DDB2_DANRE
ID DDB2_DANRE Reviewed; 496 AA.
AC Q2YDS1; Q1LUF7; Q1LUF8;
DT 23-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 2.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=DNA damage-binding protein 2;
DE AltName: Full=Damage-specific DNA-binding protein 2;
GN Name=ddb2; ORFNames=si:dkey-45f10.3;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Olfactory epithelium;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 60-423 IN COMPLEX WITH DDB1,
RP SUBUNIT, AND WD REPEATS.
RX PubMed=19109893; DOI=10.1016/j.cell.2008.10.045;
RA Scrima A., Konickova R., Czyzewski B.K., Kawasaki Y., Jeffrey P.D.,
RA Groisman R., Nakatani Y., Iwai S., Pavletich N.P., Thoma N.H.;
RT "Structural basis of UV DNA-damage recognition by the DDB1-DDB2 complex.";
RL Cell 135:1213-1223(2008).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 60-423 IN COMPLEXES WITH DDB1 AND
RP RBX1, AND SUBUNIT.
RX PubMed=22118460; DOI=10.1016/j.cell.2011.10.035;
RA Fischer E.S., Scrima A., Bohm K., Matsumoto S., Lingaraju G.M., Faty M.,
RA Yasuda T., Cavadini S., Wakasugi M., Hanaoka F., Iwai S., Gut H.,
RA Sugasawa K., Thoma N.H.;
RT "The molecular basis of CRL4DDB2/CSA ubiquitin ligase architecture,
RT targeting, and activation.";
RL Cell 147:1024-1039(2011).
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.
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 (PubMed:19109893). Component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-
CC protein ligase complex that includes cul4a, or cul4b, ddb1, ddb2 and
CC rbx1 (PubMed:22118460). 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 ECO:0000269|PubMed:19109893, ECO:0000269|PubMed:22118460}.
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q2YDS1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q2YDS1-2; Sequence=VSP_035462;
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. {ECO:0000269|PubMed:19109893}.
CC -!- SIMILARITY: Belongs to the WD repeat DDB2/WDR76 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI10097.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAK11059.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=CAK11060.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; BX942814; CAK11059.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BX942814; CAK11060.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC110096; AAI10097.1; ALT_INIT; mRNA.
DR PDB; 3EI1; X-ray; 2.80 A; B=60-423.
DR PDB; 3EI2; X-ray; 2.60 A; B=60-423.
DR PDB; 3EI3; X-ray; 2.30 A; B=60-423.
DR PDB; 4A08; X-ray; 3.00 A; B=60-423.
DR PDB; 4A09; X-ray; 3.10 A; B=60-423.
DR PDB; 4A0A; X-ray; 3.60 A; B=60-423.
DR PDB; 4A0B; X-ray; 3.80 A; B/D=60-423.
DR PDB; 4A0K; X-ray; 5.93 A; D=60-423.
DR PDB; 4A0L; X-ray; 7.40 A; B/D=60-423.
DR PDBsum; 3EI1; -.
DR PDBsum; 3EI2; -.
DR PDBsum; 3EI3; -.
DR PDBsum; 4A08; -.
DR PDBsum; 4A09; -.
DR PDBsum; 4A0A; -.
DR PDBsum; 4A0B; -.
DR PDBsum; 4A0K; -.
DR PDBsum; 4A0L; -.
DR AlphaFoldDB; Q2YDS1; -.
DR SMR; Q2YDS1; -.
DR DIP; DIP-53463N; -.
DR IntAct; Q2YDS1; 2.
DR STRING; 7955.ENSDARP00000091438; -.
DR Ensembl; ENSDART00000060302; ENSDARP00000060301; ENSDARG00000041140. [Q2YDS1-1]
DR Ensembl; ENSDART00000180316; ENSDARP00000152759; ENSDARG00000114723. [Q2YDS1-1]
DR ZFIN; ZDB-GENE-050419-169; ddb2.
DR eggNOG; KOG4328; Eukaryota.
DR GeneTree; ENSGT00510000047881; -.
DR HOGENOM; CLU_036401_0_0_1; -.
DR InParanoid; Q2YDS1; -.
DR OMA; FIKGKGP; -.
DR PhylomeDB; Q2YDS1; -.
DR TreeFam; TF331587; -.
DR Reactome; R-DRE-5689880; Ub-specific processing proteases.
DR Reactome; R-DRE-5696394; DNA Damage Recognition in GG-NER.
DR Reactome; R-DRE-5696395; Formation of Incision Complex in GG-NER.
DR Reactome; R-DRE-5696400; Dual Incision in GG-NER.
DR Reactome; R-DRE-8951664; Neddylation.
DR SignaLink; Q2YDS1; -.
DR UniPathway; UPA00143; -.
DR EvolutionaryTrace; Q2YDS1; -.
DR PRO; PR:Q2YDS1; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 18.
DR Bgee; ENSDARG00000041140; Expressed in tail and 22 other tissues.
DR ExpressionAtlas; Q2YDS1; baseline and differential.
DR GO; GO:0080008; C:Cul4-RING E3 ubiquitin ligase complex; IEA:InterPro.
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:InterPro.
DR GO; GO:0006281; P:DNA repair; IBA:GO_Central.
DR GO; GO:0006289; P:nucleotide-excision repair; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0009411; P:response to UV; IBA:GO_Central.
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; 2.
DR SMART; SM00320; WD40; 5.
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 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromosome; DNA damage; DNA repair;
KW DNA-binding; Nucleus; Reference proteome; Repeat; Ubl conjugation pathway;
KW WD repeat.
FT CHAIN 1..496
FT /note="DNA damage-binding protein 2"
FT /id="PRO_0000351090"
FT REPEAT 118..153
FT /note="WD 1"
FT REPEAT 161..196
FT /note="WD 2"
FT REPEAT 205..240
FT /note="WD 3"
FT REPEAT 246..289
FT /note="WD 4"
FT REPEAT 292..332
FT /note="WD 5"
FT REPEAT 346..386
FT /note="WD 6"
FT REPEAT 396..420
FT /note="WD 7"
FT REGION 1..51
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 337..339
FT /note="Photolesion recognition"
FT /evidence="ECO:0000269|PubMed:19109893"
FT REGION 435..496
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 258..276
FT /note="DWD box"
FT /evidence="ECO:0000250|UniProtKB:Q92466"
FT COMPBIAS 20..34
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 453..487
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 155..203
FT /note="MGPGDAITGMKFNQFNTNQLFVSSIWGATTLRDFSGSVIQVFAKTDSWD ->
FT KGAGDFIGCPRDSSKVFVASGDGTVSVQSFEGLQSQILSRTPDCGHDHHDLC (in
FT isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_035462"
FT CONFLICT 45
FT /note="S -> T (in Ref. 2; AAI10097)"
FT /evidence="ECO:0000305"
FT CONFLICT 146
FT /note="L -> Q (in Ref. 2; AAI10097)"
FT /evidence="ECO:0000305"
FT CONFLICT 180
FT /note="W -> R (in Ref. 2; AAI10097)"
FT /evidence="ECO:0000305"
FT HELIX 71..79
FT /evidence="ECO:0007829|PDB:3EI3"
FT HELIX 85..100
FT /evidence="ECO:0007829|PDB:3EI3"
FT STRAND 104..109
FT /evidence="ECO:0007829|PDB:3EI3"
FT STRAND 116..121
FT /evidence="ECO:0007829|PDB:3EI3"
FT STRAND 128..134
FT /evidence="ECO:0007829|PDB:3EI3"
FT STRAND 138..142
FT /evidence="ECO:0007829|PDB:3EI3"
FT STRAND 149..152
FT /evidence="ECO:0007829|PDB:3EI3"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:3EI2"
FT STRAND 160..167
FT /evidence="ECO:0007829|PDB:3EI3"
FT STRAND 170..178
FT /evidence="ECO:0007829|PDB:3EI3"
FT TURN 179..181
FT /evidence="ECO:0007829|PDB:3EI3"
FT STRAND 182..187
FT /evidence="ECO:0007829|PDB:3EI3"
FT TURN 188..190
FT /evidence="ECO:0007829|PDB:4A08"
FT STRAND 192..197
FT /evidence="ECO:0007829|PDB:3EI3"
FT STRAND 206..212
FT /evidence="ECO:0007829|PDB:3EI3"
FT TURN 213..216
FT /evidence="ECO:0007829|PDB:3EI3"
FT STRAND 217..222
FT /evidence="ECO:0007829|PDB:3EI3"
FT STRAND 225..231
FT /evidence="ECO:0007829|PDB:3EI3"
FT STRAND 236..241
FT /evidence="ECO:0007829|PDB:3EI3"
FT STRAND 243..245
FT /evidence="ECO:0007829|PDB:3EI3"
FT STRAND 247..252
FT /evidence="ECO:0007829|PDB:3EI3"
FT STRAND 254..256
FT /evidence="ECO:0007829|PDB:4A08"
FT STRAND 259..264
FT /evidence="ECO:0007829|PDB:3EI3"
FT STRAND 267..273
FT /evidence="ECO:0007829|PDB:3EI3"
FT HELIX 274..276
FT /evidence="ECO:0007829|PDB:3EI3"
FT STRAND 279..281
FT /evidence="ECO:0007829|PDB:3EI1"
FT STRAND 283..288
FT /evidence="ECO:0007829|PDB:3EI3"
FT STRAND 293..298
FT /evidence="ECO:0007829|PDB:3EI3"
FT TURN 300..302
FT /evidence="ECO:0007829|PDB:3EI3"
FT STRAND 305..319
FT /evidence="ECO:0007829|PDB:3EI3"
FT STRAND 322..325
FT /evidence="ECO:0007829|PDB:3EI1"
FT STRAND 327..331
FT /evidence="ECO:0007829|PDB:3EI3"
FT STRAND 349..357
FT /evidence="ECO:0007829|PDB:3EI3"
FT TURN 362..364
FT /evidence="ECO:0007829|PDB:3EI3"
FT STRAND 372..376
FT /evidence="ECO:0007829|PDB:3EI3"
FT TURN 377..379
FT /evidence="ECO:0007829|PDB:3EI3"
FT STRAND 382..386
FT /evidence="ECO:0007829|PDB:3EI3"
FT STRAND 397..400
FT /evidence="ECO:0007829|PDB:3EI3"
FT STRAND 404..411
FT /evidence="ECO:0007829|PDB:3EI3"
FT STRAND 414..419
FT /evidence="ECO:0007829|PDB:3EI3"
SQ SEQUENCE 496 AA; 55863 MW; 0B4435B115B15D9D CRC64;
MARGRAQTDS AASKQTKTVN SKKRPNEETP QPSTKKLKAK QQHKSKQKEE TYIQASVKWT
GGQKKVGQTS ILHYIYKSSL GQSIHAQLRQ CLQEPFIRSL KSYKLHRTAS PFDRRVTSLE
WHPTHPTTVA VGSKGGDIIL WDYDVLNKTS FIQGMGPGDA ITGMKFNQFN TNQLFVSSIW
GATTLRDFSG SVIQVFAKTD SWDYWYCCVD VSVSRQMLAT GDSTGRLLLL GLDGHEIFKE
KLHKAKVTHA EFNPRCDWLM ATSSVDATVK LWDLRNIKDK NSYIAEMPHE KPVNAAYFNP
TDSTKLLTTD QRNEIRVYSS YDWSKPDQII IHPHRQFQHL TPIKATWHPM YDLIVAGRYP
DDQLLLNDKR TIDIYDANSG GLVHQLRDPN AAGIISLNKF SPTGDVLASG MGFNILIWNR
EDTLSSVNRK QTIVTGEDVG GRAGGSRSQR SSQQRPSRDR RAAADEAKLK KKLSATETKS
KTKSKTESKT SKSKKK
