RAD23A RAD23 homolog A, nucleotide excision repair protein [Homo sapiens (human)] - Gene

Summary

Official Symbol: RAD23Aprovided by HGNC
Official Full Name: RAD23 homolog A, nucleotide excision repair proteinprovided by HGNC
Primary source: HGNC:HGNC:9812
See related: Ensembl:ENSG00000179262 MIM:600061; AllianceGenome:HGNC:9812
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HR23A; HHR23A
Summary: The protein encoded by this gene is one of two human homologs of Saccharomyces cerevisiae Rad23, a protein involved in nucleotide excision repair. Proteins in this family have a modular domain structure consisting of an ubiquitin-like domain (UbL), ubiquitin-associated domain 1 (UbA1), XPC-binding domain and UbA2. The protein encoded by this gene plays an important role in nucleotide excision repair and also in delivery of polyubiquitinated proteins to the proteasome. Alternative splicing results in multiple transcript variants encoding multiple isoforms. [provided by RefSeq, Jun 2012]
Expression: Ubiquitous expression in fat (RPKM 50.3), heart (RPKM 47.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19p13.13

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (12945862..12953642)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (13070347..13078125)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (13056676..13064456)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Structure of HIV-1 Vpr in complex with the human nucleotide excision repair protein hHR23A.
Title: Structure of HIV-1 Vpr in complex with the human nucleotide excision repair protein hHR23A.
Kinetic Constraints in the Specific Interaction between Phosphorylated Ubiquitin and Proteasomal Shuttle Factors.
Title: Kinetic Constraints in the Specific Interaction between Phosphorylated Ubiquitin and Proteasomal Shuttle Factors.
Histone H4K20 Demethylation by Two hHR23 Proteins.
Title: Histone H4K20 Demethylation by Two hHR23 Proteins.
The HR23A-knockdown cells appear to undergo epithelial-mesenchymal transition and take on certain attributes of cancer stemness.
Title: HR23A-knockdown lung cancer cells exhibit epithelial-to-mesenchymal transition and gain stemness properties through increased Twist1 stability.
Data indicate that HR23A protein-depleted cells exhibit enhanced autophagy when treated with DNA-damaging agents.
Title: Human Rad23A plays a regulatory role in autophagy.
HR23A role in DNA reapair, in protein degradation and stability, tumorigenesis and neurodegenerative disorders [review]
Title: Two mammalian homologs of yeast Rad23, HR23A and HR23B, as multifunctional proteins.
hHR23A associates with Chk1 through its ubiquitin-associated domains, and knockdown of hHR23A increases and stabilizes the protein level of Chk1 and its phosphorylation at S347.
Title: hHR23A is required to control the basal turnover of Chk1.
Data indicate that phosphorylation provides a mechanism to regulate Rad23/proteasome interaction.
Title: Rad23 interaction with the proteasome is regulated by phosphorylation of its ubiquitin-like (UbL) domain.
Here, we show that hHR23A utilizes both the UBA2 and XPCB domains to form a stable complex with Vpr, linking Vpr directly to cellular DNA repair pathways and their probable exploitation by the virus.
Title: Binding of HIV-1 Vpr protein to the human homolog of the yeast DNA repair protein RAD23 (hHR23A) requires its xeroderma pigmentosum complementation group C binding (XPCB) domain as well as the ubiquitin-associated 2 (UBA2) domain.
this study identified RAD23A as a novel negative regulator of RIG-I/MDA5 mediated anti-virus response.
Title: RAD23A negatively regulates RIG-I/MDA5 signaling through promoting TRAF2 polyubiquitination and degradation.

Submit: New GeneRIF Correction See all GeneRIFs (28)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of RAD23 homolog A by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Vpr	vpr	Binding of HIV-1 Vpr (amino acids 25-77) to the UBA(2) domain of RAD23A (HHR23A) (amino acids 319-363) affects the cell cycle arrest induced by Vpr	PubMed
	vpr	NMR chemical shift analysis demonstrates that HIV-1 Vpr binds hHR23A through the contact surfaces on the XPCB (residues 232-286) and UBA2 (residues 316-363) domains of hHR23A	PubMed
	vpr	A di-Ub(K48)-hHR23A-Vpr ternary complex is formed with Lys-48-linked di-ubiquitin binding to the UBA1 domain in the Vpr-hHR23A complex	PubMed
	vpr	Residues Q249, L255, L259, N266, and N285 in XPCB domain and residues R326, G331, F332, E334, L336, F342, K346, E348, N349, A351, N353, and Q358 in UBA2 domain of hHR23A are involved in the binding to HIV-1 Vpr	PubMed
	vpr	HIV-1 Vpr promotes cellular protein polyubiquitination via hHR23A. Depletion of hHR23A significantly reduces HIV-1 replication in a Vpr-dependent manner	PubMed
	vpr	Co-expression of HIV-1 Vpr with HHR23A neutralizes inhibitory effects of HHR23A on p53 transcriptional activity	PubMed
	vpr	Overexpression of HHR23A causes apoptosis of cells, suggesting that Vpr binding to HHR23A may be involved in Vpr-induced apoptosis	PubMed
	vpr	Two reports indicate overexpression of HHR23A can inhibit HIV-1 Vpr-induced cell cycle arrest, while a third report indicates Vpr binding to HHR23A does not correlate with the ability of Vpr to induce cell cycle arrest	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-31478 (e-PCR)
- UniSTS:31238

D19S631E (e-PCR)
- UniSTS:150554

STS-M84739 (e-PCR)
- UniSTS:36938

RH41793 (e-PCR)
- UniSTS:70531

STS-D21235 (e-PCR)
- UniSTS:50370

RAD23A (e-PCR)
- UniSTS:265927

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables damaged DNA binding	IEA Inferred from Electronic Annotation more info
enables kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables polyubiquitin modification-dependent protein binding	IBA Inferred from Biological aspect of Ancestor more info
enables polyubiquitin modification-dependent protein binding	IDA Inferred from Direct Assay more info	PubMed
enables proteasome binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables single-stranded DNA binding	TAS Traceable Author Statement more info	PubMed
enables ubiquitin binding	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquitin-specific protease binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in nucleotide-excision repair	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell cycle	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of proteasomal ubiquitin-dependent protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of viral genome replication	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein destabilization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of proteasomal ubiquitin-dependent protein catabolic process	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
is_active_in nucleoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of proteasome complex	IEA Inferred from Electronic Annotation more info
part_of protein-containing complex	IMP Inferred from Mutant Phenotype more info	PubMed

General protein information

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Preferred Names: UV excision repair protein RAD23 homolog A

Names: RAD23, yeast homolog, A

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001270362.2 → NP_001257291.1 UV excision repair protein RAD23 homolog A isoform 2

See identical proteins and their annotated locations for NP_001257291.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the coding region, compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1.

Source sequence(s)

AI081136, AK289908, BC014026, BP213821

Consensus CDS

CCDS59358.1

UniProtKB/TrEMBL

A8K1J3

Related

ENSP00000321365.3, ENST00000316856.7

Conserved Domains (1) summary

TIGR00601
Location:3 → 360

rad23; UV excision repair protein Rad23
NM_001270363.2 → NP_001257292.1 UV excision repair protein RAD23 homolog A isoform 3

See identical proteins and their annotated locations for NP_001257292.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate in-frame exon in the 3' coding region compared to variant 1. It encodes isoform 3 which is shorter than isoform 1.

Source sequence(s)

AC092069, BC014026, BP213821, BX448989

Consensus CDS

CCDS59357.1

UniProtKB/TrEMBL

A0A494C0B4

Related

ENSP00000468674.1, ENST00000592268.5

Conserved Domains (1) summary

cl28408
Location:3 → 306

UBQ; Ubiquitin homologues
NM_005053.4 → NP_005044.1 UV excision repair protein RAD23 homolog A isoform 1

See identical proteins and their annotated locations for NP_005044.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

BC014026, BP213821

Consensus CDS

CCDS12289.1

UniProtKB/Swiss-Prot

K7ESE3, P54725, Q59EU8, Q5M7Z1

UniProtKB/TrEMBL

A8K1J3

Related

ENSP00000467024.1, ENST00000586534.6

Conserved Domains (1) summary

TIGR00601
Location:3 → 361

rad23; UV excision repair protein Rad23

RNA

NR_072976.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks an alternate internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AI057203, AK293219, BP213821

Related

ENST00000593114.5