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P23475 (XRCC6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
X-ray repair cross-complementing protein 6

EC=3.6.4.-
EC=4.2.99.-
Alternative name(s):
5'-deoxyribose-5-phosphate lyase Ku70
Short name=5'-dRP/AP lyase Ku70
ATP-dependent DNA helicase 2 subunit 1
ATP-dependent DNA helicase II 70 kDa subunit
CTC box-binding factor 75 kDa subunit
Short name=CTC75
Short name=CTCBF
DNA repair protein XRCC6
Ku autoantigen protein p70 homolog
Short name=Ku70
Gene names
Name:Xrcc6
Synonyms:G22p1, Ku70
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length608 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Single-stranded DNA-dependent ATP-dependent helicase. Has a role in chromosome translocation. The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner. It works in the 3'-5' direction. Binding to DNA may be mediated by XRCC6. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination. The XRCC5/6 dimer acts as regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold. The XRCC5/6 dimer is probably involved in stabilizing broken DNA ends and bringing them together. The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step. Required for osteocalcin gene expression. Probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks. 5'-dRP lyase activity allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined. The XRCC5/6 dimer together with APEX1 acts as a negative regulator of transcription. Ref.9

Subunit structure

Heterodimer of a 70 kDa (XRCC6) and a 80 kDa (XRCC5) subunit. The dimer associates in a DNA-dependent manner with PRKDC to form the DNA-dependent protein kinase complex DNA-PK, and with the LIG4-XRCC4 complex. The dimer also associates with NAA15, and this complex binds to the osteocalcin promoter and activates osteocalcin expression. In addition, XRCC6 interacts with the osteoblast-specific transcription factors MSX2, RUNX2 and DLX5. Interacts with ELF3. Interacts with XRCC6BP1. The XRCC5/6 dimer associates in a DNA-dependent manner with APEX1. Binds to CDK9 By similarity. Identified in a complex with DEAF1 and XRCC5. Interacts with DEAF1 (via the SAND domain); the interaction is direct and may be inhibited by DNA-binding By similarity. Interacts with CLU. Ref.10

Subcellular location

Nucleus. Chromosome.

Developmental stage

Expression increases during promyelocyte differentiation. Ref.8

Post-translational modification

Phosphorylation by PRKDC may enhance helicase activity. Phosphorylation of Ser-49 does not affect DNA repair By similarity.

Miscellaneous

In osteoblasts from XRCC6 knockout mice, osteocalcin gene expression is nearly abolished.

Sequence similarities

Belongs to the ku70 family.

Contains 1 Ku domain.

Contains 1 SAP domain.

Ontologies

Keywords
   Biological processDNA damage
DNA recombination
DNA repair
Transcription
Transcription regulation
   Cellular componentChromosome
Nucleus
   LigandATP-binding
DNA-binding
Nucleotide-binding
   Molecular functionActivator
Helicase
Hydrolase
Lyase
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Multifunctional enzyme
Reference proteome
Gene Ontology (GO)
   Biological_processV(D)J recombination

Inferred from mutant phenotype PubMed 10716994. Source: MGI

brain development

Inferred from electronic annotation. Source: Ensembl

cellular hyperosmotic salinity response

Inferred from electronic annotation. Source: Ensembl

cellular response to DNA damage stimulus

Inferred from mutant phenotype PubMed 15979950. Source: MGI

cellular response to X-ray

Inferred from electronic annotation. Source: Ensembl

double-strand break repair

Inferred from mutant phenotype PubMed 11751629. Source: MGI

double-strand break repair via nonhomologous end joining

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of neurogenesis

Inferred from mutant phenotype PubMed 10716994. Source: MGI

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

response to ionizing radiation

Inferred from mutant phenotype PubMed 15979950. Source: MGI

telomere maintenance

Inferred from electronic annotation. Source: InterPro

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentKu70:Ku80 complex

Inferred from sequence or structural similarity. Source: UniProtKB

chromosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from direct assay PubMed 12604618. Source: MGI

nonhomologous end joining complex

Inferred from sequence or structural similarity. Source: UniProtKB

nucleolus

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay PubMed 12604618. Source: MGI

transcription factor complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_function5'-deoxyribose-5-phosphate lyase activity

Inferred from sequence or structural similarity. Source: UniProtKB

ATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

ATP-dependent DNA helicase activity

Inferred from electronic annotation. Source: InterPro

damaged DNA binding

Inferred from electronic annotation. Source: InterPro

double-stranded telomeric DNA binding

Inferred from electronic annotation. Source: Ensembl

transcription regulatory region DNA binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 608607X-ray repair cross-complementing protein 6
PRO_0000210180

Regions

Domain259 – 466208Ku
Domain571 – 60535SAP
Region548 – 60760Interaction with DEAF1 By similarity
Compositional bias11 – 2717Asp/Glu-rich (acidic)
Compositional bias328 – 34013Asp/Glu-rich (acidic)

Sites

Active site291Schiff-base intermediate with DNA; for 5'-deoxyribose-5-phosphate lyase activity By similarity

Amino acid modifications

Modified residue21N-acetylserine By similarity
Modified residue61Phosphoserine; by PRKDC By similarity
Modified residue291N6-acetyllysine By similarity
Modified residue491Phosphoserine; by PRKDC By similarity
Modified residue3291N6-acetyllysine By similarity
Modified residue3361N6-acetyllysine By similarity
Modified residue4591N6-acetyllysine By similarity
Modified residue4751Phosphoserine By similarity
Modified residue5181Phosphoserine By similarity
Modified residue5481Phosphoserine By similarity

Experimental info

Sequence conflict2251E → G in BAE27139. Ref.4
Sequence conflict2251E → G in BAE27137. Ref.4
Sequence conflict2251E → G in BAE27135. Ref.4
Sequence conflict3911K → E in BAE25441. Ref.3
Sequence conflict3911K → E in AAL90775. Ref.3
Sequence conflict3911K → E in AAL90774. Ref.3
Sequence conflict4001P → H in AAA39396. Ref.7
Sequence conflict466 – 4672KL → NV in AAC52675. Ref.1
Sequence conflict466 – 4672KL → NV in AAA39396. Ref.7

Sequences

Sequence LengthMass (Da)Tools
P23475 [UniParc].

Last modified February 5, 2008. Version 5.
Checksum: 1C27DBF1DB7A1154

FASTA60869,484
        10         20         30         40         50         60 
MSEWESYYKT EGEEEEEEEE SPDTGGEYKY SGRDSLIFLV DASRAMFESQ GEDELTPFDM 

        70         80         90        100        110        120 
SIQCIQSVYT SKIISSDRDL LAVVFYGTEK DKNSVNFKNI YVLQDLDNPG AKRVLELDQF 

       130        140        150        160        170        180 
KGQQGKKHFR DTVGHGSDYS LSEVLWVCAN LFSDVQLKMS HKRIMLFTNE DDPHGRDSAK 

       190        200        210        220        230        240 
ASRARTKASD LRDTGIFLDL MHLKKPGGFD VSVFYRDIIT TAEDEDLGVH FEESSKLEDL 

       250        260        270        280        290        300 
LRKVRAKETK KRVLSRLKFK LGEDVVLMVG IYNLVQKANK PFPVRLYRET NEPVKTKTRT 

       310        320        330        340        350        360 
FNVNTGSLLL PSDTKRSLTY GTRQIVLEKE ETEELKRFDE PGLILMGFKP TVMLKKQHYL 

       370        380        390        400        410        420 
RPSLFVYPEE SLVSGSSTLF SALLTKCVEK KVIAVCRYTP RKNVSPYFVA LVPQEEELDD 

       430        440        450        460        470        480 
QNIQVTPGGF QLVFLPYADD KRKVPFTEKV TANQEQIDKM KAIVQKLRFT YRSDSFENPV 

       490        500        510        520        530        540 
LQQHFRNLEA LALDMMESEQ VVDLTLPKVE AIKKRLGSLA DEFKELVYPP GYNPEGKVAK 

       550        560        570        580        590        600 
RKQDDEGSTS KKPKVELSEE ELKAHFRKGT LGKLTVPTLK DICKAHGLKS GPKKQELLDA 


LIRHLEKN 

« Hide

References

« Hide 'large scale' references
[1]"Genomic structure and chromosomal assignment of the mouse Ku70 gene."
Takiguchi Y., Kurimasa A., Chen F., Pardington P.E., Kuriyama T., Okinaka R.T., Moyzis R., Chen D.J.
Genomics 35:129-135(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: 129.
[2]"Murine cell line SX9 bearing a mutation in the DNA-PKcs gene exhibits aberrant V(D)J recombination not only in the coding joint but also in the signal joint."
Fukumura R., Araki R., Fujimori A., Mori M., Saito T., Watanabe F., Sarashi M., Itsukaichi H., Eguch-Kasai K., Sato K., Tatsumi K., Abe M.
J. Biol. Chem. 273:13058-13064(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Mammary carcinoma.
[3]"High-throughput sequence identification of gene coding variants within alcohol-related QTLs."
Ehringer M.A., Thompson J., Conroy O., Xu Y., Yang F., Canniff J., Beeson M., Gordon L., Bennett B., Johnson T.E., Sikela J.M.
Mamm. Genome 12:657-663(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: ILS and ISS.
[4]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J and DBA/2.
Tissue: Spleen.
[5]"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: Mammary tumor.
[6]"Nucleotide sequence of the 5' region of the murine p70 Ku autoantigen cDNA."
Baughman G.A., Nemeth J.E., Bourgeois S.
Submitted (AUG-1992) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-46.
Strain: BALB/c.
Tissue: Thymus.
[7]"Antigenic determinants of the Ku (p70/p80) autoantigen are poorly conserved between species."
Porges A.J., Ng T., Reeves W.H.
J. Immunol. 145:4222-4228(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 18-608.
[8]"Non-histone protein 1 (NHP1) is a member of the Ku protein family which is upregulated in differentiating mouse myoblasts and human promyelocytes."
Oderwald H., Hughes M.J., Jost J.-P.
FEBS Lett. 382:313-318(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: DEVELOPMENTAL STAGE.
[9]"Regulation of osteocalcin gene expression by a novel Ku antigen transcription factor complex."
Willis D.M., Loewy A.P., Charlton-Kachigian N., Shao J.-S., Ornitz D.M., Towler D.A.
J. Biol. Chem. 277:37280-37291(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
Tissue: Osteoblast.
[10]"Synthesis and functional analyses of nuclear clusterin, a cell death protein."
Leskov K.S., Klokov D.Y., Li J., Kinsella T.J., Boothman D.A.
J. Biol. Chem. 278:11590-11600(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CLU.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U50378 expand/collapse EMBL AC list , U50367, U50368, U50369, U50370, U50371, U50372, U50373, U50374, U50375, U50376, U50377 Genomic DNA. Translation: AAC52675.1.
U34878 Genomic DNA. Translation: AAC53575.1.
AB010282 mRNA. Translation: BAA28874.1.
AF483500 mRNA. Translation: AAL90774.1.
AF483501 mRNA. Translation: AAL90775.1.
AK143570 mRNA. Translation: BAE25441.1.
AK146392 mRNA. Translation: BAE27135.1.
AK146394 mRNA. Translation: BAE27137.1.
AK146396 mRNA. Translation: BAE27139.1.
BC031422 mRNA. Translation: AAH31422.1.
Z14157 mRNA. Translation: CAA78526.1.
M38700 mRNA. Translation: AAA39396.1.
PIRA43534.
S25149.
RefSeqNP_034377.2. NM_010247.2.
XP_006520503.1. XM_006520440.1.
XP_006520504.1. XM_006520441.1.
XP_006520505.1. XM_006520442.1.
XP_006520506.1. XM_006520443.1.
UniGeneMm.288809.

3D structure databases

ProteinModelPortalP23475.
SMRP23475. Positions 32-606.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199785. 4 interactions.
IntActP23475. 4 interactions.
MINTMINT-2568472.

PTM databases

PhosphoSiteP23475.

Proteomic databases

PaxDbP23475.
PRIDEP23475.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000069530; ENSMUSP00000068559; ENSMUSG00000022471.
ENSMUST00000100399; ENSMUSP00000097968; ENSMUSG00000022471.
GeneID14375.
KEGGmmu:14375.
UCSCuc007wxy.1. mouse.

Organism-specific databases

CTD2547.
MGIMGI:95606. Xrcc6.

Phylogenomic databases

eggNOGNOG305318.
GeneTreeENSGT00390000001422.
HOVERGENHBG006236.
InParanoidP23475.
KOK10884.
OrthoDBEOG7QG43F.
TreeFamTF315101.

Gene expression databases

ArrayExpressP23475.
BgeeP23475.
GenevestigatorP23475.

Family and domain databases

Gene3D1.10.1600.10. 1 hit.
1.10.720.30. 1 hit.
2.40.290.10. 1 hit.
3.40.50.410. 1 hit.
4.10.970.10. 1 hit.
InterProIPR006165. Ku70.
IPR006164. Ku70/Ku80_beta-barrel_dom.
IPR027388. Ku70_bridge/pillars_dom.
IPR005160. Ku_C.
IPR005161. Ku_N.
IPR003034. SAP_dom.
IPR016194. SPOC_like_C_dom.
IPR002035. VWF_A.
[Graphical view]
PANTHERPTHR12604:SF2. PTHR12604:SF2. 1 hit.
PfamPF02735. Ku. 1 hit.
PF03730. Ku_C. 1 hit.
PF03731. Ku_N. 1 hit.
PF02037. SAP. 1 hit.
[Graphical view]
PIRSFPIRSF003033. Ku70. 1 hit.
SMARTSM00559. Ku78. 1 hit.
SM00513. SAP. 1 hit.
SM00327. VWA. 1 hit.
[Graphical view]
SUPFAMSSF100939. SSF100939. 1 hit.
SSF53300. SSF53300. 1 hit.
TIGRFAMsTIGR00578. ku70. 1 hit.
PROSITEPS50800. SAP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio285869.
PROP23475.
SOURCESearch...

Entry information

Entry nameXRCC6_MOUSE
AccessionPrimary (citable) accession number: P23475
Secondary accession number(s): O88212 expand/collapse secondary AC list , Q3UJL8, Q62027, Q62382, Q62453, Q6GTV8, Q8QZX7
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: February 5, 2008
Last modified: April 16, 2014
This is version 135 of the entry and version 5 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot