DDB2_BOVIN
ID DDB2_BOVIN Reviewed; 426 AA.
AC Q0VBY8;
DT 23-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 1.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=DNA damage-binding protein 2;
DE AltName: Full=Damage-specific DNA-binding protein 2;
GN Name=DDB2;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Basal ganglia;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Protein, which is both involved in DNA repair and protein
CC ubiquitination, as part of the UV-DDB complex and DCX (DDB1-CUL4-X-box)
CC complexes, respectively. Core component of the UV-DDB complex (UV-
CC damaged DNA-binding protein complex), a complex that recognizes UV-
CC induced DNA damage and recruit proteins of the nucleotide excision
CC repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB
CC complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-
CC 4 photoproducts (6-4 PP), apurinic sites and short mismatches. Also
CC functions as the substrate recognition module for the DCX (DDB2-CUL4-X-
CC box) E3 ubiquitin-protein ligase complex DDB2-CUL4-ROC1 (also known as
CC CUL4-DDB-ROC1 and CUL4-DDB-RBX1). The DDB2-CUL4-ROC1 complex may
CC ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-
CC induced DNA damage. The ubiquitination of histones may facilitate their
CC removal from the nucleosome and promote subsequent DNA repair. The
CC DDB2-CUL4-ROC1 complex also ubiquitinates XPC, which may enhance DNA-
CC binding by XPC and promote NER. The DDB2-CUL4-ROC1 complex also
CC ubiquitinates KAT7/HBO1 in response to DNA damage, leading to its
CC degradation: recognizes KAT7/HBO1 following phosphorylation by ATR.
CC {ECO:0000250|UniProtKB:Q92466}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Component of the UV-DDB complex which includes DDB1 and DDB2.
CC The UV-DDB complex interacts with monoubiquitinated histone H2A and
CC binds to XPC via the DDB2 subunit. Component of the DCX (DDB1-CUL4-X-
CC box) E3 ubiquitin-protein ligase complex DDB1-CUL4-ROC1 (also known as
CC CUL4-DDB-ROC1 and CUL4-DDB-RBX1), which includes CUL4A or CUL4B, DDB1,
CC DDB2 and RBX1. DDB2 may function as the substrate recognition module
CC within this complex. The DDB1-CUL4-ROC1 complex may associate with the
CC COP9 signalosome, and this inhibits the E3 ubiquitin-protein ligase
CC activity of the complex. A large number of other DCX complexes may also
CC exist in which an alternate substrate targeting subunit replaces DDB2.
CC These targeting subunits are generally known as DCAF (DDB1- and CUL4-
CC associated factor) or CDW (CUL4-DDB1-associated WD40-repeat) proteins
CC (By similarity). {ECO:0000250|UniProtKB:Q92466}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q92466}.
CC Chromosome {ECO:0000250|UniProtKB:Q92466}. Note=Accumulates at sites of
CC DNA damage following UV irradiation. {ECO:0000250|UniProtKB:Q92466}.
CC -!- DOMAIN: The DWD box is required for interaction with DDB1.
CC {ECO:0000250|UniProtKB:Q92466}.
CC -!- DOMAIN: Interblade loops of the WD repeat region mediate most of the
CC interaction with DNA. A hairpin between blades 5 and 6 inserts into DNA
CC minor groove and mediates recognition of lesions and separation of the
CC damaged and undamaged strands (By similarity).
CC {ECO:0000250|UniProtKB:Q92466}.
CC -!- PTM: Phosphorylation by ABL1 negatively regulate UV-DDB activity.
CC {ECO:0000250|UniProtKB:Q99J79}.
CC -!- PTM: Ubiquitinated by CUL4A in response to UV irradiation.
CC Ubiquitination appears to both impair DNA-binding and promotes
CC ubiquitin-dependent proteolysis. Degradation of DDB2 at sites of DNA
CC damage may be a prerequisite for their recognition by XPC and
CC subsequent repair. CUL4A-mediated degradation appears to be promoted by
CC ABL1. {ECO:0000250|UniProtKB:Q92466}.
CC -!- PTM: Ubiquitinated, leading to proteasomal degradation, and
CC deubiquitinated by USP24. {ECO:0000250|UniProtKB:Q92466}.
CC -!- PTM: Acetylated. Deacetylation by SIRT6 in response to UV stress
CC facilitates nucleotide excision repair pathway (the NER pathway)
CC transduction. {ECO:0000250|UniProtKB:Q92466}.
CC -!- SIMILARITY: Belongs to the WD repeat DDB2/WDR76 family. {ECO:0000305}.
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DR EMBL; BC120440; AAI20441.1; -; mRNA.
DR RefSeq; NP_001069256.1; NM_001075788.1.
DR RefSeq; XP_015330376.1; XM_015474890.1.
DR AlphaFoldDB; Q0VBY8; -.
DR SMR; Q0VBY8; -.
DR STRING; 9913.ENSBTAP00000027965; -.
DR PaxDb; Q0VBY8; -.
DR PRIDE; Q0VBY8; -.
DR Ensembl; ENSBTAT00000086532; ENSBTAP00000072203; ENSBTAG00000020999.
DR GeneID; 519357; -.
DR KEGG; bta:519357; -.
DR CTD; 1643; -.
DR VEuPathDB; HostDB:ENSBTAG00000020999; -.
DR VGNC; VGNC:27942; DDB2.
DR eggNOG; KOG4328; Eukaryota.
DR GeneTree; ENSGT00510000047881; -.
DR HOGENOM; CLU_036401_1_0_1; -.
DR InParanoid; Q0VBY8; -.
DR OMA; FIKGKGP; -.
DR OrthoDB; 559605at2759; -.
DR TreeFam; TF331587; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000009136; Chromosome 15.
DR Bgee; ENSBTAG00000020999; Expressed in monocyte and 105 other tissues.
DR ExpressionAtlas; Q0VBY8; baseline and differential.
DR GO; GO:0030054; C:cell junction; IEA:Ensembl.
DR GO; GO:0031465; C:Cul4B-RING E3 ubiquitin ligase complex; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0090734; C:site of DNA damage; ISS:UniProtKB.
DR GO; GO:0003684; F:damaged DNA binding; IEA:Ensembl.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IEA:Ensembl.
DR GO; GO:0006281; P:DNA repair; IBA:GO_Central.
DR GO; GO:0035518; P:histone H2A monoubiquitination; IEA:Ensembl.
DR GO; GO:0006289; P:nucleotide-excision repair; ISS:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; IEA:Ensembl.
DR GO; GO:0000209; P:protein polyubiquitination; IEA:Ensembl.
DR GO; GO:0006290; P:pyrimidine dimer repair; IEA:Ensembl.
DR GO; GO:0009411; P:response to UV; IBA:GO_Central.
DR GO; GO:0070914; P:UV-damage excision repair; IEA:Ensembl.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR033312; DDB2.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR15169; PTHR15169; 1.
DR Pfam; PF00400; WD40; 1.
DR SMART; SM00320; WD40; 4.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 1.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Chromosome; DNA damage; DNA repair; DNA-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Ubl conjugation;
KW Ubl conjugation pathway; WD repeat.
FT CHAIN 1..426
FT /note="DNA damage-binding protein 2"
FT /id="PRO_0000351088"
FT REPEAT 115..150
FT /note="WD 1"
FT REPEAT 158..193
FT /note="WD 2"
FT REPEAT 202..237
FT /note="WD 3"
FT REPEAT 243..286
FT /note="WD 4"
FT REPEAT 289..328
FT /note="WD 5"
FT REPEAT 342..385
FT /note="WD 6"
FT REPEAT 395..419
FT /note="WD 7"
FT REGION 1..33
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 67..78
FT /note="Required for interaction with DDB1"
FT /evidence="ECO:0000250|UniProtKB:Q92466"
FT REGION 86..97
FT /note="Required for interaction with DDB1"
FT /evidence="ECO:0000250|UniProtKB:Q92466"
FT REGION 333..335
FT /note="Photolesion recognition"
FT /evidence="ECO:0000250|UniProtKB:Q92466"
FT MOTIF 255..273
FT /note="DWD box"
FT /evidence="ECO:0000250|UniProtKB:Q92466"
FT MOD_RES 26
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92466"
FT MOD_RES 35
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q92466"
FT MOD_RES 76
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q92466"
SQ SEQUENCE 426 AA; 47591 MW; 5A4430F97A8FBD22 CRC64;
MAPRKRPENQ KTPEVVVRPK SKRNRSPREL EPEAKKLCVK GPGSSRRFDS GLWAGLASLR
VPPLCSSIVR ALHQHKLGTA AWPSLQQGLQ QSFLNSLASY RIFQKAAPFD RRATSLAWHP
THPSTLAVGS KGGDILLWNF GIKDKPTFIK GIGAGGSITG MKFNPLNTNQ FFTSSMEGTT
RLQDFKGNTL RVFASSDTCN VWFCSLDVSV KSRVVVTGDN VGHVILLNMD GRELWNLRMH
KKKVTHVALN PCCDWLLATA SVDQTVKIWD LRQVRGKSSF LHSLPHRHPV NAAHFSPDGA
QLLTTDQKSE IRVYSACQWD CPPSLIPHPH RHFQHLTPIK ASWHPRYNLI VVGRYPDPNF
KSCSPHELRT IDVFDGSSGK IMYQLYDPES SGIMSLNEFN PMGDTLASVM GYHILVWSPE
DAGTQK
