ID   DDB2_MOUSE              Reviewed;         432 AA.
AC   Q99J79;
DT   19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2001, sequence version 1.
DT   27-MAR-2024, entry version 157.
DE   RecName: Full=DNA damage-binding protein 2;
DE   AltName: Full=Damage-specific DNA-binding protein 2;
GN   Name=Ddb2;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Plasmacytoma;
RX   PubMed=10713455; DOI=10.1016/s0378-1119(00)00022-6;
RA   Zolezzi F., Linn S.;
RT   "Studies of the murine DDB1 and DDB2 genes.";
RL   Gene 245:151-159(2000).
RN   [2]
RP   FUNCTION, INTERACTION WITH DDB2, AND PHOSPHORYLATION BY ABL1.
RX   PubMed=12107171; DOI=10.1074/jbc.m204416200;
RA   Cong F., Tang J., Hwang B.J., Vuong B.Q., Chu G., Goff S.P.;
RT   "Interaction between UV-damaged DNA binding activity proteins and the c-Abl
RT   tyrosine kinase.";
RL   J. Biol. Chem. 277:34870-34878(2002).
RN   [3]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=14769931; DOI=10.1073/pnas.0306551101;
RA   Itoh T., Cado D., Kamide R., Linn S.;
RT   "DDB2 gene disruption leads to skin tumors and resistance to apoptosis
RT   after exposure to ultraviolet light but not a chemical carcinogen.";
RL   Proc. Natl. Acad. Sci. U.S.A. 101:2052-2057(2004).
RN   [4]
RP   DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX   PubMed=15558025; DOI=10.1038/sj.onc.1208211;
RA   Yoon T., Chakrabortty A., Franks R., Valli T., Kiyokawa H.,
RA   Raychaudhuri P.;
RT   "Tumor-prone phenotype of the DDB2-deficient mice.";
RL   Oncogene 24:469-478(2005).
RN   [5]
RP   SUBCELLULAR LOCATION.
RX   PubMed=17635991; DOI=10.1242/jcs.008367;
RA   Luijsterburg M.S., Goedhart J., Moser J., Kool H., Geverts B.,
RA   Houtsmuller A.B., Mullenders L.H.F., Vermeulen W., van Driel R.;
RT   "Dynamic in vivo interaction of DDB2 E3 ubiquitin ligase with UV-damaged
RT   DNA is independent of damage-recognition protein XPC.";
RL   J. Cell Sci. 120:2706-2716(2007).
RN   [6]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=17468495; DOI=10.1093/hmg/ddm107;
RA   Itoh T., Iwashita S., Cohen M.B., Meyerholz D.K., Linn S.;
RT   "Ddb2 is a haploinsufficient tumor suppressor and controls spontaneous germ
RT   cell apoptosis.";
RL   Hum. Mol. Genet. 16:1578-1586(2007).
RN   [7]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [8]
RP   FUNCTION, AND DEUBIQUITINATION BY USP44.
RX   PubMed=33937266; DOI=10.3389/fcell.2021.663411;
RA   Zhang Y., Mandemaker I.K., Matsumoto S., Foreman O., Holland C.P.,
RA   Lloyd W.R., Sugasawa K., Vermeulen W., Marteijn J.A., Galardy P.J.;
RT   "USP44 Stabilizes DDB2 to Facilitate Nucleotide Excision Repair and Prevent
RT   Tumors.";
RL   Front. Cell Dev. Biol. 9:663411-663411(2021).
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 (PubMed:12107171). Core component of the UV-DDB
CC       complex (UV-damaged DNA-binding protein complex), a complex that
CC       recognizes UV-induced DNA damage and recruit proteins of the nucleotide
CC       excision repair pathway (the NER pathway) to initiate DNA repair
CC       (PubMed:33937266). The UV-DDB complex preferentially binds to
CC       cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP),
CC       apurinic sites and short mismatches (By similarity). Also functions as
CC       the substrate recognition module for the DCX (DDB2-CUL4-X-box) E3
CC       ubiquitin-protein ligase complex DDB2-CUL4-ROC1 (also known as CUL4-
CC       DDB-ROC1 and CUL4-DDB-RBX1) (By similarity). The DDB2-CUL4-ROC1 complex
CC       may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-
CC       induced DNA damage (By similarity). The ubiquitination of histones may
CC       facilitate their removal from the nucleosome and promote subsequent DNA
CC       repair (By similarity). The DDB2-CUL4-ROC1 complex also ubiquitinates
CC       XPC, which may enhance DNA-binding by XPC and promote NER (By
CC       similarity). The DDB2-CUL4-ROC1 complex also ubiquitinates KAT7/HBO1 in
CC       response to DNA damage, leading to its degradation: recognizes
CC       KAT7/HBO1 following phosphorylation by ATR (By similarity).
CC       {ECO:0000250|UniProtKB:Q92466, ECO:0000269|PubMed:12107171,
CC       ECO:0000269|PubMed:33937266}.
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:0000269|PubMed:17635991}. Chromosome
CC       {ECO:0000250|UniProtKB:Q92466}. Note=Accumulates at sites of DNA damage
CC       following UV irradiation. {ECO:0000250|UniProtKB:Q92466}.
CC   -!- TISSUE SPECIFICITY: Expressed in bone marrow, liver, lung, muscle,
CC       pancreas and spleen. {ECO:0000269|PubMed:15558025}.
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:0000269|PubMed:12107171}.
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 (By similarity). Deubiquitinated by USP44;
CC       leading to its stabilization on DNA lesions (PubMed:33937266).
CC       {ECO:0000250|UniProtKB:Q92466, ECO:0000269|PubMed:33937266}.
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   -!- DISRUPTION PHENOTYPE: Mice exhibit elevated susceptibility to UV-
CC       induced skin carcinogenesis and enhanced rates of spontaneous tumor
CC       formation, particularly for lung and mammary adenocarcinomas. DDB2 is
CC       haploinsufficient as a tumor suppressor. The spleens of these animals
CC       are enlarged due to enhanced lymphoid proliferation while the testes
CC       are also enlarged due to reduced rates of apoptosis of testicular germ
CC       cells. Fibroblasts from these animals are resistant to p53-dependent
CC       apoptosis induced by UV treatment. {ECO:0000269|PubMed:14769931,
CC       ECO:0000269|PubMed:15558025, ECO:0000269|PubMed:17468495}.
CC   -!- SIMILARITY: Belongs to the WD repeat DDB2/WDR76 family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AY027937; AAK16810.1; -; mRNA.
DR   CCDS; CCDS16428.1; -.
DR   RefSeq; NP_082395.2; NM_028119.5.
DR   AlphaFoldDB; Q99J79; -.
DR   SMR; Q99J79; -.
DR   BioGRID; 223741; 1.
DR   ComplexPortal; CPX-1122; UV DNA damage recognition complex DBB1-DBB2.
DR   ComplexPortal; CPX-650; CRL4-DDB2 E3 ubiquitin ligase complex, CUL4A variant.
DR   ComplexPortal; CPX-651; CRL4-DDB2 E3 ubiquitin ligase complex, CUL4B variant.
DR   STRING; 10090.ENSMUSP00000028696; -.
DR   iPTMnet; Q99J79; -.
DR   PhosphoSitePlus; Q99J79; -.
DR   EPD; Q99J79; -.
DR   MaxQB; Q99J79; -.
DR   PaxDb; 10090-ENSMUSP00000028696; -.
DR   PeptideAtlas; Q99J79; -.
DR   ProteomicsDB; 279843; -.
DR   Pumba; Q99J79; -.
DR   Antibodypedia; 13582; 318 antibodies from 34 providers.
DR   DNASU; 107986; -.
DR   Ensembl; ENSMUST00000028696.5; ENSMUSP00000028696.5; ENSMUSG00000002109.15.
DR   GeneID; 107986; -.
DR   KEGG; mmu:107986; -.
DR   UCSC; uc008kvh.2; mouse.
DR   AGR; MGI:1355314; -.
DR   CTD; 1643; -.
DR   MGI; MGI:1355314; Ddb2.
DR   VEuPathDB; HostDB:ENSMUSG00000002109; -.
DR   eggNOG; KOG4328; Eukaryota.
DR   GeneTree; ENSGT00510000047881; -.
DR   InParanoid; Q99J79; -.
DR   OMA; CGHEHHN; -.
DR   OrthoDB; 3679036at2759; -.
DR   PhylomeDB; Q99J79; -.
DR   TreeFam; TF331587; -.
DR   Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR   Reactome; R-MMU-5696394; DNA Damage Recognition in GG-NER.
DR   Reactome; R-MMU-5696395; Formation of Incision Complex in GG-NER.
DR   Reactome; R-MMU-5696400; Dual Incision in GG-NER.
DR   Reactome; R-MMU-8951664; Neddylation.
DR   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 107986; 4 hits in 115 CRISPR screens.
DR   ChiTaRS; Ddb2; mouse.
DR   PRO; PR:Q99J79; -.
DR   Proteomes; UP000000589; Chromosome 2.
DR   RNAct; Q99J79; Protein.
DR   Bgee; ENSMUSG00000002109; Expressed in paneth cell and 248 other cell types or tissues.
DR   ExpressionAtlas; Q99J79; baseline and differential.
DR   GO; GO:0030054; C:cell junction; ISO:MGI.
DR   GO; GO:0080008; C:Cul4-RING E3 ubiquitin ligase complex; ISO:MGI.
DR   GO; GO:0031464; C:Cul4A-RING E3 ubiquitin ligase complex; EXP:ComplexPortal.
DR   GO; GO:0031465; C:Cul4B-RING E3 ubiquitin ligase complex; ISO:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; ISO:MGI.
DR   GO; GO:0032991; C:protein-containing complex; ISO:MGI.
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; ISO:MGI.
DR   GO; GO:0004842; F:ubiquitin-protein transferase activity; IEA:Ensembl.
DR   GO; GO:0034644; P:cellular response to UV; EXP:ComplexPortal.
DR   GO; GO:0006974; P:DNA damage response; EXP:ComplexPortal.
DR   GO; GO:0006281; P:DNA repair; IBA:GO_Central.
DR   GO; GO:0006289; P:nucleotide-excision repair; ISS:UniProtKB.
DR   GO; GO:0051865; P:protein autoubiquitination; ISO:MGI.
DR   GO; GO:0000209; P:protein polyubiquitination; ISO:MGI.
DR   GO; GO:0006290; P:pyrimidine dimer repair; IMP:MGI.
DR   GO; GO:0009411; P:response to UV; ISO:MGI.
DR   GO; GO:0070914; P:UV-damage excision repair; ISO:MGI.
DR   Gene3D; 4.10.640.30; -; 1.
DR   Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1.
DR   InterPro; IPR033312; DDB2.
DR   InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR   InterPro; IPR019775; WD40_repeat_CS.
DR   InterPro; IPR036322; WD40_repeat_dom_sf.
DR   InterPro; IPR001680; WD40_rpt.
DR   PANTHER; PTHR15169; DAMAGE-SPECIFIC DNA BINDING PROTEIN 2; 1.
DR   PANTHER; PTHR15169:SF0; DNA DAMAGE-BINDING PROTEIN 2; 1.
DR   Pfam; PF00400; WD40; 2.
DR   SMART; SM00320; WD40; 5.
DR   SUPFAM; SSF50978; WD40 repeat-like; 1.
DR   PROSITE; PS00678; WD_REPEATS_1; 1.
DR   PROSITE; PS50082; WD_REPEATS_2; 1.
DR   PROSITE; PS50294; WD_REPEATS_REGION; 1.
DR   Genevisible; Q99J79; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Chromosome; DNA damage; DNA repair; DNA-binding; Nucleus;
KW   Reference proteome; Repeat; Ubl conjugation; Ubl conjugation pathway;
KW   WD repeat.
FT   CHAIN           1..432
FT                   /note="DNA damage-binding protein 2"
FT                   /id="PRO_0000050954"
FT   REPEAT          116..151
FT                   /note="WD 1"
FT   REPEAT          159..194
FT                   /note="WD 2"
FT   REPEAT          203..238
FT                   /note="WD 3"
FT   REPEAT          244..287
FT                   /note="WD 4"
FT   REPEAT          290..329
FT                   /note="WD 5"
FT   REPEAT          343..386
FT                   /note="WD 6"
FT   REPEAT          396..420
FT                   /note="WD 7"
FT   REGION          1..31
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          68..79
FT                   /note="Required for interaction with DDB1"
FT                   /evidence="ECO:0000250|UniProtKB:Q92466"
FT   REGION          87..98
FT                   /note="Required for interaction with DDB1"
FT                   /evidence="ECO:0000250|UniProtKB:Q92466"
FT   REGION          334..336
FT                   /note="Photolesion recognition"
FT                   /evidence="ECO:0000250"
FT   MOTIF           256..274
FT                   /note="DWD box"
FT                   /evidence="ECO:0000250|UniProtKB:Q92466"
FT   MOD_RES         35
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q92466"
FT   MOD_RES         77
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q92466"
SQ   SEQUENCE   432 AA;  48375 MW;  9E717FE4DAAA57B2 CRC64;
     MAPKKCPETQ KSPDVAVLLR SKSRRGPQEL EPEAKKLRVQ GPVSSRTCES CCLLAELSSL
     QIPSRSSSIV RDLYQHKLGK ATWSSLQQGL QKSFLHSLAS YQVFRKAAPF DRRTTSLAWH
     PTHPSTLAVG SKGGDIMIWN FGIKDKPIFL KGIGAGGSIT GLKFNHLNTN QFFASSMEGT
     TRLQDFKGNI LRVYTSSNSC KVWFCSLDVS AKSRVVVTGD NMGHVILLST DGKELWNLRM
     HKKKVAHVAL NPCCDWLLAT ASIDQTVKIW DLRQIKGKDS FLYSLPHRHP VNAACFSPDG
     ARLLTTDQNN EIRVYSASQW DSPLNLISHP HRHFQHLTPI KATWHSRHNL IVVGRYPDPN
     LKSCVPYELR TIDVFDGSSG KMMCQLYDPG YSGITSLNEF NPMGDTLAST MGYHILIWSQ
     EEDGSQKDHE RL
//