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Ddb2 |
Protein FULL name:
DNA damage-binding protein 2 [Mus musculus].
Ddb2 (Mus musculus) is product of expression of Ddb2 gene.
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 (By similarity).
PATHWAY: Protein modification; protein ubiquitination.
SUBUNIT: Component of the UV-DDB complex which includes DDB1 and DDB2. The UV-DDB complex interacts with monoubiquitinated histone H2A and binds to XPC via the DDB2 subunit. Component of the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex DDB1-CUL4- ROC1 (also known as CUL4-DDB-ROC1 and CUL4-DDB-RBX1), which includes CUL4A or CUL4B, DDB1, DDB2 and RBX1. DDB2 may function as the substrate recognition module within this complex. The DDB1- CUL4-ROC1 complex may associate with the COP9 signalosome, and this inhibits the E3 ubiquitin-protein ligase activity of the complex. A large number of other DCX complexes may also exist in which an alternate substrate targeting subunit replaces DDB2. These targeting subunits are generally known as DCAF (DDB1- and CUL4-associated factor) or CDW (CUL4-DDB1-associated WD40-repeat) proteins (By similarity).
SUBCELLULAR LOCATION: Nucleus. Note=Accumulates at sites of DNA damage following UV irradiation.
TISSUE SPECIFICITY: Expressed in bone marrow, liver, lung, muscle, pancreas and spleen.
DOMAIN: The DWD box is required for interaction with DDB1 (By similarity).
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/c-ABL (By similarity).
DISRUPTION PHENOTYPE: Mice exhibit elevated susceptibility to UV- induced skin carcinogenesis and enhanced rates of spontaneous tumor formation, particularly for lung and mammary adenocarcinomas. DDB2 is haploinsufficient as a tumor suppressor. The spleens of these animals are enlarged due to enhanced lymphoid proliferation while the testes are also enlarged due to reduced rates of apoptosis of testicular germ cells. Fibroblasts from these animals are resistant to p53-dependent apoptosis induced by UV treatment.
SIMILARITY: Belongs to the WD repeat DDB2/WDR76 family.
SIMILARITY: Contains 5 WD repeats.
| NCBI GenPept GI number(s): |
29150251 |
| Species: | Mus musculus |
Links to other databases:
| Database | ID | Link |
| Uniprot | Q99J79 |
Q99J79 |
| PFAM: | - |
Q99J79 (Link - using uniprot id) |
| InterPro: | - |
Q99J79 (Link - using uniprot id) |
| CATH: | - | - |
| SCOP: | - | - |
| PDB: | - | - |
Protein sequence:
|
MAPKKCPETQKSPDVAVLLRSKSRRGPQELEPEAKKLRVQGPVSSRTCES CCLLAELSSLQIPSRSSSIVRDLYQHKLGKATWSSLQQGLQKSFLHSLAS YQVFRKAAPFDRRTTSLAWHPTHPSTLAVGSKGGDIMIWNFGIKDKPIFL KGIGAGGSITGLKFNHLNTNQFFASSMEGTTRLQDFKGNILRVYTSSNSC KVWFCSLDVSAKSRVVVTGDNMGHVILLSTDGKELWNLRMHKKKVAHVAL NPCCDWLLATASIDQTVKIWDLRQIKGKDSFLYSLPHRHPVNAACFSPDG ARLLTTDQNNEIRVYSASQWDSPLNLISHPHRHFQHLTPIKATWHSRHNL IVVGRYPDPNLKSCVPYELRTIDVFDGSSGKMMCQLYDPGYSGITSLNEF NPMGDTLASTMGYHILIWSQEEDGSQKDHERL |
Ddb2 (Mus musculus) belongs to following protein families:
References:
| Title | Authors | Journal |
| Studies of the murine DDB1 and DDB2 genes. | Zolezzi F, Linn S | Gene March 7, 2000 |
| DDB2 gene disruption leads to skin tumors and resistance to apoptosis after exposure to ultraviolet light but not a chemical carcinogen. | Itoh T, Cado D, Kamide R, Linn S | Proc Natl Acad Sci U S A Jan. 17, 2004 |
| Tumor-prone phenotype of the DDB2-deficient mice. | Yoon T, Chakrabortty A, Franks R, Valli T, Kiyokawa H, Raychaudhuri P | Oncogene Feb. 13, 2005 |
| Ddb2 is a haploinsufficient tumor suppressor and controls spontaneous germ cell apoptosis. | Itoh T, Iwashita S, Cohen MB, Meyerholz DK, Linn S | Hum Mol Genet July 1, 2007 |
| Dynamic in vivo interaction of DDB2 E3 ubiquitin ligase with UV-damaged DNA is independent of damage-recognition protein XPC. | Luijsterburg MS, Goedhart J, Moser J, Kool H, Geverts B, Houtsmuller AB, Mullenders LH, Vermeulen W, van Driel R | J Cell Sci Aug. 1, 2007 |
Last modification of this entry: Oct. 6, 2010.
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