You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Identification
HMDB Protein ID HMDBP10931
Secondary Accession Numbers
  • 17236
Name DNA damage-binding protein 2
Synonyms
  1. DDB p48 subunit
  2. DDBb
  3. Damage-specific DNA-binding protein 2
  4. UV-DDB 2
  5. UV-damaged DNA-binding protein 2
Gene Name DDB2
Protein Type Unknown
Biological Properties
General Function Involved in damaged DNA binding
Specific 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
Pathways Not Available
Reactions Not Available
GO Classification Not Available
Cellular Location
  1. Nucleus
Gene Properties
Chromosome Location Chromosome:1
Locus 11p12-p11
SNPs DDB2
Gene Sequence
>1284 bp
ATGGCTCCCAAGAAACGCCCAGAAACCCAGAAGACCTCCGAGATTGTATTACGCCCCAGG
AACAAGAGGAGCAGGAGTCCCCTGGAGCTGGAGCCCGAGGCCAAGAAGCTCTGTGCGAAG
GGCTCCGGTCCTAGCAGAAGATGTGACTCAGACTGCCTCTGGGTGGGGCTGGCTGGCCCA
CAGATCCTGCCACCATGCCGCAGCATCGTCAGGACCCTCCACCAGCATAAGCTGGGCAGA
GCTTCCTGGCCATCTGTCCAGCAGGGGCTCCAGCAGTCCTTTTTGCACACTCTGGATTCT
TACCGGATATTACAAAAGGCTGCCCCCTTTGACAGGAGGGCTACATCCTTGGCGTGGCAC
CCAACTCACCCCAGCACCGTGGCTGTGGGTTCCAAAGGGGGAGATATCATGCTCTGGAAT
TTTGGCATCAAGGACAAACCCACCTTCATCAAAGGGATTGGAGCTGGAGGGAGCATCACT
GGGCTGAAGTTTAACCCTCTCAATACCAACCAGTTTTACGCCTCCTCAATGGAGGGAACA
ACTAGGCTGCAAGACTTTAAAGGCAACATTCTACGAGTTTTTGCCAGCTCAGACACCATC
AACATCTGGTTTTGTAGCCTGGATGTGTCTGCTAGTAGCCGAATGGTGGTCACAGGAGAC
AACGTGGGGAACGTGATCCTGCTGAACATGGACGGCAAAGAGCTTTGGAATCTCAGAATG
CACAAAAAGAAAGTGACGCATGTGGCCCTGAACCCATGCTGTGATTGGTTCCTGGCCACA
GCCTCCGTAGATCAAACAGTGAAAATTTGGGACCTGCGCCAGGTTAGAGGGAAAGCCAGC
TTCCTCTACTCGCTGCCGCACAGGCATCCTGTCAACGCAGCTTGTTTCAGTCCCGATGGA
GCCCGGCTCCTGACCACGGACCAGAAGAGCGAGATCCGAGTTTACTCTGCTTCCCAGTGG
GACTGCCCCCTGGGCCTGATCCCGCACCCTCACCGTCACTTCCAGCACCTCACACCCATC
AAGGCAGCCTGGCATCCTCGCTACAACCTCATTGTTGTGGGCCGATACCCAGATCCTAAT
TTCAAAAGTTGTACCCCTTATGAATTGAGGACGATCGACGTGTTCGATGGAAACTCAGGG
AAGATGATGTGTCAGCTCTATGACCCAGAATCTTCTGGCATCAGTTCGCTTAATGAATTC
AATCCCATGGGGGACACGCTGGCCTCTGCAATGGGTTACCACATTCTCATCTGGAGCCAG
GAGGAAGCCAGGACACGGAAGTGA
Protein Properties
Number of Residues 427
Molecular Weight 47863.5
Theoretical pI 9.98
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>DNA damage-binding protein 2
MAPKKRPETQKTSEIVLRPRNKRSRSPLELEPEAKKLCAKGSGPSRRCDSDCLWVGLAGP
QILPPCRSIVRTLHQHKLGRASWPSVQQGLQQSFLHTLDSYRILQKAAPFDRRATSLAWH
PTHPSTVAVGSKGGDIMLWNFGIKDKPTFIKGIGAGGSITGLKFNPLNTNQFYASSMEGT
TRLQDFKGNILRVFASSDTINIWFCSLDVSASSRMVVTGDNVGNVILLNMDGKELWNLRM
HKKKVTHVALNPCCDWFLATASVDQTVKIWDLRQVRGKASFLYSLPHRHPVNAACFSPDG
ARLLTTDQKSEIRVYSASQWDCPLGLIPHPHRHFQHLTPIKAAWHPRYNLIVVGRYPDPN
FKSCTPYELRTIDVFDGNSGKMMCQLYDPESSGISSLNEFNPMGDTLASAMGYHILIWSQ
EEARTRK
GenBank ID Protein 4557515
UniProtKB/Swiss-Prot ID Q92466
UniProtKB/Swiss-Prot Entry Name DDB2_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_000107.2
GeneCard ID DDB2
GenAtlas ID DDB2
HGNC ID HGNC:2718
References
General References
  1. 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: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  2. 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: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  4. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  5. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332 ]
  6. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [PubMed:17081983 ]
  7. Imami K, Sugiyama N, Kyono Y, Tomita M, Ishihama Y: Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column. Anal Sci. 2008 Jan;24(1):161-6. [PubMed:18187866 ]
  8. Wang H, Zhai L, Xu J, Joo HY, Jackson S, Erdjument-Bromage H, Tempst P, Xiong Y, Zhang Y: Histone H3 and H4 ubiquitylation by the CUL4-DDB-ROC1 ubiquitin ligase facilitates cellular response to DNA damage. Mol Cell. 2006 May 5;22(3):383-94. [PubMed:16678110 ]
  9. Dualan R, Brody T, Keeney S, Nichols AF, Admon A, Linn S: 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. Genomics. 1995 Sep 1;29(1):62-9. [PubMed:8530102 ]
  10. Inoki T, Yamagami S, Inoki Y, Tsuru T, Hamamoto T, Kagawa Y, Mori T, Endo H: Human DDB2 splicing variants are dominant negative inhibitors of UV-damaged DNA repair. Biochem Biophys Res Commun. 2004 Feb 20;314(4):1036-43. [PubMed:14751237 ]
  11. Hwang BJ, Toering S, Francke U, Chu G: p48 Activates a UV-damaged-DNA binding factor and is defective in xeroderma pigmentosum group E cells that lack binding activity. Mol Cell Biol. 1998 Jul;18(7):4391-9. [PubMed:9632823 ]
  12. Hwang BJ, Ford JM, Hanawalt PC, Chu G: Expression of the p48 xeroderma pigmentosum gene is p53-dependent and is involved in global genomic repair. Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):424-8. [PubMed:9892649 ]
  13. Nichols AF, Itoh T, Graham JA, Liu W, Yamaizumi M, Linn S: Human damage-specific DNA-binding protein p48. Characterization of XPE mutations and regulation following UV irradiation. J Biol Chem. 2000 Jul 14;275(28):21422-8. [PubMed:10777490 ]
  14. Liu W, Nichols AF, Graham JA, Dualan R, Abbas A, Linn S: Nuclear transport of human DDB protein induced by ultraviolet light. J Biol Chem. 2000 Jul 14;275(28):21429-34. [PubMed:10777491 ]
  15. Tang JY, Hwang BJ, Ford JM, Hanawalt PC, Chu G: Xeroderma pigmentosum p48 gene enhances global genomic repair and suppresses UV-induced mutagenesis. Mol Cell. 2000 Apr;5(4):737-44. [PubMed:10882109 ]
  16. Wakasugi M, Shimizu M, Morioka H, Linn S, Nikaido O, Matsunaga T: Damaged DNA-binding protein DDB stimulates the excision of cyclobutane pyrimidine dimers in vitro in concert with XPA and replication protein A. J Biol Chem. 2001 May 4;276(18):15434-40. Epub 2001 Feb 2. [PubMed:11278856 ]
  17. Chen X, Zhang Y, Douglas L, Zhou P: UV-damaged DNA-binding proteins are targets of CUL-4A-mediated ubiquitination and degradation. J Biol Chem. 2001 Dec 21;276(51):48175-82. Epub 2001 Oct 22. [PubMed:11673459 ]
  18. Wakasugi M, Kawashima A, Morioka H, Linn S, Sancar A, Mori T, Nikaido O, Matsunaga T: DDB accumulates at DNA damage sites immediately after UV irradiation and directly stimulates nucleotide excision repair. J Biol Chem. 2002 Jan 18;277(3):1637-40. Epub 2001 Nov 8. [PubMed:11705987 ]
  19. Groisman R, Polanowska J, Kuraoka I, Sawada J, Saijo M, Drapkin R, Kisselev AF, Tanaka K, Nakatani Y: The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. Cell. 2003 May 2;113(3):357-67. [PubMed:12732143 ]
  20. Fitch ME, Nakajima S, Yasui A, Ford JM: In vivo recruitment of XPC to UV-induced cyclobutane pyrimidine dimers by the DDB2 gene product. J Biol Chem. 2003 Nov 21;278(47):46906-10. Epub 2003 Aug 27. [PubMed:12944386 ]
  21. Sugasawa K, Okuda Y, Saijo M, Nishi R, Matsuda N, Chu G, Mori T, Iwai S, Tanaka K, Tanaka K, Hanaoka F: UV-induced ubiquitylation of XPC protein mediated by UV-DDB-ubiquitin ligase complex. Cell. 2005 May 6;121(3):387-400. [PubMed:15882621 ]
  22. Wittschieben BO, Iwai S, Wood RD: DDB1-DDB2 (xeroderma pigmentosum group E) protein complex recognizes a cyclobutane pyrimidine dimer, mismatches, apurinic/apyrimidinic sites, and compound lesions in DNA. J Biol Chem. 2005 Dec 2;280(48):39982-9. Epub 2005 Aug 24. [PubMed:16223728 ]
  23. Kulaksiz G, Reardon JT, Sancar A: 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. Mol Cell Biol. 2005 Nov;25(22):9784-92. [PubMed:16260596 ]
  24. He YJ, McCall CM, Hu J, Zeng Y, Xiong Y: DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases. Genes Dev. 2006 Nov 1;20(21):2949-54. [PubMed:17079684 ]
  25. El-Mahdy MA, Zhu Q, Wang QE, Wani G, Praetorius-Ibba M, Wani AA: Cullin 4A-mediated proteolysis of DDB2 protein at DNA damage sites regulates in vivo lesion recognition by XPC. J Biol Chem. 2006 May 12;281(19):13404-11. Epub 2006 Mar 8. [PubMed:16527807 ]
  26. Chen X, Zhang J, Lee J, Lin PS, Ford JM, Zheng N, Zhou P: A kinase-independent function of c-Abl in promoting proteolytic destruction of damaged DNA binding proteins. Mol Cell. 2006 May 19;22(4):489-99. [PubMed:16713579 ]
  27. Jin J, Arias EE, Chen J, Harper JW, Walter JC: A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1. Mol Cell. 2006 Sep 1;23(5):709-21. [PubMed:16949367 ]
  28. Angers S, Li T, Yi X, MacCoss MJ, Moon RT, Zheng N: Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery. Nature. 2006 Oct 5;443(7111):590-3. [PubMed:16964240 ]
  29. Higa LA, Wu M, Ye T, Kobayashi R, Sun H, Zhang H: CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins and regulates histone methylation. Nat Cell Biol. 2006 Nov;8(11):1277-83. Epub 2006 Oct 15. [PubMed:17041588 ]
  30. Kapetanaki MG, Guerrero-Santoro J, Bisi DC, Hsieh CL, Rapic-Otrin V, Levine AS: The DDB1-CUL4ADDB2 ubiquitin ligase is deficient in xeroderma pigmentosum group E and targets histone H2A at UV-damaged DNA sites. Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2588-93. Epub 2006 Feb 10. [PubMed:16473935 ]
  31. Luijsterburg MS, Goedhart J, Moser J, Kool H, Geverts B, Houtsmuller AB, Mullenders LH, Vermeulen W, van Driel R: Dynamic in vivo interaction of DDB2 E3 ubiquitin ligase with UV-damaged DNA is independent of damage-recognition protein XPC. J Cell Sci. 2007 Aug 1;120(Pt 15):2706-16. Epub 2007 Jul 17. [PubMed:17635991 ]
  32. Guerrero-Santoro J, Kapetanaki MG, Hsieh CL, Gorbachinsky I, Levine AS, Rapic-Otrin V: The cullin 4B-based UV-damaged DNA-binding protein ligase binds to UV-damaged chromatin and ubiquitinates histone H2A. Cancer Res. 2008 Jul 1;68(13):5014-22. doi: 10.1158/0008-5472.CAN-07-6162. [PubMed:18593899 ]
  33. Nichols AF, Ong P, Linn S: Mutations specific to the xeroderma pigmentosum group E Ddb- phenotype. J Biol Chem. 1996 Oct 4;271(40):24317-20. [PubMed:8798680 ]