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)
End	61,342,596 bp
Gene location (Mouse)
Chr.	Chromosome 19 (mouse)
End	10,607,183 bp
RNA expression pattern
	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
	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
	1642
	13194
	ENSG00000167986
	ENSMUSG00000024740
	Q16531
	Q3U1J4
	NM_001923
	NM_015735
	NP_001914
	NP_056550
	Wikidata
View/Edit Human	View/Edit Mouse

DNA damage-binding protein 1 is a protein that in humans is encoded by the DDB1 gene.⁵⁶⁷

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 DDB2,¹²¹³ CUL4A,¹³ CUL4B¹³ and P21.¹⁴

References

GRCh38: Ensembl release 89: ENSG00000167986 – Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000024740 – Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
Dualan R, Brody T, Keeney S, Nichols AF, Admon A, Linn S (February 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): 62–69. doi:10.1006/geno.1995.1215. PMID 8530102.
Seki N, Hayashi A, Hattori A, Kozuma S, Sasaki M, Suzuki Y, et al. (January 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 Research. 6 (5): 319–322. doi:10.1093/dnares/6.5.319. PMID 10574459.
"Entrez Gene: DDB1 damage-specific DNA binding protein 1, 127kDa".
Iovine B, Iannella ML, Bevilacqua MA (December 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.
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.
Martinez E, Palhan VB, Tjernberg A, Lymar ES, Gamper AM, Kundu TK, et al. (October 2001). "Human STAGA complex is a chromatin-acetylating transcription coactivator that interacts with pre-mRNA splicing and DNA damage-binding factors in vivo". Molecular and Cellular Biology. 21 (20): 6782–6795. doi:10.1128/MCB.21.20.6782-6795.2001. PMC 99856. PMID 11564863.
Huang J, Chen J (July 2008). "VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation". Oncogene. 27 (29): 4056–4064. doi:10.1038/onc.2008.44. PMID 18332868. S2CID 23628888.
Bergametti F, Sitterlin D, Transy C (July 2002). "Turnover of hepatitis B virus X protein is regulated by damaged DNA-binding complex". Journal of Virology. 76 (13): 6495–6501. doi:10.1128/JVI.76.13.6495-6501.2002. PMC 136256. PMID 12050362.
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 Research. 68 (13): 5014–5022. doi:10.1158/0008-5472.CAN-07-6162. PMID 18593899.
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 & Development. 22 (18): 2496–2506. 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): 564–567. 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". Journal of Virology. 69 (2): 1107–1114. doi:10.1128/JVI.69.2.1107-1114.1995. PMC 188683. PMID 7815490.
Keeney S, Eker AP, Brody T, Vermeulen W, Bootsma D, Hoeijmakers JH, et al. (April 1994). "Correction of the DNA repair defect in xeroderma pigmentosum group E by injection of a DNA damage-binding protein". Proceedings of the National Academy of Sciences of the United States of America. 91 (9): 4053–4056. 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." The Journal of Biological Chemistry. 268 (28): 21293–21300. 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". Mutation Research. 362 (1): 105–117. 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". The Journal of Biological Chemistry. 271 (40): 24317–24320. doi:10.1074/jbc.271.40.24317. PMID 8798680.
Liu W, Nichols AF, Graham JA, Dualan R, Abbas A, Linn S (July 2000). "Nuclear transport of human DDB protein induced by ultraviolet light". The Journal of Biological Chemistry. 275 (28): 21429–21434. doi:10.1074/jbc.M000961200. PMID 10777491.
Martinez E, Palhan VB, Tjernberg A, Lymar ES, Gamper AM, Kundu TK, et al. (October 2001). "Human STAGA complex is a chromatin-acetylating transcription coactivator that interacts with pre-mRNA splicing and DNA damage-binding factors in vivo". Molecular and Cellular Biology. 21 (20): 6782–6795. 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". The Journal of Biological Chemistry. 276 (51): 48175–48182. doi:10.1074/jbc.M106808200. PMID 11673459.
Rapić-Otrin V, McLenigan MP, Bisi DC, Gonzalez M, Levine AS (June 2002). "Sequential binding of UV DNA damage binding factor and degradation of the p48 subunit as early events after UV irradiation". Nucleic Acids Research. 30 (11): 2588–2598. 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". Journal of Virology. 76 (13): 6495–6501. 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". The Journal of Biological Chemistry. 277 (41): 38847–38854. doi:10.1074/jbc.M205722200. PMID 12151405.
Andrejeva J, Poole E, Young DF, Goodbourn S, Randall RE (November 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". Journal of Virology. 76 (22): 11379–11386. doi:10.1128/JVI.76.22.11379-11386.2002. PMC 136798. PMID 12388698.
Groisman R, Polanowska J, Kuraoka I, Sawada J, Saijo M, Drapkin R, et al. (May 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): 357–367. 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". Journal of Virology. 77 (11): 6274–6283. doi:10.1128/JVI.77.11.6274-6283.2003. PMC 154990. PMID 12743284.
Wertz IE, O'Rourke KM, Zhang Z, Dornan D, Arnott D, Deshaies RJ, et al. (February 2004). "Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase". Science. 303 (5662): 1371–1374. Bibcode:2004Sci...303.1371W. doi:10.1126/science.1093549. PMID 14739464. S2CID 40501515.
Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, et al. (February 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216. S2CID 11683986.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000167986 – Ensembl, May 2017

[refGRCm38Ensembl-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.

[pmid8530102-5] Dualan R, Brody T, Keeney S, Nichols AF, Admon A, Linn S (February 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): 62–69. doi:10.1006/geno.1995.1215. PMID 8530102.

[pmid10574459-6] Seki N, Hayashi A, Hattori A, Kozuma S, Sasaki M, Suzuki Y, et al. (January 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 Research. 6 (5): 319–322. doi:10.1093/dnares/6.5.319. PMID 10574459.

[entrez-7] "Entrez Gene: DDB1 damage-specific DNA binding protein 1, 127kDa".

[Iovine2011-8] Iovine B, Iannella ML, Bevilacqua MA (December 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.

[DCAF-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.

[pmid11564863-10] Martinez E, Palhan VB, Tjernberg A, Lymar ES, Gamper AM, Kundu TK, et al. (October 2001). "Human STAGA complex is a chromatin-acetylating transcription coactivator that interacts with pre-mRNA splicing and DNA damage-binding factors in vivo". Molecular and Cellular Biology. 21 (20): 6782–6795. doi:10.1128/MCB.21.20.6782-6795.2001. PMC 99856. PMID 11564863.

[pmid18332868-11] Huang J, Chen J (July 2008). "VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation". Oncogene. 27 (29): 4056–4064. doi:10.1038/onc.2008.44. PMID 18332868. S2CID 23628888.

[pmid12050362-12] Bergametti F, Sitterlin D, Transy C (July 2002). "Turnover of hepatitis B virus X protein is regulated by damaged DNA-binding complex". Journal of Virology. 76 (13): 6495–6501. doi:10.1128/JVI.76.13.6495-6501.2002. PMC 136256. PMID 12050362.

[pmid18593899-13] 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 Research. 68 (13): 5014–5022. doi:10.1158/0008-5472.CAN-07-6162. PMID 18593899.

[pmid18794347-14] 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 & Development. 22 (18): 2496–2506. doi:10.1101/gad.1676108. PMC 2546691. PMID 18794347.

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