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O43542 (XRCC3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
DNA repair protein XRCC3
Alternative name(s):
X-ray repair cross-complementing protein 3
Gene names
Name:XRCC3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length346 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA, thought to repair chromosomal fragmentation, translocations and deletions. Part of the RAD21 paralog protein complex CX3 which acts in the BRCA1-BRCA2-dependent HR pathway. Upon DNA damage, CX3 acts downstream of RAD51 recruitment; the complex binds predominantly to the intersection of the four duplex arms of the Holliday junction (HJ) and to junctions of replication forks. Involved in HJ resolution and thus in processing HR intermediates late in the DNA repair process; the function may be linked to the CX3 complex and seems to involve GEN1 during mitotic cell cycle progression. Part of a PALB2-scaffolded HR complex containing BRCA2 and RAD51C and which is thought to play a role in DNA repair by HR. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51 and RAD51C. Ref.9 Ref.12 Ref.16 Ref.17

Subunit structure

Interacts with RAD51C and RAD51. Part of the CX3 complex consisting of RAD51C and XRCC3; the complex has a ring-like structure arranged into a flat disc around a central channel; CX3 can interact with RAD51 in vitro. Forms a complex with FANCD2, BRCA2 and phosphorylated FANCG. Interacts with SWSAP1 and ZSWIM7; involved in homologous recombination repair. Interacts directly with PALB2 which may serve as a scaffold for a HR complex containing PALB2, BRCA2, RAD51C, RAD51 and XRCC3. Ref.4 Ref.6 Ref.7 Ref.8 Ref.14 Ref.18

Subcellular location

Nucleus. Cytoplasm. Cytoplasmperinuclear region. Mitochondrion. Note: Accumulates in discrete nuclear foci prior to DNA damage, and these foci persist throughout the time course of DNA repair. Ref.10 Ref.12

Induction

Stress-induced increase in the mitochondrial levels is seen. Ref.12

Involvement in disease

Breast cancer (BC) [MIM:114480]: 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.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.5

Melanoma, cutaneous malignant 6 (CMM6) [MIM:613972]: 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.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.20

Sequence similarities

Belongs to the RecA family. RAD51 subfamily.

Ontologies

Keywords
   Biological processDNA damage
DNA recombination
DNA repair
   Cellular componentCytoplasm
Mitochondrion
Nucleus
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   LigandATP-binding
DNA-binding
Nucleotide-binding
   PTMAcetylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA catabolic process, endonucleolytic

Inferred from mutant phenotype Ref.9Ref.16. Source: GOC

DNA recombination

Traceable author statement Ref.1. Source: ProtInc

DNA repair

Inferred from genetic interaction PubMed 10422536. Source: BHF-UCL

cellular response to DNA damage stimulus

Traceable author statement PubMed 7603995. Source: ProtInc

double-strand break repair via homologous recombination

Inferred from mutant phenotype Ref.17. Source: UniProtKB

positive regulation of mitotic cell cycle spindle assembly checkpoint

Inferred from mutant phenotype Ref.16. Source: UniProtKB

regulation of centrosome duplication

Inferred from mutant phenotype Ref.16. Source: UniProtKB

resolution of mitotic recombination intermediates

Inferred from mutant phenotype Ref.16. Source: UniProtKB

response to organic substance

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentRad51C-XRCC3 complex

Inferred from direct assay Ref.4. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.10. Source: UniProtKB

mitochondrion

Inferred from direct assay Ref.12. Source: UniProtKB

nucleus

Inferred from direct assay Ref.10. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from direct assay Ref.10. Source: UniProtKB

replication fork

Inferred from direct assay Ref.19. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

DNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

DNA-dependent ATPase activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

SWSAP1Q6NVH72EBI-2849976,EBI-5281637

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 346346DNA repair protein XRCC3
PRO_0000122951

Regions

Nucleotide binding107 – 1148ATP Potential

Amino acid modifications

Modified residue11N-acetylmethionine Ref.15

Natural variations

Natural variant941R → H. Ref.2
Corresponds to variant rs3212057 [ dbSNP | Ensembl ].
VAR_020405
Natural variant2411T → M in CMM6 susceptibility; associated with cutaneous malignant melanoma. Ref.1 Ref.2 Ref.20
Corresponds to variant rs861539 [ dbSNP | Ensembl ].
VAR_013006
Natural variant2711G → R.
Corresponds to variant rs28903080 [ dbSNP | Ensembl ].
VAR_029295
Natural variant3021R → H.
Corresponds to variant rs28903081 [ dbSNP | Ensembl ].
VAR_029296

Sequences

Sequence LengthMass (Da)Tools
O43542 [UniParc].

Last modified June 1, 1998. Version 1.
Checksum: 4DDF3B163C3B3332

FASTA34637,850
        10         20         30         40         50         60 
MDLDLLDLNP RIIAAIKKAK LKSVKEVLHF SGPDLKRLTN LSSPEVWHLL RTASLHLRGS 

        70         80         90        100        110        120 
SILTALQLHQ QKERFPTQHQ RLSLGCPVLD ALLRGGLPLD GITELAGRSS AGKTQLALQL 

       130        140        150        160        170        180 
CLAVQFPRQH GGLEAGAVYI CTEDAFPHKR LQQLMAQQPR LRTDVPGELL QKLRFGSQIF 

       190        200        210        220        230        240 
IEHVADVDTL LECVNKKVPV LLSRGMARLV VIDSVAAPFR CEFDSQASAP RARHLQSLGA 

       250        260        270        280        290        300 
TLRELSSAFQ SPVLCINQVT EAMEEQGAAH GPLGFWDERV SPALGITWAN QLLVRLLADR 

       310        320        330        340 
LREEEAALGC PARTLRVLSA PHLPPSSCSY TISAEGVRGT PGTQSH 

« Hide

References

« Hide 'large scale' references
[1]"XRCC2 and XRCC3, new human Rad51-family members, promote chromosome stability and protect against DNA cross-links and other damages."
Liu N., Lamerdin J.E., Tebbs R.S., Schild D., Tucker J.D., Shen M.R., Brookman K.W., Siciliano M.J., Walter C.A., Fan W., Narayana L.S., Zhou Z.-Q., Adamson A.W., Sorensen K.J., Chen D.J., Jones N.J., Thompson L.H.
Mol. Cell 1:783-793(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT MET-241.
Tissue: Cervix carcinoma.
[2]NIEHS SNPs program
Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HIS-94 AND MET-241.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lymph, Muscle and Placenta.
[4]"Identification and purification of two distinct complexes containing the five RAD51 paralogs."
Masson J.Y., Tarsounas M.C., Stasiak A.Z., Stasiak A., Shah R., McIlwraith M.J., Benson F.E., West S.C.
Genes Dev. 15:3296-3307(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE CX3 COMPLEX WITH XRCC3.
[5]"Variants in DNA double-strand break repair genes and breast cancer susceptibility."
Kuschel B., Auranen A., McBride S., Novik K.L., Antoniou A., Lipscombe J.M., Day N.E., Easton D.F., Ponder B.A., Pharoah P.D., Dunning A.
Hum. Mol. Genet. 11:1399-1407(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN BC SUSCEPTIBILITY.
[6]"RAD51C interacts with RAD51B and is central to a larger protein complex in vivo exclusive of RAD51."
Miller K.A., Yoshikawa D.M., McConnell I.R., Clark R., Schild D., Albala J.S.
J. Biol. Chem. 277:8406-8411(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE CX3 COMPLEX WITH XRCC3.
[7]"Involvement of Rad51C in two distinct protein complexes of Rad51 paralogs in human cells."
Liu N., Schild D., Thelen M.P., Thompson L.H.
Nucleic Acids Res. 30:1009-1015(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RAD51 AND RAD51C.
[8]"Domain mapping of the Rad51 paralog protein complexes."
Miller K.A., Sawicka D., Barsky D., Albala J.S.
Nucleic Acids Res. 32:169-178(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RAD51C.
[9]"RAD51C is required for Holliday junction processing in mammalian cells."
Liu Y., Masson J.Y., Shah R., O'Regan P., West S.C.
Science 303:243-246(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Cellular localization of human Rad51C and regulation of ubiquitin-mediated proteolysis of Rad51."
Bennett B.T., Knight K.L.
J. Cell. Biochem. 96:1095-1109(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[11]"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.
Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic kidney.
[12]"Discovery of a novel function for human Rad51: maintenance of the mitochondrial genome."
Sage J.M., Gildemeister O.S., Knight K.L.
J. Biol. Chem. 285:18984-18990(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INDUCTION.
[13]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"hSWS1.SWSAP1 is an evolutionarily conserved complex required for efficient homologous recombination repair."
Liu T., Wan L., Wu Y., Chen J., Huang J.
J. Biol. Chem. 286:41758-41766(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SWSAP1 AND ZSWIM7.
[15]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"The RAD51 paralogs ensure cellular protection against mitotic defects and aneuploidy."
Rodrigue A., Coulombe Y., Jacquet K., Gagne J.P., Roques C., Gobeil S., Poirier G., Masson J.Y.
J. Cell Sci. 126:348-359(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN HOLLIDAY JUNCTION RESOLUTION.
[17]"Rad51 paralog complexes BCDX2 and CX3 act at different stages in the BRCA1-BRCA2-dependent homologous recombination pathway."
Chun J., Buechelmaier E.S., Powell S.N.
Mol. Cell. Biol. 33:387-395(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION OF THE CX3 COMPLEX.
[18]"Breast cancer-associated missense mutants of the PALB2 WD40 domain, which directly binds RAD51C, RAD51 and BRCA2, disrupt DNA repair."
Park J.Y., Singh T.R., Nassar N., Zhang F., Freund M., Hanenberg H., Meetei A.R., Andreassen P.R.
Oncogene 0:0-0(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PALB2, IDENTIFICATION IN A PALB2-CONTAINING HR COMPLEX.
[19]"Ring-shaped Rad51 paralog protein complexes bind Holliday junctions and replication forks as visualized by electron microscopy."
Compton S.A., Ozgur S., Griffith J.D.
J. Biol. Chem. 285:13349-13356(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ELECTRON MICROSCOPY OF THE CX3 COMPLEX, DNA-BINDING OF THE CX3 COMPLEX.
[20]"A variant within the DNA repair gene XRCC3 is associated with the development of melanoma skin cancer."
Winsey S.L., Haldar N.A., Marsh H.P., Bunce M., Marshall S.E., Harris A.L., Wojnarowska F., Welsh K.I.
Cancer Res. 60:5612-5616(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CMM6 SUSCEPTIBILITY MET-241.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF035586 mRNA. Translation: AAC05368.1.
AF037222 Genomic DNA. Translation: AAC04805.1.
AF508041 Genomic DNA. Translation: AAM23015.1.
BC001036 mRNA. Translation: AAH01036.1.
BC002949 mRNA. Translation: AAH02949.1.
BC011725 mRNA. Translation: AAH11725.1.
RefSeqNP_001093588.1. NM_001100118.1.
NP_001093589.1. NM_001100119.1.
NP_005423.1. NM_005432.3.
XP_005268103.1. XM_005268046.1.
UniGeneHs.592325.
Hs.733412.

3D structure databases

ProteinModelPortalO43542.
SMRO43542. Positions 4-338.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113351. 7 interactions.
DIPDIP-42016N.
IntActO43542. 4 interactions.
MINTMINT-204782.
STRING9606.ENSP00000343392.

PTM databases

PhosphoSiteO43542.

Proteomic databases

PaxDbO43542.
PRIDEO43542.

Protocols and materials databases

DNASU7517.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000352127; ENSP00000343392; ENSG00000126215.
ENST00000445556; ENSP00000412990; ENSG00000126215.
ENST00000553264; ENSP00000451974; ENSG00000126215.
ENST00000554913; ENSP00000451362; ENSG00000126215.
ENST00000555055; ENSP00000452598; ENSG00000126215.
GeneID7517.
KEGGhsa:7517.
UCSCuc001ynx.4. human.

Organism-specific databases

CTD7517.
GeneCardsGC14M104163.
HGNCHGNC:12830. XRCC3.
MIM114480. phenotype.
600675. gene.
613972. phenotype.
neXtProtNX_O43542.
PharmGKBPA37422.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0468.
HOGENOMHOG000239162.
HOVERGENHBG054179.
InParanoidO43542.
KOK10880.
OMAINQVTEA.
OrthoDBEOG73JKWZ.
PhylomeDBO43542.
TreeFamTF101203.

Gene expression databases

ArrayExpressO43542.
BgeeO43542.
CleanExHS_XRCC3.
GenevestigatorO43542.

Family and domain databases

Gene3D3.40.50.300. 1 hit.
InterProIPR013632. DNA_recomb/repair_Rad51_C.
IPR016467. DNA_recomb/repair_RecA-like.
IPR027417. P-loop_NTPase.
IPR020588. RecA_ATP-bd.
[Graphical view]
PfamPF08423. Rad51. 1 hit.
[Graphical view]
PIRSFPIRSF005856. Rad51. 1 hit.
SUPFAMSSF52540. SSF52540. 1 hit.
PROSITEPS50162. RECA_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiXRCC3.
GenomeRNAi7517.
NextBio29415.
PROO43542.
SOURCESearch...

Entry information

Entry nameXRCC3_HUMAN
AccessionPrimary (citable) accession number: O43542
Secondary accession number(s): O43568, Q9BU18
Entry history
Integrated into UniProtKB/Swiss-Prot: April 3, 2002
Last sequence update: June 1, 1998
Last modified: April 16, 2014
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM