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O43542

- XRCC3_HUMAN

UniProt

O43542 - XRCC3_HUMAN

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Protein

DNA repair protein XRCC3

Gene

XRCC3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.4 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi107 – 1148ATPSequence Analysis

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. DNA binding Source: UniProtKB-KW
  3. DNA-dependent ATPase activity Source: InterPro

GO - Biological processi

  1. cellular response to DNA damage stimulus Source: ProtInc
  2. DNA catabolic process, endonucleolytic Source: GOC
  3. DNA recombination Source: ProtInc
  4. DNA repair Source: BHF-UCL
  5. double-strand break repair via homologous recombination Source: UniProtKB
  6. positive regulation of mitotic cell cycle spindle assembly checkpoint Source: UniProtKB
  7. regulation of centrosome duplication Source: UniProtKB
  8. resolution of mitotic recombination intermediates Source: UniProtKB
  9. response to organic substance Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

DNA damage, DNA recombination, DNA repair

Keywords - Ligandi

ATP-binding, DNA-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
DNA repair protein XRCC3
Alternative name(s):
X-ray repair cross-complementing protein 3
Gene namesi
Name:XRCC3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 14

Organism-specific databases

HGNCiHGNC:12830. XRCC3.

Subcellular locationi

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.

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. mitochondrion Source: UniProtKB
  3. nucleus Source: UniProtKB
  4. perinuclear region of cytoplasm Source: UniProtKB
  5. Rad51C-XRCC3 complex Source: UniProtKB
  6. replication fork Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Nucleus

Pathology & Biotechi

Involvement in diseasei

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.1 Publication
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
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.1 Publication
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti241 – 2411T → M in CMM6 susceptibility; associated with cutaneous malignant melanoma. 3 Publications
Corresponds to variant rs861539 [ dbSNP | Ensembl ].
VAR_013006

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi114480. phenotype.
613972. phenotype.
PharmGKBiPA37422.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 346346DNA repair protein XRCC3PRO_0000122951Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionine1 Publication

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiO43542.
PaxDbiO43542.
PRIDEiO43542.

PTM databases

PhosphoSiteiO43542.

Expressioni

Inductioni

Stress-induced increase in the mitochondrial levels is seen.1 Publication

Gene expression databases

BgeeiO43542.
CleanExiHS_XRCC3.
ExpressionAtlasiO43542. baseline and differential.
GenevestigatoriO43542.

Interactioni

Subunit structurei

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 XRCC3.6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PALB2Q86YC23EBI-2849976,EBI-1222653
RAD51Q066093EBI-2849976,EBI-297202
RAD51CO435027EBI-2849976,EBI-2267048
SWSAP1Q6NVH72EBI-2849976,EBI-5281637

Protein-protein interaction databases

BioGridi113351. 12 interactions.
DIPiDIP-42016N.
IntActiO43542. 8 interactions.
MINTiMINT-204782.
STRINGi9606.ENSP00000343392.

Structurei

3D structure databases

ProteinModelPortaliO43542.
SMRiO43542. Positions 4-338.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the RecA family. RAD51 subfamily.Curated

Phylogenomic databases

eggNOGiCOG0468.
HOGENOMiHOG000239162.
HOVERGENiHBG054179.
InParanoidiO43542.
KOiK10880.
OMAiLLMRLMV.
OrthoDBiEOG73JKWZ.
PhylomeDBiO43542.
TreeFamiTF101203.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR013632. DNA_recomb/repair_Rad51_C.
IPR016467. DNA_recomb/repair_RecA-like.
IPR027417. P-loop_NTPase.
IPR020588. RecA_ATP-bd.
[Graphical view]
PfamiPF08423. Rad51. 1 hit.
[Graphical view]
PIRSFiPIRSF005856. Rad51. 1 hit.
SUPFAMiSSF52540. SSF52540. 1 hit.
PROSITEiPS50162. RECA_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O43542-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MDLDLLDLNP RIIAAIKKAK LKSVKEVLHF SGPDLKRLTN LSSPEVWHLL
60 70 80 90 100
RTASLHLRGS SILTALQLHQ QKERFPTQHQ RLSLGCPVLD ALLRGGLPLD
110 120 130 140 150
GITELAGRSS AGKTQLALQL CLAVQFPRQH GGLEAGAVYI CTEDAFPHKR
160 170 180 190 200
LQQLMAQQPR LRTDVPGELL QKLRFGSQIF IEHVADVDTL LECVNKKVPV
210 220 230 240 250
LLSRGMARLV VIDSVAAPFR CEFDSQASAP RARHLQSLGA TLRELSSAFQ
260 270 280 290 300
SPVLCINQVT EAMEEQGAAH GPLGFWDERV SPALGITWAN QLLVRLLADR
310 320 330 340
LREEEAALGC PARTLRVLSA PHLPPSSCSY TISAEGVRGT PGTQSH
Length:346
Mass (Da):37,850
Last modified:June 1, 1998 - v1
Checksum:i4DDF3B163C3B3332
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti94 – 941R → H.1 Publication
Corresponds to variant rs3212057 [ dbSNP | Ensembl ].
VAR_020405
Natural varianti241 – 2411T → M in CMM6 susceptibility; associated with cutaneous malignant melanoma. 3 Publications
Corresponds to variant rs861539 [ dbSNP | Ensembl ].
VAR_013006
Natural varianti271 – 2711G → R.
Corresponds to variant rs28903080 [ dbSNP | Ensembl ].
VAR_029295
Natural varianti302 – 3021R → H.
Corresponds to variant rs28903081 [ dbSNP | Ensembl ].
VAR_029296

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS9984.1.
RefSeqiNP_001093588.1. NM_001100118.1.
NP_001093589.1. NM_001100119.1.
NP_005423.1. NM_005432.3.
XP_005268103.1. XM_005268046.1.
UniGeneiHs.592325.
Hs.733412.

Genome annotation databases

EnsembliENST00000352127; ENSP00000343392; ENSG00000126215.
ENST00000553264; ENSP00000451974; ENSG00000126215.
ENST00000554913; ENSP00000451362; ENSG00000126215.
ENST00000555055; ENSP00000452598; ENSG00000126215.
GeneIDi7517.
KEGGihsa:7517.
UCSCiuc001ynx.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS9984.1.
RefSeqi NP_001093588.1. NM_001100118.1.
NP_001093589.1. NM_001100119.1.
NP_005423.1. NM_005432.3.
XP_005268103.1. XM_005268046.1.
UniGenei Hs.592325.
Hs.733412.

3D structure databases

ProteinModelPortali O43542.
SMRi O43542. Positions 4-338.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 113351. 12 interactions.
DIPi DIP-42016N.
IntActi O43542. 8 interactions.
MINTi MINT-204782.
STRINGi 9606.ENSP00000343392.

PTM databases

PhosphoSitei O43542.

Proteomic databases

MaxQBi O43542.
PaxDbi O43542.
PRIDEi O43542.

Protocols and materials databases

DNASUi 7517.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000352127 ; ENSP00000343392 ; ENSG00000126215 .
ENST00000553264 ; ENSP00000451974 ; ENSG00000126215 .
ENST00000554913 ; ENSP00000451362 ; ENSG00000126215 .
ENST00000555055 ; ENSP00000452598 ; ENSG00000126215 .
GeneIDi 7517.
KEGGi hsa:7517.
UCSCi uc001ynx.4. human.

Organism-specific databases

CTDi 7517.
GeneCardsi GC14M104163.
HGNCi HGNC:12830. XRCC3.
MIMi 114480. phenotype.
600675. gene.
613972. phenotype.
neXtProti NX_O43542.
PharmGKBi PA37422.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0468.
HOGENOMi HOG000239162.
HOVERGENi HBG054179.
InParanoidi O43542.
KOi K10880.
OMAi LLMRLMV.
OrthoDBi EOG73JKWZ.
PhylomeDBi O43542.
TreeFami TF101203.

Miscellaneous databases

GeneWikii XRCC3.
GenomeRNAii 7517.
NextBioi 29415.
PROi O43542.
SOURCEi Search...

Gene expression databases

Bgeei O43542.
CleanExi HS_XRCC3.
ExpressionAtlasi O43542. baseline and differential.
Genevestigatori O43542.

Family and domain databases

Gene3Di 3.40.50.300. 1 hit.
InterProi IPR013632. DNA_recomb/repair_Rad51_C.
IPR016467. DNA_recomb/repair_RecA-like.
IPR027417. P-loop_NTPase.
IPR020588. RecA_ATP-bd.
[Graphical view ]
Pfami PF08423. Rad51. 1 hit.
[Graphical view ]
PIRSFi PIRSF005856. Rad51. 1 hit.
SUPFAMi SSF52540. SSF52540. 1 hit.
PROSITEi PS50162. RECA_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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. 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. 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.

Entry informationi

Entry nameiXRCC3_HUMAN
AccessioniPrimary (citable) accession number: O43542
Secondary accession number(s): O43568, Q9BU18
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 3, 2002
Last sequence update: June 1, 1998
Last modified: October 29, 2014
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3