ID:DDB1_HUMAN DESCRIPTION: RecName: Full=DNA damage-binding protein 1; AltName: Full=DDB p127 subunit; AltName: Full=DNA damage-binding protein a; Short=DDBa; AltName: Full=Damage-specific DNA-binding protein 1; AltName: Full=HBV X-associated protein 1; Short=XAP-1; AltName: Full=UV-damaged DNA-binding factor; AltName: Full=UV-damaged DNA-binding protein 1; Short=UV-DDB 1; AltName: Full=XPE-binding factor; Short=XPE-BF; AltName: Full=Xeroderma pigmentosum group E-complementing protein; Short=XPCe; FUNCTION: Required for DNA repair. Binds to DDB2 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 a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The functional specificity of the DCX E3 ubiquitin- protein ligase complex is determined by the variable substrate recognition component recruited by DDB1. DCX(DDB2) (also known as DDB1-CUL4-ROC1, CUL4-DDB-ROC1 and CUL4-DDB-RBX1) 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. DCX(DDB2) also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication. DCX(ERCC8) (the CSA complex) plays a role in transcription-coupled repair (TCR). May also play a role in ubiquitination of CDKN1B/p27kip when associated with CUL4 and SKP2. PATHWAY: Protein modification; protein ubiquitination. SUBUNIT: 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 numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1. DDB1 may recruit specific substrate targeting subunits to the DCX complex. These substrate targeting subunits are generally known as DCAF (DDB1- and CUL4-associated factor) or CDW (CUL4-DDB1-associated WD40-repeat) proteins. Interacts with AMBRA1, ATG16L1, BTRC, DCAF1, DCAF17, DCAF16, DCAF15, DDA1, DET1, DTL, ERCC8, FBXW5, FBXW8, GRWD1, DCAF6, KATNB1, NLE1, NUP43, PAFAH1B1, PHIP, PWP1, RBBP4, RBBP5, RBBP7, RFWD2, SNRNP40, VPRBP, WDR5, WDR5B, WDR12, DCAF4, DCAF5, DCAF11, WDR26, DCAF10, WDR39, DCAF12, WDR42, DCAF8, WDR53, WDR59, WDR61, DCAF7, WSB1, WSB2 and WDTC1. DCX complexes may associate with the COP9 signalosome, and this inhibits the E3 ubiquitin-protein ligase activity of the complex. Interacts with NF2, TSC1 and TSC2. Interacts with Simian virus 5 protein V and the HBV X protein. Interaction with SV5 protein V may prevent the recruitment of DCAF proteins to DCX complexes. Interacts with EIF2C1 and EIF2C2. Associates with the E3 ligase complex containing DYRK2, EDD/UBR5, DDB1 and VPRBP proteins (EDVP complex). Interacts directly with DYRK2. INTERACTION: Q9H9F9:ACTR5; NbExp=3; IntAct=EBI-350322, EBI-769418; Q92466:DDB2; NbExp=3; IntAct=EBI-350322, EBI-1176171; Q9NZJ0:DTL; NbExp=3; IntAct=EBI-350322, EBI-1176075; Q9ULG1:INO80; NbExp=4; IntAct=EBI-350322, EBI-769345; P42224:STAT1; NbExp=2; IntAct=EBI-350322, EBI-1057697; Q04725:TLE2; NbExp=2; IntAct=EBI-350322, EBI-1176061; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Primarily cytoplasmic. Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage. PTM: Phosphorylated by ABL1 (By similarity). PTM: Ubiquitinated by CUL4A. Subsequently degraded by ubiquitin- dependent proteolysis. SIMILARITY: Belongs to the DDB1 family. WEB RESOURCE: Name=Allelic variations of the XP genes; URL="http://www.xpmutations.org/"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/ddb1/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q16531
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000715 nucleotide-excision repair, DNA damage recognition GO:0006281 DNA repair GO:0006283 transcription-coupled nucleotide-excision repair GO:0006289 nucleotide-excision repair GO:0006293 nucleotide-excision repair, preincision complex stabilization GO:0006294 nucleotide-excision repair, preincision complex assembly GO:0006296 nucleotide-excision repair, DNA incision, 5'-to lesion GO:0006511 ubiquitin-dependent protein catabolic process GO:0006974 cellular response to DNA damage stimulus GO:0010498 proteasomal protein catabolic process GO:0016032 viral process GO:0016055 Wnt signaling pathway GO:0016567 protein ubiquitination GO:0033683 nucleotide-excision repair, DNA incision GO:0035518 histone H2A monoubiquitination GO:0042769 DNA damage response, detection of DNA damage GO:0043066 negative regulation of apoptotic process GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0043687 post-translational protein modification GO:0045070 positive regulation of viral genome replication GO:0045732 positive regulation of protein catabolic process GO:0046726 positive regulation by virus of viral protein levels in host cell GO:0051702 interaction with symbiont GO:0070911 global genome nucleotide-excision repair GO:0070914 UV-damage excision repair GO:1901990 regulation of mitotic cell cycle phase transition GO:1902188 positive regulation of viral release from host cell
BC032080 - Homo sapiens damage-specific DNA binding protein 1, 127kDa, mRNA (cDNA clone IMAGE:5122376). BC011686 - Homo sapiens damage-specific DNA binding protein 1, 127kDa, mRNA (cDNA clone MGC:19563 IMAGE:3845478), complete cds. U32986 - Human xeroderma pigmentosum group E UV-damaged DNA binding factor mRNA, complete cds. AL831958 - Homo sapiens mRNA; cDNA DKFZp451P0416 (from clone DKFZp451P0416). BC050530 - Homo sapiens damage-specific DNA binding protein 1, 127kDa, mRNA (cDNA clone MGC:57561 IMAGE:5563018), complete cds. BC021044 - Homo sapiens damage-specific DNA binding protein 1, 127kDa, mRNA (cDNA clone IMAGE:2907109). BC051764 - Homo sapiens damage-specific DNA binding protein 1, 127kDa, mRNA (cDNA clone MGC:54119 IMAGE:6063274), complete cds. U18299 - Human damage-specific DNA binding protein DDBa p127 subunit (DDB1) mRNA, complete cds. L40326 - Homo sapiens Hepatitis B virus X-associated protein 1 mRNA, complete cds. AK294341 - Homo sapiens cDNA FLJ52436 complete cds, highly similar to DNA damage-binding protein 1. AJ002955 - Homo sapiens mRNA for xeroderma pigmentosum complementation group E protein. AK299650 - Homo sapiens cDNA FLJ51067 complete cds, highly similar to DNA damage-binding protein 1. AK294493 - Homo sapiens cDNA FLJ56068 complete cds, highly similar to DNA damage-binding protein 1. AK303032 - Homo sapiens cDNA FLJ51165 complete cds, highly similar to DNA damage-binding protein 1. AK312436 - Homo sapiens cDNA, FLJ92782, highly similar to Homo sapiens damage-specific DNA binding protein 1, 127kDa (DDB1), mRNA. KJ904449 - Synthetic construct Homo sapiens clone ccsbBroadEn_13843 DDB1-like gene, encodes complete protein. AB384683 - Synthetic construct DNA, clone: pF1KB0087, Homo sapiens DDB1 gene for DNA damage-binding protein 1, complete cds, without stop codon, in Flexi system. JD042608 - Sequence 23632 from Patent EP1572962. JD457916 - Sequence 438940 from Patent EP1572962. DQ584159 - Homo sapiens piRNA piR-51271, complete sequence. JD536866 - Sequence 517890 from Patent EP1572962. JD454192 - Sequence 435216 from Patent EP1572962. JD328975 - Sequence 309999 from Patent EP1572962. JD126328 - Sequence 107352 from Patent EP1572962. JD519219 - Sequence 500243 from Patent EP1572962. JD391843 - Sequence 372867 from Patent EP1572962. JD271011 - Sequence 252035 from Patent EP1572962. JD423979 - Sequence 405003 from Patent EP1572962. JD192739 - Sequence 173763 from Patent EP1572962. JD167448 - Sequence 148472 from Patent EP1572962. JD113075 - Sequence 94099 from Patent EP1572962. AK311112 - Homo sapiens cDNA, FLJ18154. AK302924 - Homo sapiens cDNA FLJ51163 complete cds, highly similar to DNA damage-binding protein 1. AK311476 - Homo sapiens cDNA, FLJ18518. JD137823 - Sequence 118847 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q16531 (Reactome details) participates in the following event(s):
R-HSA-8955245 CAND1 binds CRL4 E3 ubiquitin ligase in the nucleus R-HSA-8955285 COMMDs displace CAND1 from CRL4 E3 ubiquitin ligase complex R-HSA-8952639 NEDD8:AcM-UBE2M binds CRL4 E3 ubiquitin ligase complex R-HSA-8956045 COP9 signalosome deneddylates nuclear CRL4 E3 ubiquitin ligase complex R-HSA-5652005 RAD18:UBE2B or RBX1:CUL4:DDB1:DTL ubiquitin ligase complex binds PCNA:POLD,POLE:RPA:RFC associated with damaged dsDNA R-HSA-5652009 RAD18:UBE2B or RBX1:CUL4:DDB1:DTL monoubiquitinates PCNA R-HSA-5690988 3'-incision of DNA by ERCC5 (XPG) in GG-NER R-HSA-6781867 ERCC8:DDB1:CUL4:RBX1 ubiquitinates ERCC6 and RNA Pol II R-HSA-6781833 ERCC8 (CSA) binds stalled RNA Pol II R-HSA-6782004 Assembly of the pre-incision complex in TC-NER R-HSA-6782211 DNA polymerases delta, epsilon or kappa bind the TC-NER site R-HSA-6782204 5' incision of damaged DNA strand by ERCC1:ERCC4 in TC-NER R-HSA-6782224 3' incision by ERCC5 (XPG) in TC-NER R-HSA-6782227 Ligation of newly synthesized repair patch to incised DNA in TC-NER R-HSA-6782208 Repair DNA synthesis of ~27-30 bases long patch by POLD, POLE or POLK in TC-NER R-HSA-8952638 AcM-UBE2M transfers NEDD8 to CRL4 E3 ubiquitin ligase complex R-HSA-6782943 UV-DDB ubiquitinates XPC R-HSA-5691006 XPC:RAD23:CETN2 and UV-DDB bind distorted dsDNA site R-HSA-5696664 PARP1 or PARP2 binds DDB2 at GG-NER site R-HSA-5690213 DNA polymerases delta, epsilon or kappa bind the GG-NER site R-HSA-5690990 5'- incision of DNA by ERCC1:ERCC4 in GG-NER R-HSA-6790487 RNF111 ubiquitinates SUMOylated XPC R-HSA-6790454 SUMOylation of XPC R-HSA-5689317 Formation of the pre-incision complex in GG-NER R-HSA-6782069 UVSSA:USP7 deubiquitinates ERCC6 R-HSA-6782131 RNA Pol II backtracking in TC-NER R-HSA-6782138 ERCC5 and RPA bind TC-NER site R-HSA-5696655 PARP1 or PARP2 PARylates DDB2 and autoPARylates R-HSA-5690996 ERCC2 and ERCC3 DNA helicases form an open bubble structure in damaged DNA R-HSA-5691000 TFIIH binds GG-NER site to form a verification complex R-HSA-5690991 Binding of ERCC1:ERCC4 (ERCC1:XPF) to pre-incision complex in GG-NER R-HSA-6782141 Binding of ERCC1:ERCC4 (ERCC1:XPF) to pre-incision complex in TC-NER R-HSA-5696670 CHD1L is recruited to GG-NER site R-HSA-5689861 Recruitment of XPA and release of CAK R-HSA-8951664 Neddylation R-HSA-6781827 Transcription-Coupled Nucleotide Excision Repair (TC-NER) R-HSA-597592 Post-translational protein modification R-HSA-110314 Recognition of DNA damage by PCNA-containing replication complex R-HSA-5696400 Dual Incision in GG-NER R-HSA-6781823 Formation of TC-NER Pre-Incision Complex R-HSA-6782135 Dual incision in TC-NER R-HSA-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER R-HSA-5696398 Nucleotide Excision Repair R-HSA-392499 Metabolism of proteins R-HSA-73893 DNA Damage Bypass R-HSA-5696394 DNA Damage Recognition in GG-NER R-HSA-5696395 Formation of Incision Complex in GG-NER R-HSA-5696399 Global Genome Nucleotide Excision Repair (GG-NER) R-HSA-73894 DNA Repair
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
