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Q99J79 (DDB2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 98. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
DNA damage-binding protein 2
Alternative name(s):
Damage-specific DNA-binding protein 2
Gene names
Name:Ddb2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length432 AA.
Sequence statusComplete.
Protein existenceEvidence 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. Ref.2

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 By similarity. Ref.2

Subcellular location

Nucleus. Note: Accumulates at sites of DNA damage following UV irradiation. Ref.5

Tissue specificity

Expressed in bone marrow, liver, lung, muscle, pancreas and spleen. Ref.4

Domain

The DWD box is required for interaction with DDB1 By similarity.

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 By similarity.

Post-translational modification

Phosphorylation by ABL1 negatively regulate UV-DDB activity.

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 By similarity.

Disruption phenotype

Mice exhibit elevated susceptibility to UV-induced skin carcinogenesis and enhanced rates of spontaneous tumor formation, particularly for lung and mammary adenocarcinomas. DDB2 is haploinsufficient as a tumor suppressor. The spleens of these animals are enlarged due to enhanced lymphoid proliferation while the testes are also enlarged due to reduced rates of apoptosis of testicular germ cells. Fibroblasts from these animals are resistant to p53-dependent apoptosis induced by UV treatment. Ref.3 Ref.4 Ref.6

Sequence similarities

Belongs to the WD repeat DDB2/WDR76 family.

Contains 7 WD repeats.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 432432DNA damage-binding protein 2
PRO_0000050954

Regions

Repeat116 – 15136WD 1
Repeat159 – 19436WD 2
Repeat203 – 23836WD 3
Repeat244 – 28744WD 4
Repeat290 – 32940WD 5
Repeat343 – 38644WD 6
Repeat396 – 42025WD 7
Region68 – 7912Required for interaction with DDB1 By similarity
Region87 – 9812Required for interaction with DDB1 By similarity
Region334 – 3363Photolesion recognition By similarity
Motif256 – 27419DWD box

Sequences

Sequence LengthMass (Da)Tools
Q99J79 [UniParc].

Last modified June 1, 2001. Version 1.
Checksum: 9E717FE4DAAA57B2

FASTA43248,375
        10         20         30         40         50         60 
MAPKKCPETQ KSPDVAVLLR SKSRRGPQEL EPEAKKLRVQ GPVSSRTCES CCLLAELSSL 

        70         80         90        100        110        120 
QIPSRSSSIV RDLYQHKLGK ATWSSLQQGL QKSFLHSLAS YQVFRKAAPF DRRTTSLAWH 

       130        140        150        160        170        180 
PTHPSTLAVG SKGGDIMIWN FGIKDKPIFL KGIGAGGSIT GLKFNHLNTN QFFASSMEGT 

       190        200        210        220        230        240 
TRLQDFKGNI LRVYTSSNSC KVWFCSLDVS AKSRVVVTGD NMGHVILLST DGKELWNLRM 

       250        260        270        280        290        300 
HKKKVAHVAL NPCCDWLLAT ASIDQTVKIW DLRQIKGKDS FLYSLPHRHP VNAACFSPDG 

       310        320        330        340        350        360 
ARLLTTDQNN EIRVYSASQW DSPLNLISHP HRHFQHLTPI KATWHSRHNL IVVGRYPDPN 

       370        380        390        400        410        420 
LKSCVPYELR TIDVFDGSSG KMMCQLYDPG YSGITSLNEF NPMGDTLAST MGYHILIWSQ 

       430 
EEDGSQKDHE RL 

« Hide

References

[1]"Studies of the murine DDB1 and DDB2 genes."
Zolezzi F., Linn S.
Gene 245:151-159(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Plasmacytoma.
[2]"Interaction between UV-damaged DNA binding activity proteins and the c-Abl tyrosine kinase."
Cong F., Tang J., Hwang B.J., Vuong B.Q., Chu G., Goff S.P.
J. Biol. Chem. 277:34870-34878(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DDB2, PHOSPHORYLATION BY ABL1.
[3]"DDB2 gene disruption leads to skin tumors and resistance to apoptosis after exposure to ultraviolet light but not a chemical carcinogen."
Itoh T., Cado D., Kamide R., Linn S.
Proc. Natl. Acad. Sci. U.S.A. 101:2052-2057(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[4]"Tumor-prone phenotype of the DDB2-deficient mice."
Yoon T., Chakrabortty A., Franks R., Valli T., Kiyokawa H., Raychaudhuri P.
Oncogene 24:469-478(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
[5]"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.
[6]"Ddb2 is a haploinsufficient tumor suppressor and controls spontaneous germ cell apoptosis."
Itoh T., Iwashita S., Cohen M.B., Meyerholz D.K., Linn S.
Hum. Mol. Genet. 16:1578-1586(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY027937 mRNA. Translation: AAK16810.1.
CCDSCCDS16428.1.
RefSeqNP_082395.2. NM_028119.5.
UniGeneMm.389334.

3D structure databases

ProteinModelPortalQ99J79.
SMRQ99J79. Positions 20-421.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid223741. 1 interaction.
STRING10090.ENSMUSP00000028696.

PTM databases

PhosphoSiteQ99J79.

Proteomic databases

PaxDbQ99J79.
PRIDEQ99J79.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000028696; ENSMUSP00000028696; ENSMUSG00000002109.
GeneID107986.
KEGGmmu:107986.
UCSCuc008kvh.2. mouse.

Organism-specific databases

CTD1643.
MGIMGI:1355314. Ddb2.

Phylogenomic databases

eggNOGCOG2319.
GeneTreeENSGT00510000047881.
HOGENOMHOG000231440.
HOVERGENHBG000713.
InParanoidQ99J79.
KOK10140.
OMAFASSMEG.
PhylomeDBQ99J79.
TreeFamTF331587.

Enzyme and pathway databases

UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ99J79.
BgeeQ99J79.
CleanExMM_DDB2.
GenevestigatorQ99J79.

Family and domain databases

Gene3D2.130.10.10. 1 hit.
InterProIPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamPF00400. WD40. 3 hits.
[Graphical view]
SMARTSM00320. WD40. 5 hits.
[Graphical view]
SUPFAMSSF50978. SSF50978. 1 hit.
PROSITEPS00678. WD_REPEATS_1. 1 hit.
PS50082. WD_REPEATS_2. 1 hit.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio359837.
PROQ99J79.
SOURCESearch...

Entry information

Entry nameDDB2_MOUSE
AccessionPrimary (citable) accession number: Q99J79
Entry history
Integrated into UniProtKB/Swiss-Prot: July 19, 2005
Last sequence update: June 1, 2001
Last modified: July 9, 2014
This is version 98 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot