O43542 (XRCC3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA repair protein XRCC3

Alternative name(s):
X-ray repair cross-complementing protein 3

Gene names

Name:

XRCC3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	346 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51 and RAD51C. Ref.9
Subunit structure	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. Ref.5 Ref.6 Ref.11
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. Ref.7 Ref.9
Induction	Stress-induced increase in the mitochondrial levels is seen. Ref.9
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.4 Cutaneous malignant melanoma 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.12
Sequence similarities	Belongs to the RecA family. RAD51 subfamily.

Ontologies

Keywords
Biological process	DNA damage DNA recombination DNA repair
Cellular component	Cytoplasm Mitochondrion Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Ligand	ATP-binding DNA-binding Nucleotide-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA recombination Traceable author statement Ref.1. Source: ProtInc DNA repair Inferred from genetic interaction PubMed 10422536. Source: BHF-UCL response to organic substance Inferred from electronic annotation. Source: Compara
Cellular_component	mitochondrion Inferred from direct assay Ref.9. Source: UniProtKB nucleus Inferred from direct assay Ref.7. Source: UniProtKB perinuclear region of cytoplasm Inferred from direct assay Ref.7. Source: UniProtKB
Molecular_function	ATP 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
SWSAP1	Q6NVH7	2	EBI-2849976,EBI-5281637

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 346	346	DNA repair protein XRCC3		PRO_0000122951
Regions
	Nucleotide binding	107 – 114	8	ATP Potential
Natural variations
	Natural variant	94	1	R → H. Ref.2 Corresponds to variant rs3212057 [ dbSNP | Ensembl ].		VAR_020405
	Natural variant	241	1	T → M in CMM6 susceptibility; associated with cutaneous malignant melanoma. Ref.1 Ref.2 Ref.12 Corresponds to variant rs861539 [ dbSNP | Ensembl ].		VAR_013006
	Natural variant	271	1	G → R. Corresponds to variant rs28903080 [ dbSNP | Ensembl ].		VAR_029295
	Natural variant	302	1	R → H. Corresponds to variant rs28903081 [ dbSNP | Ensembl ].		VAR_029296

Sequences

	Sequence		Length	Mass (Da)
	O43542 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: 4DDF3B163C3B3332	FASTA	346	37,850
	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

References

	« Hide 'large scale' referencesShow '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]	"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.
[5]	"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 A COMPLEX WITH RAD51B; RAD51C; RAD51D AND XRCC3.
[6]	"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.
[7]	"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.
[8]	"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.
[9]	"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.
[10]	"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].
[11]	"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.
[12]	"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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

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.
IPI	IPI00023073.
RefSeq	NP_001093588.1. NM_001100118.1. NP_001093589.1. NM_001100119.1. NP_005423.1. NM_005432.3.
UniGene	Hs.592325. Hs.733412.
3D structure databases
ProteinModelPortal	O43542.
ModBase	Search...
Protein-protein interaction databases
IntAct	O43542. 4 interactions.
STRING	9606.ENSP00000343392.
PTM databases
PhosphoSite	O43542.
Proteomic databases
PaxDb	O43542.
PRIDE	O43542.
Protocols and materials databases
DNASU	7517.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000352127; ENSP00000343392; ENSG00000126215. ENST00000445556; ENSP00000412990; ENSG00000126215. ENST00000553264; ENSP00000451974; ENSG00000126215. ENST00000554913; ENSP00000451362; ENSG00000126215. ENST00000555055; ENSP00000452598; ENSG00000126215.
GeneID	7517.
KEGG	hsa:7517.
UCSC	uc001ynx.4. human.
Organism-specific databases
CTD	7517.
GeneCards	GC14M104163.
HGNC	HGNC:12830. XRCC3.
MIM	114480. phenotype. 600675. gene. 613972. phenotype.
neXtProt	NX_O43542.
PharmGKB	PA37422.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0468.
HOGENOM	HOG000239162.
HOVERGEN	HBG054179.
InParanoid	O43542.
KO	K10880.
OMA	INQVTEA.
OrthoDB	EOG47D9GS.
PhylomeDB	O43542.
Gene expression databases
ArrayExpress	O43542.
Bgee	O43542.
CleanEx	HS_XRCC3.
Genevestigator	O43542.
GermOnline	ENSG00000126215. Homo sapiens.
Family and domain databases
InterPro	IPR013632. DNA_recomb/repair_Rad51_C. IPR016467. DNA_recomb/repair_RecA-like. IPR020588. DNA_recomb_RecA/RadB_ATP-bd. [Graphical view]
Pfam	PF08423. Rad51. 1 hit. [Graphical view]
PIRSF	PIRSF005856. Rad51. 1 hit.
PROSITE	PS50162. RECA_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	7517.
NextBio	29415.
SOURCE	Search...

Entry information

Entry name

XRCC3_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 114 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.