XRCC5
X-ray repair cross-complementing protein 5
Also known as: KARP-1, KU80, Ku86, KUB2, XRCC5_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P13010
- Gene
- XRCC5
- Ensembl
- ENSG00000079246
- Chromosome
- 2
- Canonical length
- 732 aa
- Protein class
- Cancer-related genes, Plasma proteins, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm
OverviewNCBI Gene
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]
Canonical amino-acid sequenceUniProt
732 residues, UniProt reviewed canonical sequence.
>P13010|XRCC5
1 MVRSGNKAAV VLCMDVGFTM SNSIPGIESP FEQAKKVITM FVQRQVFAEN KDEIALVLFG
61 TDGTDNPLSG GDQYQNITVH RHLMLPDFDL LEDIESKIQP GSQQADFLDA LIVSMDVIQH
121 ETIGKKFEKR HIEIFTDLSS RFSKSQLDII IHSLKKCDIS LQFFLPFSLG KEDGSGDRGD
181 GPFRLGGHGP SFPLKGITEQ QKEGLEIVKM VMISLEGEDG LDEIYSFSES LRKLCVFKKI
241 ERHSIHWPCR LTIGSNLSIR IAAYKSILQE RVKKTWTVVD AKTLKKEDIQ KETVYCLNDD
301 DETEVLKEDI IQGFRYGSDI VPFSKVDEEQ MKYKSEGKCF SVLGFCKSSQ VQRRFFMGNQ
361 VLKVFAARDD EAAAVALSSL IHALDDLDMV AIVRYAYDKR ANPQVGVAFP HIKHNYECLV
421 YVQLPFMEDL RQYMFSSLKN SKKYAPTEAQ LNAVDALIDS MSLAKKDEKT DTLEDLFPTT
481 KIPNPRFQRL FQCLLHRALH PREPLPPIQQ HIWNMLNPPA EVTTKSQIPL SKIKTLFPLI
541 EAKKKDQVTA QEIFQDNHED GPTAKKLKTE QGGAHFSVSS LAEGSVTSVG SVNPAENFRV
601 LVKQKKASFE EASNQLINHI EQFLDTNETP YFMKSIDCIR AFREEAIKFS EEQRFNNFLK
661 ALQEKVEIKQ LNHFWEIVVQ DGITLITKEE ASGSSVTAEE AKKFLAPKDK PSGDTAAVFE
721 EGGDVDDLLD MILocalizationUniProt · AlphaFold · HPA
Whether an antibody against XRCC5 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.36
- Highest tissue expression
- 165 nTPM
Expression across tissuesHPA
Tissue
- thymus: 165 nTPM
- tonsil: 132 nTPM
- liver: 132 nTPM
- urinary bladder: 123 nTPM
- thyroid gland: 121 nTPM
- lymph node: 119 nTPM
Single-cell type
- neutrophil progenitors: 552 nCPM
- neutrophils: 543 nCPM
- erythrocyte progenitors: 489 nCPM
- megakaryocyte progenitors: 420 nCPM
- monocyte progenitors: 368 nCPM
- hepatocytes: 346 nCPM
Immune cell
- total PBMC: 330 nTPM
- basophil: 253 nTPM
- non-classical monocyte: 218 nTPM
- neutrophil: 193 nTPM
- intermediate monocyte: 177 nTPM
- eosinophil: 175 nTPM
Brain region
- white matter: 122 nTPM
- spinal cord: 113 nTPM
- basal ganglia: 109 nTPM
- cerebral cortex: 109 nTPM
- hypothalamus: 107 nTPM
- cerebellum: 105 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about XRCC5.
Disease | ImmuneIEDB
Conditions an epitope on XRCC5 was assayed in.
- systemic lupus erythematosus B cell
Disease | AutoantibodyPubMed
Conditions in which antibodies against XRCC5 are reported. Each links to that disease's full target list.
Showing 1 of 2 — disease pages carrying at least 10 antigens.
ReferencesPubMed · IEDB
Publications for XRCC5 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
7 publications
- Ku80 autoantigen as a cellular coreceptor for human parvovirus B19 infection.
2005 · Blood · RCR 3.2 · 129 citations - Dynamic binding of Ku80, Ku70 and NF90 to the IL-2 promoter in vivo in activated T-cells.
2007 · Nucleic Acids Res · RCR 1 · 58 citations - Screening and characterization of myositis-related autoantibodies in COVID-19 patients.
2023 · Clin Transl Sci · RCR 0.8 · 6 citations - Serum anti-Ku86 is a potential biomarker for early detection of hepatitis C virus-related hepatocellular carcinoma.
2012 · Biochem Biophys Res Commun · RCR 0.7 · 21 citations - KARP-1: a novel leucine zipper protein expressed from the Ku86 autoantigen locus is implicated in the control of DNA-dependent protein kinase activity.
1997 · EMBO J · RCR 0.7 · 44 citations
Show 2 more
- Expression of Ku86 and presence of Ku86 antibody as biomarkers of hepatitis B virus related hepatocellular carcinoma.
2014 · Dig Dis Sci · RCR 0.3 · 7 citations - [Serum anti-Ku86: a potential biomarker for early detection of hepatocellular carcinoma].
2014 · Zhonghua Zhong Liu Za Zhi · RCR 0.1 · 3 citations
Reference: B cellIEDB
2 publications
- Mapping of epitopes on the 86 kDa subunit of the Ku autoantigen.
1990 · Mol Immunol · RCR 0.5 · 22 citations - Mass spectral analysis of a protein complex using single-chain antibodies selected on a peptide target: applications to functional genomics.
2000 · J Mol Biol · RCR 0.4 · 15 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.15
- gnomAD pLI
- 1
- gnomAD missense Z
- 2.81
- DepMap mean gene effect
- -1.23
- DepMap dependency class
- common
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- activation of innate immune response
- cellular response to gamma radiation
- cellular response to leukemia inhibitory factor
- DNA damage response
- DNA recombination
- double-strand break repair
- double-strand break repair via nonhomologous end joining
- hematopoietic stem cell differentiation
- hematopoietic stem cell proliferation
- innate immune response
- negative regulation of DNA-templated transcription
- negative regulation of t-circle formation
- neurogenesis
- positive regulation of neurogenesis
- protein localization to chromosome, telomeric region
- recombinational repair
- regulation of smooth muscle cell proliferation
- regulation of telomere maintenance
- small-subunit processome assembly
- telomere maintenance
- telomere maintenance via telomerase
Molecular functions
- ATP binding
- ATP hydrolysis activity
- ATP-dependent activity, acting on DNA
- damaged DNA binding
- DNA binding
- DNA end binding
- DNA helicase activity
- double-stranded DNA binding
- enzyme activator activity
- protein-containing complex binding
- RNA binding
- telomeric DNA binding
- transcription cis-regulatory region binding
- U3 snoRNA binding
- ubiquitin protein ligase binding
Cellular components
- chromosome, telomeric region
- cytosol
- DNA-dependent protein kinase complex
- DNA-dependent protein kinase-DNA ligase 4 complex
- extracellular region
- Ku70:Ku80 complex
- membrane
- nonhomologous end joining complex
- nuclear telomere cap complex
- nucleolus
- nucleoplasm
- nucleus
- plasma membrane
- protein-containing complex
- protein-DNA complex
- ribonucleoprotein complex
- secretory granule lumen
- site of DNA damage
- small-subunit processome
Protein domainsUniProt · Pfam · InterPro
- von Willebrand factor, type A
- Ku70/Ku80 C-terminal arm
- Ku70/Ku80, N-terminal alpha/beta
- Ku70/Ku80, DNA-binding domain
- SPOC-like, C-terminal domain superfamily
- von Willebrand factor A-like domain superfamily
- Ku70/Ku80 beta-barrel domain
- Ku70/Ku80 C-terminal arm
- Ku70/Ku80 N-terminal alpha/beta domain
- Ku, C-terminal
- Ku80
- Ku, C-terminal domain superfamily
- Ku C terminal domain like
KeywordsUniProt
- Acetylation
- Activator
- ADP-ribosylation
- ATP-binding
- Chromosome
- DNA damage
- DNA recombination
- DNA repair
- DNA-binding
- Helicase
- Host-virus interaction
- Hydrolase
- Immunity
- Innate immunity
- Isomerase
- Isopeptide bond
- Lyase
- Nucleotide-binding
- Nucleus
- Phosphoprotein
- Ribosome biogenesis
- Systemic lupus erythematosus
- Transcription
- Transcription regulation
- Ubl conjugation
InteractionsUniProt · HPA
Protein binding partners of XRCC5 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads XRCC5 as an antibody target. Whether an autoantibody or antibody against XRCC5 could matter depends on whether native XRCC5 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
XRCC5 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label XRCC5 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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