Q92466 (DDB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA damage-binding protein 2

Alternative name(s):
DDB p48 subunit
Short name=DDBb
Damage-specific DNA-binding protein 2
UV-damaged DNA-binding protein 2
Short name=UV-DDB 2

Gene names

Name:

DDB2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	427 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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. Ref.2 Ref.9 Ref.12 Ref.13 Ref.15 Ref.16 Ref.17 Ref.18 Ref.20 Ref.24 Ref.29 Ref.31
Pathway	Protein modification; protein ubiquitination.
Subunit structure	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. Ref.2 Ref.8 Ref.14 Ref.16 Ref.18 Ref.19 Ref.20 Ref.22 Ref.23 Ref.24 Ref.26 Ref.27 Ref.28 Ref.29 Ref.31
Subcellular location	Nucleus. Note: Accumulates at sites of DNA damage following UV irradiation. Ref.2 Ref.10 Ref.11 Ref.15 Ref.17 Ref.25 Ref.29 Ref.30 Ref.31
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. Ref.2
Induction	Expression is induced in response to treatment with IR or UV and this requires p53/TP53 activity. Ref.10
Domain	The DWD box is required for interaction with DDB1. Ref.22 Interblade loops of the WD repeat region mediate most of the interaction with DNA. A hairpin between blades 5 and 6 inserts into DNA minor groove and mediates recognition of lesions and separation of the damaged and undamaged strands. Ref.22
Post-translational modification	Phosphorylation by ABL1 negatively regulate UV-DDB activity By similarity. 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. Ref.14 Ref.18 Ref.23 Ref.25
Involvement in disease	Xeroderma pigmentosum complementation group E (XP-E) [MIM:278740]: An autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. The skin develops marked freckling and other pigmentation abnormalities. XP-E patients show a mild phenotype with minimal or no neurologic features. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.37
Sequence similarities	Belongs to the WD repeat DDB2/WDR76 family. Contains 7 WD repeats.

Ontologies

Keywords
Biological process	DNA damage DNA repair Ubl conjugation pathway
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Xeroderma pigmentosum
Domain	Repeat WD repeat
Ligand	DNA-binding
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	nucleotide-excision repair, DNA damage removal Traceable author statement. Source: Reactome protein autoubiquitination Inferred from direct assay Ref.16. Source: UniProtKB protein polyubiquitination Inferred from direct assay Ref.16. Source: UniProtKB pyrimidine dimer repair Inferred from electronic annotation. Source: Compara response to UV Inferred from direct assay Ref.16. Source: UniProtKB
Cellular_component	nucleoplasm Traceable author statement. Source: Reactome protein complex Inferred from direct assay Ref.16. Source: UniProtKB
Molecular_function	damaged DNA binding Traceable author statement PubMed 8407967. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CUL4A	Q13619	2	EBI-1176171,EBI-456106
DDB1	Q16531	3	EBI-1176171,EBI-350322
E2F1	Q01094	2	EBI-1176171,EBI-448924

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q92466-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform D1 (identifier: Q92466-2)

The sequence of this isoform differs from the canonical sequence as follows:
     153-341: Missing.

Isoform D2 (identifier: Q92466-3)

The sequence of this isoform differs from the canonical sequence as follows:
     153-156: IGAG → HLVL
     157-427: Missing.

Isoform D3 (identifier: Q92466-4)

The sequence of this isoform differs from the canonical sequence as follows:
     89-152: Missing.

Isoform D4 (identifier: Q92466-5)

The sequence of this isoform differs from the canonical sequence as follows:
     236-244: WNLRMHKKK → VSVPMEPGS
     245-427: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 427

427

DNA damage-binding protein 2

PRO_0000050953

Regions

Repeat

116 – 151

36

WD 1

Repeat

159 – 194

36

WD 2

Repeat

203 – 238

36

WD 3

Repeat

244 – 287

44

WD 4

Repeat

290 – 329

40

WD 5

Repeat

343 – 386

44

WD 6

Repeat

396 – 420

25

WD 7

Region

68 – 79

12

Required for interaction with DDB1

Region

87 – 98

12

Required for interaction with DDB1

Region

334 – 336

3

Photolesion recognition

Motif

256 – 274

19

DWD box

Amino acid modifications

Modified residue

24

1

Phosphoserine Ref.21

Modified residue

26

1

Phosphoserine Ref.21 Ref.33 Ref.34 Ref.35

Natural variations

Alternative sequence

89 – 152

64

Missing in isoform D3.

VSP_014674

Alternative sequence

153 – 341

189

Missing in isoform D1.

VSP_014675

Alternative sequence

153 – 156

4

IGAG → HLVL in isoform D2.

VSP_014676

Alternative sequence

157 – 427

271

Missing in isoform D2.

VSP_014677

Alternative sequence

236 – 244

9

WNLRMHKKK → VSVPMEPGS in isoform D4.

VSP_014678

Alternative sequence

245 – 427

183

Missing in isoform D4.

VSP_014679

Natural variant

215

1

M → T. Ref.4
Corresponds to variant rs4647750 [ dbSNP | Ensembl ].

VAR_016337

Natural variant

244

1

K → E in XP-E; impairs DNA-binding of the UV-DDB complex. Ref.8 Ref.10 Ref.19 Ref.37

VAR_010141

Natural variant

273

1

R → H in XP-E; impairs interaction with DDB1 and CUL4A. Ref.8 Ref.10 Ref.14 Ref.19 Ref.26 Ref.27 Ref.37

VAR_010142

Natural variant

293

1

A → T. Ref.4
Corresponds to variant rs4647751 [ dbSNP | Ensembl ].

VAR_016338

Experimental info

Mutagenesis

258

1

L → A: Impairs interaction with DDB1. Ref.22

Mutagenesis

262

1

S → A: Impairs interaction with DDB1. Ref.22

Mutagenesis

264

1

D → A: Impairs interaction with DDB1. Ref.22

Mutagenesis

269

1

I → A: Impairs interaction with DDB1. Ref.22

Mutagenesis

270

1

W → A: Impairs interaction with DDB1. Ref.22

Mutagenesis

272

1

L → A: Impairs interaction with DDB1. Ref.22

Mutagenesis

273

1

R → A: Impairs interaction with DDB1. Ref.22

Mutagenesis

350

1

L → P: Impairs interaction with DDB1. Ref.26

Secondary structure

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427

Helix Strand Turn

Details...

Helix

21 – 25

5

Beta strand

30 – 32

3

Helix

39 – 42

4

Turn

44 – 47

4

Beta strand

49 – 51

3

Helix

58 – 62

5

Turn

63 – 65

3

Helix

69 – 77

9

Helix

83 – 91

9

Turn

92 – 94

3

Turn

96 – 102

7

Beta strand

106 – 109

4

Beta strand

114 – 119

6

Beta strand

127 – 131

5

Beta strand

136 – 139

4

Beta strand

148 – 150

3

Beta strand

154 – 156

3

Beta strand

161 – 164

4

Beta strand

171 – 175

5

Beta strand

177 – 179

3

Beta strand

181 – 185

5

Turn

186 – 188

3

Beta strand

190 – 195

6

Beta strand

198 – 201

4

Beta strand

207 – 210

4

Turn

211 – 214

4

Beta strand

215 – 219

5

Beta strand

221 – 232

12

Beta strand

241 – 243

3

Beta strand

245 – 250

6

Turn

252 – 254

3

Beta strand

255 – 262

8

Turn

263 – 265

3

Beta strand

269 – 271

3

Turn

272 – 274

3

Beta strand

277 – 279

3

Beta strand

282 – 286

5

Beta strand

291 – 293

3

Beta strand

300 – 310

11

Beta strand

312 – 326

15

Beta strand

335 – 337

3

Beta strand

346 – 349

4

Beta strand

351 – 354

4

Beta strand

359 – 361

3

Beta strand

364 – 366

3

Beta strand

372 – 375

4

Beta strand

377 – 379

3

Beta strand

382 – 386

5

Turn

389 – 391

3

Beta strand

397 – 400

4

Beta strand

407 – 410

4

Beta strand

412 – 417

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 1, 1997. Version 1. Checksum: E881F21242CA44D2	FASTA	427	47,864
	10 20 30 40 50 60 MAPKKRPETQ KTSEIVLRPR NKRSRSPLEL EPEAKKLCAK GSGPSRRCDS DCLWVGLAGP 70 80 90 100 110 120 QILPPCRSIV RTLHQHKLGR ASWPSVQQGL QQSFLHTLDS YRILQKAAPF DRRATSLAWH 130 140 150 160 170 180 PTHPSTVAVG SKGGDIMLWN FGIKDKPTFI KGIGAGGSIT GLKFNPLNTN QFYASSMEGT 190 200 210 220 230 240 TRLQDFKGNI LRVFASSDTI NIWFCSLDVS ASSRMVVTGD NVGNVILLNM DGKELWNLRM 250 260 270 280 290 300 HKKKVTHVAL NPCCDWFLAT ASVDQTVKIW DLRQVRGKAS FLYSLPHRHP VNAACFSPDG 310 320 330 340 350 360 ARLLTTDQKS EIRVYSASQW DCPLGLIPHP HRHFQHLTPI KAAWHPRYNL IVVGRYPDPN 370 380 390 400 410 420 FKSCTPYELR TIDVFDGNSG KMMCQLYDPE SSGISSLNEF NPMGDTLASA MGYHILIWSQ EEARTRK
	Isoform D1 [UniParc]. Checksum: F40BD646C1C26FDA	FASTA	238	26,744
	10 20 30 40 50 60 MAPKKRPETQ KTSEIVLRPR NKRSRSPLEL EPEAKKLCAK GSGPSRRCDS DCLWVGLAGP 70 80 90 100 110 120 QILPPCRSIV RTLHQHKLGR ASWPSVQQGL QQSFLHTLDS YRILQKAAPF DRRATSLAWH 130 140 150 160 170 180 PTHPSTVAVG SKGGDIMLWN FGIKDKPTFI KGAAWHPRYN LIVVGRYPDP NFKSCTPYEL 190 200 210 220 230 RTIDVFDGNS GKMMCQLYDP ESSGISSLNE FNPMGDTLAS AMGYHILIWS QEEARTRK
	Isoform D2 [UniParc]. Checksum: FBC8A060B4DC7A4D	FASTA	156	17,434
	10 20 30 40 50 60 MAPKKRPETQ KTSEIVLRPR NKRSRSPLEL EPEAKKLCAK GSGPSRRCDS DCLWVGLAGP 70 80 90 100 110 120 QILPPCRSIV RTLHQHKLGR ASWPSVQQGL QQSFLHTLDS YRILQKAAPF DRRATSLAWH 130 140 150 PTHPSTVAVG SKGGDIMLWN FGIKDKPTFI KGHLVL
	Isoform D3 [UniParc]. Checksum: 2A90D5BD9E322889	FASTA	363	40,772
	10 20 30 40 50 60 MAPKKRPETQ KTSEIVLRPR NKRSRSPLEL EPEAKKLCAK GSGPSRRCDS DCLWVGLAGP 70 80 90 100 110 120 QILPPCRSIV RTLHQHKLGR ASWPSVQQIG AGGSITGLKF NPLNTNQFYA SSMEGTTRLQ 130 140 150 160 170 180 DFKGNILRVF ASSDTINIWF CSLDVSASSR MVVTGDNVGN VILLNMDGKE LWNLRMHKKK 190 200 210 220 230 240 VTHVALNPCC DWFLATASVD QTVKIWDLRQ VRGKASFLYS LPHRHPVNAA CFSPDGARLL 250 260 270 280 290 300 TTDQKSEIRV YSASQWDCPL GLIPHPHRHF QHLTPIKAAW HPRYNLIVVG RYPDPNFKSC 310 320 330 340 350 360 TPYELRTIDV FDGNSGKMMC QLYDPESSGI SSLNEFNPMG DTLASAMGYH ILIWSQEEAR TRK
	Isoform D4 [UniParc]. Checksum: 367D99AA1DD984F9	FASTA	244	26,758
	10 20 30 40 50 60 MAPKKRPETQ KTSEIVLRPR NKRSRSPLEL EPEAKKLCAK GSGPSRRCDS DCLWVGLAGP 70 80 90 100 110 120 QILPPCRSIV RTLHQHKLGR ASWPSVQQGL QQSFLHTLDS YRILQKAAPF DRRATSLAWH 130 140 150 160 170 180 PTHPSTVAVG SKGGDIMLWN FGIKDKPTFI KGIGAGGSIT GLKFNPLNTN QFYASSMEGT 190 200 210 220 230 240 TRLQDFKGNI LRVFASSDTI NIWFCSLDVS ASSRMVVTGD NVGNVILLNM DGKELVSVPM EPGS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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 A.F., Admon A., Linn S. Genomics 29:62-69(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Epidermis.
[2]	"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. 314:1036-1043(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS D1; D2; D3 AND D4), FUNCTION, INTERACTION WITH DDB1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Epithelium.
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	NIEHS SNPs program Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-215 AND THR-293.
[5]	"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 T.-O., 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. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Placenta.
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[8]	"p48 Activates a UV-damaged-DNA binding factor and is defective in xeroderma pigmentosum group E cells that lack binding activity." Hwang B.J., Toering S., Francke U., Chu G. Mol. Cell. Biol. 18:4391-4399(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DDB1, DNA-BINDING, CHARACTERIZATION OF VARIANTS GLU-244 AND HIS-273.
[9]	"Expression of the p48 xeroderma pigmentosum gene is p53-dependent and is involved in global genomic repair." Hwang B.J., Ford J.M., Hanawalt P.C., Chu G. Proc. Natl. Acad. Sci. U.S.A. 96:424-428(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DNA-BINDING.
[10]	"Human damage-specific DNA-binding protein p48. Characterization of XPE mutations and regulation following UV irradiation." Nichols A.F., Itoh T., Graham J.A., Liu W., Yamaizumi M., Linn S. J. Biol. Chem. 275:21422-21428(2000) [PubMed] [Europe PMC] [Abstract] Cited for: DNA-BINDING, SUBCELLULAR LOCATION, INDUCTION, CHARACTERIZATION OF VARIANTS GLU-244 AND HIS-273.
[11]	"Nuclear transport of human DDB protein induced by ultraviolet light." Liu W., Nichols A.F., Graham J.A., Dualan R., Abbas A., Linn S. J. Biol. Chem. 275:21429-21434(2000) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[12]	"Xeroderma pigmentosum p48 gene enhances global genomic repair and suppresses UV-induced mutagenesis." Tang J.Y., Hwang B.J., Ford J.M., Hanawalt P.C., Chu G. Mol. Cell 5:737-744(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[13]	"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. 276:15434-15440(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DNA-BINDING.
[14]	"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. 276:48175-48182(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CUL4A, UBIQUITINATION, CHARACTERIZATION OF VARIANT HIS-273.
[15]	"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. 277:1637-1640(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DNA-BINDING, SUBCELLULAR LOCATION.
[16]	"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 A.F., Tanaka K., Nakatani Y. Cell 113:357-367(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN A COMPLEX WITH CUL4A; DDB1 AND RBX1 AND THE COP9 SIGNALOSOME, DNA-BINDING.
[17]	"In vivo recruitment of XPC to UV-induced cyclobutane pyrimidine dimers by the DDB2 gene product." Fitch M.E., Nakajima S., Yasui A., Ford J.M. J. Biol. Chem. 278:46906-46910(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[18]	"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 121:387-400(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CUL4A; DDB1; RBX1 AND XPC, DNA-BINDING, UBIQUITINATION.
[19]	"DDB1-DDB2 (xeroderma pigmentosum group E) protein complex recognizes a cyclobutane pyrimidine dimer, mismatches, apurinic/apyrimidinic sites, and compound lesions in DNA." Wittschieben B.O., Iwai S., Wood R.D. J. Biol. Chem. 280:39982-39989(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DDB1, DNA-BINDING, CHARACTERIZATION OF VARIANTS GLU-244 AND HIS-273.
[20]	"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 J.T., Sancar A. Mol. Cell. Biol. 25:9784-9792(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CUL4A; DDB1; RBX1 AND THE COP9 SIGNALOSOME, DNA-BINDING.
[21]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24 AND SER-26, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[22]	"DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases." He Y.J., McCall C.M., Hu J., Zeng Y., Xiong Y. Genes Dev. 20:2949-2954(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CUL4A AND DDB1, DOMAIN DWD BOX MOTIF, MUTAGENESIS OF LEU-258; SER-262; ASP-264; ILE-269; TRP-270; LEU-272 AND ARG-273.
[23]	"Cullin 4A-mediated proteolysis of DDB2 protein at DNA damage sites regulates in vivo lesion recognition by XPC." El-Mahdy M.A., Zhu Q., Wang Q.-E., Wani G., Praetorius-Ibba M., Wani A.A. J. Biol. Chem. 281:13404-13411(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CUL4A AND DDB1, UBIQUITINATION.
[24]	"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 H.-Y., Jackson S., Erdjument-Bromage H., Tempst P., Xiong Y., Zhang Y. Mol. Cell 22:383-394(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN A COMPLEX WITH DDB1; CUL4A; CUL4B AND RBX1, FUNCTION.
[25]	"A kinase-independent function of c-Abl in promoting proteolytic destruction of damaged DNA binding proteins." Chen X., Zhang J., Lee J., Lin P.S., Ford J.M., Zheng N., Zhou P. Mol. Cell 22:489-499(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, UBIQUITINATION.
[26]	"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 E.E., Chen J., Harper J.W., Walter J.C. Mol. Cell 23:709-721(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH DDB1, MUTAGENESIS OF LEU-350, CHARACTERIZATION OF VARIANT HIS-273.
[27]	"Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery." Angers S., Li T., Yi X., MacCoss M.J., Moon R.T., Zheng N. Nature 443:590-593(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DDB1, CHARACTERIZATION OF VARIANT HIS-273.
[28]	"CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins and regulates histone methylation." Higa L.A., Wu M., Ye T., Kobayashi R., Sun H., Zhang H. Nat. Cell Biol. 8:1277-1283(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CUL4A AND CUL4B.
[29]	"The DDB1-CUL4ADDB2 ubiquitin ligase is deficient in xeroderma pigmentosum group E and targets histone H2A at UV-damaged DNA sites." Kapetanaki M.G., Guerrero-Santoro J., Bisi D.C., Hsieh C.L., Rapic-Otrin V., Levine A.S. Proc. Natl. Acad. Sci. U.S.A. 103:2588-2593(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CUL4A; DDB1; HISTONE H2A AND RBX1, DNA-BINDING, SUBCELLULAR LOCATION.
[30]	"Dynamic in vivo interaction of DDB2 E3 ubiquitin ligase with UV-damaged DNA is independent of damage-recognition protein XPC." Luijsterburg M.S., Goedhart J., Moser J., Kool H., Geverts B., Houtsmuller A.B., Mullenders L.H.F., Vermeulen W., van Driel R. J. Cell Sci. 120:2706-2716(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[31]	"The cullin 4B-based UV-damaged DNA-binding protein ligase binds to UV-damaged chromatin and ubiquitinates histone H2A." Guerrero-Santoro J., Kapetanaki M.G., Hsieh C.L., Gorbachinsky I., Levine A.S., Rapic-Otrin V. Cancer Res. 68:5014-5022(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CUL4A; CUL4B AND DDB1, SUBCELLULAR LOCATION.
[32]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[33]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[34]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[35]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26, MASS SPECTROMETRY.
[36]	"Structural basis of UV DNA-damage recognition by the DDB1-DDB2 complex." Scrima A., Konickova R., Czyzewski B.K., Kawasaki Y., Jeffrey P.D., Groisman R., Nakatani Y., Iwai S., Pavletich N.P., Thoma N.H. Cell 135:1213-1223(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 10-427 IN COMPLEX WITH DDB1 AND DNA, WD REPEATS.
[37]	"Mutations specific to the xeroderma pigmentosum group E Ddb-phenotype." Nichols A.F., Ong P., Linn S. J. Biol. Chem. 271:24317-24320(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS XP-E GLU-244 AND HIS-273.
+	Additional computationally mapped references.

Web resources

Allelic variations of the XP genes

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U18300 mRNA. Translation: AAB07897.1.
AB107037 mRNA. Translation: BAD12557.1.
AB107038 mRNA. Translation: BAD12558.1.
AB107039 mRNA. Translation: BAD12559.1.
AB107040 mRNA. Translation: BAD12560.1.
BT007139 mRNA. Translation: AAP35803.1.
AY220533 Genomic DNA. Translation: AAO25655.1.
AK313262 mRNA. Translation: BAG36072.1.
CH471064 Genomic DNA. Translation: EAW67952.1.
BC000093 mRNA. Translation: AAH00093.1.

IPI

IPI00021518.
IPI00446284.
IPI00549348.
IPI00607674.
IPI00607727.

PIR

I38909.

RefSeq

NP_000098.1. NM_000107.2.

UniGene

Hs.700338.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3EI4	X-ray	3.30	B/D/F	10-427	[»]
3I7L	X-ray	2.80	B	68-81	[»]
4E54	X-ray	2.85	B	2-427	[»]
4E5Z	X-ray	3.22	B	2-419	[»]

ProteinModelPortal

Q92466.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-36670N.

IntAct

Q92466. 9 interactions.

STRING

9606.ENSP00000256996.

PTM databases

PhosphoSite

Q92466.

Polymorphism databases

DMDM

12230033.

Proteomic databases

PaxDb

Q92466.

PRIDE

Q92466.

Protocols and materials databases

DNASU

1643.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000256996; ENSP00000256996; ENSG00000134574.
ENST00000378600; ENSP00000367863; ENSG00000134574.
ENST00000378601; ENSP00000367864; ENSG00000134574.
ENST00000378603; ENSP00000367866; ENSG00000134574.

GeneID

1643.

KEGG

hsa:1643.

UCSC

uc001neb.2. human.
uc001nee.2. human.
uc009yli.1. human.

Organism-specific databases

CTD

1643.

GeneCards

GC11P047193.

HGNC

HGNC:2718. DDB2.

HPA

CAB025912.

MIM

278740. phenotype.
600811. gene.

neXtProt

NX_Q92466.

Orphanet

276261. Xeroderma pigmentosum complementation group E.

PharmGKB

PA27188.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2319.

HOGENOM

HOG000231440.

HOVERGEN

HBG000713.

InParanoid

Q92466.

KO

K10140.

OMA

NSAYFNP.

OrthoDB

EOG40K7ZV.

PhylomeDB

Q92466.

Enzyme and pathway databases

Reactome

REACT_216. DNA Repair.

SignaLink

Q92466.

UniPathway

UPA00143.

Gene expression databases

Bgee

Q92466.

CleanEx

HS_DDB2.

Genevestigator

Q92466.

GermOnline

ENSG00000134574. Homo sapiens.

Family and domain databases

Gene3D

2.130.10.10. 1 hit.

InterPro

IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]

Pfam

PF00400. WD40. 3 hits.
[Graphical view]

SMART

SM00320. WD40. 5 hits.
[Graphical view]

SUPFAM

SSF50978. WD40_like. 1 hit.

PROSITE

PS00678. WD_REPEATS_1. 1 hit.
PS50082. WD_REPEATS_2. 1 hit.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

DDB2. human.

EvolutionaryTrace

Q92466.

GenomeRNAi

1643.

NextBio

6758.

SOURCE

Search...

Entry information

Entry name

DDB2_HUMAN

Accession

Primary (citable) accession number: Q92466
Secondary accession number(s): B2R875 , Q76E54, Q76E55, Q76E56, Q76E57

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 11, 2001
Last sequence update:	February 1, 1997
Last modified:	May 29, 2013
This is version 137 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.