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Q99J79

- DDB2_MOUSE

UniProt

Q99J79 - DDB2_MOUSE

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
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    • History
      Entry version 100 (01 Oct 2014)
      Sequence version 1 (01 Jun 2001)
      Previous versions | rss
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    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

    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

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

    GO - Cellular componenti

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

    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

    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.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.
    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...
    MobiDBi 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: October 1, 2014
    This is version 100 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