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Protein

DNA damage-binding protein 2

Gene

Ddb2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Pathway:iprotein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

DNA damage, DNA repair, Ubl conjugation pathway

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_296832. Dual incision reaction in GG-NER.
REACT_314261. Formation of incision complex in GG-NER.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA damage-binding protein 2
Alternative name(s):
Damage-specific DNA-binding protein 2
Gene namesi
Name:Ddb2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1355314. Ddb2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

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.3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 432432DNA damage-binding protein 2PRO_0000050954Add
BLAST

Post-translational modificationi

Phosphorylation by ABL1 negatively regulate UV-DDB activity.1 Publication
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).By similarity
Ubiquitinated, leading to proteasomal degradation, and deubiquitinated by USP24.By similarity

Keywords - PTMi

Ubl conjugation

Proteomic databases

MaxQBiQ99J79.
PaxDbiQ99J79.
PRIDEiQ99J79.

PTM databases

PhosphoSiteiQ99J79.

Expressioni

Tissue specificityi

Expressed in bone marrow, liver, lung, muscle, pancreas and spleen.1 Publication

Gene expression databases

BgeeiQ99J79.
CleanExiMM_DDB2.
ExpressionAtlasiQ99J79. baseline and differential.
GenevisibleiQ99J79. MM.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

BioGridi223741. 1 interaction.
STRINGi10090.ENSMUSP00000028696.

Structurei

3D structure databases

ProteinModelPortaliQ99J79.
SMRiQ99J79. Positions 20-421.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati116 – 15136WD 1Add
BLAST
Repeati159 – 19436WD 2Add
BLAST
Repeati203 – 23836WD 3Add
BLAST
Repeati244 – 28744WD 4Add
BLAST
Repeati290 – 32940WD 5Add
BLAST
Repeati343 – 38644WD 6Add
BLAST
Repeati396 – 42025WD 7Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni68 – 7912Required for interaction with DDB1By similarityAdd
BLAST
Regioni87 – 9812Required for interaction with DDB1By similarityAdd
BLAST
Regioni334 – 3363Photolesion recognitionBy similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi256 – 27419DWD boxAdd
BLAST

Domaini

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).By similarity

Sequence similaritiesi

Belongs to the WD repeat DDB2/WDR76 family.Curated
Contains 7 WD repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiCOG2319.
GeneTreeiENSGT00510000047881.
HOGENOMiHOG000231440.
HOVERGENiHBG000713.
InParanoidiQ99J79.
KOiK10140.
OMAiVTCLEWH.
PhylomeDBiQ99J79.
TreeFamiTF331587.

Family and domain databases

Gene3Di2.130.10.10. 1 hit.
InterProiIPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamiPF00400. WD40. 3 hits.
[Graphical view]
SMARTiSM00320. WD40. 5 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 1 hit.
PROSITEiPS00678. WD_REPEATS_1. 1 hit.
PS50082. WD_REPEATS_2. 1 hit.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q99J79-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAPKKCPETQ KSPDVAVLLR SKSRRGPQEL EPEAKKLRVQ GPVSSRTCES
60 70 80 90 100
CCLLAELSSL QIPSRSSSIV RDLYQHKLGK ATWSSLQQGL QKSFLHSLAS
110 120 130 140 150
YQVFRKAAPF DRRTTSLAWH PTHPSTLAVG SKGGDIMIWN FGIKDKPIFL
160 170 180 190 200
KGIGAGGSIT GLKFNHLNTN QFFASSMEGT TRLQDFKGNI LRVYTSSNSC
210 220 230 240 250
KVWFCSLDVS AKSRVVVTGD NMGHVILLST DGKELWNLRM HKKKVAHVAL
260 270 280 290 300
NPCCDWLLAT ASIDQTVKIW DLRQIKGKDS FLYSLPHRHP VNAACFSPDG
310 320 330 340 350
ARLLTTDQNN EIRVYSASQW DSPLNLISHP HRHFQHLTPI KATWHSRHNL
360 370 380 390 400
IVVGRYPDPN LKSCVPYELR TIDVFDGSSG KMMCQLYDPG YSGITSLNEF
410 420 430
NPMGDTLAST MGYHILIWSQ EEDGSQKDHE RL
Length:432
Mass (Da):48,375
Last modified:June 1, 2001 - v1
Checksum:i9E717FE4DAAA57B2
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY027937 mRNA. Translation: AAK16810.1.
CCDSiCCDS16428.1.
RefSeqiNP_082395.2. NM_028119.5.
UniGeneiMm.389334.

Genome annotation databases

EnsembliENSMUST00000028696; ENSMUSP00000028696; ENSMUSG00000002109.
GeneIDi107986.
KEGGimmu:107986.
UCSCiuc008kvh.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY027937 mRNA. Translation: AAK16810.1.
CCDSiCCDS16428.1.
RefSeqiNP_082395.2. NM_028119.5.
UniGeneiMm.389334.

3D structure databases

ProteinModelPortaliQ99J79.
SMRiQ99J79. Positions 20-421.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi223741. 1 interaction.
STRINGi10090.ENSMUSP00000028696.

PTM databases

PhosphoSiteiQ99J79.

Proteomic databases

MaxQBiQ99J79.
PaxDbiQ99J79.
PRIDEiQ99J79.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000028696; ENSMUSP00000028696; ENSMUSG00000002109.
GeneIDi107986.
KEGGimmu:107986.
UCSCiuc008kvh.2. mouse.

Organism-specific databases

CTDi1643.
MGIiMGI:1355314. Ddb2.

Phylogenomic databases

eggNOGiCOG2319.
GeneTreeiENSGT00510000047881.
HOGENOMiHOG000231440.
HOVERGENiHBG000713.
InParanoidiQ99J79.
KOiK10140.
OMAiVTCLEWH.
PhylomeDBiQ99J79.
TreeFamiTF331587.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiREACT_296832. Dual incision reaction in GG-NER.
REACT_314261. Formation of incision complex in GG-NER.

Miscellaneous databases

NextBioi359837.
PROiQ99J79.
SOURCEiSearch...

Gene expression databases

BgeeiQ99J79.
CleanExiMM_DDB2.
ExpressionAtlasiQ99J79. baseline and differential.
GenevisibleiQ99J79. MM.

Family and domain databases

Gene3Di2.130.10.10. 1 hit.
InterProiIPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamiPF00400. WD40. 3 hits.
[Graphical view]
SMARTiSM00320. WD40. 5 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 1 hit.
PROSITEiPS00678. WD_REPEATS_1. 1 hit.
PS50082. WD_REPEATS_2. 1 hit.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  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. 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.

Entry informationi

Entry nameiDDB2_MOUSE
AccessioniPrimary (citable) accession number: Q99J79
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2005
Last sequence update: June 1, 2001
Last modified: June 24, 2015
This is version 107 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.