DNA damage-binding protein 1 (DDB1)
The protein contains 1140 amino acids for an estimated molecular weight of 126968 Da.
Protein, which is both involved in DNA repair and protein ubiquitination, as part of the UV-DDB complex and DCX (DDB1-CUL4-X-box) complexes, respectively (PubMed:15448697, PubMed:14739464, PubMed:16260596, PubMed:16482215, PubMed:17079684, PubMed:16407242, PubMed:16407252, PubMed:16940174). Core component of the UV-DDB complex (UV-damaged DNA-binding protein complex), a complex that recognizes UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair (PubMed:15448697, PubMed:16260596, PubMed:16407242, PubMed:16940174). The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches (PubMed:15448697, PubMed:16260596, PubMed:16407242, PubMed:16940174). Also functions 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 (PubMed:14739464, PubMed:16407252, PubMed:16482215, PubMed:17079684, PubMed:25043012, PubMed:25108355, PubMed:18332868, PubMed:18381890, PubMed:19966799, PubMed:22118460, PubMed:28886238). The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1 (PubMed:14739464, PubMed:16407252, PubMed:16482215, PubMed:17079684, PubMed:25043012, PubMed:25108355, PubMed:18332868, PubMed:18381890, PubMed:199 (updated: April 22, 2020)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| dbSNP:rs28720299 |
Biological Process
Biological process involved in interaction with symbiont
Cellular response to DNA damage stimulus
DNA damage response, detection of DNA damage
DNA repair
Global genome nucleotide-excision repair
Histone H2A monoubiquitination
Negative regulation of apoptotic process
Nucleotide-excision repair
Nucleotide-excision repair, DNA damage recognition
Nucleotide-excision repair, DNA damage removal
Nucleotide-excision repair, DNA duplex unwinding
Nucleotide-excision repair, DNA incision
Nucleotide-excision repair, DNA incision, 3'-to lesion
Nucleotide-excision repair, DNA incision, 5'-to lesion
Nucleotide-excision repair, preincision complex assembly
Nucleotide-excision repair, preincision complex stabilization
Positive regulation by virus of viral protein levels in host cell
Positive regulation of gluconeogenesis
Positive regulation of protein catabolic process
Positive regulation of viral genome replication
Positive regulation of viral release from host cell
Post-translational protein modification
Proteasomal protein catabolic process
Proteasome-mediated ubiquitin-dependent protein catabolic process
Protein ubiquitination
Protein ubiquitination involved in ubiquitin-dependent protein catabolic process
Regulation of circadian rhythm
Regulation of mitotic cell cycle phase transition
Rhythmic process
Transcription-coupled nucleotide-excision repair
Ubiquitin-dependent protein catabolic process
UV-damage excision repair
Viral process
Wnt signaling pathway
Cellular Component
Chromosome, telomeric region
Cul4-RING E3 ubiquitin ligase complex
Cul4A-RING E3 ubiquitin ligase complex
Cul4B-RING E3 ubiquitin ligase complex
Cullin-RING ubiquitin ligase complex
Cytoplasm
Extracellular exosome
Extracellular space
Nuclear chromosome, telomeric region
Nucleoplasm
Nucleus
Protein complex
Protein-containing complex
Site of double-strand break
The reference OMIM entry for this protein is 600045
Dna damage-binding protein 1; ddb1
Ddb, p127 subunit
CLONING
Chu and Chang (1988) found that cells from 2 consanguineous patients with xeroderma pigmentosum complementation group E (XPE; 278740) lacked a DNA damage-binding activity that recognizes UV-irradiated DNA. Keeney et al. (1993) purified the DDB protein to apparent homogeneity and characterized it from human placenta and from HeLa cells. It was apparently identical to an activity first described from human placenta. DDB activity was associated with a polypeptide of approximately 124 kD, which was found to be complexed with a 41-kD protein. This stable heterodimer could, in turn, form a higher order complex. To test whether the DNA-repair defect in the subset of XPE patients that lack DNA damage-binding activity is caused by a defect in DDB, Keeney et al. (1994) injected purified human DDB protein into XPE cells. The injected DDB protein stimulated DNA repair to normal levels in those strains that lacked the DDB activity but did not stimulate repair in cells from XPE patients that contained the activity. These results provided direct evidence that defective DDB activity causes the repair defect in a subset of XPE patients and establishes a role for this activity in nucleotide-excision repair in vivo. The DNA damage-binding protein from HeLa cells is associated with polypeptides of relative mass 124,000 and 41,000 (DDB2; 600811) as determined by SDS-polyacrylamide gels. Dualan et al. (1995) isolated full-length human cDNAs encoding each polypeptide of DDB. The predicted peptide molecular masses based on open reading frames were 127,000 and 48,000. When expressed in an in vitro rabbit reticulocyte system, the p48 subunit migrated with a relative mass of 41 kD on SDS-polyacrylamide gels, similarly to the peptide purified from HeLa cells. There was no significant homology between the derived p48 peptide sequence in any proteins in databases, and the derived peptide sequence of p127 had homology only with the monkey DDB p127 (98% nucleotide identity and only 1 conserved amino acid substitution).GENE FUNCTION
Wertz et al. (2004) reported that human DET1 (608727) promotes ubiquitination and degradation of the protooncogenic transcription factor c-Jun (165160) by assembling a multisubunit ubiquitin ligase containing DDB1, cullin 4A (CUL4A; 603137), regulator of cullins-1 (ROC1; 603814), and constitutively photomorphogenic-1 (COP1; 608067). Ablation of any subunit by RNA interference stabilized c-Jun and increased c-Jun-activated transcription. Wertz et al. (2004) concluded that their findings characterized a c-Jun ubiquitin ligase and define a specific function for DET1 in mammalian cells. By analyzing proteins that immunoprecipitated with anti-CENPA (117139) antibodies from HeLa cell nuclear lysates, Obuse et al. (2004) showed that DDB1 associated with a centromeric complex, which also contained the major centromeric proteins CENPB (117140), CENPC (117141), CENPH (605607), CENPI (300065), and MIS12 (609178), and many others. DDB1 colocalized with CENPA at centromeres throughout the cell cycle in HeLa cells; it appeared in both the cytoplasm and nucleus in interphase and associated with chromosomes in metaphase. By mass spectrometric analysis, Higa et al. (2006) identified over 20 WD40 repeat-containing (WDR) proteins that interacted with the CUL4-DDB1-ROC1 complex. Sequence alignment revealed that most of the interacting WDR proteins had a centrally positioned WDxR/K submotif. Knockdown studies suggested that the WD ... More on the omim web site
April 25, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Jan. 22, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 600045 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed