P27641 (XRCC5_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
X-ray repair cross-complementing protein 5
EC=3.6.4.-

Alternative name(s):
ATP-dependent DNA helicase 2 subunit 2
ATP-dependent DNA helicase II 80 kDa subunit
CTC box-binding factor 85 kDa subunit
Short name=CTC85
Short name=CTCBF
DNA repair protein XRCC5
Ku autoantigen protein p86 homolog
Ku80
Nuclear factor IV

Gene names

Name:	Xrcc5
Synonyms:	G22p2

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	732 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript 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. In association with NAA15, the XRCC5/6 dimer binds to the osteocalcin promoter and activates osteocalcin expression. expression. The XRCC5/6 dimer 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. XRCC5 probably acts as the catalytic subunit of 5'-dRP activity, and 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 By similarity.
Subunit structure	Heterodimer of a 70 kDa and a 80 kDa 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 displays DNA binding activity towards the osteocalcin FGF response element (OCFRE). In addition, the 80 kDa subunit binds to the osteoblast-specific transcription factors MSX2 and RUNX2. Interacts with ELF3. May interact with APLF. The XRCC5/6 dimer associates in a DNA-dependent manner with APEX1 By similarity.
Subcellular location	Nucleus. Nucleus › nucleolus By similarity. Chromosome.
Developmental stage	Expression increases during promyelocyte differentiation. Ref.5
Induction	Up-regulation during myogenesis is inhibited by cAMP, 3-aminobenzamide and sodium butyrate. Expression in myoblasts is unaffected by X-rays and UV light. Ref.5
Domain	The EEXXXDDL motif is required for the interaction with catalytic subunit PRKDC and its recruitment to sites of DNA damage By similarity.
Post-translational modification	Phosphorylated on serine residues. Phosphorylation by PRKDC may enhance helicase activity By similarity. Sumoylated By similarity. Ubiquitinated by RNF8 via 'Lys-48'-linked ubiquitination following DNA damage, leading to its degradation and removal from DNA damage sites By similarity.
Sequence similarities	Belongs to the ku80 family. Contains 1 Ku 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
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA recombination Inferred from electronic annotation. Source: UniProtKB-KW cell proliferation Inferred from mutant phenotype PubMed 17554309. Source: MGI double-strand break repair via nonhomologous end joining Inferred from sequence or structural similarity. Source: UniProtKB hematopoietic stem cell differentiation Inferred from mutant phenotype PubMed 17554309. Source: MGI negative regulation of apoptotic process Inferred from mutant phenotype PubMed 17554309. Source: MGI 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 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 cytoplasm Inferred from direct assay PubMed 12604618. Source: MGI nonhomologous end joining complex Inferred from sequence or structural similarity. Source: UniProtKB nuclear chromosome, telomeric region Inferred from electronic annotation. Source: Compara nucleolus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	5'-deoxyribose-5-phosphate lyase activity Inferred from electronic annotation. Source: Compara 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 – 732	731	X-ray repair cross-complementing protein 5		PRO_0000084341
Regions
	Domain	251 – 460	210	Ku
	Region	138 – 165	28	Leucine-zipper
	Motif	720 – 728	9	EEXXXDL motif
	Compositional bias	478 – 520	43	Pro-rich
Amino acid modifications
	Modified residue	265	1	N6-acetyllysine By similarity
	Modified residue	332	1	N6-acetyllysine By similarity
	Modified residue	578	1	Phosphoserine; by PRKDC By similarity
	Modified residue	580	1	Phosphoserine; by PRKDC By similarity
	Modified residue	581	1	Phosphoserine; by PRKDC By similarity
	Modified residue	666	1	N6-acetyllysine By similarity
	Modified residue	716	1	Phosphothreonine; by PRKDC By similarity
Experimental info
	Sequence conflict	5	1	G → V in CAA46999. Ref.1
	Sequence conflict	24	1	F → I in CAA46999. Ref.1
	Sequence conflict	57	1	V → A in CAA46999. Ref.1
	Sequence conflict	66 – 69	4	NALA → MPLS in CAA46999. Ref.1
	Sequence conflict	120	1	R → H in AAD49720. Ref.2
	Sequence conflict	139	1	S → G in BAE38207. Ref.3
	Sequence conflict	139	1	S → R in CAA46999. Ref.1
	Sequence conflict	144	1	Q → K in CAA46999. Ref.1
	Sequence conflict	157	1	S → C in CAA46999. Ref.1
	Sequence conflict	226	1	S → F in AAD49720. Ref.2
	Sequence conflict	409 – 410	2	FP → SL in CAA46999. Ref.1
	Sequence conflict	414	1	D → G in BAC38276. Ref.3
	Sequence conflict	415	1	A → T in AAD49720. Ref.2
	Sequence conflict	418	1	C → R in CAA46999. Ref.1
	Sequence conflict	442	1	K → M in AAD49720. Ref.2
	Sequence conflict	479	1	T → A in CAA46999. Ref.1
	Sequence conflict	515 – 516	2	ML → IW in CAA46999. Ref.1
	Sequence conflict	524	1	A → Q in CAA46999. Ref.1
	Sequence conflict	530 – 531	2	LS → PL in CAA46999. Ref.1
	Sequence conflict	558	1	N → H in AAD49720. Ref.2
	Sequence conflict	692	1	G → A in CAA46999. Ref.1
	Sequence conflict	703	1	T → K in CAA46999. Ref.1
	Sequence conflict	708	1	P → H in BAE39415. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P27641 [UniParc]. Last modified February 5, 2008. Version 4. Checksum: 391F0FAF7EB04288	FASTA	732	83,057
	10 20 30 40 50 60 MAWSGNKAAV VLCVDVGVAM GNSFPGEESP IEQAKKVMTM FVQRQVFSES KDEIALVLYG 70 80 90 100 110 120 TDGTDNALAG KDQYQNITVC RHLMLPDFDL LEDIGNKIQP SSQQADFLDA LIVCMDLIQR 130 140 150 160 170 180 ETIGKKFGKK HIEVFTDLSS PFSQDQLDVI ICNLKKSGIS LQFFLPFPID KNGEPGERGD 190 200 210 220 230 240 LDSGLDHLKP SFPQKGLTEQ QKEGIRMVTR VMLSLEGEDG LDEIYSFSES LRQLCVFKKI 250 260 270 280 290 300 ERRSMPWPCQ LTIGPNLSIK IVAYKSIVQE KFKKSWVVVD ARTLKKEDIQ KETVYCLNDD 310 320 330 340 350 360 DETEVSKEDT IQGYRYGSDI IPFSKVDEEQ MKYKSEGKCF SVLGFCKSSQ VHRRFFMGHQ 370 380 390 400 410 420 VLKVFAAKDD EAAAVALSSL VHALDELNMV AIVRYAYDKR SNPQVGVAFP YIKDAYECLV 430 440 450 460 470 480 YVQLPFMEDL RQYMFSSLKN NKKCTPTEAQ LSAIDDLIDS MSLVKKNEEE DIVEDLFPTS 490 500 510 520 530 540 KIPNPEFQRL YQCLLHRALH LQERLPPIQQ HILNMLDPPT EMKAKCESPL SKVKTLFPLT 550 560 570 580 590 600 EVIKKKNQVT AQDVFQDNHE EGPAAKKYKT EKEEDHISIS SLAEGNITKV GSVNPVENFR 610 620 630 640 650 660 FLVRQKIASF EEASLQLISH IEQFLDTNET LYFMKSMDCI KAFREEAIQF SEEQRFNSFL 670 680 690 700 710 720 EALREKVEIK QLNHFWEIVV QDGVTLITKD EGPGSSITAE EATKFLAPKD KAKEDTTGPE 730 EAGDVDDLLD MI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The nucleotide sequence of a mouse cDNA encoding the 80 kDa subunit of the Ku (p70/p80) autoantigen." Falzon M., Kuff E.L. Nucleic Acids Res. 20:3784-3784(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: BALB/c.
[2]	"Ku gene mutation of radiosensitive mouse mammary carcinoma cell line SX-9." Jiang G.C., Yuan L.Z., Wei K. Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Mammary carcinoma.
[3]	"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 NOD. Tissue: Embryonic head, Embryonic heart, Embryonic liver, Kidney and Thymus.
[4]	"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]. Strain: 129/Sv X 129SvCp and FVB/N. Tissue: Embryonic stem cell and Mammary tumor.
[5]	"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, INDUCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X66323 mRNA. Translation: CAA46999.1. AF166486 mRNA. Translation: AAD49720.1. AK081633 mRNA. Translation: BAC38276.1. AK165470 mRNA. Translation: BAE38207.1. AK167312 mRNA. Translation: BAE39415.1. AK168913 mRNA. Translation: BAE40726.1. AK169838 mRNA. Translation: BAE41402.1. BC029218 mRNA. Translation: AAH29218.1. BC051660 mRNA. Translation: AAH51660.1.
IPI	IPI00321154.
PIR	S26303.
RefSeq	NP_033559.2. NM_009533.2.
UniGene	Mm.246952.
3D structure databases
ProteinModelPortal	P27641.
SMR	P27641. Positions 6-545, 591-710.
ModBase	Search...
Protein-protein interaction databases
IntAct	P27641. 3 interactions.
PTM databases
PhosphoSite	P27641.
Proteomic databases
PaxDb	P27641.
PRIDE	P27641.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000027379; ENSMUSP00000027379; ENSMUSG00000026187.
GeneID	22596.
KEGG	mmu:22596.
UCSC	uc007bkl.2. mouse.
Organism-specific databases
CTD	7520.
MGI	MGI:104517. Xrcc5.
Phylogenomic databases
eggNOG	NOG299744.
GeneTree	ENSGT00390000015674.
HOVERGEN	HBG006237.
InParanoid	P27641.
KO	K10885.
OMA	GYMLGGT.
OrthoDB	EOG4NZTSV.
Gene expression databases
ArrayExpress	P27641.
Bgee	P27641.
Genevestigator	P27641.
GermOnline	ENSMUSG00000026187. Mus musculus.
Family and domain databases
Gene3D	1.10.1600.10. 1 hit. 1.25.40.240. 1 hit. 2.40.290.10. 1 hit.
InterPro	IPR006164. Ku70/Ku80_beta-barrel_dom. IPR024193. Ku80. IPR005160. Ku_C. IPR005161. Ku_N. IPR014893. Ku_PK_bind. IPR016194. SPOC_like_C_dom. IPR002035. VWF_A. [Graphical view]
PANTHER	PTHR12604:SF3. PTHR12604:SF3. 1 hit.
Pfam	PF02735. Ku. 1 hit. PF03730. Ku_C. 1 hit. PF03731. Ku_N. 1 hit. PF08785. Ku_PK_bind. 1 hit. [Graphical view]
PIRSF	PIRSF016570. Ku80. 1 hit.
SMART	SM00559. Ku78. 1 hit. SM00327. VWA. 1 hit. [Graphical view]
SUPFAM	SSF101420. Ku_PK_bind. 1 hit. SSF100939. SPOC-like. 1 hit.
ProtoNet	Search...
Other
NextBio	302945.
SOURCE	Search...

Entry information

Entry name

XRCC5_MOUSE

Accession

Primary (citable) accession number: P27641
Secondary accession number(s): Q3TE46 , Q3TJT0, Q3TN82, Q80UT1, Q8C4N6, Q8K1K7, Q9R169

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	February 5, 2008
Last modified:	May 1, 2013
This is version 120 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program