XRCC5 X-ray repair cross complementing 5 [Homo sapiens (human)] - Gene

Summary

Official Symbol: XRCC5provided by HGNC
Official Full Name: X-ray repair cross complementing 5provided by HGNC
Primary source: HGNC:HGNC:12833
See related: Ensembl:ENSG00000079246 MIM:194364
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: KU80; KUB2; Ku86; NFIV; KARP1; KARP-1
Summary: The protein encoded by this gene is the 80-kilodalton subunit of the Ku heterodimer protein which is also known as ATP-dependant DNA helicase II or DNA repair protein XRCC5. Ku is the DNA-binding component of the DNA-dependent protein kinase, and it functions together with the DNA ligase IV-XRCC4 complex in the repair of DNA double-strand break by non-homologous end joining and the completion of V(D)J recombination events. This gene functionally complements Chinese hamster xrs-6, a mutant defective in DNA double-strand break repair and in ability to undergo V(D)J recombination. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in thyroid (RPKM 87.8), lymph node (RPKM 70.4) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 2q35

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
109.20190905	current	GRCh38.p13 (GCF_000001405.39)	2	NC_000002.12 (216109348..216206293)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (216972381..217071016)

Chromosome 2 - NC_000002.12 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
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?

The crystal structures of the Ku-binding motifs (KBM) of the non-homologous end joining (NHEJ) proteins APLF (A-KBM) and XLF (X-KBM) bound to a Ku-DNA complex are discussed.
Title: XLF and APLF bind Ku80 at two remote sites to ensure DNA repair by non-homologous end joining.
Ku80 overexpression associates with unfavorable prognosis of superficial ESCC patients, and silencing of Ku80 could inhibit the malignant behavior of ESCC cells. We provide evidence that Ku80 has unrecognized roles in carcinogenesis and development of ESCC.
Title: Clinical values of Ku80 upregulation in superficial esophageal squamous cell carcinoma.
ATM-dependent phosphorylation of CtIP and the epistatic and coordinated actions of MRE11 and CtIP nuclease activities are required to limit the stable loading of Ku on single-ended DNA double-strand breaks.
Title: Coordinated nuclease activities counteract Ku at single-ended DNA double-strand breaks.
these results suggest that polymorphisms of XRCC5 play an important role in astrocytoma prognosis in the Chinese Han population which could be used in the determination of astrocytoma prognosis in clinical researches
Title: The relationship between polymorphisms of XRCC5 genes with astrocytoma prognosis in the Han Chinese population.
SAF-A, in concert with Ku, temporally regulates base damage repair in irradiated cell genome.
Title: Scaffold attachment factor A (SAF-A) and Ku temporally regulate repair of radiation-induced clustered genome lesions.
High XRCC5 expresiion is associated with medullary thyroid carcinoma.
Title: Genetic and epigenetic background and protein expression profiles in relation to telomerase activation in medullary thyroid carcinoma.
Ku80 can be cleaved by caspases-2 at D726 upon a transient etoposide treatment. Caspase-2-mediated Ku80 cleavage promotes Ku80/DNA-PKcs interaction as the D726A mutation diminished Ku80 interaction with DNA-PKcs
Title: Cleavage of Ku80 by caspase-2 promotes non-homologous end joining-mediated DNA repair.
m-calpain translocated as the result of calcium influx was involved in DNA double-strand breaks repair, especially in the non-homologous end-joining pathway through proteolysis of nuclear Ku80. Cleaved Ku80 was still able to form a heterodimer with Ku70 and enhance DNA repair activity.
Title: Calcium influx-mediated translocation of m-calpain induces Ku80 cleavage and enhances the Ku80-related DNA repair pathway.
Ku80 CTR (C-terminal region) is required for interaction with DNA-PKcs on short segments of blunt ended 25bp dsDNA or 25bp dsDNA with a 15-base poly dA ssDNA extension, but this requirement is less stringent on longer dsDNA molecules (35bp blunt ended dsDNA) or 25bp duplex DNA with either a 15-base poly dT or poly dC ssDNA extension. Moreover, DNA-PKcs-Ku complex forms on 25 bp DNA with poly-pyrimidine ssDNA extension.
Title: DNA requirements for interaction of the C-terminal region of Ku80 with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs).
Ku80 could predict the probability of resistance to neoadjuvant chemotherapy in lung adenocarcinoma, and reduced cisplatin and pemetrexed-induced apoptosis in A549 cells
Title: Ku80 correlates with neoadjuvant chemotherapy resistance in human lung adenocarcinoma, but reduces cisplatin/pemetrexed-induced apoptosis in A549 cells.

Submit: New GeneRIF Correction See all GeneRIFs (154)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

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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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	Ku protein binds to HIV-1 TAR RNA and is involved in the stimulation of the elongation property of RNA polymerase II as well as the activation of several transcription factors, suggesting a role in HIV-1 gene expression and Tat transactivation	PubMed
integrase	gag-pol	Ku80 associates with viral preintegration complexes containing HIV-1 Integrase	PubMed
	gag-pol	DNA-PK, along with Ku70 and Ku80, is proposed to play a role in retroviral DNA integration and protects cells against toxicity induced by HIV-1 Integrase or integration	PubMed
matrix	gag	HIV-1 MA interacts with XRCC5 (Ku80)	PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

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2-LTR circle formation, organism-specific biosystem (from REACTOME)
2-LTR circle formation, organism-specific biosystemThe formation of 2-LTR circles requires the action of the cellular non-homologous DNA end-joining pathway. Specifically the cellular Ku, XRCC4 and ligase IV proteins are needed. Evidence for this i...
BARD1 signaling events, organism-specific biosystem (from Pathway Interaction Database)
BARD1 signaling events, organism-specific biosystem
BARD1 signaling events
Coregulation of Androgen receptor activity, organism-specific biosystem (from Pathway Interaction Database)
Coregulation of Androgen receptor activity, organism-specific biosystem
Coregulation of Androgen receptor activity
Cytosolic sensors of pathogen-associated DNA, organism-specific biosystem (from REACTOME)
Cytosolic sensors of pathogen-associated DNA, organism-specific biosystemPresence of pathogen-associated DNA in cytosol induces type I IFN production. Several intracellular receptors have been implicated to some degree. These include DNA-dependent activator of interferon ...
DNA Double-Strand Break Repair, organism-specific biosystem (from REACTOME)
DNA Double-Strand Break Repair, organism-specific biosystemNumerous types of DNA damage can occur within a cell due to the endogenous production of oxygen free radicals, normal alkylation reactions, or exposure to exogenous radiations and chemicals. Double-s...
DNA Repair, organism-specific biosystem (from REACTOME)
DNA Repair, organism-specific biosystemDNA repair is a phenomenal multi-enzyme, multi-pathway system required to ensure the integrity of the cellular genome. Living organisms are constantly exposed to harmful metabolic by-products, enviro...
DNA-PK complex, organism-specific biosystem (from KEGG)
DNA-PK complex, organism-specific biosystemStructural complex; Genetic information processing; Repair system
DNA-PK complex, conserved biosystem (from KEGG)
DNA-PK complex, conserved biosystemStructural complex; Genetic information processing; Repair system
Disease, organism-specific biosystem (from REACTOME)
Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
Early Phase of HIV Life Cycle, organism-specific biosystem (from REACTOME)
Early Phase of HIV Life Cycle, organism-specific biosystemIn the early phase of HIV lifecycle, an active virion binds and enters a target cell mainly by specific interactions of the viral envelope proteins with host cell surface receptors. The virion core...
HIV Infection, organism-specific biosystem (from REACTOME)
HIV Infection, organism-specific biosystemThe global pandemic of Human Immunodeficiency Virus (HIV) infection has resulted in tens of millions of people infected by the virus and millions more affected. UNAIDS estimates around 40 million ...
HIV Life Cycle, organism-specific biosystem (from REACTOME)
HIV Life Cycle, organism-specific biosystemThe life cycle of HIV-1 is divided into early and late phases, shown schematically in the figure. In the early phase, an HIV-1 virion binds to receptors and co-receptors on the human host cell surfac...
IRF3-mediated induction of type I IFN, organism-specific biosystem (from REACTOME)
IRF3-mediated induction of type I IFN, organism-specific biosystemTANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3) are central regulators of type-I interferon induction during bacterial or viral infection. TBK1 was found to form complexes with...
Immune System, organism-specific biosystem (from REACTOME)
Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
Infectious disease, organism-specific biosystem (from REACTOME)
Infectious disease, organism-specific biosystem
Infectious disease
Innate Immune System, organism-specific biosystem (from REACTOME)
Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
Integration of provirus, organism-specific biosystem (from REACTOME)
Integration of provirus, organism-specific biosystemFor retroviral DNA to direct production of progeny virions it must become covalently integrated into the host cell chromosome (reviewed in Coffin et al. 1997; Hansen et al. 1998). Analyses of mutants...
Neutrophil degranulation, organism-specific biosystem (from REACTOME)
Neutrophil degranulation, organism-specific biosystemNeutrophils are the most abundant leukocytes (white blood cells), indispensable in defending the body against invading microorganisms. In response to infection, neutrophils leave the circulation and ...
Non-homologous end joining, organism-specific biosystem (from WikiPathways)
Non-homologous end joining, organism-specific biosystem(From http://en.wikipedia.org/wiki/Non-homologous_end_joining) Non-homologous end joining (NHEJ) is a pathway that repairs double-strand breaks in DNA. NHEJ is referred to as "non-homologous" because...
Non-homologous end-joining, organism-specific biosystem (from KEGG)
Non-homologous end-joining, organism-specific biosystemNonhomologous end joining (NHEJ) eliminates DNA double-strand breaks (DSBs) by direct ligation. NHEJ involves binding of the KU heterodimer to double-stranded DNA ends, recruitment of DNA-PKcs (MRX c...
Non-homologous end-joining, conserved biosystem (from KEGG)
Non-homologous end-joining, conserved biosystemNonhomologous end joining (NHEJ) eliminates DNA double-strand breaks (DSBs) by direct ligation. NHEJ involves binding of the KU heterodimer to double-stranded DNA ends, recruitment of DNA-PKcs (MRX c...
Nonhomologous End-Joining (NHEJ), organism-specific biosystem (from REACTOME)
Nonhomologous End-Joining (NHEJ), organism-specific biosystemThe nonhomologous end joining (NHEJ) pathway is initiated in response to the formation of DNA double-strand breaks (DSBs) induced by DNA-damaging agents, such as ionizing radiation. DNA DSBs are reco...
Regulation of Telomerase, organism-specific biosystem (from Pathway Interaction Database)
Regulation of Telomerase, organism-specific biosystem
Regulation of Telomerase
STING mediated induction of host immune responses, organism-specific biosystem (from REACTOME)
STING mediated induction of host immune responses, organism-specific biosystemSTING (stimulator of IFN genes; also known as MITA/ERIS/MPYS/TMEM173) is an endoplasmic reticulum (ER) resident, which is required for effective type I IFN production in response to nucleic acids. In...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

HSC2AF082 (e-PCR)
- UniSTS:79121

PMC22716P1 (e-PCR)
- UniSTS:272151

RH104285 (e-PCR)
- UniSTS:98610

G67228 (e-PCR)
- UniSTS:186433

G67229 (e-PCR)
- UniSTS:186434

G67230 (e-PCR)
- UniSTS:186435

G67232 (e-PCR)
- UniSTS:186436

G67231 (e-PCR)
- UniSTS:186437

D2S2881 (e-PCR)
- UniSTS:26736

A004W06 (e-PCR)
- UniSTS:30865

SHGC-33338 (e-PCR)
- UniSTS:32425

SHGC-11966 (e-PCR)
- UniSTS:16811

D2S2382 (e-PCR), detects polymorphism
- UniSTS:8379

D2S2606 (e-PCR)
- UniSTS:58598

XRCC5_1894 (e-PCR)
- UniSTS:281081

PMC117391P1 (e-PCR)
- UniSTS:270331

PMC117391P2 (e-PCR)
- UniSTS:270332

Homology

Homologs of the XRCC5 gene: The XRCC5 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, mosquito, S.pombe, M.oryzae, N.crassa, A.thaliana, and frog.
Orthologs from Annotation Pipeline: 290 organisms have orthologs with human gene XRCC5
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
contributes_to 5'-deoxyribose-5-phosphate lyase activity	IMP Inferred from Mutant Phenotype more info	PubMed
ATP binding	IEA Inferred from Electronic Annotation more info
DNA binding	NAS Non-traceable Author Statement more info	PubMed
DNA end binding	IDA Inferred from Direct Assay more info	PubMed
DNA helicase activity	TAS Traceable Author Statement more info	PubMed
RNA binding	HDA more info	PubMed
RNA binding	IDA Inferred from Direct Assay more info	PubMed
damaged DNA binding	IEA Inferred from Electronic Annotation more info
contributes_to double-stranded DNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
contributes_to double-stranded telomeric DNA binding	IDA Inferred from Direct Assay more info	PubMed
enzyme activator activity	TAS Traceable Author Statement more info	PubMed
protein C-terminus binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein-containing complex binding	IPI Inferred from Physical Interaction more info	PubMed
telomeric DNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
telomeric DNA binding	IDA Inferred from Direct Assay more info	PubMed
telomeric DNA binding	TAS Traceable Author Statement more info	PubMed
transcription regulatory region DNA binding	IDA Inferred from Direct Assay more info	PubMed
ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
DNA duplex unwinding	IEA Inferred from Electronic Annotation more info
DNA recombination	IEA Inferred from Electronic Annotation more info
activation of innate immune response	IDA Inferred from Direct Assay more info	PubMed
brain development	IEA Inferred from Electronic Annotation more info
cell proliferation	IEA Inferred from Electronic Annotation more info
cellular hyperosmotic salinity response	IEA Inferred from Electronic Annotation more info
cellular response to DNA damage stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
cellular response to X-ray	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cellular response to fatty acid	IEA Inferred from Electronic Annotation more info
cellular response to gamma radiation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cellular response to gamma radiation	IDA Inferred from Direct Assay more info	PubMed
cellular response to leukemia inhibitory factor	IEA Inferred from Electronic Annotation more info
double-strand break repair	IMP Inferred from Mutant Phenotype more info	PubMed
double-strand break repair via nonhomologous end joining	IBA Inferred from Biological aspect of Ancestor more info	PubMed
double-strand break repair via nonhomologous end joining	IDA Inferred from Direct Assay more info	PubMed
double-strand break repair via nonhomologous end joining	IMP Inferred from Mutant Phenotype more info	PubMed
double-strand break repair via nonhomologous end joining	TAS Traceable Author Statement more info	PubMed
establishment of integrated proviral latency	TAS Traceable Author Statement more info
hematopoietic stem cell differentiation	IEA Inferred from Electronic Annotation more info
innate immune response	IEA Inferred from Electronic Annotation more info
negative regulation of t-circle formation	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of transcription, DNA-templated	IMP Inferred from Mutant Phenotype more info	PubMed
neutrophil degranulation	TAS Traceable Author Statement more info
positive regulation of catalytic activity	TAS Traceable Author Statement more info	PubMed
positive regulation of neurogenesis	IEA Inferred from Electronic Annotation more info
positive regulation of protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of telomerase activity	TAS Traceable Author Statement more info	PubMed
positive regulation of telomere maintenance via telomerase	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of type I interferon production	TAS Traceable Author Statement more info
protein localization to chromosome, telomeric region	TAS Traceable Author Statement more info	PubMed
regulation of smooth muscle cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of telomere maintenance	TAS Traceable Author Statement more info	PubMed
response to drug	IEA Inferred from Electronic Annotation more info
telomere maintenance	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Component	Evidence Code	Pubs
Ku70:Ku80 complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
Ku70:Ku80 complex	IDA Inferred from Direct Assay more info	PubMed
Ku70:Ku80 complex	TAS Traceable Author Statement more info	PubMed
cytosol	TAS Traceable Author Statement more info
extracellular region	TAS Traceable Author Statement more info
membrane	HDA more info	PubMed
nonhomologous end joining complex	IDA Inferred from Direct Assay more info	PubMed
nuclear chromosome, telomeric region	HDA more info	PubMed
nuclear chromosome, telomeric region	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nuclear chromosome, telomeric region	IDA Inferred from Direct Assay more info	PubMed
nuclear telomere cap complex	TAS Traceable Author Statement more info	PubMed
nucleolus	IEA Inferred from Electronic Annotation more info
nucleoplasm	IDA Inferred from Direct Assay more info
nucleoplasm	TAS Traceable Author Statement more info
nucleus	IDA Inferred from Direct Assay more info
plasma membrane	IDA Inferred from Direct Assay more info
protein-DNA complex	IDA Inferred from Direct Assay more info	PubMed
protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
ribonucleoprotein complex	IDA Inferred from Direct Assay more info	PubMed
secretory granule lumen	TAS Traceable Author Statement more info
site of DNA damage	IMP Inferred from Mutant Phenotype more info	PubMed

General protein information

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Preferred Names: X-ray repair cross-complementing protein 5

Names: 86 kDa subunit of Ku antigen; ATP-dependent DNA helicase 2 subunit 2; ATP-dependent DNA helicase II 80 kDa subunit; CTC box-binding factor 85 kDa subunit; CTC85; CTCBF; DNA repair protein XRCC5; Ku autoantigen, 80kDa; Ku86 autoantigen related protein 1; TLAA; X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining); lupus Ku autoantigen protein p86; nuclear factor IV; thyroid-lupus autoantigen

NP_066964.1

EC 3.6.4.-

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.

Genomic

NG_029780.1 RefSeqGene

Range

5052..101997

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_021141.4 → NP_066964.1 X-ray repair cross-complementing protein 5

See identical proteins and their annotated locations for NP_066964.1

Status: REVIEWED

Source sequence(s)

BG717693, BP375944, BU184024, M30938, X57500

Consensus CDS

CCDS2402.1

UniProtKB/Swiss-Prot

P13010

Related

ENSP00000375977.2, ENST00000392132.7

Conserved Domains (3) summary

cd00873
Location:244 → 543

KU80; Ku-core domain, Ku80 subfamily; Ku80 is a subunit of the Ku protein, which plays a key role in multiple nuclear processes such as DNA repair, chromosome maintenance, transcription regulation, and V(D)J recombination. The mechanism underlying the ...

pfam03731
Location:9 → 244

Ku_N; Ku70/Ku80 N-terminal alpha/beta domain

pfam08785
Location:593 → 705

Ku_PK_bind; Ku C terminal domain like