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Reviewed, UniProtKB/Swiss-Prot P18887 (XRCC1_HUMAN)

Last modified July 7, 2009. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    DNA repair protein XRCC1
Alternative name(s):
    X-ray repair cross-complementing protein 1
Gene names
Name: XRCC1
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length633 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence 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 processDNA damage
DNA repair
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   DomainRepeat
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Gene Ontology (GO)
   Biological processsingle strand break repair

Inferred from electronic annotation. Source: InterPro

   Cellular componentnucleoplasm

Inferred from Experiment. Source: Reactome

   Molecular functiondamaged 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...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 633633DNA repair protein XRCC1
PRO_0000066044

Regions

Domain315 – 40389BRCT 1
Domain538 – 62992BRCT 2

Amino acid modifications

Modified residue1991Phosphoserine Ref.13
Modified residue2261Phosphoserine Ref.13
Modified residue2411Phosphoserine Ref.13
Modified residue2571Phosphothreonine Ref.13
Modified residue2591Phosphoserine Ref.13
Modified residue2661Phosphoserine Ref.13 Ref.12
Modified residue3711Phosphoserine; by PRKDC Ref.10
Modified residue4081Phosphoserine Ref.13 Ref.9
Modified residue4091Phosphoserine Ref.13 Ref.9
Modified residue4101Phosphoserine Ref.13 Ref.9
Modified residue4161Phosphoserine Ref.9
Modified residue4181Phosphoserine Ref.13 Ref.9
Modified residue4211Phosphoserine Ref.13 Ref.9
Modified residue4471Phosphoserine Ref.13 Ref.12
Modified residue4531Phosphothreonine Ref.13 Ref.12

Natural variations

Natural variant71R → L: dbSNP rs2307186.
VAR_014773
Natural variant101V → M: dbSNP rs2307171.
VAR_014774
Natural variant721V → A: dbSNP rs25496. Ref.2
VAR_016168
Natural variant1071R → H: dbSNP rs2228487.
VAR_029228
Natural variant1571E → K: dbSNP rs2307180.
VAR_014775
Natural variant1611P → L: dbSNP rs2307191. Ref.2
VAR_014776
Natural variant1941R → W: dbSNP rs1799782. Ref.2 Ref.16
VAR_013400
Natural variant2801R → H: dbSNP rs25489. Ref.2 Ref.16
VAR_013401
Natural variant2981K → N: dbSNP rs2307188.
VAR_014777
Natural variant3041T → A: dbSNP rs25490. Ref.2
VAR_018775
Natural variant3091P → S: dbSNP rs25491. Ref.2
VAR_014778
Natural variant3501R → W in a colorectal cancer sample; somatic mutation. Ref.19
VAR_036277
Natural variant3991R → Q: dbSNP rs25487. Ref.2 Ref.16 Ref.17 Ref.18
VAR_011487
Natural variant4851S → Y: dbSNP rs2307184.
VAR_014779
Natural variant5141P → L: dbSNP rs25474.
VAR_016169
Natural variant5591R → Q: dbSNP rs2307167.
VAR_014780
Natural variant5601R → W: dbSNP rs2307166.
VAR_014781
Natural variant5761Y → S: dbSNP rs2307177. Ref.2
VAR_014782

Experimental info

Sequence conflict5761Y → N in AAG09061. Ref.3

Secondary structure

.................................................................... 633
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P18887-1 [UniParc].

Last modified November 1, 1990. Version 1.
Checksum: 30CC2421345ABFC2

FASTA63369,526
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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

Cross-references

Sequence databases

M36089 mRNA. Translation: AAA63270.1.
AF512504 Genomic DNA. Translation: AAM34791.1.
AC018758 Genomic DNA. Translation: AAG09061.1.
IPIIPI00002564.
PIRA36353.
UniGeneHs.98493

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1CDZX-ray3.20A538-633[»]
1XNANMR-A1-183[»]
1XNTNMR-A1-183[»]
2D8MNMR-A305-420[»]
2W3OX-ray1.85C/D515-522[»]
SMRP18887. Positions 301-415.
ModBaseSearch...

Protein-protein interaction databases

IntActP18887. 8 interactions.

PTM databases

PhosphoSiteP18887.

Proteomic databases

PRIDEP18887.

Genome annotation databases

EnsemblENSG00000073050. Homo sapiens. [Contig view]

Organism-specific databases

GeneCardsGC19M048739.
H-InvDBHIX0040090.
HGNCHGNC:12828. XRCC1.
HPACAB005427.
HPA006717.
MIM194360. gene.
PharmGKBPA369.
GenAtlasSearch...

Phylogenomic databases

HOVERGENP18887.

Enzyme and pathway databases

Pathway_Interaction_DBfoxm1pathway. FOXM1 transcription factor network.
ReactomeREACT_216. DNA Repair.

Gene expression databases

ArrayExpressP18887.
BgeeP18887.
CleanExHS_XRCC1.
GermOnlineENSG00000073050. Homo sapiens.

Family and domain databases

InterProIPR001357. BRCT.
IPR002706. Xrcc1_N.
[Graphical view]
PfamPF00533. BRCT. 2 hits.
PF01834. XRCC1_N. 1 hit.
[Graphical view]
ProDomPD023136. Xrcc1_N. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00292. BRCT. 2 hits.
[Graphical view]
PROSITEPS50172. BRCT. 2 hits.
[Graphical view]
ProtoNetSearch...

Other Resources

SOURCESearch...

Entry information

Entry nameXRCC1_HUMAN
AccessionPrimary (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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents