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{{Infobox_gene}}
{{PBB_Controls
'''DNA damage-binding protein 1''' is a [[protein]] that in humans is encoded by the ''DDB1'' [[gene]].<ref name="pmid8530102"/><ref name="pmid10574459"/><ref name="entrez"/>
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{{GNF_Protein_box
| image = PBB_Protein_DDB1_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 2b5l.
| PDB = {{PDB2|2b5l}}, {{PDB2|2b5m}}, {{PDB2|2b5n}}, {{PDB2|2hye}}
| Name = Damage-specific DNA binding protein 1, 127kDa
| HGNCid = 2717
| Symbol = DDB1
| AltSymbols =; DDBA; UV-DDB1; XAP1; XPCE; XPE; XPE-BF
| OMIM = 600045
| ECnumber = 
| Homologene = 1448
| MGIid = 1202384
| Function = {{GNF_GO|id=GO:0003676 |text = nucleic acid binding}} {{GNF_GO|id=GO:0003684 |text = damaged DNA binding}} {{GNF_GO|id=GO:0005515 |text = protein binding}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}}
| Process = {{GNF_GO|id=GO:0006289 |text = nucleotide-excision repair}} {{GNF_GO|id=GO:0006512 |text = ubiquitin cycle}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 1642
    | Hs_Ensembl = 
    | Hs_RefseqProtein = XP_001128974
    | Hs_RefseqmRNA = XM_001128974
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 
    | Hs_GenLoc_start = 
    | Hs_GenLoc_end = 
    | Hs_Uniprot = 
    | Mm_EntrezGene = 13194
    | Mm_Ensembl = ENSMUSG00000024740
    | Mm_RefseqmRNA = NM_015735
    | Mm_RefseqProtein = NP_056550
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 19
    | Mm_GenLoc_start = 10672670
    | Mm_GenLoc_end = 10696867
    | Mm_Uniprot = 
  }}
}}
'''Damage-specific DNA binding protein 1, 127kDa''', also known as '''DDB1''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: DDB1 damage-specific DNA binding protein 1, 127kDa| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1642| accessdate = }}</ref>
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{{PBB_Summary
 
| section_title =  
==Gene==
| summary_text = This gene encodes the large subunit of DNA damage-binding protein which is a heterodimer composed of a large and a small subunit. This protein functions in nucleotide-excision repair. Its defective activity causes the repair defect in the patients with xeroderma pigmentosum complementation group E (XPE). However, it remains for mutation analysis to demonstrate whether the defect in XPE patients is in this gene or the gene encoding the small subunit. In addition, Best vitelliform mascular dystrophy is mapped to the same region as this gene on 11q, but no sequence alternations of this gene are demonstrated in Best disease patients.<ref name="entrez">{{cite web | title = Entrez Gene: DDB1 damage-specific DNA binding protein 1, 127kDa| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1642| accessdate = }}</ref>
The gene's position is on chromosome 11q12-q13.<ref name=Iovine2011/>
 
==Protein==
The DDB1 gene encodes the large subunit of [[DNA damage-binding protein]], a [[heterodimer]] composed of a large and a small ([[DDB2]]) subunit. DDB1 contains 1140 amino acids, amounting to a mass of 127 kDa.<ref name=Iovine2011/>
 
==Function==
As its name suggests, DDB1 was initially implicated in the process of a specific type of DNA repair known as [[nucleotide excision repair]]. Since then, researchers have found that DDB1 primarily functions as a core component of the [[CUL4A]]- and [[CUL4B]]-based E3 [[ubiquitin ligase]] complexes. DDB1 serves as a bridge or adaptor protein which interacts with dozens of proteins known as DDB1 and CUL4-associated factors (DCAFs).<ref name="DCAF">{{cite journal|url = http://www.sciencedirect.com/science/article/pii/S1097276507003619 | doi=10.1016/j.molcel.2007.06.001 | volume=26 | title=DCAFs, the Missing Link of the CUL4-DDB1 Ubiquitin Ligase | year=2007 | journal=Molecular Cell | pages=775–780 | vauthors=Lee J}}</ref> These DCAFs are often ubiquitin ligase [[enzyme substrate (biology)|substrates]] and regulate numerous essential processes in the cell including DNA repair (DDB2), DNA replication, chromatin remodeling ([[DTL (gene)|Cdt2]]) and more.
 
== Interactions ==
DDB1 has been shown to [[Protein-protein interaction|interact]] with [[Transcription initiation protein SPT3 homolog]],<ref name="pmid11564863"/> [[GCN5L2]],<ref name="pmid18332868"/> [[DDB2]],<ref name="pmid12050362"/><ref name="pmid18593899"/> [[CUL4A]],<ref name=pmid18593899/> [[CUL4B]]<ref name=pmid18593899/> and [[P21]].<ref name="pmid18794347"/>
 
== References ==
{{reflist|30em|refs=
<ref name="pmid8530102">{{cite journal |vauthors=Dualan R, Brody T, Keeney S, Nichols AF, Admon A, Linn S |title=Chromosomal localization and cDNA cloning of the genes (DDB1 and DDB2) for the p127 and p48 subunits of a human damage-specific DNA binding protein |journal=Genomics |volume=29 |issue=1 |pages=62–9 |date=Feb 1996 |pmid=8530102 |pmc= |doi=10.1006/geno.1995.1215 }}</ref>
<ref name="pmid10574459">{{cite journal |vauthors=Seki N, Hayashi A, Hattori A, Kozuma S, Sasaki M, Suzuki Y, Sugano S, Muramatsu M, Saito T |title=cDNA cloning, tissue expression, and chromosomal assignment of a mouse gene, encoding a 127 kDa UV-damaged DNA binding protein which is defective in XPE cells |journal=DNA Res |volume=6 |issue=5 |pages=319–22 |date=Jan 2000 |pmid=10574459 |pmc= |doi =10.1093/dnares/6.5.319 }}</ref>
<ref name="entrez">{{cite web |title=Entrez Gene: DDB1 damage-specific DNA binding protein 1, 127kDa|url=https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1642|accessdate=}}</ref>
<ref name=Iovine2011>{{cite journal |last1=Iovine |first1=Barbara |last2=Iannella |first2=Maria Luigia |last3=Bevilacqua |first3=Maria Assunta |title=Damage-specific DNA binding protein 1 (DDB1): a protein with a wide range of functions |journal=The International Journal of Biochemistry & Cell Biology |volume=43 |pp=1664–1667 |publisher=Elsevier |date=2011 |url=https://www.researchgate.net/profile/Maria_Bevilacqua/publication/51681484_Damage-specific_DNA_binding_protein_1_DDB1_A_protein_with_a_wide_range_of_functions/links/5534f9a60cf2ea51c13371a5.pdf |doi=10.1016/j.biocel.2011.09.001}}</ref>
<ref name="pmid11564863">{{cite journal |vauthors=Martinez E, Palhan VB, Tjernberg A, Lymar ES, Gamper AM, Kundu TK, Chait BT, Roeder RG |title=Human STAGA complex is a chromatin-acetylating transcription coactivator that interacts with pre-mRNA splicing and DNA damage-binding factors in vivo |journal=Mol. Cell. Biol. |volume=21 |issue=20 |pages=6782–95 |date=October 2001 |pmid=11564863 |pmc=99856 |doi=10.1128/MCB.21.20.6782-6795.2001 |url=|issn=}}</ref>
<ref name="pmid18332868">{{cite journal |vauthors=Huang J, Chen J |title=VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation |journal=Oncogene |volume=27 |issue=29 |pages=4056–64 |date=July 2008 |pmid=18332868 |doi=10.1038/onc.2008.44 |url=|issn=}}</ref>
<ref name="pmid12050362">{{cite journal |vauthors=Bergametti F, Sitterlin D, Transy C |title=Turnover of hepatitis B virus X protein is regulated by damaged DNA-binding complex |journal=J. Virol. |volume=76 |issue=13 |pages=6495–501 |date=July 2002 |pmid=12050362 |pmc=136256 |doi=10.1128/JVI.76.13.6495-6501.2002|url=|issn=}}</ref>
<ref name="pmid18593899">{{cite journal |vauthors=Guerrero-Santoro J, Kapetanaki MG, Hsieh CL, Gorbachinsky I, Levine AS, Rapić-Otrin V |title=The cullin 4B-based UV-damaged DNA-binding protein ligase binds to UV-damaged chromatin and ubiquitinates histone H2A |journal=Cancer Res. |volume=68 |issue=13 |pages=5014–22 |date=July 2008 |pmid=18593899 |doi=10.1158/0008-5472.CAN-07-6162 |url=|issn=}}</ref>
<ref name="pmid18794347">{{cite journal |vauthors=Abbas T, Sivaprasad U, Terai K, Amador V, Pagano M, Dutta A |title=PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex |journal=Genes Dev. |volume=22 |issue=18 |pages=2496–506 |date=September 2008 |pmid=18794347 |pmc=2546691 |doi=10.1101/gad.1676108 |url=|issn=}}</ref>
}}
}}


==References==
== Further reading ==
{{reflist|2}}
==Further reading==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading  
{{PBB_Further_reading  
| citations =  
| citations =  
*{{cite journal  | author=Chu G, Chang E |title=Xeroderma pigmentosum group E cells lack a nuclear factor that binds to damaged DNA. |journal=Science |volume=242 |issue= 4878 |pages= 564-7 |year= 1988 |pmid= 3175673 |doi=  }}
*{{cite journal  | vauthors=Chu G, Chang E |title=Xeroderma pigmentosum group E cells lack a nuclear factor that binds to damaged DNA. |journal=Science |volume=242 |issue= 4878 |pages= 564–7 |year= 1988 |pmid= 3175673 |doi=10.1126/science.3175673 }}
*{{cite journal  | author=Lee TH, Elledge SJ, Butel JS |title=Hepatitis B virus X protein interacts with a probable cellular DNA repair protein. |journal=J. Virol. |volume=69 |issue= 2 |pages= 1107-14 |year= 1995 |pmid= 7815490 |doi=  }}
*{{cite journal  | vauthors=Lee TH, Elledge SJ, Butel JS |title=Hepatitis B virus X protein interacts with a probable cellular DNA repair protein. |journal=J. Virol. |volume=69 |issue= 2 |pages= 1107–14 |year= 1995 |pmid= 7815490 |doi= | pmc=188683 }}
*{{cite journal  | author=Keeney S, Eker AP, Brody T, ''et al.'' |title=Correction of the DNA repair defect in xeroderma pigmentosum group E by injection of a DNA damage-binding protein. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=91 |issue= 9 |pages= 4053-6 |year= 1994 |pmid= 8171034 |doi= }}
*{{cite journal  | vauthors=Keeney S, Eker AP, Brody T |title=Correction of the DNA repair defect in xeroderma pigmentosum group E by injection of a DNA damage-binding protein. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=91 |issue= 9 |pages= 4053–6 |year= 1994 |pmid= 8171034 |doi=10.1073/pnas.91.9.4053  | pmc=43721  |display-authors=etal|url=https://repub.eur.nl/pub/3066/9600.pdf}}
*{{cite journal  | author=Keeney S, Chang GJ, Linn S |title=Characterization of a human DNA damage binding protein implicated in xeroderma pigmentosum E. |journal=J. Biol. Chem. |volume=268 |issue= 28 |pages= 21293-300 |year= 1993 |pmid= 8407967 |doi=  }}
*{{cite journal  | vauthors=Keeney S, Chang GJ, Linn S |title=Characterization of a human DNA damage binding protein implicated in xeroderma pigmentosum E. |journal=J. Biol. Chem. |volume=268 |issue= 28 |pages= 21293–300 |year= 1993 |pmid= 8407967 |doi=  }}
*{{cite journal  | author=Dualan R, Brody T, Keeney S, ''et al.'' |title=Chromosomal localization and cDNA cloning of the genes (DDB1 and DDB2) for the p127 and p48 subunits of a human damage-specific DNA binding protein. |journal=Genomics |volume=29 |issue= 1 |pages= 62-9 |year= 1996 |pmid= 8530102 |doi= 10.1006/geno.1995.1215 }}
*{{cite journal  | vauthors=Hwang BJ, Liao JC, Chu G |title=Isolation of a cDNA encoding a UV-damaged DNA binding factor defective in xeroderma pigmentosum group E cells. |journal=Mutat. Res. |volume=362 |issue= 1 |pages= 105–17 |year= 1996 |pmid= 8538642 |doi= 10.1016/0921-8777(95)00040-2}}
*{{cite journal  | author=Hwang BJ, Liao JC, Chu G |title=Isolation of a cDNA encoding a UV-damaged DNA binding factor defective in xeroderma pigmentosum group E cells. |journal=Mutat. Res. |volume=362 |issue= 1 |pages= 105-17 |year= 1996 |pmid= 8538642 |doi=  }}
*{{cite journal  | vauthors=Nichols AF, Ong P, Linn S |title=Mutations specific to the xeroderma pigmentosum group E Ddb- phenotype. |journal=J. Biol. Chem. |volume=271 |issue= 40 |pages= 24317–20 |year= 1996 |pmid= 8798680 |doi=10.1074/jbc.271.40.24317 }}
*{{cite journal  | author=Nichols AF, Ong P, Linn S |title=Mutations specific to the xeroderma pigmentosum group E Ddb- phenotype. |journal=J. Biol. Chem. |volume=271 |issue= 40 |pages= 24317-20 |year= 1996 |pmid= 8798680 |doi= }}
*{{cite journal  | vauthors=Liu W, Nichols AF, Graham JA |title=Nuclear transport of human DDB protein induced by ultraviolet light. |journal=J. Biol. Chem. |volume=275 |issue= 28 |pages= 21429–34 |year= 2000 |pmid= 10777491 |doi= 10.1074/jbc.M000961200 |display-authors=etal}}
*{{cite journal  | author=Seki N, Hayashi A, Hattori A, ''et al.'' |title=cDNA cloning, tissue expression, and chromosomal assignment of a mouse gene, encoding a 127 kDa UV-damaged DNA binding protein which is defective in XPE cells. |journal=DNA Res. |volume=6 |issue= 5 |pages= 319-22 |year= 2000 |pmid= 10574459 |doi=  }}
*{{cite journal  | vauthors=Martinez E, Palhan VB, Tjernberg A |title=Human STAGA complex is a chromatin-acetylating transcription coactivator that interacts with pre-mRNA splicing and DNA damage-binding factors in vivo. |journal=Mol. Cell. Biol. |volume=21 |issue= 20 |pages= 6782–95 |year= 2001 |pmid= 11564863 |doi= 10.1128/MCB.21.20.6782-6795.2001 | pmc=99856 |display-authors=etal}}
*{{cite journal  | author=Liu W, Nichols AF, Graham JA, ''et al.'' |title=Nuclear transport of human DDB protein induced by ultraviolet light. |journal=J. Biol. Chem. |volume=275 |issue= 28 |pages= 21429-34 |year= 2000 |pmid= 10777491 |doi= 10.1074/jbc.M000961200 }}
*{{cite journal  | vauthors=Chen X, Zhang Y, Douglas L, Zhou P |title=UV-damaged DNA-binding proteins are targets of CUL-4A-mediated ubiquitination and degradation. |journal=J. Biol. Chem. |volume=276 |issue= 51 |pages= 48175–82 |year= 2002 |pmid= 11673459 |doi= 10.1074/jbc.M106808200 }}
*{{cite journal  | author=Martinez E, Palhan VB, Tjernberg A, ''et al.'' |title=Human STAGA complex is a chromatin-acetylating transcription coactivator that interacts with pre-mRNA splicing and DNA damage-binding factors in vivo. |journal=Mol. Cell. Biol. |volume=21 |issue= 20 |pages= 6782-95 |year= 2001 |pmid= 11564863 |doi= 10.1128/MCB.21.20.6782-6795.2001 }}
*{{cite journal  | vauthors=Rapić-Otrin V, McLenigan MP, Bisi DC |title=Sequential binding of UV DNA damage binding factor and degradation of the p48 subunit as early events after UV irradiation. |journal=Nucleic Acids Res. |volume=30 |issue= 11 |pages= 2588–98 |year= 2002 |pmid= 12034848 |doi=10.1093/nar/30.11.2588  | pmc=117178  |display-authors=etal}}
*{{cite journal  | author=Chen X, Zhang Y, Douglas L, Zhou P |title=UV-damaged DNA-binding proteins are targets of CUL-4A-mediated ubiquitination and degradation. |journal=J. Biol. Chem. |volume=276 |issue= 51 |pages= 48175-82 |year= 2002 |pmid= 11673459 |doi= 10.1074/jbc.M106808200 }}
*{{cite journal  | vauthors=Bergametti F, Sitterlin D, Transy C |title=Turnover of hepatitis B virus X protein is regulated by damaged DNA-binding complex. |journal=J. Virol. |volume=76 |issue= 13 |pages= 6495–501 |year= 2002 |pmid= 12050362 |doi=10.1128/JVI.76.13.6495-6501.2002  | pmc=136256  }}
*{{cite journal  | author=Rapić-Otrin V, McLenigan MP, Bisi DC, ''et al.'' |title=Sequential binding of UV DNA damage binding factor and degradation of the p48 subunit as early events after UV irradiation. |journal=Nucleic Acids Res. |volume=30 |issue= 11 |pages= 2588-98 |year= 2002 |pmid= 12034848 |doi= }}
*{{cite journal  | vauthors=Bontron S, Lin-Marq N, Strubin M |title=Hepatitis B virus X protein associated with UV-DDB1 induces cell death in the nucleus and is functionally antagonized by UV-DDB2. |journal=J. Biol. Chem. |volume=277 |issue= 41 |pages= 38847–54 |year= 2002 |pmid= 12151405 |doi= 10.1074/jbc.M205722200 }}
*{{cite journal  | author=Bergametti F, Sitterlin D, Transy C |title=Turnover of hepatitis B virus X protein is regulated by damaged DNA-binding complex. |journal=J. Virol. |volume=76 |issue= 13 |pages= 6495-501 |year= 2002 |pmid= 12050362 |doi= }}
*{{cite journal  | vauthors=Andrejeva J, Poole E, Young DF |title=The p127 subunit (DDB1) of the UV-DNA damage repair binding protein is essential for the targeted degradation of STAT1 by the V protein of the paramyxovirus simian virus 5. |journal=J. Virol. |volume=76 |issue= 22 |pages= 11379–86 |year= 2002 |pmid= 12388698 |doi=10.1128/JVI.76.22.11379-11386.2002  | pmc=136798  |display-authors=etal}}
*{{cite journal  | author=Bontron S, Lin-Marq N, Strubin M |title=Hepatitis B virus X protein associated with UV-DDB1 induces cell death in the nucleus and is functionally antagonized by UV-DDB2. |journal=J. Biol. Chem. |volume=277 |issue= 41 |pages= 38847-54 |year= 2002 |pmid= 12151405 |doi= 10.1074/jbc.M205722200 }}
*{{cite journal  | vauthors=Strausberg RL, Feingold EA, Grouse LH |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899  | pmc=139241 |display-authors=etal}}
*{{cite journal  | author=Andrejeva J, Poole E, Young DF, ''et al.'' |title=The p127 subunit (DDB1) of the UV-DNA damage repair binding protein is essential for the targeted degradation of STAT1 by the V protein of the paramyxovirus simian virus 5. |journal=J. Virol. |volume=76 |issue= 22 |pages= 11379-86 |year= 2002 |pmid= 12388698 |doi=  }}
*{{cite journal  | vauthors=Groisman R, Polanowska J, Kuraoka I |title=The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. |journal=Cell |volume=113 |issue= 3 |pages= 357–67 |year= 2003 |pmid= 12732143 |doi=10.1016/S0092-8674(03)00316-7 |display-authors=etal}}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal  | vauthors=Leupin O, Bontron S, Strubin M |title=Hepatitis B virus X protein and simian virus 5 V protein exhibit similar UV-DDB1 binding properties to mediate distinct activities. |journal=J. Virol. |volume=77 |issue= 11 |pages= 6274–83 |year= 2003 |pmid= 12743284 |doi=10.1128/JVI.77.11.6274-6283.2003  | pmc=154990  }}
*{{cite journal  | author=Groisman R, Polanowska J, Kuraoka I, ''et al.'' |title=The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. |journal=Cell |volume=113 |issue= 3 |pages= 357-67 |year= 2003 |pmid= 12732143 |doi= }}
*{{cite journal  | vauthors=Wertz IE, O'Rourke KM, Zhang Z |title=Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase. |journal=Science |volume=303 |issue= 5662 |pages= 1371–4 |year= 2004 |pmid= 14739464 |doi= 10.1126/science.1093549 |display-authors=etal}}
*{{cite journal  | author=Leupin O, Bontron S, Strubin M |title=Hepatitis B virus X protein and simian virus 5 V protein exhibit similar UV-DDB1 binding properties to mediate distinct activities. |journal=J. Virol. |volume=77 |issue= 11 |pages= 6274-83 |year= 2003 |pmid= 12743284 |doi= }}
*{{cite journal  | vauthors=Bouwmeester T, Bauch A, Ruffner H |title=A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. |journal=Nat. Cell Biol. |volume=6 |issue= 2 |pages= 97–105 |year= 2004 |pmid= 14743216 |doi= 10.1038/ncb1086 |display-authors=etal}}
*{{cite journal  | author=Wertz IE, O'Rourke KM, Zhang Z, ''et al.'' |title=Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase. |journal=Science |volume=303 |issue= 5662 |pages= 1371-4 |year= 2004 |pmid= 14739464 |doi= 10.1126/science.1093549 }}
*{{cite journal  | author=Bouwmeester T, Bauch A, Ruffner H, ''et al.'' |title=A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. |journal=Nat. Cell Biol. |volume=6 |issue= 2 |pages= 97-105 |year= 2004 |pmid= 14743216 |doi= 10.1038/ncb1086 }}
}}
}}
{{refend}}
{{refend}}


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Latest revision as of 13:57, 4 November 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

DNA damage-binding protein 1 is a protein that in humans is encoded by the DDB1 gene.[1][2][3]

Gene

The gene's position is on chromosome 11q12-q13.[4]

Protein

The DDB1 gene encodes the large subunit of DNA damage-binding protein, a heterodimer composed of a large and a small (DDB2) subunit. DDB1 contains 1140 amino acids, amounting to a mass of 127 kDa.[4]

Function

As its name suggests, DDB1 was initially implicated in the process of a specific type of DNA repair known as nucleotide excision repair. Since then, researchers have found that DDB1 primarily functions as a core component of the CUL4A- and CUL4B-based E3 ubiquitin ligase complexes. DDB1 serves as a bridge or adaptor protein which interacts with dozens of proteins known as DDB1 and CUL4-associated factors (DCAFs).[5] These DCAFs are often ubiquitin ligase substrates and regulate numerous essential processes in the cell including DNA repair (DDB2), DNA replication, chromatin remodeling (Cdt2) and more.

Interactions

DDB1 has been shown to interact with Transcription initiation protein SPT3 homolog,[6] GCN5L2,[7] DDB2,[8][9] CUL4A,[9] CUL4B[9] and P21.[10]

References

  1. ↑ Dualan R, Brody T, Keeney S, Nichols AF, Admon A, Linn S (Feb 1996). "Chromosomal localization and cDNA cloning of the genes (DDB1 and DDB2) for the p127 and p48 subunits of a human damage-specific DNA binding protein". Genomics. 29 (1): 62–9. doi:10.1006/geno.1995.1215. PMID 8530102.
  2. ↑ Seki N, Hayashi A, Hattori A, Kozuma S, Sasaki M, Suzuki Y, Sugano S, Muramatsu M, Saito T (Jan 2000). "cDNA cloning, tissue expression, and chromosomal assignment of a mouse gene, encoding a 127 kDa UV-damaged DNA binding protein which is defective in XPE cells". DNA Res. 6 (5): 319–22. doi:10.1093/dnares/6.5.319. PMID 10574459.
  3. ↑ "Entrez Gene: DDB1 damage-specific DNA binding protein 1, 127kDa".
  4. ↑ 4.0 4.1 Iovine, Barbara; Iannella, Maria Luigia; Bevilacqua, Maria Assunta (2011). "Damage-specific DNA binding protein 1 (DDB1): a protein with a wide range of functions" (PDF). The International Journal of Biochemistry & Cell Biology. Elsevier. 43: 1664–1667. doi:10.1016/j.biocel.2011.09.001.
  5. ↑ Lee J (2007). "DCAFs, the Missing Link of the CUL4-DDB1 Ubiquitin Ligase". Molecular Cell. 26: 775–780. doi:10.1016/j.molcel.2007.06.001.
  6. ↑ Martinez E, Palhan VB, Tjernberg A, Lymar ES, Gamper AM, Kundu TK, Chait BT, Roeder RG (October 2001). "Human STAGA complex is a chromatin-acetylating transcription coactivator that interacts with pre-mRNA splicing and DNA damage-binding factors in vivo". Mol. Cell. Biol. 21 (20): 6782–95. doi:10.1128/MCB.21.20.6782-6795.2001. PMC 99856. PMID 11564863.
  7. ↑ Huang J, Chen J (July 2008). "VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation". Oncogene. 27 (29): 4056–64. doi:10.1038/onc.2008.44. PMID 18332868.
  8. ↑ Bergametti F, Sitterlin D, Transy C (July 2002). "Turnover of hepatitis B virus X protein is regulated by damaged DNA-binding complex". J. Virol. 76 (13): 6495–501. doi:10.1128/JVI.76.13.6495-6501.2002. PMC 136256. PMID 12050362.
  9. ↑ 9.0 9.1 9.2 Guerrero-Santoro J, Kapetanaki MG, Hsieh CL, Gorbachinsky I, Levine AS, Rapić-Otrin V (July 2008). "The cullin 4B-based UV-damaged DNA-binding protein ligase binds to UV-damaged chromatin and ubiquitinates histone H2A". Cancer Res. 68 (13): 5014–22. doi:10.1158/0008-5472.CAN-07-6162. PMID 18593899.
  10. ↑ Abbas T, Sivaprasad U, Terai K, Amador V, Pagano M, Dutta A (September 2008). "PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex". Genes Dev. 22 (18): 2496–506. doi:10.1101/gad.1676108. PMC 2546691. PMID 18794347.

Further reading


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