P23475 (XRCC6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	608 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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. 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 process	DNA damage DNA recombination DNA repair Transcription Transcription regulation
Cellular component	Chromosome Nucleus
Ligand	ATP-binding DNA-binding Nucleotide-binding
Molecular function	Activator Helicase Hydrolase Lyase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	V(D)J recombination Inferred from mutant phenotype PubMed 10716994. Source: MGI double-strand break repair via nonhomologous end joining Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of transcription, DNA-dependent 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: Compara response to ionizing radiation Inferred from mutant phenotype PubMed 15979950. Source: MGI telomere maintenance Inferred from electronic annotation. Source: InterPro transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	Ku70: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 transcription factor complex Inferred from electronic annotation. Source: Compara
Molecular_function	5'-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: Compara transcription regulatory region DNA binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 608	607	X-ray repair cross-complementing protein 6		PRO_0000210180
Regions
	Domain	259 – 466	208	Ku
	Domain	571 – 605	35	SAP
	Compositional bias	11 – 27	17	Asp/Glu-rich (acidic)
	Compositional bias	328 – 340	13	Asp/Glu-rich (acidic)
Sites
	Active site	29	1	Schiff-base intermediate with DNA; for 5'-deoxyribose-5-phosphate lyase activity By similarity
Amino acid modifications
	Modified residue	6	1	Phosphoserine; by PRKDC By similarity
	Modified residue	29	1	N6-acetyllysine By similarity
	Modified residue	49	1	Phosphoserine; by PRKDC By similarity
	Modified residue	329	1	N6-acetyllysine By similarity
	Modified residue	336	1	N6-acetyllysine By similarity
	Modified residue	459	1	N6-acetyllysine By similarity
	Modified residue	475	1	Phosphoserine By similarity
	Modified residue	518	1	Phosphoserine By similarity
	Modified residue	548	1	Phosphoserine By similarity
Experimental info
	Sequence conflict	225	1	E → G in BAE27139. Ref.4
	Sequence conflict	225	1	E → G in BAE27137. Ref.4
	Sequence conflict	225	1	E → G in BAE27135. Ref.4
	Sequence conflict	391	1	K → E in BAE25441. Ref.3
	Sequence conflict	391	1	K → E in AAL90775. Ref.3
	Sequence conflict	391	1	K → E in AAL90774. Ref.3
	Sequence conflict	400	1	P → H in AAA39396. Ref.7
	Sequence conflict	466 – 467	2	KL → NV in AAC52675. Ref.1
	Sequence conflict	466 – 467	2	KL → NV in AAA39396. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	P23475 [UniParc]. Last modified February 5, 2008. Version 5. Checksum: 1C27DBF1DB7A1154	FASTA	608	69,484
	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

References

	« Hide 'large scale' referencesShow '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. , 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 , 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.
IPI	IPI00132424.
PIR	A43534. S25149.
RefSeq	NP_034377.2. NM_010247.2.
UniGene	Mm.288809.
3D structure databases
ProteinModelPortal	P23475.
SMR	P23475. Positions 32-606.
ModBase	Search...
Protein-protein interaction databases
IntAct	P23475. 2 interactions.
MINT	MINT-2568472.
PTM databases
PhosphoSite	P23475.
Proteomic databases
PaxDb	P23475.
PRIDE	P23475.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000069530; ENSMUSP00000068559; ENSMUSG00000022471. ENSMUST00000100399; ENSMUSP00000097968; ENSMUSG00000022471.
GeneID	14375.
KEGG	mmu:14375.
UCSC	uc007wxy.1. mouse.
Organism-specific databases
CTD	2547.
MGI	MGI:95606. Xrcc6.
Phylogenomic databases
eggNOG	NOG305318.
GeneTree	ENSGT00390000001422.
HOVERGEN	HBG006236.
InParanoid	P23475.
KO	K10884.
OrthoDB	EOG451DQB.
Gene expression databases
ArrayExpress	P23475.
Bgee	P23475.
Genevestigator	P23475.
GermOnline	ENSMUSG00000022471. Mus musculus.
Family and domain databases
Gene3D	1.10.1600.10. 1 hit. 1.10.720.30. 1 hit. 2.40.290.10. 1 hit.
InterPro	IPR006165. Ku70. IPR006164. Ku70/Ku80_beta-barrel_dom. IPR005160. Ku_C. IPR005161. Ku_N. IPR003034. SAP_dom. IPR016194. SPOC_like_C_dom. IPR002035. VWF_A. [Graphical view]
PANTHER	PTHR12604:SF2. PTHR12604:SF2. 1 hit.
Pfam	PF02735. Ku. 1 hit. PF03730. Ku_C. 1 hit. PF03731. Ku_N. 1 hit. PF02037. SAP. 1 hit. [Graphical view]
PIRSF	PIRSF003033. Ku70. 1 hit.
SMART	SM00559. Ku78. 1 hit. SM00513. SAP. 1 hit. SM00327. VWA. 1 hit. [Graphical view]
SUPFAM	SSF100939. SPOC-like. 1 hit.
TIGRFAMs	TIGR00578. ku70. 1 hit.
PROSITE	PS50800. SAP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	285869.
SOURCE	Search...

Entry information

Entry name

XRCC6_MOUSE

Accession

Primary (citable) accession number: P23475
Secondary accession number(s): O88212 , Q3UJL8, Q62027, Q62382, Q62453, Q6GTV8, Q8QZX7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1991
Last sequence update:	February 5, 2008
Last modified:	May 1, 2013
This is version 126 of the entry and version 5 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program