UV excision repair protein RAD23 homolog A (RAD23A)
The protein contains 363 amino acids for an estimated molecular weight of 39609 Da.
Multiubiquitin chain receptor involved in modulation of proteasomal degradation. Binds to 'Lys-48'-linked polyubiquitin chains in a length-dependent manner and with a lower affinity to 'Lys-63'-linked 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.Involved in nucleotide excision repair and is thought to be functional equivalent for RAD23B in global genome nucleotide excision repair (GG-NER) by association with XPC. In vitro, the XPC:RAD23A dimer has NER activity. Can stabilize XPC.', '(Microbial infection) Involved in Vpr-dependent replication of HIV-1 in non-proliferating cells and primary macrophages. Required for the association of HIV-1 Vpr with the host proteasome. (updated: July 18, 2018)
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:rs11558955 | |
| dbSNP:rs4987203 | |
| dbSNP:rs4987202 |
Biological Process
Nucleotide-excision repair
Positive regulation of cell cycle
Positive regulation of proteasomal ubiquitin-dependent protein catabolic process
Positive regulation of viral genome replication
Proteasome-mediated ubiquitin-dependent protein catabolic process
Protein destabilization
Protein deubiquitination
Regulation of proteasomal ubiquitin-dependent protein catabolic process
Viral process
The reference OMIM entry for this protein is 600061
Rad23, yeast, homolog of, a; rad23a
Hhr23a
DESCRIPTION
RAD23A and RAD23B (600062), 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) reported the purification to homogeneity and subsequent cDNA cloning from HeLa cells of a repair complex by in vitro complementation of the xeroderma pigmentosum group C (278720) defect in a cell-free repair system containing UV-damaged SV40 minichromosomes. The complex had a high affinity for ssDNA and consisted of 2 tightly associated proteins of 125 and 58 kD. The 125-kD subunit represented the previously reported XPC gene (613208) product, which represents the human homolog of the NER gene RAD4 of Saccharomyces cerevisiae. The 58-kD species turned out to be a human homolog of yeast RAD23. Unexpectedly, a second human counterpart of RAD23 was identified. The 2 genes, which Masutani et al. (1994) referred to as HHR23A (RAD23A) and HHR23B (RAD23B), 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 the XPC purification scheme, however, only the RAD23B protein was found in a complex with p125/XPC. In mouse, van der Spek et al. (1996) cloned the homologs of 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.MAPPING
Using fluorescence in situ hybridization (FISH), van der Spek et al. (1994) demonstrated that the RAD23A gene is located on 19p13.2. By FISH, van der Spek et al. (1996) assigned the Rad23a gene to mouse chromosome 8C3 and the Rad23b gene to mouse chromosome 4B3.GENE FUNCTION
Masutani et al. (1994) commented that no human mutant defective in RAD23A had been identified. They suggested that the nature of the defect in xeroderma pigmentosum group C implies that the XPC-RAD23B complex exerts a unique function in the genome-overall repair pathway that is important for prevention of skin cancer. Van der Spek et al. (1996) found that although the RAD23 equivalents are well conserved during evolution, the mammalian genes do not express the UV-inducible phenotype of their yeast counterpart. The authors stated that this discovery may point to a fundamental difference between the UV responses of yeast and human. 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 RAD23 proteins, which is a motif important for nucleotide exci ... 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 600061 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed