Reviewed, UniProtKB/Swiss-Prot P18887 (XRCC1_HUMAN)

Names and origin

Protein names

Recommended name:
    DNA repair protein XRCC1
Alternative name(s):
    X-ray repair cross-complementing protein 1

Gene names

Name:

XRCC1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	633 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Corrects defective DNA strand-break repair and sister chromatid exchange following treatment with ionizing radiation and alkylating agents.
Subunit structure	Homodimer. Interacts with polynucleotide kinase (PNK), DNA polymerase-beta (POLB) and DNA ligase III (LIG3). Interacts with APTX and APLF. Ref.4 Ref.5 Ref.6 Ref.7 Ref.10 Ref.11
Subcellular location	Nucleus. Note: Accumulates at sites of DNA damage. Ref.11
Post-translational modification	Phosphorylation of Ser-371 causes dimer dissociation. Phosphorylation by CK2 promotes interaction with APTX and APLF. Sumoylated. Ref.8
Polymorphism	Carriers of the polymorphic Gln-399 allele may be at greater risk for tobacco- and age-related DNA damage.
Sequence similarities	Contains 2 BRCT domains.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	single strand break repair Inferred from electronic annotation. Source: InterPro
Cellular component	nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	damaged DNA binding Inferred from electronic annotation. Source: InterPro protein binding Ref.5 Ref.7 Ref.11 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
APLF	Q8IW19	4	EBI-947466,EBI-1256044
FYN	P06241	1	EBI-947466,EBI-515315
LIG3	P49916	1	EBI-947466,EBI-1753381
PNKP	Q96T60	1	EBI-947466,EBI-1045072

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 633

633

DNA repair protein XRCC1

PRO_0000066044

Regions

Domain

315 – 403

89

BRCT 1

Domain

538 – 629

92

BRCT 2

Amino acid modifications

Modified residue

199

1

Phosphoserine Ref.13

Modified residue

226

1

Phosphoserine Ref.13

Modified residue

241

1

Phosphoserine Ref.13

Modified residue

257

1

Phosphothreonine Ref.13

Modified residue

259

1

Phosphoserine Ref.13

Modified residue

266

1

Phosphoserine Ref.13 Ref.12

Modified residue

371

1

Phosphoserine; by PRKDC Ref.10

Modified residue

408

1

Phosphoserine Ref.13 Ref.9

Modified residue

409

1

Phosphoserine Ref.13 Ref.9

Modified residue

410

1

Phosphoserine Ref.13 Ref.9

Modified residue

416

1

Phosphoserine Ref.9

Modified residue

418

1

Phosphoserine Ref.13 Ref.9

Modified residue

421

1

Phosphoserine Ref.13 Ref.9

Modified residue

447

1

Phosphoserine Ref.13 Ref.12

Modified residue

453

1

Phosphothreonine Ref.13 Ref.12

Natural variations

Natural variant

7

1

R → L: dbSNP rs2307186.

VAR_014773

Natural variant

10

1

V → M: dbSNP rs2307171.

VAR_014774

Natural variant

72

1

V → A: dbSNP rs25496. Ref.2

VAR_016168

Natural variant

107

1

R → H: dbSNP rs2228487.

VAR_029228

Natural variant

157

1

E → K: dbSNP rs2307180.

VAR_014775

Natural variant

161

1

P → L: dbSNP rs2307191. Ref.2

VAR_014776

Natural variant

194

1

R → W: dbSNP rs1799782. Ref.2 Ref.16

VAR_013400

Natural variant

280

1

R → H: dbSNP rs25489. Ref.2 Ref.16

VAR_013401

Natural variant

298

1

K → N: dbSNP rs2307188.

VAR_014777

Natural variant

304

1

T → A: dbSNP rs25490. Ref.2

VAR_018775

Natural variant

309

1

P → S: dbSNP rs25491. Ref.2

VAR_014778

Natural variant

350

1

R → W in a colorectal cancer sample; somatic mutation. Ref.19

VAR_036277

Natural variant

399

1

R → Q: dbSNP rs25487. Ref.2 Ref.16 Ref.17 Ref.18

VAR_011487

Natural variant

485

1

S → Y: dbSNP rs2307184.

VAR_014779

Natural variant

514

1

P → L: dbSNP rs25474.

VAR_016169

Natural variant

559

1

R → Q: dbSNP rs2307167.

VAR_014780

Natural variant

560

1

R → W: dbSNP rs2307166.

VAR_014781

Natural variant

576

1

Y → S: dbSNP rs2307177. Ref.2

VAR_014782

Experimental info

Sequence conflict

576

1

Y → N in AAG09061. Ref.3

Secondary structure

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633

Helix Strand Turn

Details...

Beta strand

10 – 14

5

Helix

21 – 26

6

Beta strand

27 – 30

4

Beta strand

36 – 39

4

Beta strand

41 – 53

13

Beta strand

56 – 64

9

Beta strand

67 – 73

7

Beta strand

75 – 77

3

Beta strand

85 – 92

8

Turn

96 – 102

7

Beta strand

107 – 111

5

Helix

118 – 121

4

Beta strand

125 – 133

9

Beta strand

138 – 140

3

Beta strand

143 – 150

8

Helix

313 – 316

4

Turn

317 – 319

3

Beta strand

323 – 329

7

Helix

334 – 344

11

Beta strand

347 – 352

6

Beta strand

359 – 366

8

Helix

368 – 376

9

Beta strand

379 – 382

4

Helix

384 – 391

8

Helix

398 – 401

4

Beta strand

404 – 407

4

Turn

542 – 545

4

Beta strand

547 – 550

4

Helix

557 – 568

12

Beta strand

582 – 585

4

Helix

592 – 598

7

Beta strand

605 – 607

3

Helix

610 – 616

7

Turn

617 – 619

3

Helix

624 – 627

4

Sequences

	Sequence		Length	Mass (Da)
	P18887-1 [UniParc]. Last modified November 1, 1990. Version 1. Checksum: 30CC2421345ABFC2	FASTA	633	69,526
	10 20 30 40 50 60 MPEIRLRHVV SCSSQDSTHC AENLLKADTY RKWRAAKAGE KTISVVLQLE KEEQIHSVDI 70 80 90 100 110 120 GNDGSAFVEV LVGSSAGGAG EQDYEVLLVT SSFMSPSESR SGSNPNRVRM FGPDKLVRAA 130 140 150 160 170 180 AEKRWDRVKI VCSQPYSKDS PFGLSFVRFH SPPDKDEAEA PSQKVTVTKL GQFRVKEEDE 190 200 210 220 230 240 SANSLRPGAL FFSRINKTSP VTASDPAGPS YAAATLQASS AASSASPVSR AIGSTSKPQE 250 260 270 280 290 300 SPKGKRKLDL NQEEKKTPSK PPAQLSPSVP KRPKLPAPTR TPATAPVPAR AQGAVTGKPR 310 320 330 340 350 360 GEGTEPRRPR AGPEELGKIL QGVVVVLSGF QNPFRSELRD KALELGAKYR PDWTRDSTHL 370 380 390 400 410 420 ICAFANTPKY SQVLGLGGRI VRKEWVLDCH RMRRRLPSRR YLMAGPGSSS EEDEASHSGG 430 440 450 460 470 480 SGDEAPKLPQ KQPQTKTKPT QAAGPSSPQK PPTPEETKAA SPVLQEDIDI EGVQSEGQDN 490 500 510 520 530 540 GAEDSGDTED ELRRVAEQKE HRLPPGQEEN GEDPYAGSTD ENTDSEEHQE PPDLPVPELP 550 560 570 580 590 600 DFFQGKHFFL YGEFPGDERR KLIRYVTAFN GELEDYMSDR VQFVITAQEW DPSFEEALMD 610 620 630 NPSLAFVRPR WIYSCNEKQK LLPHQLYGVV PQA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of the human XRCC1 gene, which corrects defective DNA strand break repair and sister chromatid exchange." Thompson L.H., Brookman K.W., Jones N.J., Allen S.A., Carrano A.V. Mol. Cell. Biol. 10:6160-6171(1990) [PubMed: 2247054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	NIEHS SNPs program Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ALA-72; LEU-161; TRP-194; HIS-280; ALA-304; SER-309; GLN-399 AND SER-576.
[3]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed: 15057824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair." Whitehouse C.J., Taylor R.M., Thistlethwaite A., Zhang H., Karimi-Busheri F., Lasko D.D., Weinfeld M., Caldecott K.W. Cell 104:107-117(2001) [PubMed: 11163244] [Abstract] Cited for: INTERACTION.
[5]	"Aprataxin, the causative protein for EAOH is a nuclear protein with a potential role as a DNA repair protein." Sano Y., Date H., Igarashi S., Onodera O., Oyake M., Takahashi T., Hayashi S., Morimatsu M., Takahashi H., Makifuchi T., Fukuhara N., Tsuji S. Ann. Neurol. 55:241-249(2004) [PubMed: 14755728] [Abstract] Cited for: INTERACTION WITH APTX.
[6]	"The ataxia-oculomotor apraxia 1 gene product has a role distinct from ATM and interacts with the DNA strand break repair proteins XRCC1 and XRCC4." Clements P.M., Breslin C., Deeks E.D., Byrd P.J., Ju L., Bieganowski P., Brenner C., Moreira M.-C., Taylor A.M.R., Caldecott K.W. DNA Repair 3:1493-1502(2004) [PubMed: 15380105] [Abstract] Cited for: INTERACTION WITH APTX, PHOSPHORYLATION.
[7]	"Aprataxin, a novel protein that protects against genotoxic stress." Gueven N., Becherel O.J., Kijas A.W., Chen P., Howe O., Rudolph J.H., Gatti R., Date H., Onodera O., Taucher-Scholz G., Lavin M.F. Hum. Mol. Genet. 13:1081-1093(2004) [PubMed: 15044383] [Abstract] Cited for: INTERACTION WITH APTX.
[8]	"Systematic identification and analysis of mammalian small ubiquitin-like modifier substrates." Gocke C.B., Yu H., Kang J. J. Biol. Chem. 280:5004-5012(2005) [PubMed: 15561718] [Abstract] Cited for: SUMOYLATION.
[9]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-408; SER-409; SER-410; SER-416; SER-418 AND SER-421, MASS SPECTROMETRY. Tissue: Epithelium.
[10]	"XRCC1 is phosphorylated by DNA-dependent protein kinase in response to DNA damage." Levy N., Martz A., Bresson A., Spenlehauer C., de Murcia G., Menissier-de Murcia J. Nucleic Acids Res. 34:32-41(2006) [PubMed: 16397295] [Abstract] Cited for: SUBUNIT, PHOSPHORYLATION AT SER-371.
[11]	"APLF (C2orf13) is a novel human protein involved in the cellular response to chromosomal DNA strand breaks." Iles N., Rulten S., El-Khamisy S.F., Caldecott K.W. Mol. Cell. Biol. 27:3793-3803(2007) [PubMed: 17353262] [Abstract] Cited for: INTERACTION WITH APLF, PHOSPHORYLATION, SUBCELLULAR LOCATION.
[12]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-266; SER-447 AND THR-453, MASS SPECTROMETRY.
[13]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-199; SER-226; SER-241; THR-257; SER-259; SER-266; SER-408; SER-409; SER-410; SER-418; SER-421; SER-447 AND THR-453, MASS SPECTROMETRY.
[14]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[15]	"Solution structure of the first BRCT domain of DNA-repair protein xrcc1." RIKEN structural genomics initiative (RSGI) Submitted (JUN-2006) to the PDB data bank Cited for: STRUCTURE BY NMR OF 306-422.
[16]	"Nonconservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans." Shen M.R., Jones I.M., Mohrenweiser H. Cancer Res. 58:604-608(1998) [PubMed: 9485007] [Abstract] Cited for: VARIANTS TRP-194; HIS-280 AND GLN-399.
[17]	"Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells." Duell E.J., Wiencke J.K., Cheng T.J., Varkonyi A., Zuo Z.F., Ashok T.D., Mark E.J., Wain J.C., Christiani D.C., Kelsey K.T. Carcinogenesis 21:965-971(2000) [PubMed: 10783319] [Abstract] Cited for: VARIANT GLN-399.
[18]	"The XRCC1 Arg399Gln polymorphism, sunburn, and non-melanoma skin cancer: evidence of gene-environment interaction." Nelson H.H., Kelsey K.T., Mott L.A., Karagas M.R. Cancer Res. 62:152-155(2002) [PubMed: 11782372] [Abstract] Cited for: VARIANT GLN-399.
[19]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] TRP-350.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

M36089 mRNA. Translation: AAA63270.1.
AF512504 Genomic DNA. Translation: AAM34791.1.
AC018758 Genomic DNA. Translation: AAG09061.1.

IPI

IPI00002564.

PIR

A36353.

UniGene

Hs.98493

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CDZ	X-ray	3.20	A	538-633	[»]
1XNA	NMR	-	A	1-183	[»]
1XNT	NMR	-	A	1-183	[»]
2D8M	NMR	-	A	305-420	[»]
2W3O	X-ray	1.85	C/D	515-522	[»]

SMR

P18887. Positions 301-415.

ModBase

Search...

Protein-protein interaction databases

IntAct

P18887. 8 interactions.

PTM databases

PhosphoSite

P18887.

Proteomic databases

PRIDE

P18887.

Genome annotation databases

Ensembl

ENSG00000073050. Homo sapiens. [Contig view]

Organism-specific databases

GeneCards

GC19M048739.

H-InvDB

HIX0040090.

HGNC

HGNC:12828. XRCC1.

HPA

CAB005427.
HPA006717.

MIM

194360. gene.

PharmGKB

PA369.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P18887.

Enzyme and pathway databases

Pathway_Interaction_DB

foxm1pathway. FOXM1 transcription factor network.

Reactome

REACT_216. DNA Repair.

Gene expression databases

ArrayExpress

P18887.

Bgee

P18887.

CleanEx

HS_XRCC1.

GermOnline

ENSG00000073050. Homo sapiens.

Family and domain databases

InterPro

IPR001357. BRCT.
IPR002706. Xrcc1_N.
[Graphical view]

Pfam

PF00533. BRCT. 2 hits.
PF01834. XRCC1_N. 1 hit.
[Graphical view]

ProDom

PD023136. Xrcc1_N. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00292. BRCT. 2 hits.
[Graphical view]

PROSITE

PS50172. BRCT. 2 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

SOURCE

Search...

Entry information

Entry name

XRCC1_HUMAN

Accession

Primary (citable) accession number: P18887
Secondary accession number(s): Q9HCB1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	November 1, 1990
Last modified:	July 7, 2009
This is version 109 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)