Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

DNA damage-binding protein 2

Gene

Ddb2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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: protein 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

Keywordsi

Molecular functionDNA-binding
Biological processDNA damage, DNA repair, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-MMU-5689880 Ub-specific processing proteases
R-MMU-5696394 DNA Damage Recognition in GG-NER
R-MMU-5696395 Formation of Incision Complex in GG-NER
R-MMU-5696400 Dual Incision in GG-NER
R-MMU-8951664 Neddylation
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1355314 Ddb2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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)DescriptionActionsGraphical viewLength
ChainiPRO_00000509541 – 432DNA damage-binding protein 2Add BLAST432

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

EPDiQ99J79
MaxQBiQ99J79
PaxDbiQ99J79
PeptideAtlasiQ99J79
PRIDEiQ99J79

PTM databases

iPTMnetiQ99J79
PhosphoSitePlusiQ99J79

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSMUSG00000002109
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 interactor
STRINGi10090.ENSMUSP00000028696

Structurei

3D structure databases

ProteinModelPortaliQ99J79
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati116 – 151WD 1Add BLAST36
Repeati159 – 194WD 2Add BLAST36
Repeati203 – 238WD 3Add BLAST36
Repeati244 – 287WD 4Add BLAST44
Repeati290 – 329WD 5Add BLAST40
Repeati343 – 386WD 6Add BLAST44
Repeati396 – 420WD 7Add BLAST25

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni68 – 79Required for interaction with DDB1By similarityAdd BLAST12
Regioni87 – 98Required for interaction with DDB1By similarityAdd BLAST12
Regioni334 – 336Photolesion recognitionBy similarity3

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi256 – 274DWD boxAdd BLAST19

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

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG4328 Eukaryota
ENOG410XRID LUCA
GeneTreeiENSGT00510000047881
HOGENOMiHOG000231440
HOVERGENiHBG000713
InParanoidiQ99J79
KOiK10140
OMAiVTCLEWH
OrthoDBiEOG091G06BL
PhylomeDBiQ99J79
TreeFamiTF331587

Family and domain databases

Gene3Di2.130.10.10, 1 hit
InterProiView protein in InterPro
IPR033312 DDB2
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR001680 WD40_repeat
IPR019775 WD40_repeat_CS
IPR017986 WD40_repeat_dom
IPR036322 WD40_repeat_dom_sf
PANTHERiPTHR15169 PTHR15169, 1 hit
PfamiView protein in Pfam
PF00400 WD40, 2 hits
SMARTiView protein in SMART
SM00320 WD40, 5 hits
SUPFAMiSSF50978 SSF50978, 1 hit
PROSITEiView protein in PROSITE
PS00678 WD_REPEATS_1, 1 hit
PS50082 WD_REPEATS_2, 1 hit
PS50294 WD_REPEATS_REGION, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiDDB2_MOUSE
AccessioniPrimary (citable) accession number: Q99J79
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2005
Last sequence update: June 1, 2001
Last modified: May 23, 2018
This is version 127 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health