CPLM-018700

Genbank Nucleotide ID

DNA damage-binding protein 2

Protein Synonyms/Alias

DDB p48 subunit; DDBb; Damage-specific DNA-binding protein 2; UV-damaged DNA-binding protein 2; UV-DDB 2

Homo sapiens (Human)

Position	Peptide	Type	References
40	EAKKLCAKGSGPSRR	ubiquitination	[1]
106	DSYRILQKAAPFDRR	ubiquitination	[2, 3]
146	WNFGIKDKPTFIKGI	ubiquitination	[2, 3]
151	KDKPTFIKGIGAGGS	ubiquitination	[1, 2, 3, 4, 5, 6]
163	GGSITGLKFNPLNTN	ubiquitination	[2, 5, 7]
187	TTRLQDFKGNILRVF	ubiquitination	[1, 2, 3, 4, 5, 6]
278	DLRQVRGKASFLYSL	acetylation	[8, 9]
278	DLRQVRGKASFLYSL	ubiquitination	[4, 6]
309	RLLTTDQKSEIRVYS	ubiquitination	[2, 3, 5, 7]
341	FQHLTPIKAAWHPRY	ubiquitination	[2]
362	RYPDPNFKSCTPYEL	ubiquitination	[1, 2, 3, 4, 6, 7, 10]

[1] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
[2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[3] Integrated proteomic analysis of post-translational modifications by serial enrichment.
Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
[4] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[5] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[6] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
Chen Z, Zhou Y, Song J, Zhang Z.
Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
[7] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
[8] 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. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
[9] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
[10] Global identification of modular cullin-RING ligase substrates.
Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]

Functional 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.

REPEAT 116 151 WD 1.
REPEAT 159 194 WD 2.
REPEAT 203 238 WD 3.
REPEAT 244 287 WD 4.
REPEAT 290 329 WD 5.
REPEAT 343 386 WD 6.
REPEAT 396 420 WD 7.
REGION 68 79 Required for interaction with DDB1.
REGION 87 98 Required for interaction with DDB1.
REGION 334 336 Photolesion recognition.
MOTIF 256 274 DWD box.
MOD_RES 24 24 Phosphoserine.
MOD_RES 26 26 Phosphoserine.

3D-structure; Alternative splicing; Complete proteome; Disease mutation; DNA damage; DNA repair; DNA-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Ubl conjugation; Ubl conjugation pathway; WD repeat; Xeroderma pigmentosum.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005654; C:nucleoplasm; TAS:Reactome.
GO:0043234; C:protein complex; IDA:UniProtKB.
GO:0003684; F:damaged DNA binding; TAS:ProtInc.
GO:0000718; P:nucleotide-excision repair, DNA damage removal; TAS:Reactome.
GO:0051865; P:protein autoubiquitination; IDA:UniProtKB.
GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
GO:0006290; P:pyrimidine dimer repair; IEA:Compara.
GO:0009411; P:response to UV; IDA:UniProtKB.

IPR015943; WD40/YVTN_repeat-like_dom.
IPR001680; WD40_repeat.
IPR019775; WD40_repeat_CS.
IPR017986; WD40_repeat_dom.

PS00678; WD_REPEATS_1
PS50082; WD_REPEATS_2
PS50294; WD_REPEATS_REGION