Tbio RAD23B UV excision repair protein RAD23 homolog B

Protein Summary

Description

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-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair. In vitro, the XPC:RAD23B dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts. XPC:RAD23B contacts DNA both 5' and 3' of a cisplatin lesion with a preference for the 5' side. XPC:RAD23B induces a bend in DNA upon binding. XPC:RAD23B stimulates the activity of DNA glycosylases TDG and SMUG1. The protein encoded by this gene is one of two human homologs of Saccharomyces cerevisiae Rad23, a protein involved in the nucleotide excision repair (NER). This protein was found to be a component of the protein complex that specifically complements the NER defect of xeroderma pigmentosum group C (XP-c) cell extracts in vitro. This protein was also shown to interact with, and elevate the nucleotide excision activity of 3-methyladenine-DNA glycosylase (MPG), which suggested a role in DNA damage recognition in base excision repair. This protein contains an N-terminal ubiquitin-like domain, which was reported to interact with 26S proteasome, and thus this protein may be involved in the ubiquitin mediated proteolytic pathway in cells. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Sep 2011]

Uniprot Accession IDs

• P54727
• B3KWK8
• G5E9P0
• Q7Z5K8
• Q8WUB0
• HR23B

Gene Name

• RAD23B

Ensembl ID

• ENST00000358015
• ENSP00000350708
• ENSG00000119318
• ENST00000416373
• ENSP00000405623

Symbol

• P58
• HR23B
• HHR23B

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
disease perturbation	1
co-expressed gene	0.97
protein domain	0.97
transcription factor binding site profile	0.94
kinase perturbation	0.93

Protein Classes

PANTHER Classes

Protein / Nucleic Acid Binding / Dna Binding Protein / Damaged Dna-binding Protein / Uv Excision Repair Protein Rad23 Homolog B

DTO Classes

Protein / Nucleic Acid Binding / Dna Binding Protein / Damaged Dna-binding Protein / Uv Excision Repair Protein Rad23 Homolog B

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 152.64   (req: < 5)

Gene RIFs: 46   (req: <= 3)

Antibodies: 428   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 152.64   (req: >= 5)

Gene RIFs: 46   (req: > 3)

Antibodies: 428   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 15

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0