UV excision repair protein RAD23 homolog B (RAD23B)
The protein contains 409 amino acids for an estimated molecular weight of 43171 Da.
Multiubiquitin chain receptor involved in modulation of proteasomal degradation. Binds to polyubiquitin chains. Proposed to be capable to bind simultaneously to the 26S proteasome and to polyubiquitinated substrates and to deliver ubiquitinated proteins to the proteasome. May play a role in endoplasmic reticulum-associated degradation (ERAD) of misfolded glycoproteins by association with PNGase and delivering deglycosylated proteins to the proteasome.', 'Involved in global genome nucleotide excision repair (GG-NER) by acting as component of the XPC complex. Cooperatively with CETN2 appears to stabilize XPC. May protect XPC from proteasomal degradation.', "The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single-stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-in (updated: March 4, 2015)
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.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| dbSNP:rs1805329 |
Biological Process
Cellular response to interleukin-7
DNA repair
Embryonic organ development
Global genome nucleotide-excision repair
Nucleotide-excision repair
Nucleotide-excision repair, DNA damage recognition
Nucleotide-excision repair, DNA damage removal
Nucleotide-excision repair, DNA duplex unwinding
Nucleotide-excision repair, preincision complex assembly
Proteasome-mediated ubiquitin-dependent protein catabolic process
Protein deubiquitination
Protein folding
Regulation of proteasomal ubiquitin-dependent protein catabolic process
Spermatogenesis
Cellular Component
Cytoplasm
Cytosol
Host cell nucleus
Nucleoplasm
Nucleus
Proteasome complex
XPC complex
The reference OMIM entry for this protein is 600062
Rad23, yeast, homolog of, b; rad23b
Hhr23b
Hr23b
DESCRIPTION
RAD23A (600061) and RAD23B, the human orthologs of yeast RAD23, play distinct roles in nucleotide excision DNA repair (NER) and in the ubiquitin-proteasome system (UPS). NER is a genome maintenance pathway responsible for repair of bulky DNA lesions, and UPS performs protein degradation in diverse cellular processes, including DNA repair (summary by Bergink et al., 2013).CLONING
Masutani et al. (1994) cloned human RAD23A and RAD23B, which they called HHR23A and HHR23B, from a HeLa cell cDNA library. The deduced proteins contain 363 and 409 amino acids, respectively, and both have an N-terminal domain that shares significant similarity with ubiquitin (UBB; 191339) and various ubiquitin fusion proteins. Both RAD23A and RAD23B were expressed in the same cells. In mouse, van der Spek et al. (1996) cloned the homologs of both RAD23A and RAD23B. Detailed sequence comparisons permitted deductions concerning the structure of all RAD23 homologs. Northern blot analysis revealed constitutive expression of both RAD23 genes in all tissues examined. Elevated RNA expression of both genes was observed in testis.GENE FUNCTION
Using a DNA damage recognition-competition assay, Sugasawa et al. (1998) identified XPC-RAD23B as the earliest damage detector to initiate NER; it acts before the known damage-binding protein XPA. Coimmunoprecipitation and DNase I footprinting showed that XPC-RAD23B binds to a variety of NER lesions. This provides a plausible explanation for the extreme damage specificity exhibited by global genome repair. Machado-Joseph disease (MJD; 109150) is an autosomal dominant neurodegenerative disorder caused by an expansion of the polyglutamine tract near the C terminus of the MJD1 gene product, ataxin-3. The mutant ataxin-3 forms intranuclear inclusions in cultured cells as well as in diseased human brain and also causes cell death in transfected cells. Using a 2-hybrid system, Wang et al. (2000) found that ataxin-3 interacts with 2 human homologs of the yeast DNA repair protein RAD23, RAD23A and RAD23B. Both normal and mutant ataxin-3 proteins interact with the ubiquitin-like domain at the N terminus of the HHR23 proteins, which is a motif important for nucleotide excision repair. However, in human embryonic kidney cells, HHR23A is recruited to intranuclear inclusions formed by the mutant ataxin-3 through its interaction with ataxin-3. The authors suggested that this interaction is associated with the normal function of ataxin-3, and that some functional abnormality of the RAD23 proteins may exist in MJD. Volker et al. (2001) described the assembly of the NER complex in normal and repair-deficient (xeroderma pigmentosum) human cells by employing a novel technique of local ultraviolet irradiation combined with fluorescent antibody labeling. The damage-recognition complex XPC (613208)-HHR23B appeared to be essential for the recruitment of all subsequent NER factors in the preincision complex, including transcription repair factor TFIIH (see 189972). Volker et al. (2001) found that XPA (611153) associates relatively late, is required for anchoring of ERCC1 (126380)-XPF (133520), and may be essential for activation of the endonuclease activity of XPG (133530). These findings identified XPC as the earliest known NER factor in the reaction mechanism, gave insight into the order of subsequent NER components, provided evidence for a dual role of XPA, and supported a concept of sequential assembly of ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 600062 was added.
Sept. 16, 2015: Protein entry updated
Automatic update: model status changed