagggg gagatatcat gctctggaat
       430        440        450        460        470        480
tttggcatca aggacaaacc caccttcatc aaagggattg gagctggagg gagcatcact
       490        500        510        520        530        540
gggctgaagt ttaaccctct caataccaac cagttttacg cctcctcaat ggagggaaca
       550        560        570        580        590        600
actaggctgc aagactttaa aggcaacatt ctacgagttt ttgccagctc agacaccatc
       610        620        630        640        650        660
aacatctggt tttgtagcct ggatgtgtct gctagtagcc gaatggtggt cacaggagac
       670        680        690        700        710        720
aacgtgggga acgtgatcct gctgaacatg gacggcaaag agctttggaa tctcagaatg
       730        740        750        760        770        780
cacaaaaaga aagtgacgca tgtggccctg aacccatgct gtgattggtt cctggccaca
       790        800        810        820        830        840
gcctccgtag atcaaacagt gaaaatttgg gacctgcgcc aggttagagg gaaagccagc
       850        860        870        880        890        900
ttcctctact cgctgccgca caggcatcct gtcaacgcag cttgtttcag tcccgatgga
       910        920        930        940        950        960
gcccggctcc tgaccacgga ccagaagagc gagatccgag tttactctgc ttcccagtgg
       970        980        990       1000       1010       1020
gactgccccc tgggcctgat cccgcaccct caccgtcact tccagcacct cacacccatc
      1030       1040       1050       1060       1070       1080
aaggcagcct ggcatcctcg ctacaacctc attgttgtgg gccgataccc agatcctaat
      1090       1100       1110       1120       1130       1140
ttcaaaagtt gtacccctta tgaattgagg acgatcgacg tgttcgatgg aaactcaggg
      1150       1160       1170       1180       1190       1200
aagatgatgt gtcagctcta tgacccagaa tcttctggca tcagttcgct taatgaattc
      1210       1220       1230       1240       1250       1260
aatcccatgg gggacacgct ggcctctgca atgggttacc acattctcat ctggagccag
      1270       1280
gaggaagcca ggacacggaa gtga   

Last modification date: Oct. 2, 2011