DDB1

DDB1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2B5L, 2B5M, 2B5N, 2HYE, 3E0C, 3EI1, 3EI2, 3EI3, 3EI4, 3I7H, 3I7K, 3I7L, 3I7N, 3I7O, 3I7P, 3I89, 3I8C, 3I8E, 4A08, 4A09, 4A0A, 4A0B, 4A0K, 4A0L, 4A11, 4CI1, 4CI2, 4CI3, 4E54, 4E5Z, 4TZ4, 5FQD, 5HXB
Identifiers
Aliases	DDB1 , DDBA, UV-XAP1, XPCE, XPE, XPE-BF, damage specific DNA binding protein 1, WHIKERS
External IDs	OMIM: 600045; MGI: 1202384; HomoloGene: 1448; GeneCards: DDB1; OMA:DDB1 - orthologs
Gene location (Human) Chr. Chromosome 11 (human) [1] Band 11q12.2 Start 61,299,451 bp [1] End 61,342,596 bp [1]
Gene location (Mouse) Chr. Chromosome 19 (mouse) [2] Band 19 A|19 6.66 cM Start 10,582,691 bp [2] End 10,607,183 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right adrenal gland right adrenal cortex left adrenal gland left adrenal cortex ventricular zone stromal cell of endometrium right testis ganglionic eminence left testis right uterine tube Top expressed in Ileal epithelium neural layer of retina spermatocyte choroid plexus of fourth ventricle gastrula ventricular zone epiblast tail of embryo lactiferous gland hand More reference expression data BioGPS n/a
Gene ontology Molecular function DNA binding protein binding nucleic acid binding damaged DNA binding protein-macromolecule adaptor activity cullin family protein binding WD40-repeat domain binding protein-containing complex binding Cellular component cytoplasm nucleoplasm Cul4A-RING E3 ubiquitin ligase complex Cul4B-RING E3 ubiquitin ligase complex extracellular exosome nucleus extracellular space Cul4-RING E3 ubiquitin ligase complex protein-containing complex Biological process regulation of mitotic cell cycle phase transition nucleotide-excision repair nucleotide-excision repair, DNA damage recognition positive regulation by virus of viral protein levels in host cell histone H2A monoubiquitination negative regulation of apoptotic process Wnt signaling pathway global genome nucleotide-excision repair biological process involved in interaction with symbiont positive regulation of viral genome replication transcription-coupled nucleotide-excision repair viral process nucleotide-excision repair, DNA incision UV-damage excision repair DNA repair proteasome-mediated ubiquitin-dependent protein catabolic process nucleotide-excision repair, DNA incision, 3'-to lesion nucleotide-excision repair, preincision complex stabilization nucleotide-excision repair, DNA duplex unwinding nucleotide-excision repair, preincision complex assembly nucleotide-excision repair, DNA incision, 5'-to lesion post-translational protein modification proteasomal protein catabolic process cellular response to DNA damage stimulus protein ubiquitination positive regulation of protein catabolic process ubiquitin-dependent protein catabolic process regulation of circadian rhythm positive regulation of gluconeogenesis rhythmic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1642 13194 Ensembl ENSG00000167986 ENSMUSG00000024740 UniProt Q16531 Q3U1J4 RefSeq (mRNA) NM_001923 NM_015735 RefSeq (protein) NP_001914 NP_056550 Location (UCSC) Chr 11: 61.3 – 61.34 Mb Chr 19: 10.58 – 10.61 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

DNA damage-binding protein 1 is a protein that in humans is encoded by the DDB1 gene. ^{[5] [6] [7]}

Gene

The gene's position is on chromosome 11q12-q13. ^[8]

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. ^[8]

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). ^[9] 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, ^[10] GCN5L2, ^[11] DDB2, ^{[12] [13]} CUL4A, ^[13] CUL4B ^[13] and P21. ^[14]

References

1. GRCh38: Ensembl release 89: ENSG00000167986 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000024740 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. 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.
7. "Entrez Gene: DDB1 damage-specific DNA binding protein 1, 127kDa".
8. Iovine B, Iannella ML, Bevilacqua MA (2011). "Damage-specific DNA binding protein 1 (DDB1): a protein with a wide range of functions". The International Journal of Biochemistry & Cell Biology. 43 (12). Elsevier: 1664–1667. doi:10.1016/j.biocel.2011.09.001. PMID   21959250.
9. Lee J (2007). "DCAFs, the Missing Link of the CUL4-DDB1 Ubiquitin Ligase". Molecular Cell. 26 (6): 775–780. doi: 10.1016/j.molcel.2007.06.001 . PMID   17588513.
10. 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.
11. 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. S2CID   23628888.
12. 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.
13. 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.
14. 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

• Chu G, Chang E (1988). "Xeroderma pigmentosum group E cells lack a nuclear factor that binds to damaged DNA". Science. 242 (4878): 564–7. Bibcode:1988Sci...242..564C. doi:10.1126/science.3175673. PMID   3175673.
• Lee TH, Elledge SJ, Butel JS (1995). "Hepatitis B virus X protein interacts with a probable cellular DNA repair protein". J. Virol. 69 (2): 1107–14. doi:10.1128/JVI.69.2.1107-1114.1995. PMC   188683 . PMID   7815490.
• Keeney S, Eker AP, Brody T, et al. (1994). "Correction of the DNA repair defect in xeroderma pigmentosum group E by injection of a DNA damage-binding protein" (PDF). Proc. Natl. Acad. Sci. U.S.A. 91 (9): 4053–6. Bibcode:1994PNAS...91.4053K. doi: 10.1073/pnas.91.9.4053 . PMC   43721 . PMID   8171034.
• Keeney S, Chang GJ, Linn S (1993). "Characterization of a human DNA damage binding protein implicated in xeroderma pigmentosum E." J. Biol. Chem. 268 (28): 21293–300. doi: 10.1016/S0021-9258(19)36923-6 . PMID   8407967.
• Hwang BJ, Liao JC, Chu G (1996). "Isolation of a cDNA encoding a UV-damaged DNA binding factor defective in xeroderma pigmentosum group E cells". Mutat. Res. 362 (1): 105–17. doi: 10.1016/0921-8777(95)00040-2 . PMID   8538642.
• Nichols AF, Ong P, Linn S (1996). "Mutations specific to the xeroderma pigmentosum group E Ddb- phenotype". J. Biol. Chem. 271 (40): 24317–20. doi: 10.1074/jbc.271.40.24317 . PMID   8798680.
• Liu W, Nichols AF, Graham JA, et al. (2000). "Nuclear transport of human DDB protein induced by ultraviolet light". J. Biol. Chem. 275 (28): 21429–34. doi: 10.1074/jbc.M000961200 . PMID   10777491.
• Martinez E, Palhan VB, Tjernberg A, et al. (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.
• Chen X, Zhang Y, Douglas L, Zhou P (2002). "UV-damaged DNA-binding proteins are targets of CUL-4A-mediated ubiquitination and degradation". J. Biol. Chem. 276 (51): 48175–82. doi: 10.1074/jbc.M106808200 . PMID   11673459.
• Rapić-Otrin V, McLenigan MP, Bisi DC, et al. (2002). "Sequential binding of UV DNA damage binding factor and degradation of the p48 subunit as early events after UV irradiation". Nucleic Acids Res. 30 (11): 2588–98. doi:10.1093/nar/30.11.2588. PMC   117178 . PMID   12034848.
• Bergametti F, Sitterlin D, Transy C (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.
• Bontron S, Lin-Marq N, Strubin M (2002). "Hepatitis B virus X protein associated with UV-DDB1 induces cell death in the nucleus and is functionally antagonized by UV-DDB2". J. Biol. Chem. 277 (41): 38847–54. doi: 10.1074/jbc.M205722200 . PMID   12151405.
• Andrejeva J, Poole E, Young DF, et al. (2002). "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". J. Virol. 76 (22): 11379–86. doi:10.1128/JVI.76.22.11379-11386.2002. PMC   136798 . PMID   12388698.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Groisman R, Polanowska J, Kuraoka I, et al. (2003). "The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage". Cell. 113 (3): 357–67. doi: 10.1016/S0092-8674(03)00316-7 . PMID   12732143. S2CID   11639677.
• Leupin O, Bontron S, Strubin M (2003). "Hepatitis B virus X protein and simian virus 5 V protein exhibit similar UV-DDB1 binding properties to mediate distinct activities". J. Virol. 77 (11): 6274–83. doi:10.1128/JVI.77.11.6274-6283.2003. PMC   154990 . PMID   12743284.
• Wertz IE, O'Rourke KM, Zhang Z, et al. (2004). "Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase" (PDF). Science. 303 (5662): 1371–4. Bibcode:2004Sci...303.1371W. doi:10.1126/science.1093549. PMID   14739464. S2CID   40501515.
• Bouwmeester T, Bauch A, Ruffner H, et al. (2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. 6 (2): 97–105. doi:10.1038/ncb1086. PMID   14743216. S2CID   11683986.