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Q99J79

- DDB2_MOUSE

UniProt

Q99J79 - DDB2_MOUSE

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Protein
DNA damage-binding protein 2
Gene
Ddb2
Organism
Mus musculus (Mouse)
Status
Reviewed - 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

Pathwayi

GO - Molecular functioni

  1. DNA binding Source: UniProtKB-KW
  2. ubiquitin-protein transferase activity Source: Ensembl
Complete GO annotation...

GO - Biological processi

  1. protein autoubiquitination Source: Ensembl
  2. protein polyubiquitination Source: Ensembl
  3. pyrimidine dimer repair Source: MGI
  4. response to UV Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

DNA damage, DNA repair, Ubl conjugation pathway

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

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: Chromosome 2

Organism-specific databases

MGIiMGI:1355314. Ddb2.

Subcellular locationi

Nucleus
Note: Accumulates at sites of DNA damage following UV irradiation.1 Publication

GO - Cellular componenti

  1. nucleus Source: UniProtKB-SubCell
  2. protein complex Source: Ensembl
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 2
PRO_0000050954Add
BLAST

Post-translational modificationi

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.
Ubiquitinated, leading to proteasomal degradation, and deubiquitinated by USP24 By similarity.

Keywords - PTMi

Ubl conjugation

Proteomic databases

PaxDbiQ99J79.
PRIDEiQ99J79.

PTM databases

PhosphoSiteiQ99J79.

Expressioni

Tissue specificityi

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

Gene expression databases

ArrayExpressiQ99J79.
BgeeiQ99J79.
CleanExiMM_DDB2.
GenevestigatoriQ99J79.

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.1 Publication

Protein-protein interaction databases

BioGridi223741. 1 interaction.
STRINGi10090.ENSMUSP00000028696.

Structurei

3D structure databases

ProteinModelPortaliQ99J79.
SMRiQ99J79. Positions 20-421.

Family & Domainsi

Domains and Repeats

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

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni68 – 7912Required for interaction with DDB1 By similarity
Add
BLAST
Regioni87 – 9812Required for interaction with DDB1 By similarity
Add
BLAST
Regioni334 – 3363Photolesion recognition By similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi256 – 27419DWD box
Add
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.

Sequence similaritiesi

Contains 7 WD repeats.

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiCOG2319.
GeneTreeiENSGT00510000047881.
HOGENOMiHOG000231440.
HOVERGENiHBG000713.
InParanoidiQ99J79.
KOiK10140.
OMAiFASSMEG.
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

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MAPKKCPETQ KSPDVAVLLR SKSRRGPQEL EPEAKKLRVQ GPVSSRTCES    50
CCLLAELSSL QIPSRSSSIV RDLYQHKLGK ATWSSLQQGL QKSFLHSLAS 100
YQVFRKAAPF DRRTTSLAWH PTHPSTLAVG SKGGDIMIWN FGIKDKPIFL 150
KGIGAGGSIT GLKFNHLNTN QFFASSMEGT TRLQDFKGNI LRVYTSSNSC 200
KVWFCSLDVS AKSRVVVTGD NMGHVILLST DGKELWNLRM HKKKVAHVAL 250
NPCCDWLLAT ASIDQTVKIW DLRQIKGKDS FLYSLPHRHP VNAACFSPDG 300
ARLLTTDQNN EIRVYSASQW DSPLNLISHP HRHFQHLTPI KATWHSRHNL 350
IVVGRYPDPN LKSCVPYELR TIDVFDGSSG KMMCQLYDPG YSGITSLNEF 400
NPMGDTLAST MGYHILIWSQ EEDGSQKDHE RL 432
Length:432
Mass (Da):48,375
Last modified:June 1, 2001 - v1
Checksum:i9E717FE4DAAA57B2
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
AY027937 mRNA. Translation: AAK16810.1 .
CCDSi CCDS16428.1.
RefSeqi NP_082395.2. NM_028119.5.
UniGenei Mm.389334.

3D structure databases

ProteinModelPortali Q99J79.
SMRi Q99J79. Positions 20-421.
ModBasei Search...

Protein-protein interaction databases

BioGridi 223741. 1 interaction.
STRINGi 10090.ENSMUSP00000028696.

PTM databases

PhosphoSitei Q99J79.

Proteomic databases

PaxDbi Q99J79.
PRIDEi Q99J79.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000028696 ; ENSMUSP00000028696 ; ENSMUSG00000002109 .
GeneIDi 107986.
KEGGi mmu:107986.
UCSCi uc008kvh.2. mouse.

Organism-specific databases

CTDi 1643.
MGIi MGI:1355314. Ddb2.

Phylogenomic databases

eggNOGi COG2319.
GeneTreei ENSGT00510000047881.
HOGENOMi HOG000231440.
HOVERGENi HBG000713.
InParanoidi Q99J79.
KOi K10140.
OMAi FASSMEG.
PhylomeDBi Q99J79.
TreeFami TF331587.

Enzyme and pathway databases

UniPathwayi UPA00143 .

Miscellaneous databases

NextBioi 359837.
PROi Q99J79.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q99J79.
Bgeei Q99J79.
CleanExi MM_DDB2.
Genevestigatori Q99J79.

Family and domain databases

Gene3Di 2.130.10.10. 1 hit.
InterProi IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view ]
Pfami PF00400. WD40. 3 hits.
[Graphical view ]
SMARTi SM00320. WD40. 5 hits.
[Graphical view ]
SUPFAMi SSF50978. SSF50978. 1 hit.
PROSITEi PS00678. WD_REPEATS_1. 1 hit.
PS50082. WD_REPEATS_2. 1 hit.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: September 3, 2014
This is version 99 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

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