Human Gene XRCC3 (uc001yny.4)
  Description: Homo sapiens X-ray repair complementing defective repair in Chinese hamster cells 3 (XRCC3), transcript variant 2, mRNA.
RefSeq Summary (NM_005432): This gene encodes a member of the RecA/Rad51-related protein family that participates in homologous recombination to maintain chromosome stability and repair DNA damage. This gene functionally complements Chinese hamster irs1SF, a repair-deficient mutant that exhibits hypersensitivity to a number of different DNA-damaging agents and is chromosomally unstable. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008].
Transcript (Including UTRs)
   Position: hg19 chr14:104,163,954-104,181,823 Size: 17,870 Total Exon Count: 10 Strand: -
Coding Region
   Position: hg19 chr14:104,165,135-104,177,424 Size: 12,290 Coding Exon Count: 7 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr14:104,163,954-104,181,823)mRNA (may differ from genome)Protein (346 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMalacards
MGIneXtProtOMIMPubMedReactomeUniProtKB
WikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: XRCC3_HUMAN
DESCRIPTION: RecName: Full=DNA repair protein XRCC3; AltName: Full=X-ray repair cross-complementing protein 3;
FUNCTION: Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA, thought to repair chromosomal fragmentation, translocations and deletions. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51 and RAD51C.
SUBUNIT: Interacts with RAD51C and RAD51. Part of a complex consisting of RAD51B, RAD51C, RAD51D, XRCC2 and XRCC3. Forms a complex with FANCD2, BRCA2 and phosphorylated FANCG. Interacts with SWSAP1 and ZSWIM7; involved in homologous recombination repair.
INTERACTION: Q6NVH7:SWSAP1; NbExp=2; IntAct=EBI-2849976, EBI-5281637;
SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Cytoplasm, perinuclear region. Mitochondrion. Note=Accumulates in discrete nuclear foci prior to DNA damage, and these foci persist throughout the time course of DNA repair.
INDUCTION: Stress-induced increase in the mitochondrial levels is seen.
PTM: Phosphorylated upon DNA damage, probably by ATM or ATR.
DISEASE: Defects in XRCC3 are the cause of susceptibility to breast cancer (BC) [MIM:114480]. BC is a common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.
DISEASE: Defects in XRCC3 are the cause of susceptibility to cutaneous malignant melanoma type 6 (CMM6) [MIM:613972]. CMM6 is a malignant neoplasm of melanocytes, arising de novo or from a pre- existing benign nevus, which occurs most often in the skin but also may involve other sites.
SIMILARITY: Belongs to the RecA family. RAD51 subfamily.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/XRCC3ID335ch14q32.html";
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/xrcc3/";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): XRCC3
CDC HuGE Published Literature: XRCC3
Positive Disease Associations: Adenocarcinoma|Carcinoma, Squamous Cell|Deglutition Disorders|Head and Neck Neoplasms|Radiodermatitis , benzene toxicity , bladder cancer , breast cancer , cancer , cardia cancer stomach cancer , colorectal cancer , cytogenetic studies , lung cancer , Lupus Erythematosus, Systemic , melanoma , melanoma skin cancer , multiple myeloma , Neoplasms , radiotherapy response
Related Studies:
  1. Adenocarcinoma|Carcinoma, Squamous Cell|Deglutition Disorders|Head and Neck Neoplasms|Radiodermatitis
    Joke Werbrouck , et al. International journal of radiation oncology, biology, physics 2009 73(4):1187-95, Acute normal tissue reactions in head-and-neck cancer patients treated with IMRT: influence of dose and association with genetic polymorphisms in DNA DSB repair genes., International journal of radiation oncology, biology, physics 2009 73(4):1187-95. [PubMed 19251090]
  2. benzene toxicity
    Huang, H. L. et al. 2007, Association between genetic polymorphisms of DNA repair genes XRCC1, XRCC3 and susceptibility to chronic benzene poisoning., Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 2007 25(4) 193-6. [PubMed 17535647]
    Subjects with XRCC3 18067T variant allele are tolerance sub-group to benzene poisoning. Patients carrying XRCC1 27466 G/G genotype develop chronic benzene poisoning later.
  3. bladder cancer
    Matullo, G. et al. 2001, DNA repair gene polymorphisms, bulky DNA adducts in white blood cells and bladder cancer in a case-control study., International journal of cancer. Journal international du cancer. 2001 May;92(4):562-7. [PubMed 11304692]
    Our results suggest that bladder-cancer risk can be genetically modulated by XRCC3, which may repair DNA cross-link lesions produced by aromatic amines and other environmental chemicals.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: XRCC3
Diseases sorted by gene-association score: melanoma, cutaneous malignant, 6* (904), breast cancer* (136), breast cancer susceptibility, xrcc3-related* (100), xrcc3-related cutaneous malignant melanoma* (100), cardiomyopathy, hypertrophic, 15 (12), xeroderma pigmentosum, variant type (9), mutagen sensitivity (7), xeroderma pigmentosum, group d (7), xeroderma pigmentosum, group g (6), xeroderma pigmentosum, group f (5), diffuse gastric cancer (5), melanoma (3), differentiated thyroid carcinoma (3), lung cancer (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 10.43 RPKM in Spleen
Total median expression: 222.52 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -138.22380-0.364 Picture PostScript Text
3' UTR -587.501181-0.497 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR013632 - DNA_recomb/repair_Rad51_C
IPR016467 - DNA_recomb/repair_RecA-like
IPR020588 - DNA_recomb_RecA/RadB_ATP-bd

Pfam Domains:
PF08423 - Rad51
PF13481 - AAA domain

SCOP Domains:
52540 - P-loop containing nucleoside triphosphate hydrolases

ModBase Predicted Comparative 3D Structure on O43542
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
      
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000150 recombinase activity
GO:0000166 nucleotide binding
GO:0003677 DNA binding
GO:0003690 double-stranded DNA binding
GO:0003697 single-stranded DNA binding
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0008094 DNA-dependent ATPase activity
GO:0000400 four-way junction DNA binding
GO:0008821 crossover junction endodeoxyribonuclease activity

Biological Process:
GO:0000707 meiotic DNA recombinase assembly
GO:0000722 telomere maintenance via recombination
GO:0000724 double-strand break repair via homologous recombination
GO:0006281 DNA repair
GO:0006310 DNA recombination
GO:0006974 cellular response to DNA damage stimulus
GO:0007131 reciprocal meiotic recombination
GO:0010033 response to organic substance
GO:0010212 response to ionizing radiation
GO:0010824 regulation of centrosome duplication
GO:0036297 interstrand cross-link repair
GO:0042148 strand invasion
GO:0071140 resolution of mitotic recombination intermediates
GO:0090267 positive regulation of mitotic cell cycle spindle assembly checkpoint
GO:0090656 t-circle formation
GO:0090657 telomeric loop disassembly

Cellular Component:
GO:0000784 nuclear chromosome, telomeric region
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005657 replication fork
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005829 cytosol
GO:0033063 Rad51B-Rad51C-Rad51D-XRCC2 complex
GO:0033065 Rad51C-XRCC3 complex
GO:0048471 perinuclear region of cytoplasm


-  Descriptions from all associated GenBank mRNAs
  AK022829 - Homo sapiens cDNA FLJ12767 fis, clone NT2RP2001536, highly similar to DNA-repair protein XRCC3.
BC002949 - Homo sapiens, clone IMAGE:3543559, mRNA, partial cds.
AF035586 - Homo sapiens X-ray repair cross-complementing protein 3 (XRCC3) mRNA, complete cds.
BC011725 - Homo sapiens X-ray repair complementing defective repair in Chinese hamster cells 3, mRNA (cDNA clone MGC:19630 IMAGE:4138588), complete cds.
BC001036 - Homo sapiens X-ray repair complementing defective repair in Chinese hamster cells 3, mRNA (cDNA clone MGC:1435 IMAGE:3139703), complete cds.
LF384891 - JP 2014500723-A/192394: Polycomb-Associated Non-Coding RNAs.
AK126706 - Homo sapiens cDNA FLJ44752 fis, clone BRACE3030057, highly similar to Homo sapiens X-ray repair complementing defective repair in Chinese hamster cells 3 (XRCC3).
AK124498 - Homo sapiens cDNA FLJ42507 fis, clone BRACE2040514, highly similar to DNA-repair protein XRCC3.
AK023646 - Homo sapiens cDNA FLJ13584 fis, clone PLACE1009113, highly similar to DNA-repair protein XRCC3.
BX161398 - human full-length cDNA clone CS0DC014YE11 of Neuroblastoma of Homo sapiens (human).
JD546131 - Sequence 527155 from Patent EP1572962.
JD320869 - Sequence 301893 from Patent EP1572962.
JD115716 - Sequence 96740 from Patent EP1572962.
JD516362 - Sequence 497386 from Patent EP1572962.
JD320868 - Sequence 301892 from Patent EP1572962.
JD151168 - Sequence 132192 from Patent EP1572962.
JD398957 - Sequence 379981 from Patent EP1572962.
JD526879 - Sequence 507903 from Patent EP1572962.
JD076154 - Sequence 57178 from Patent EP1572962.
JD493587 - Sequence 474611 from Patent EP1572962.
JD099738 - Sequence 80762 from Patent EP1572962.
JD400885 - Sequence 381909 from Patent EP1572962.
JD544418 - Sequence 525442 from Patent EP1572962.
JD443901 - Sequence 424925 from Patent EP1572962.
JD296123 - Sequence 277147 from Patent EP1572962.
JD321811 - Sequence 302835 from Patent EP1572962.
JD321810 - Sequence 302834 from Patent EP1572962.
JD110660 - Sequence 91684 from Patent EP1572962.
JD204390 - Sequence 185414 from Patent EP1572962.
JD143586 - Sequence 124610 from Patent EP1572962.
JD219079 - Sequence 200103 from Patent EP1572962.
JD120809 - Sequence 101833 from Patent EP1572962.
JD393302 - Sequence 374326 from Patent EP1572962.
JD060216 - Sequence 41240 from Patent EP1572962.
JD123480 - Sequence 104504 from Patent EP1572962.
JD426471 - Sequence 407495 from Patent EP1572962.
JD215941 - Sequence 196965 from Patent EP1572962.
BT007417 - Homo sapiens X-ray repair complementing defective repair in Chinese hamster cells 3 mRNA, complete cds.
DQ892162 - Synthetic construct clone IMAGE:100004792; FLH183586.01X; RZPDo839E04142D X-ray repair complementing defective repair in Chinese hamster cells 3 (XRCC3) gene, encodes complete protein.
DQ895355 - Synthetic construct Homo sapiens clone IMAGE:100009815; FLH183583.01L; RZPDo839E04141D X-ray repair complementing defective repair in Chinese hamster cells 3 (XRCC3) gene, encodes complete protein.
AB529168 - Synthetic construct DNA, clone: pF1KE1047, Homo sapiens XRCC3 gene for X-ray repair complementing defective repair in Chinese hamster cells 3, without stop codon, in Flexi system.
KJ901055 - Synthetic construct Homo sapiens clone ccsbBroadEn_10449 XRCC3 gene, encodes complete protein.
BC127808 - Homo sapiens cDNA clone IMAGE:40133605.
CU674514 - Synthetic construct Homo sapiens gateway clone IMAGE:100017051 5' read XRCC3 mRNA.
JD376364 - Sequence 357388 from Patent EP1572962.
JD051173 - Sequence 32197 from Patent EP1572962.
JD111491 - Sequence 92515 from Patent EP1572962.
JD535192 - Sequence 516216 from Patent EP1572962.
JD451009 - Sequence 432033 from Patent EP1572962.
MA620468 - JP 2018138019-A/192394: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa03440 - Homologous recombination

Reactome (by CSHL, EBI, and GO)

Protein O43542 (Reactome details) participates in the following event(s):

R-HSA-5685319 CX3 complex formation
R-HSA-5685838 CX3 complex binds D-loop structures
R-HSA-5686410 BLM mediates dissolution of double Holliday junction
R-HSA-5693589 D-loop dissociation and strand annealing
R-HSA-5693593 D-loop extension by DNA polymerases
R-HSA-5686440 MUS81:EME1,EME2 cleaves D-loop
R-HSA-5693584 Cleavage of Holliday junctions by GEN1 or SLX1A:SLX4:MUS81:EME1,(MUS81:EME2)
R-HSA-5693579 Homologous DNA Pairing and Strand Exchange
R-HSA-5693568 Resolution of D-loop Structures through Holliday Junction Intermediates
R-HSA-5693554 Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)
R-HSA-5685942 HDR through Homologous Recombination (HRR)
R-HSA-5693537 Resolution of D-Loop Structures
R-HSA-5693567 HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)
R-HSA-5693538 Homology Directed Repair
R-HSA-5693532 DNA Double-Strand Break Repair
R-HSA-73894 DNA Repair

-  Other Names for This Gene
  Alternate Gene Symbols: NM_005432, NP_005423, O43542, O43568, Q9BU18, XRCC3_HUMAN
UCSC ID: uc001yny.4
RefSeq Accession: NM_005432
Protein: O43542 (aka XRCC3_HUMAN or XRC3_HUMAN)
CCDS: CCDS9984.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_005432.3
exon count: 10CDS single in 3' UTR: no RNA size: 2620
ORF size: 1041CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2065.50frame shift in genome: no % Coverage: 99.31
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.