ID:DDB2_HUMAN DESCRIPTION: RecName: Full=DNA damage-binding protein 2; AltName: Full=DDB p48 subunit; Short=DDBb; AltName: Full=Damage-specific DNA-binding protein 2; AltName: Full=UV-damaged DNA-binding protein 2; Short=UV-DDB 2; 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. 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. Isoform D1 and isoform D2 do not interact with DDB1. INTERACTION: Q13619:CUL4A; NbExp=2; IntAct=EBI-1176171, EBI-456106; Q16531:DDB1; NbExp=3; IntAct=EBI-1176171, EBI-350322; Q01094:E2F1; NbExp=2; IntAct=EBI-1176171, EBI-448924; SUBCELLULAR LOCATION: Nucleus. Note=Accumulates at sites of DNA damage following UV irradiation. 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. INDUCTION: Expression is induced in response to treatment with IR or UV and this requires p53/TP53 activity. DOMAIN: The DWD box is required for interaction with DDB1. PTM: Phosphorylation by ABL1 negatively regulate UV-DDB activity (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. DISEASE: Defects in DDB2 are a cause of xeroderma pigmentosum complementation group E (XP-E) [MIM:278740]; also known as xeroderma pigmentosum V (XP5). XP-E is a rare human autosomal recessive disease characterized by solar sensitivity, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. SIMILARITY: Belongs to the WD repeat DDB2/WDR76 family. SIMILARITY: Contains 5 WD repeats. WEB RESOURCE: Name=Allelic variations of the XP genes; URL="http://www.xpmutations.org/"; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/XPEID298.html"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/DDB2"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/ddb2/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q92466
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
LF385479 - JP 2014500723-A/192982: Polycomb-Associated Non-Coding RNAs. U18300 - Human damage-specific DNA binding protein p48 subunit (DDB2) mRNA, complete cds. AK313262 - Homo sapiens cDNA, FLJ93771, Homo sapiens damage-specific DNA binding protein 2, 48kDa (DDB2),mRNA. BC001160 - Homo sapiens cDNA clone IMAGE:3354063, **** WARNING: chimeric clone ****. JD129373 - Sequence 110397 from Patent EP1572962. JD076022 - Sequence 57046 from Patent EP1572962. BC050455 - Homo sapiens damage-specific DNA binding protein 2, 48kDa, mRNA (cDNA clone IMAGE:5757413), with apparent retained intron. JD507422 - Sequence 488446 from Patent EP1572962. AK091640 - Homo sapiens cDNA FLJ34321 fis, clone FEBRA2008755, highly similar to Damage-specific DNA binding protein 2. AX747106 - Sequence 631 from Patent EP1308459. BC000093 - Homo sapiens damage-specific DNA binding protein 2, 48kDa, mRNA (cDNA clone MGC:1561 IMAGE:3508134), complete cds. AB527602 - Synthetic construct DNA, clone: pF1KB6679, Homo sapiens DDB2 gene for damage-specific DNA binding protein 2, 48kDa, without stop codon, in Flexi system. CU674030 - Synthetic construct Homo sapiens gateway clone IMAGE:100018262 5' read DDB2 mRNA. BT007139 - Homo sapiens damage-specific DNA binding protein 2, 48kDa mRNA, complete cds. DQ890719 - Synthetic construct clone IMAGE:100003349; FLH165444.01X; RZPDo839C05160D damage-specific DNA binding protein 2, 48kDa (DDB2) gene, encodes complete protein. HQ447914 - Synthetic construct Homo sapiens clone IMAGE:100071270; CCSB003586_01 damage-specific DNA binding protein 2, 48kDa (DDB2) gene, encodes complete protein. KJ896693 - Synthetic construct Homo sapiens clone ccsbBroadEn_06087 DDB2 gene, encodes complete protein. KR709821 - Synthetic construct Homo sapiens clone CCSBHm_00006418 DDB2 (DDB2) mRNA, encodes complete protein. KR709822 - Synthetic construct Homo sapiens clone CCSBHm_00006419 DDB2 (DDB2) mRNA, encodes complete protein. KR709823 - Synthetic construct Homo sapiens clone CCSBHm_00006420 DDB2 (DDB2) mRNA, encodes complete protein. KR709824 - Synthetic construct Homo sapiens clone CCSBHm_00006422 DDB2 (DDB2) mRNA, encodes complete protein. AB107037 - Homo sapiens ddb2 mRNA for damage-specific DNA binding protein 2 splicing variant D1, complete cds. AB107038 - Homo sapiens ddb2 mRNA for damage-specific DNA binding protein 2 splicing variant D2, complete cds. AB107039 - Homo sapiens ddb2 mRNA for damage-specific DNA binding protein 2 splicing variant D3, complete cds. AB107040 - Homo sapiens ddb2 mRNA for damage-specific DNA binding protein 2 splicing variant D4, complete cds. LF205768 - JP 2014500723-A/13271: Polycomb-Associated Non-Coding RNAs. LF347945 - JP 2014500723-A/155448: Polycomb-Associated Non-Coding RNAs. LF347943 - JP 2014500723-A/155446: Polycomb-Associated Non-Coding RNAs. LF347942 - JP 2014500723-A/155445: Polycomb-Associated Non-Coding RNAs. JD311263 - Sequence 292287 from Patent EP1572962. JD285033 - Sequence 266057 from Patent EP1572962. JD465502 - Sequence 446526 from Patent EP1572962. JD045498 - Sequence 26522 from Patent EP1572962. JD381275 - Sequence 362299 from Patent EP1572962. MA621056 - JP 2018138019-A/192982: Polycomb-Associated Non-Coding RNAs. MA583522 - JP 2018138019-A/155448: Polycomb-Associated Non-Coding RNAs. MA583520 - JP 2018138019-A/155446: Polycomb-Associated Non-Coding RNAs. MA583519 - JP 2018138019-A/155445: Polycomb-Associated Non-Coding RNAs. MA441345 - JP 2018138019-A/13271: Polycomb-Associated Non-Coding RNAs.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q92466 (Reactome details) participates in the following event(s):
R-HSA-5696997 USP24 deubiquitinates DDB2 R-HSA-8955245 CAND1 binds CRL4 E3 ubiquitin ligase in the nucleus R-HSA-5690988 3'-incision of DNA by ERCC5 (XPG) in GG-NER R-HSA-6782943 UV-DDB ubiquitinates XPC R-HSA-5691006 XPC:RAD23:CETN2 and UV-DDB bind distorted dsDNA site R-HSA-5696664 PARP1 or PARP2 binds DDB2 at GG-NER site R-HSA-8955285 COMMDs displace CAND1 from CRL4 E3 ubiquitin ligase complex R-HSA-8952639 NEDD8:AcM-UBE2M binds CRL4 E3 ubiquitin ligase complex R-HSA-8956045 COP9 signalosome deneddylates nuclear CRL4 E3 ubiquitin ligase complex R-HSA-8952638 AcM-UBE2M transfers NEDD8 to CRL4 E3 ubiquitin ligase complex R-HSA-5690213 DNA polymerases delta, epsilon or kappa bind the GG-NER site R-HSA-5690990 5'- incision of DNA by ERCC1:ERCC4 in GG-NER R-HSA-6790487 RNF111 ubiquitinates SUMOylated XPC R-HSA-6790454 SUMOylation of XPC R-HSA-5689317 Formation of the pre-incision complex in GG-NER R-HSA-5696655 PARP1 or PARP2 PARylates DDB2 and autoPARylates R-HSA-5690996 ERCC2 and ERCC3 DNA helicases form an open bubble structure in damaged DNA R-HSA-5691000 TFIIH binds GG-NER site to form a verification complex R-HSA-5690991 Binding of ERCC1:ERCC4 (ERCC1:XPF) to pre-incision complex in GG-NER R-HSA-5696670 CHD1L is recruited to GG-NER site R-HSA-5689861 Recruitment of XPA and release of CAK R-HSA-6796648 TP53 Regulates Transcription of DNA Repair Genes R-HSA-5689880 Ub-specific processing proteases R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-5688426 Deubiquitination R-HSA-8951664 Neddylation R-HSA-212436 Generic Transcription Pathway R-HSA-5696400 Dual Incision in GG-NER R-HSA-5696394 DNA Damage Recognition in GG-NER R-HSA-597592 Post-translational protein modification R-HSA-73857 RNA Polymerase II Transcription R-HSA-5696395 Formation of Incision Complex in GG-NER R-HSA-5696399 Global Genome Nucleotide Excision Repair (GG-NER) R-HSA-392499 Metabolism of proteins R-HSA-74160 Gene expression (Transcription) R-HSA-5696398 Nucleotide Excision Repair R-HSA-73894 DNA Repair
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
