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DDB2 (xeroderma pigmentosum, complementation group E)

Identity

Other namesXPE (xeroderma pigmentosum, complementation group E)
UV-DDB
DDB2
HGNC (Hugo) DDB2
LocusID (NCBI) 1643
Location 11p11.2
Location_base_pair Starts at 47236493 and ends at 47260769 bp from pter ( according to hg19-Feb_2009)  [Mapping]
 
  XPE (11p11) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.

DNA/RNA

Transcription 4193 bp

Protein

Description DDB1: 1140 amino acids, 127 kDa; DDB2: 427 amino acids, 48 kDa; DDB1 (p127) and DDB2 (p48) form a stable heterodimer UV-DDB
Function The damage-specific DNA binding (UV-DDB) activity purified as a heterodimer (p127 and p48) is expected to play a role in damage recognition prior to the Nucleotide Excision Repair (NER) because the DDB protein is reported to recognize many types of DNA lesions and is inducible by treatment with DNA-damaging agents. After UV irradiation, dynamic nuclear accumulation of DDB1 from the cytoplasm was found after 24 h. The function of the gene product is not completely clarified yet. Band shift assays suggested that the XPE gene product acts as a damaged DNA binding protein (DDB), with high affinity to UV-induced 6-4Pyrimidine-Pyrimidone photoproducts. However, defective DDB binding activity is not a common feature of XPE mutant cell lines and in fact two (or even more) proteins may be involved in the binding activity: p48 and p125. In cells from several XPE patient mutations in p48 have been found but so far no mutations have been found in the p125 gene. XPE patients show mild dermatological symptoms and cells from these patients have a relatively high repair capacity. XPE cells are not necessarily defective in repair: p125 is proposed to play a role in opening up chromatin to make CPD accessible to the NER machinery, but is not required for repair of 6-4PP. Interestingly, cell lines and primary tissues from rodents are fully deficient in the expression of the p48 protein . This explains the absence of GGR of CPD in these cells. Exogenous expression of p48 in hamster cells confers enhanced removal of CPD from genomic DNA and nontranscribed strand of active genes. The p48 protein is upregulated by p53.

Mutations

Germinal three single base substitutions only in DDB2 (p48) gene

Implicated in

Entity xeroderma pigmentosum, XP group E
Oncogenesis Early skin tumours
  

External links

Nomenclature
HGNC (Hugo)DDB2   2718
Cards
AtlasXPEID298
Entrez_Gene (NCBI)DDB2  1643  damage-specific DNA binding protein 2, 48kDa
GeneCards (Weizmann)DDB2
Ensembl (Hinxton)ENSG00000134574 [Gene_View]  chr11:47236493-47260769 [Contig_View]  DDB2 [Vega]
ICGC DataPortalENSG00000134574
cBioPortalDDB2
AceView (NCBI)DDB2
Genatlas (Paris)DDB2
WikiGenes1643
SOURCE (Princeton)NM_000107 NM_001300734
Genomic and cartography
GoldenPath (UCSC)DDB2  -  11p11.2   chr11:47236493-47260769 +  11p12-p11   [Description]    (hg19-Feb_2009)
EnsemblDDB2 - 11p12-p11 [CytoView]
Mapping of homologs : NCBIDDB2 [Mapview]
OMIM278740   600811   
Gene and transcription
Genbank (Entrez)AA278953 AB107037 AB107038 AB107039 AB107040
RefSeq transcript (Entrez)NM_000107 NM_001300734
RefSeq genomic (Entrez)AC_000143 NC_000011 NC_018922 NG_009365 NT_009237 NW_001838022 NW_004929378
Consensus coding sequences : CCDS (NCBI)DDB2
Cluster EST : UnigeneHs.700338 [ NCBI ]
CGAP (NCI)Hs.700338
Alternative Splicing : Fast-db (Paris)GSHG0004801
Alternative Splicing GalleryENSG00000134574
Gene ExpressionDDB2 [ NCBI-GEO ]     DDB2 [ SEEK ]   DDB2 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ92466 (Uniprot)
NextProtQ92466  [Medical]
With graphics : InterProQ92466
Splice isoforms : SwissVarQ92466 (Swissvar)
Domaine pattern : Prosite (Expaxy)WD_REPEATS_1 (PS00678)    WD_REPEATS_2 (PS50082)    WD_REPEATS_REGION (PS50294)   
Domains : Interpro (EBI)WD40/YVTN_repeat-like_dom [organisation]   WD40_repeat [organisation]   WD40_repeat_CS [organisation]   WD40_repeat_dom [organisation]  
Related proteins : CluSTrQ92466
Domain families : Pfam (Sanger)WD40 (PF00400)   
Domain families : Pfam (NCBI)pfam00400   
Domain families : Smart (EMBL)WD40 (SM00320)  
DMDM Disease mutations1643
Blocks (Seattle)Q92466
PDB (SRS)3EI4    3I7L    4E54    4E5Z   
PDB (PDBSum)3EI4    3I7L    4E54    4E5Z   
PDB (IMB)3EI4    3I7L    4E54    4E5Z   
PDB (RSDB)3EI4    3I7L    4E54    4E5Z   
Human Protein AtlasENSG00000134574 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasQ92466
HPRD02886
IPIIPI00021518   IPI00549348   IPI00607674   IPI00446284   IPI00607727   
Protein Interaction databases
DIP (DOE-UCLA)Q92466
IntAct (EBI)Q92466
FunCoupENSG00000134574
BioGRIDDDB2
InParanoidQ92466
Interologous Interaction database Q92466
IntegromeDBDDB2
STRING (EMBL)DDB2
Ontologies - Pathways
Ontology : AmiGOprotein polyubiquitination  nucleotide-excision repair, DNA damage removal  DNA binding  damaged DNA binding  ubiquitin-protein transferase activity  protein binding  nucleoplasm  DNA repair  nucleotide-excision repair  pyrimidine dimer repair  response to UV  Cul4B-RING E3 ubiquitin ligase complex  histone H2A monoubiquitination  protein complex  protein autoubiquitination  UV-damage excision repair  
Ontology : EGO-EBIprotein polyubiquitination  nucleotide-excision repair, DNA damage removal  DNA binding  damaged DNA binding  ubiquitin-protein transferase activity  protein binding  nucleoplasm  DNA repair  nucleotide-excision repair  pyrimidine dimer repair  response to UV  Cul4B-RING E3 ubiquitin ligase complex  histone H2A monoubiquitination  protein complex  protein autoubiquitination  UV-damage excision repair  
Pathways : KEGGNucleotide excision repair    p53 signaling pathway    Ubiquitin mediated proteolysis    Hepatitis B   
Protein Interaction DatabaseDDB2
Wikipedia pathwaysDDB2
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)DDB2
snp3D : Map Gene to Disease1643
SNP (GeneSNP Utah)DDB2
SNP : HGBaseDDB2
Genetic variants : HAPMAPDDB2
Exome VariantDDB2
1000_GenomesDDB2 
ICGC programENSG00000134574 
Cancer Gene: CensusDDB2 
Somatic Mutations in Cancer : COSMICDDB2 
CONAN: Copy Number AnalysisDDB2 
Mutations and Diseases : HGMDDDB2
Mutations and Diseases : intOGenDDB2
Genomic VariantsDDB2  DDB2 [DGVbeta]
dbVarDDB2
ClinVarDDB2
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM278740    600811   
MedgenDDB2
GENETestsDDB2
Disease Genetic AssociationDDB2
Huge Navigator DDB2 [HugePedia]  DDB2 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneDDB2
Homology/Alignments : Family Browser (UCSC)DDB2
Phylogenetic Trees/Animal Genes : TreeFamDDB2
Chemical/Protein Interactions : CTD1643
Chemical/Pharm GKB GenePA27188
Clinical trialDDB2
Cancer Resource (Charite)ENSG00000134574
Other databases
Probes
ProbeCancer Cytogenetics (Bari)
Litterature
PubMed120 Pubmed reference(s) in Entrez
CoreMineDDB2
iHOPDDB2
OncoSearchDDB2

Bibliography

Induction of a novel damage-specific DNA binding protein correlates with enhanced DNA repair in primate cells.
Protičß M, Hirschfeld S, Tsang AP, Wagner M, Dixon K, Levine AS
Molecular toxicology. 1989 ; 2 (4) : 255-270.
PMID 2518795
 
Purification of an ultraviolet-inducible, damage-specific DNA-binding protein from primate cells.
Abramičß M, Levine AS, Protičß M
The Journal of biological chemistry. 1991 ; 266 (33) : 22493-22500.
PMID 1657999
 
Comparative analysis of binding of human damaged DNA-binding protein (XPE) and Escherichia coli damage recognition protein (UvrA) to the major ultraviolet photoproducts: T[c,s]T, T[t,s]T, T[6-4]T, and T[Dewar]T.
Reardon JT, Nichols AF, Keeney S, Smith CA, Taylor JS, Linn S, Sancar A
The Journal of biological chemistry. 1993 ; 268 (28) : 21301-21308.
PMID 8407968
 
A 127 kDa component of a UV-damaged DNA-binding complex, which is defective in some xeroderma pigmentosum group E patients, is homologous to a slime mold protein.
Takao M, Abramic M, Moos M Jr, Otrin VR, Wootton JC, McLenigan M, Levine AS, Protic M
Nucleic acids research. 1993 ; 21 (17) : 4111-4118.
PMID 8371985
 
Mammalian DNA nucleotide excision repair reconstituted with purified protein components.
Aboussekhra A, Biggerstaff M, Shivji MK, Vilpo JA, Moncollin V, Podust VN, Protičß M, Hł║bscher U, Egly JM, Wood RD
Cell. 1995 ; 80 (6) : 859-868.
PMID 7697716
 
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. 1995 ; 29 (1) : 62-69.
PMID 8530102
 
Isolation of a cDNA encoding a UV-damaged DNA binding factor defective in xeroderma pigmentosum group E cells.
Hwang BJ, Liao JC, Chu G
Mutation research. 1996 ; 362 (1) : 105-117.
PMID 8538642
 
Functional complementation of xeroderma pigmentosum complementation group E by replication protein A in an in vitro system.
Kazantsev A, Mu D, Nichols AF, Zhao X, Linn S, Sancar A
Proceedings of the National Academy of Sciences of the United States of America. 1996 ; 93 (10) : 5014-5018.
PMID 8643521
 
Mutations specific to the xeroderma pigmentosum group E Ddb- phenotype.
Nichols AF, Ong P, Linn S
The Journal of biological chemistry. 1996 ; 271 (40) : 24317-24320.
PMID 8798680
 
Translocation of a UV-damaged DNA binding protein into a tight association with chromatin after treatment of mammalian cells with UV light.
Otrin VR, McLenigan M, Takao M, Levine AS, Protičß M
Journal of cell science. 1997 ; 110 ( Pt 10) : 1159-1168.
PMID 9191040
 
DDB, a putative DNA repair protein, can function as a transcriptional partner of E2F1.
Hayes S, Shiyanov P, Chen X, Raychaudhuri P
Molecular and cellular biology. 1998 ; 18 (1) : 240-249.
PMID 9418871
 
The V protein of the paramyxovirus SV5 interacts with damage-specific DNA binding protein.
Lin GY, Paterson RG, Richardson CD, Lamb RA
Virology. 1998 ; 249 (1) : 189-200.
PMID 9740790
 
Relationship of the xeroderma pigmentosum group E DNA repair defect to the chromatin and DNA binding proteins UV-DDB and replication protein A.
Rapičß Otrin V, Kuraoka I, Nardo T, McLenigan M, Eker AP, Stefanini M, Levine AS, Wood RD
Molecular and cellular biology. 1998 ; 18 (6) : 3182-3190.
PMID 9584159
 
Refined mapping of the gene encoding the p127 kDa UV-damaged DNA-binding protein (DDB1) within 11q12-q13.1 and its exclusion in Best's vitelliform macular dystrophy.
StłĆhr H, Marquardt A, Rivera A, Kellner U, Weber BH
European journal of human genetics : EJHG. 1998 ; 6 (4) : 400-405.
PMID 9781049
 
A summary of mutations in the UV-sensitive disorders: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy.
Cleaver JE, Thompson LH, Richardson AS, States JC
Human mutation. 1999 ; 14 (1) : 9-22.
PMID 10447254
 
Characterization of DNA recognition by the human UV-damaged DNA-binding protein.
Fujiwara Y, Masutani C, Mizukoshi T, Kondo J, Hanaoka F, Iwai S
The Journal of biological chemistry. 1999 ; 274 (28) : 20027-20033.
PMID 10391953
 
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
Proceedings of the National Academy of Sciences of the United States of America. 1999 ; 96 (2) : 424-428.
PMID 9892649
 
A newly identified patient with clinical xeroderma pigmentosum phenotype has a non-sense mutation in the DDB2 gene and incomplete repair in (6-4) photoproducts.
Itoh T, Mori T, Ohkubo H, Yamaizumi M
The Journal of investigative dermatology. 1999 ; 113 (2) : 251-257.
PMID 10469312
 
DNA structures recognized by the human UV-DDB protein.
Mizukoshi T, Fujiwara Y, Iwai S
Nucleic acids symposium series. 1999 : 265-266.
PMID 10780481
 
The naturally occurring mutants of DDB are impaired in stimulating nuclear import of the p125 subunit and E2F1-activated transcription.
Shiyanov P, Hayes SA, Donepudi M, Nichols AF, Linn S, Slagle BL, Raychaudhuri P
Molecular and cellular biology. 1999 ; 19 (7) : 4935-4943.
PMID 10373543
 
Cullin 4A associates with the UV-damaged DNA-binding protein DDB.
Shiyanov P, Nag A, Raychaudhuri P
The Journal of biological chemistry. 1999 ; 274 (50) : 35309-35312.
PMID 10585395
 
Effect of DNA lesions on transcription elongation.
Tornaletti S, Hanawalt PC
Biochimie. 1999 ; 81 (1-2) : 139-146.
PMID 10214918
 
A 127-kDa protein (UV-DDB) binds to the cytoplasmic domain of the Alzheimer's amyloid precursor protein.
Watanabe T, Sukegawa J, Sukegawa I, Tomita S, Iijima K, Oguchi S, Suzuki T, Nairn AC, Greengard P
Journal of neurochemistry. 1999 ; 72 (2) : 549-556.
PMID 9930726
 
Reinvestigation of the classification of five cell strains of xeroderma pigmentosum group E with reclassification of three of them.
Itoh T, Linn S, Ono T, Yamaizumi M
The Journal of investigative dermatology. 2000 ; 114 (5) : 1022-1029.
PMID 10771487
 
Nuclear transport of human DDB protein induced by ultraviolet light.
Liu W, Nichols AF, Graham JA, Dualan R, Abbas A, Linn S
The Journal of biological chemistry. 2000 ; 275 (28) : 21429-21434.
PMID 10777491
 
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
The Journal of biological chemistry. 2000 ; 275 (28) : 21422-21428.
PMID 10777490
 
Correct binding of viral X protein to UVDDB-p127 cellular protein is critical for efficient infection by hepatitis B viruses.
Sitterlin D, Bergametti F, Tiollais P, Tennant BC, Transy C
Oncogene. 2000 ; 19 (38) : 4427-4431.
PMID 10980618
 
UVDDB p127-binding modulates activities and intracellular distribution of hepatitis B virus X protein.
Sitterlin D, Bergametti F, Transy C
Oncogene. 2000 ; 19 (38) : 4417-4426.
PMID 10980617
 
Xeroderma pigmentosum p48 gene enhances global genomic repair and suppresses UV-induced mutagenesis.
Tang JY, Hwang BJ, Ford JM, Hanawalt PC, Chu G
Molecular cell. 2000 ; 5 (4) : 737-744.
PMID 10882109
 
Cloning and characterization of a senescence inducing and class II tumor suppressor gene in ovarian carcinoma at chromosome region 6q27.
Acquati F, Morelli C, Cinquetti R, Bianchi MG, Porrini D, Varesco L, Gismondi V, Rocchetti R, Talevi S, Possati L, Magnanini C, Tibiletti MG, Bernasconi B, Daidone MG, Shridhar V, Smith DI, Negrini M, Barbanti-Brodano G, Taramelli R
Oncogene. 2001 ; 20 (8) : 980-988.
PMID 11314033
 
The p48 subunit of the damaged-DNA binding protein DDB associates with the CBP/p300 family of histone acetyltransferase.
Datta A, Bagchi S, Nag A, Shiyanov P, Adami GR, Yoon T, Raychaudhuri P
Mutation research. 2001 ; 486 (2) : 89-97.
PMID 11425514
 
Genetically determined susceptibility markers in skin cancer and their application to chemoprevention.
Hahn H
IARC scientific publications. 2001 ; 154 : 93-100.
PMID 11220672
 
Controlling the efficiency of excision repair.
Hanawalt PC
Mutation research. 2001 ; 485 (1) : 3-13.
PMID 11341989
 
Importance of DNA repair in carcinogenesis: evidence from transgenic and gene targeting studies.
Ishikawa T, Ide F, Qin X, Zhang S, Takahashi Y, Sekiguchi M, Tanaka K, Nakatsuru Y
Mutation research. 2001 ; 477 (1-2) : 41-49.
PMID 11376685
 
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
The Journal of biological chemistry. 2001 ; 276 (18) : 15434-15440.
PMID 11278856
 
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Contributor(s)

Written09-2001Anne Stary, Alain Sarasin

Citation

This paper should be referenced as such :
Stary, A ; Sarasin, A
XPE (xeroderma pigmentosum, complementation group E)
Atlas Genet Cytogenet Oncol Haematol. 2002;6(1):13-15.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/XPEID298.html

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indexed on : Tue Aug 26 15:29:53 CEST 2014

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