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DDB2 |
Protein FULL name:
DNA damage-binding protein 2, Damage-specific DNA-binding protein 2, DDB p48 subunit, UV-damaged DNA-binding protein 2,
Protein SHORT name:
DDBb UV-DDB 2.
DDB2 (Homo sapiens) is product of expression of DDB2 gene.
DDB2 is involved in:
NER in Homo sapiens
Keywords:
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=1; 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 activity.
DOMAIN: The DWD box is required for interaction with DDB1.
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.
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; [LINK]
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; [LINK]
WEB RESOURCE: Name=GeneReviews; [LINK]
WEB RESOURCE: Name=NIEHS-SNPs; [LINK]
| NCBI GenPept GI number(s): |
12230033 4557515 |
| Species: | Homo sapiens |
Links to other databases:
| Database | ID | Link |
| Uniprot | Q92466 |
Q92466 |
| PFAM: |
PF00400 |
PF00400 |
| InterPro: |
IPR015943 IPR001680 IPR011046 IPR019782 IPR019775 IPR017986 IPR019781 |
IPR015943 IPR001680 IPR011046 IPR019782 IPR019775 IPR017986 IPR019781 |
| CATH: | - | - |
| SCOP: | - | - |
| PDB: | - | - |
Protein sequence:
|
MAPKKRPETQKTSEIVLRPRNKRSRSPLELEPEAKKLCAKGSGPSRRCDS DCLWVGLAGPQILPPCRSIVRTLHQHKLGRASWPSVQQGLQQSFLHTLDS YRILQKAAPFDRRATSLAWHPTHPSTVAVGSKGGDIMLWNFGIKDKPTFI KGIGAGGSITGLKFNPLNTNQFYASSMEGTTRLQDFKGNILRVFASSDTI NIWFCSLDVSASSRMVVTGDNVGNVILLNMDGKELWNLRMHKKKVTHVAL NPCCDWFLATASVDQTVKIWDLRQVRGKASFLYSLPHRHPVNAACFSPDG ARLLTTDQKSEIRVYSASQWDCPLGLIPHPHRHFQHLTPIKAAWHPRYNL IVVGRYPDPNFKSCTPYELRTIDVFDGNSGKMMCQLYDPESSGISSLNEF NPMGDTLASAMGYHILIWSQEEARTRK |
DDB2 (Homo sapiens) is able to recognize following damages:
- Dewar TT
- cyclobutane pyrimidine dimer
- base dimerization
- 6-4PP
- CPD
- pyrimidine dimer
- thymidine dimer
- bulky adduct
DDB2 (Homo sapiens) belongs to following protein families:
References:
| Title | Authors | Journal |
| Chromosomal localization and cDNA cloning of the genes (DDB1 and DDB2) for the p127 and p48 subunits of a human damage-specific DNA binding protein. | Dualan R, Brody T, Keeney S, Nichols AF, Admon A, Linn S | Genomics Sept. 1, 1995 |
| Mutations specific to the xeroderma pigmentosum group E Ddb- phenotype. | Nichols AF, Ong P, Linn S | J Biol Chem Oct. 4, 1996 |
| p48 Activates a UV-damaged-DNA binding factor and is defective in xeroderma pigmentosum group E cells that lack binding activity. | Hwang BJ, Toering S, Francke U, Chu G | Mol Cell Biol July 1, 1998 |
| Expression of the p48 xeroderma pigmentosum gene is p53-dependent and is involved in global genomic repair. | Hwang BJ, Ford JM, Hanawalt PC, Chu G | Proc Natl Acad Sci U S A Feb. 19, 1999 |
| Xeroderma pigmentosum p48 gene enhances global genomic repair and suppresses UV-induced mutagenesis. | Tang JY, Hwang BJ, Ford JM, Hanawalt PC, Chu G | Mol Cell April 1, 2000 |
| Nuclear transport of human DDB protein induced by ultraviolet light. | Liu W, Nichols AF, Graham JA, Dualan R, Abbas A, Linn S | J Biol Chem July 14, 2000 |
| Human damage-specific DNA-binding protein p48. Characterization of XPE mutations and regulation following UV irradiation. | Nichols AF, Itoh T, Graham JA, Liu W, Yamaizumi M, Linn S | J Biol Chem July 14, 2000 |
| Damaged DNA-binding protein DDB stimulates the excision of cyclobutane pyrimidine dimers in vitro in concert with XPA and replication protein A. | Wakasugi M, Shimizu M, Morioka H, Linn S, Nikaido O, Matsunaga T | J Biol Chem May 4, 2001 |
| UV-damaged DNA-binding proteins are targets of CUL-4A-mediated ubiquitination and degradation. | Chen X, Zhang Y, Douglas L, Zhou P | J Biol Chem Dec. 21, 2001 |
| DDB accumulates at DNA damage sites immediately after UV irradiation and directly stimulates nucleotide excision repair. | Wakasugi M, Kawashima A, Morioka H, Linn S, Sancar A, Mori T, Nikaido O, Matsunaga T | J Biol Chem Feb. 18, 2002 |
| The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. | Groisman R, Polanowska J, Kuraoka I, Sawada J, Saijo M, Drapkin R, Kisselev AF, Tanaka K, Nakatani Y | Cell May 2, 2003 |
| In vivo recruitment of XPC to UV-induced cyclobutane pyrimidine dimers by the DDB2 gene product. | Fitch ME, Nakajima S, Yasui A, Ford JM | J Biol Chem Nov. 21, 2003 |
| Human DDB2 splicing variants are dominant negative inhibitors of UV-damaged DNA repair. | Inoki T, Yamagami S, Inoki Y, Tsuru T, Hamamoto T, Kagawa Y, Mori T, Endo H | Biochem Biophys Res Commun Jan. 20, 2004 |
| Complete sequencing and characterization of 21,243 full-length human cDNAs. | Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S | Nat Genet Feb. 1, 2004 |
| The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). | Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J | Genome Res Oct. 1, 2004 |
| UV-induced ubiquitylation of XPC protein mediated by UV-DDB-ubiquitin ligase complex. | Sugasawa K, Okuda Y, Saijo M, Nishi R, Matsuda N, Chu G, Mori T, Iwai S, Tanaka K, Tanaka K, Hanaoka F | Cell May 6, 2005 |
| Xeroderma pigmentosum complementation group E protein (XPE/DDB2): purification of various complexes of XPE and analyses of their damaged DNA binding and putative DNA repair properties. | Kulaksiz G, Reardon JT, Sancar A | Mol Cell Biol Nov. 1, 2005 |
| DDB1-DDB2 (xeroderma pigmentosum group E) protein complex recognizes a cyclobutane pyrimidine dimer, mismatches, apurinic/apyrimidinic sites, and compound lesions in DNA. | Wittschieben BO, Iwai S, Wood RD | J Biol Chem Dec. 2, 2005 |
| The DDB1-CUL4ADDB2 ubiquitin ligase is deficient in xeroderma pigmentosum group E and targets histone H2A at UV-damaged DNA sites. | Kapetanaki MG, Guerrero-Santoro J, Bisi DC, Hsieh CL, Rapic-Otrin V, Levine AS | Proc Natl Acad Sci U S A Jan. 21, 2006 |
| Histone H3 and H4 ubiquitylation by the CUL4-DDB-ROC1 ubiquitin ligase facilitates cellular response to DNA damage. | Wang H, Zhai L, Xu J, Joo HY, Jackson S, Erdjument-Bromage H, Tempst P, Xiong Y, Zhang Y | Mol Cell May 5, 2006 |
| Cullin 4A-mediated proteolysis of DDB2 protein at DNA damage sites regulates in vivo lesion recognition by XPC. | El-Mahdy MA, Zhu Q, Wang QE, Wani G, Praetorius-Ibba M, Wani AA | J Biol Chem May 12, 2006 |
| A kinase-independent function of c-Abl in promoting proteolytic destruction of damaged DNA binding proteins. | Chen X, Zhang J, Lee J, Lin PS, Ford JM, Zheng N, Zhou P | Mol Cell May 19, 2006 |
| A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1. | Jin J, Arias EE, Chen J, Harper JW, Walter JC | Mol Cell Sept. 1, 2006 |
| Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery. | Angers S, Li T, Yi X, MacCoss MJ, Moon RT, Zheng N | Nature Oct. 5, 2006 |
| DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases. | He YJ, McCall CM, Hu J, Zeng Y, Xiong Y | Genes Dev Nov. 1, 2006 |
| CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins and regulates histone methylation. | Higa LA, Wu M, Ye T, Kobayashi R, Sun H, Zhang H | Nat Cell Biol Nov. 1, 2006 |
| Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. | Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M | Cell Nov. 3, 2006 |
| 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 |
| Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column. | Imami K, Sugiyama N, Kyono Y, Tomita M, Ishihama Y | Anal Sci Feb. 1, 2008 |
| The cullin 4B-based UV-damaged DNA-binding protein ligase binds to UV-damaged chromatin and ubiquitinates histone H2A. | Guerrero-Santoro J, Kapetanaki MG, Hsieh CL, Gorbachinsky I, Levine AS, Rapic-Otrin V | Cancer Res July 1, 2008 |
| A quantitative atlas of mitotic phosphorylation. | Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP | Proc Natl Acad Sci U S A Aug. 5, 2008 |
| Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. | Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK | Sci Signal Jan. 1, 2009 |
| Lysine acetylation targets protein complexes and co-regulates major cellular functions. | Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M | Science Aug. 14, 2009 |
Last modification of this entry: Oct. 19, 2010.
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