XRCC1_HUMAN
ID XRCC1_HUMAN Reviewed; 633 AA.
AC P18887; Q6IBS4; Q9HCB1;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 3.
DT 03-AUG-2022, entry version 222.
DE RecName: Full=DNA repair protein XRCC1 {ECO:0000305};
DE AltName: Full=X-ray repair cross-complementing protein 1;
GN Name=XRCC1 {ECO:0000312|HGNC:HGNC:12828};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ARG-399.
RX PubMed=2247054; DOI=10.1128/mcb.10.12.6160-6171.1990;
RA Thompson L.H., Brookman K.W., Jones N.J., Allen S.A., Carrano A.V.;
RT "Molecular cloning of the human XRCC1 gene, which corrects defective DNA
RT strand break repair and sister chromatid exchange.";
RL Mol. Cell. Biol. 10:6160-6171(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ALA-72; LEU-161; TRP-194;
RP HIS-280; ALA-304; SER-309; ARG-399 AND SER-576.
RG NIEHS SNPs program;
RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ASN-576.
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INTERACTION.
RX PubMed=11163244; DOI=10.1016/s0092-8674(01)00195-7;
RA Whitehouse C.J., Taylor R.M., Thistlethwaite A., Zhang H.,
RA Karimi-Busheri F., Lasko D.D., Weinfeld M., Caldecott K.W.;
RT "XRCC1 stimulates human polynucleotide kinase activity at damaged DNA
RT termini and accelerates DNA single-strand break repair.";
RL Cell 104:107-117(2001).
RN [7]
RP INTERACTION WITH APTX.
RX PubMed=14755728; DOI=10.1002/ana.10808;
RA Sano Y., Date H., Igarashi S., Onodera O., Oyake M., Takahashi T.,
RA Hayashi S., Morimatsu M., Takahashi H., Makifuchi T., Fukuhara N.,
RA Tsuji S.;
RT "Aprataxin, the causative protein for EAOH is a nuclear protein with a
RT potential role as a DNA repair protein.";
RL Ann. Neurol. 55:241-249(2004).
RN [8]
RP PHOSPHORYLATION AT SER-485 AND THR-488, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=15066279; DOI=10.1016/s0092-8674(04)00206-5;
RA Loizou J.I., El-Khamisy S.F., Zlatanou A., Moore D.J., Chan D.W., Qin J.,
RA Sarno S., Meggio F., Pinna L.A., Caldecott K.W.;
RT "The protein kinase CK2 facilitates repair of chromosomal DNA single-strand
RT breaks.";
RL Cell 117:17-28(2004).
RN [9]
RP INTERACTION WITH APTX, AND PHOSPHORYLATION.
RX PubMed=15380105; DOI=10.1016/j.dnarep.2004.06.017;
RA Clements P.M., Breslin C., Deeks E.D., Byrd P.J., Ju L., Bieganowski P.,
RA Brenner C., Moreira M.-C., Taylor A.M.R., Caldecott K.W.;
RT "The ataxia-oculomotor apraxia 1 gene product has a role distinct from ATM
RT and interacts with the DNA strand break repair proteins XRCC1 and XRCC4.";
RL DNA Repair 3:1493-1502(2004).
RN [10]
RP INTERACTION WITH APTX.
RX PubMed=15044383; DOI=10.1093/hmg/ddh122;
RA Gueven N., Becherel O.J., Kijas A.W., Chen P., Howe O., Rudolph J.H.,
RA Gatti R., Date H., Onodera O., Taucher-Scholz G., Lavin M.F.;
RT "Aprataxin, a novel protein that protects against genotoxic stress.";
RL Hum. Mol. Genet. 13:1081-1093(2004).
RN [11]
RP SUMOYLATION.
RX PubMed=15561718; DOI=10.1074/jbc.m411718200;
RA Gocke C.B., Yu H., Kang J.;
RT "Systematic identification and analysis of mammalian small ubiquitin-like
RT modifier substrates.";
RL J. Biol. Chem. 280:5004-5012(2005).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-421, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [13]
RP SUBUNIT, AND PHOSPHORYLATION AT SER-371.
RX PubMed=16397295; DOI=10.1093/nar/gkj409;
RA Levy N., Martz A., Bresson A., Spenlehauer C., de Murcia G.,
RA Menissier-de Murcia J.;
RT "XRCC1 is phosphorylated by DNA-dependent protein kinase in response to DNA
RT damage.";
RL Nucleic Acids Res. 34:32-41(2006).
RN [14]
RP INTERACTION WITH APLF.
RX PubMed=17507382; DOI=10.1074/jbc.c700060200;
RA Bekker-Jensen S., Fugger K., Danielsen J.R., Gromova I., Sehested M.,
RA Celis J., Bartek J., Lukas J., Mailand N.;
RT "Human Xip1 (C2orf13) is a novel regulator of cellular responses to DNA
RT strand breaks.";
RL J. Biol. Chem. 282:19638-19643(2007).
RN [15]
RP INTERACTION WITH APLF, PHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=17353262; DOI=10.1128/mcb.02269-06;
RA Iles N., Rulten S., El-Khamisy S.F., Caldecott K.W.;
RT "APLF (C2orf13) is a novel human protein involved in the cellular response
RT to chromosomal DNA strand breaks.";
RL Mol. Cell. Biol. 27:3793-3803(2007).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226; SER-241; THR-257;
RP SER-259; SER-408; SER-409; SER-410 AND THR-453, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-198; SER-199; SER-226;
RP SER-241; THR-453; SER-461; SER-485 AND THR-488, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [19]
RP INTERACTION WITH APEX1.
RX PubMed=19934257; DOI=10.1093/nar/gkp1039;
RA Yamamori T., DeRicco J., Naqvi A., Hoffman T.A., Mattagajasingh I.,
RA Kasuno K., Jung S.B., Kim C.S., Irani K.;
RT "SIRT1 deacetylates APE1 and regulates cellular base excision repair.";
RL Nucleic Acids Res. 38:832-845(2010).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-140; THR-202; SER-204;
RP SER-241 AND THR-257, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-241; THR-453 AND THR-457, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226; SER-241; SER-266;
RP THR-281; SER-447; THR-453 AND THR-457, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-446; SER-447; THR-453;
RP THR-457 AND SER-461, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [24]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-176, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [25]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-176, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [26]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-176, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033;
RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V.,
RA Vertegaal A.C.;
RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage.";
RL Cell Rep. 10:1778-1791(2015).
RN [27]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-176, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [28]
RP STRUCTURE BY NMR OF 306-422.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the first BRCT domain of DNA-repair protein XRCC1.";
RL Submitted (JUN-2006) to the PDB data bank.
RN [29]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 515-522 IN COMPLEX WITH PNKP, AND
RP PHOSPHORYLATION AT SER-518; THR-519 AND THR-523.
RX PubMed=19155274; DOI=10.1093/nar/gkn1086;
RA Ali A.A., Jukes R.M., Pearl L.H., Oliver A.W.;
RT "Specific recognition of a multiply phosphorylated motif in the DNA repair
RT scaffold XRCC1 by the FHA domain of human PNK.";
RL Nucleic Acids Res. 37:1701-1712(2009).
RN [30]
RP VARIANTS TRP-194; HIS-280 AND ARG-399.
RX PubMed=9485007;
RA Shen M.R., Jones I.M., Mohrenweiser H.;
RT "Nonconservative amino acid substitution variants exist at polymorphic
RT frequency in DNA repair genes in healthy humans.";
RL Cancer Res. 58:604-608(1998).
RN [31]
RP VARIANT ARG-399.
RX PubMed=10783319; DOI=10.1093/carcin/21.5.965;
RA Duell E.J., Wiencke J.K., Cheng T.J., Varkonyi A., Zuo Z.F., Ashok T.D.,
RA Mark E.J., Wain J.C., Christiani D.C., Kelsey K.T.;
RT "Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of
RT DNA damage in human blood mononuclear cells.";
RL Carcinogenesis 21:965-971(2000).
RN [32]
RP VARIANT ARG-399.
RX PubMed=11782372;
RA Nelson H.H., Kelsey K.T., Mott L.A., Karagas M.R.;
RT "The XRCC1 Arg399Gln polymorphism, sunburn, and non-melanoma skin cancer:
RT evidence of gene-environment interaction.";
RL Cancer Res. 62:152-155(2002).
RN [33]
RP VARIANT [LARGE SCALE ANALYSIS] TRP-350.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [34]
RP INVOLVEMENT IN SCAR26, VARIANTS SCAR26 ASN-431 AND 465-GLN--ALA-633 DEL,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=28002403; DOI=10.1038/nature20790;
RG Care4Rare Canada Consortium;
RA Hoch N.C., Hanzlikova H., Rulten S.L., Tetreault M., Komulainen E., Ju L.,
RA Hornyak P., Zeng Z., Gittens W., Rey S.A., Staras K., Mancini G.M.,
RA McKinnon P.J., Wang Z.Q., Wagner J.D., Yoon G., Caldecott K.W.;
RT "XRCC1 mutation is associated with PARP1 hyperactivation and cerebellar
RT ataxia.";
RL Nature 541:87-91(2017).
RN [35]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Involved in DNA single-strand break repair by mediating the
CC assembly of DNA break repair protein complexes. Probably during DNA
CC repair, negatively regulates ADP-ribose levels by modulating ADP-
CC ribosyltransferase PARP1 activity. {ECO:0000269|PubMed:28002403}.
CC -!- SUBUNIT: Homodimer. Interacts with polynucleotide kinase (PNK), DNA
CC polymerase-beta (POLB) and DNA ligase III (LIG3). Interacts with APTX
CC and APLF. Interacts with APEX1; the interaction is induced by SIRT1 and
CC increases with the acetylated form of APEX1.
CC {ECO:0000269|PubMed:11163244, ECO:0000269|PubMed:14755728,
CC ECO:0000269|PubMed:15044383, ECO:0000269|PubMed:15380105,
CC ECO:0000269|PubMed:16397295, ECO:0000269|PubMed:17353262,
CC ECO:0000269|PubMed:17507382, ECO:0000269|PubMed:19155274,
CC ECO:0000269|PubMed:19934257}.
CC -!- INTERACTION:
CC P18887; Q8IW19: APLF; NbExp=11; IntAct=EBI-947466, EBI-1256044;
CC P18887; Q7Z2E3: APTX; NbExp=11; IntAct=EBI-947466, EBI-847814;
CC P18887; O96017: CHEK2; NbExp=8; IntAct=EBI-947466, EBI-1180783;
CC P18887; P61244: MAX; NbExp=2; IntAct=EBI-947466, EBI-751711;
CC P18887; P09874: PARP1; NbExp=6; IntAct=EBI-947466, EBI-355676;
CC P18887; Q96T60: PNKP; NbExp=6; IntAct=EBI-947466, EBI-1045072;
CC P18887; P06746: POLB; NbExp=3; IntAct=EBI-947466, EBI-713836;
CC P18887; Q9UNA4: POLI; NbExp=2; IntAct=EBI-947466, EBI-741774;
CC P18887; Q9NUW8: TDP1; NbExp=2; IntAct=EBI-947466, EBI-2902553;
CC P18887; P06766: Polb; Xeno; NbExp=4; IntAct=EBI-947466, EBI-15845002;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17353262,
CC ECO:0000269|PubMed:28002403}. Note=Moves from the nucleoli to the
CC global nuclear chromatin upon DNA damage.
CC {ECO:0000269|PubMed:28002403}.
CC -!- TISSUE SPECIFICITY: Expressed in fibroblasts, retinal pigmented
CC epithelial cells and lymphoblastoid cells (at protein level).
CC {ECO:0000269|PubMed:28002403}.
CC -!- PTM: Phosphorylation of Ser-371 causes dimer dissociation.
CC Phosphorylation by CK2 promotes interaction with APTX and APLF.
CC {ECO:0000269|PubMed:15066279, ECO:0000269|PubMed:15380105,
CC ECO:0000269|PubMed:16397295, ECO:0000269|PubMed:17353262,
CC ECO:0000269|PubMed:19155274}.
CC -!- PTM: Sumoylated. {ECO:0000269|PubMed:15561718}.
CC -!- POLYMORPHISM: Carriers of the polymorphic Gln-399 allele may be at
CC greater risk for tobacco- and age-related DNA damage.
CC -!- DISEASE: Spinocerebellar ataxia, autosomal recessive, 26 (SCAR26)
CC [MIM:617633]: A form of spinocerebellar ataxia, a clinically and
CC genetically heterogeneous group of cerebellar disorders due to
CC degeneration of the cerebellum with variable involvement of the
CC brainstem and spinal cord. SCAR26 is a progressive disease
CC characterized by gait and limb ataxia, loss of independent ambulation,
CC oculomotor apraxia, and peripheral neuropathy with distal muscle
CC weakness and areflexia. {ECO:0000269|PubMed:28002403}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/xrcc1/";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M36089; AAA63270.1; -; mRNA.
DR EMBL; AF512504; AAM34791.1; -; Genomic_DNA.
DR EMBL; CR456728; CAG33009.1; -; mRNA.
DR EMBL; AC018758; AAG09061.1; -; Genomic_DNA.
DR EMBL; KC877750; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L34079; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC023593; AAH23593.1; -; mRNA.
DR CCDS; CCDS12624.1; -.
DR PIR; A36353; A36353.
DR RefSeq; NP_006288.2; NM_006297.2.
DR PDB; 1CDZ; X-ray; 3.20 A; A=538-633.
DR PDB; 1XNA; NMR; -; A=1-183.
DR PDB; 1XNT; NMR; -; A=1-183.
DR PDB; 2D8M; NMR; -; A=305-420.
DR PDB; 2W3O; X-ray; 1.85 A; C/D=515-522.
DR PDB; 3K75; X-ray; 2.95 A; B/C=1-183.
DR PDB; 3K77; X-ray; 2.60 A; A/B/C/D/E/F/G/H=1-155.
DR PDB; 3LQC; X-ray; 2.35 A; A=1-183.
DR PDB; 5E6Q; X-ray; 2.31 A; A=241-276.
DR PDB; 5W7X; X-ray; 2.00 A; E/F/G/H=514-522.
DR PDB; 5W7Y; X-ray; 2.10 A; C/D=514-521.
DR PDB; 6WH1; X-ray; 2.40 A; A=538-633.
DR PDB; 6WH2; X-ray; 2.41 A; A/B=538-633.
DR PDBsum; 1CDZ; -.
DR PDBsum; 1XNA; -.
DR PDBsum; 1XNT; -.
DR PDBsum; 2D8M; -.
DR PDBsum; 2W3O; -.
DR PDBsum; 3K75; -.
DR PDBsum; 3K77; -.
DR PDBsum; 3LQC; -.
DR PDBsum; 5E6Q; -.
DR PDBsum; 5W7X; -.
DR PDBsum; 5W7Y; -.
DR PDBsum; 6WH1; -.
DR PDBsum; 6WH2; -.
DR AlphaFoldDB; P18887; -.
DR BMRB; P18887; -.
DR SASBDB; P18887; -.
DR BioGRID; 113349; 186.
DR CORUM; P18887; -.
DR DIP; DIP-39067N; -.
DR IntAct; P18887; 72.
DR MINT; P18887; -.
DR STRING; 9606.ENSP00000262887; -.
DR GlyGen; P18887; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P18887; -.
DR PhosphoSitePlus; P18887; -.
DR BioMuta; XRCC1; -.
DR DMDM; 317373290; -.
DR EPD; P18887; -.
DR jPOST; P18887; -.
DR MassIVE; P18887; -.
DR MaxQB; P18887; -.
DR PaxDb; P18887; -.
DR PeptideAtlas; P18887; -.
DR PRIDE; P18887; -.
DR ProteomicsDB; 53619; -.
DR Antibodypedia; 1863; 594 antibodies from 44 providers.
DR DNASU; 7515; -.
DR Ensembl; ENST00000262887.10; ENSP00000262887.5; ENSG00000073050.12.
DR GeneID; 7515; -.
DR KEGG; hsa:7515; -.
DR MANE-Select; ENST00000262887.10; ENSP00000262887.5; NM_006297.3; NP_006288.2.
DR UCSC; uc002owt.3; human.
DR CTD; 7515; -.
DR DisGeNET; 7515; -.
DR GeneCards; XRCC1; -.
DR HGNC; HGNC:12828; XRCC1.
DR HPA; ENSG00000073050; Low tissue specificity.
DR MalaCards; XRCC1; -.
DR MIM; 194360; gene.
DR MIM; 617633; phenotype.
DR neXtProt; NX_P18887; -.
DR OpenTargets; ENSG00000073050; -.
DR PharmGKB; PA369; -.
DR VEuPathDB; HostDB:ENSG00000073050; -.
DR eggNOG; KOG3226; Eukaryota.
DR GeneTree; ENSGT00390000004140; -.
DR HOGENOM; CLU_030026_0_0_1; -.
DR InParanoid; P18887; -.
DR OrthoDB; 539462at2759; -.
DR PhylomeDB; P18887; -.
DR TreeFam; TF101201; -.
DR PathwayCommons; P18887; -.
DR Reactome; R-HSA-110381; Resolution of AP sites via the single-nucleotide replacement pathway.
DR Reactome; R-HSA-5649702; APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway.
DR Reactome; R-HSA-5685939; HDR through MMEJ (alt-NHEJ).
DR Reactome; R-HSA-5696397; Gap-filling DNA repair synthesis and ligation in GG-NER.
DR Reactome; R-HSA-6782210; Gap-filling DNA repair synthesis and ligation in TC-NER.
DR SignaLink; P18887; -.
DR SIGNOR; P18887; -.
DR BioGRID-ORCS; 7515; 114 hits in 1085 CRISPR screens.
DR ChiTaRS; XRCC1; human.
DR EvolutionaryTrace; P18887; -.
DR GeneWiki; XRCC1; -.
DR GenomeRNAi; 7515; -.
DR Pharos; P18887; Tbio.
DR PRO; PR:P18887; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P18887; protein.
DR Bgee; ENSG00000073050; Expressed in ventricular zone and 202 other tissues.
DR ExpressionAtlas; P18887; baseline and differential.
DR Genevisible; P18887; HS.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0000781; C:chromosome, telomeric region; IEA:Ensembl.
DR GO; GO:0070522; C:ERCC4-ERCC1 complex; IEA:Ensembl.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:1990599; F:3' overhang single-stranded DNA endodeoxyribonuclease activity; IEA:Ensembl.
DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR GO; GO:0032356; F:oxidized DNA binding; IMP:UniProtKB.
DR GO; GO:0006284; P:base-excision repair; IBA:GO_Central.
DR GO; GO:0021587; P:cerebellum morphogenesis; IEA:Ensembl.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IEA:Ensembl.
DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl.
DR GO; GO:1905765; P:negative regulation of protection from non-homologous end joining at telomere; IEA:Ensembl.
DR GO; GO:0010836; P:negative regulation of protein ADP-ribosylation; IMP:UniProtKB.
DR GO; GO:1904877; P:positive regulation of DNA ligase activity; IMP:UniProtKB.
DR GO; GO:1903518; P:positive regulation of single strand break repair; IMP:UniProtKB.
DR GO; GO:1990414; P:replication-born double-strand break repair via sister chromatid exchange; IMP:UniProtKB.
DR GO; GO:0033194; P:response to hydroperoxide; IDA:UniProtKB.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0010033; P:response to organic substance; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0000012; P:single strand break repair; IEA:InterPro.
DR GO; GO:0061819; P:telomeric DNA-containing double minutes formation; IEA:Ensembl.
DR GO; GO:0050882; P:voluntary musculoskeletal movement; IMP:UniProtKB.
DR CDD; cd17725; BRCT_XRCC1_rpt1; 1.
DR Gene3D; 3.40.50.10190; -; 2.
DR InterPro; IPR001357; BRCT_dom.
DR InterPro; IPR036420; BRCT_dom_sf.
DR InterPro; IPR045080; BRCT_XRCC1_rpt1.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR002706; Xrcc1_N.
DR Pfam; PF00533; BRCT; 1.
DR Pfam; PF16589; BRCT_2; 1.
DR Pfam; PF01834; XRCC1_N; 1.
DR SMART; SM00292; BRCT; 2.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF52113; SSF52113; 2.
DR PROSITE; PS50172; BRCT; 2.
PE 1: Evidence at protein level;
KW 3D-structure; DNA damage; DNA repair; Isopeptide bond; Neurodegeneration;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Ubl conjugation.
FT CHAIN 1..633
FT /note="DNA repair protein XRCC1"
FT /id="PRO_0000066044"
FT DOMAIN 315..403
FT /note="BRCT 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 538..629
FT /note="BRCT 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT REGION 221..313
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 400..462
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 471..490
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 498..536
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 221..239
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 240..256
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 263..283
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 428..444
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 140
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 198
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 199
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 202
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 204
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 226
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 241
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 257
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 259
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 266
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 281
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 371
FT /note="Phosphoserine; by PRKDC"
FT /evidence="ECO:0000269|PubMed:16397295"
FT MOD_RES 408
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 409
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 410
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 421
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983"
FT MOD_RES 446
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 447
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 453
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 457
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 461
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 485
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:15066279,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 488
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:15066279,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 518
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19155274"
FT MOD_RES 519
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:19155274"
FT MOD_RES 523
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:19155274"
FT CROSSLNK 176
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CROSSLNK 176
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733"
FT VARIANT 7
FT /note="R -> L (in dbSNP:rs2307186)"
FT /id="VAR_014773"
FT VARIANT 10
FT /note="V -> M (in dbSNP:rs2307171)"
FT /id="VAR_014774"
FT VARIANT 72
FT /note="V -> A (in dbSNP:rs25496)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_016168"
FT VARIANT 107
FT /note="R -> H (in dbSNP:rs2228487)"
FT /id="VAR_029228"
FT VARIANT 157
FT /note="E -> K (in dbSNP:rs2307180)"
FT /id="VAR_014775"
FT VARIANT 161
FT /note="P -> L (in dbSNP:rs2307191)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_014776"
FT VARIANT 194
FT /note="R -> W (in dbSNP:rs1799782)"
FT /evidence="ECO:0000269|PubMed:9485007, ECO:0000269|Ref.2"
FT /id="VAR_013400"
FT VARIANT 280
FT /note="R -> H (in dbSNP:rs25489)"
FT /evidence="ECO:0000269|PubMed:9485007, ECO:0000269|Ref.2"
FT /id="VAR_013401"
FT VARIANT 298
FT /note="K -> N (in dbSNP:rs2307188)"
FT /id="VAR_014777"
FT VARIANT 304
FT /note="T -> A (in dbSNP:rs25490)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_018775"
FT VARIANT 309
FT /note="P -> S (in dbSNP:rs25491)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_014778"
FT VARIANT 350
FT /note="R -> W (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs754041352)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036277"
FT VARIANT 399
FT /note="Q -> R (in dbSNP:rs25487)"
FT /evidence="ECO:0000269|PubMed:10783319,
FT ECO:0000269|PubMed:11782372, ECO:0000269|PubMed:2247054,
FT ECO:0000269|PubMed:9485007, ECO:0000269|Ref.2"
FT /id="VAR_011487"
FT VARIANT 431
FT /note="K -> N (in SCAR26; may result in aberrant splicing;
FT dbSNP:rs761564262)"
FT /evidence="ECO:0000269|PubMed:28002403"
FT /id="VAR_079140"
FT VARIANT 465..633
FT /note="Missing (in SCAR26)"
FT /evidence="ECO:0000269|PubMed:28002403"
FT /id="VAR_079141"
FT VARIANT 485
FT /note="S -> Y (in dbSNP:rs2307184)"
FT /id="VAR_014779"
FT VARIANT 514
FT /note="P -> L (in dbSNP:rs25474)"
FT /id="VAR_016169"
FT VARIANT 559
FT /note="R -> Q (in dbSNP:rs2307167)"
FT /id="VAR_014780"
FT VARIANT 560
FT /note="R -> W (in dbSNP:rs2307166)"
FT /id="VAR_014781"
FT VARIANT 576
FT /note="Y -> N (in dbSNP:rs2682557)"
FT /evidence="ECO:0000269|PubMed:15057824"
FT /id="VAR_061727"
FT VARIANT 576
FT /note="Y -> S (in dbSNP:rs2307177)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_014782"
FT HELIX 4..6
FT /evidence="ECO:0007829|PDB:3LQC"
FT STRAND 7..12
FT /evidence="ECO:0007829|PDB:3LQC"
FT HELIX 17..25
FT /evidence="ECO:0007829|PDB:3LQC"
FT HELIX 28..36
FT /evidence="ECO:0007829|PDB:3LQC"
FT TURN 37..39
FT /evidence="ECO:0007829|PDB:3LQC"
FT STRAND 41..53
FT /evidence="ECO:0007829|PDB:3LQC"
FT STRAND 57..64
FT /evidence="ECO:0007829|PDB:3LQC"
FT STRAND 66..73
FT /evidence="ECO:0007829|PDB:3LQC"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:1XNA"
FT HELIX 81..83
FT /evidence="ECO:0007829|PDB:3LQC"
FT STRAND 85..93
FT /evidence="ECO:0007829|PDB:3LQC"
FT HELIX 96..101
FT /evidence="ECO:0007829|PDB:3LQC"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:3LQC"
FT HELIX 113..115
FT /evidence="ECO:0007829|PDB:3LQC"
FT HELIX 118..121
FT /evidence="ECO:0007829|PDB:3LQC"
FT STRAND 125..133
FT /evidence="ECO:0007829|PDB:3LQC"
FT STRAND 138..140
FT /evidence="ECO:0007829|PDB:3K75"
FT STRAND 143..150
FT /evidence="ECO:0007829|PDB:3LQC"
FT HELIX 313..316
FT /evidence="ECO:0007829|PDB:2D8M"
FT TURN 317..319
FT /evidence="ECO:0007829|PDB:2D8M"
FT STRAND 323..329
FT /evidence="ECO:0007829|PDB:2D8M"
FT HELIX 334..344
FT /evidence="ECO:0007829|PDB:2D8M"
FT STRAND 347..352
FT /evidence="ECO:0007829|PDB:2D8M"
FT STRAND 359..366
FT /evidence="ECO:0007829|PDB:2D8M"
FT HELIX 368..376
FT /evidence="ECO:0007829|PDB:2D8M"
FT STRAND 379..382
FT /evidence="ECO:0007829|PDB:2D8M"
FT HELIX 384..391
FT /evidence="ECO:0007829|PDB:2D8M"
FT HELIX 398..401
FT /evidence="ECO:0007829|PDB:2D8M"
FT STRAND 404..407
FT /evidence="ECO:0007829|PDB:2D8M"
FT TURN 542..545
FT /evidence="ECO:0007829|PDB:6WH1"
FT STRAND 547..550
FT /evidence="ECO:0007829|PDB:6WH1"
FT HELIX 558..568
FT /evidence="ECO:0007829|PDB:6WH1"
FT STRAND 583..585
FT /evidence="ECO:0007829|PDB:6WH1"
FT HELIX 592..600
FT /evidence="ECO:0007829|PDB:6WH1"
FT STRAND 605..607
FT /evidence="ECO:0007829|PDB:6WH1"
FT HELIX 609..618
FT /evidence="ECO:0007829|PDB:6WH1"
FT HELIX 624..627
FT /evidence="ECO:0007829|PDB:6WH1"
SQ SEQUENCE 633 AA; 69498 MW; 76174967D034F89F CRC64;
MPEIRLRHVV SCSSQDSTHC AENLLKADTY RKWRAAKAGE KTISVVLQLE KEEQIHSVDI
GNDGSAFVEV LVGSSAGGAG EQDYEVLLVT SSFMSPSESR SGSNPNRVRM FGPDKLVRAA
AEKRWDRVKI VCSQPYSKDS PFGLSFVRFH SPPDKDEAEA PSQKVTVTKL GQFRVKEEDE
SANSLRPGAL FFSRINKTSP VTASDPAGPS YAAATLQASS AASSASPVSR AIGSTSKPQE
SPKGKRKLDL NQEEKKTPSK PPAQLSPSVP KRPKLPAPTR TPATAPVPAR AQGAVTGKPR
GEGTEPRRPR AGPEELGKIL QGVVVVLSGF QNPFRSELRD KALELGAKYR PDWTRDSTHL
ICAFANTPKY SQVLGLGGRI VRKEWVLDCH RMRRRLPSQR YLMAGPGSSS EEDEASHSGG
SGDEAPKLPQ KQPQTKTKPT QAAGPSSPQK PPTPEETKAA SPVLQEDIDI EGVQSEGQDN
GAEDSGDTED ELRRVAEQKE HRLPPGQEEN GEDPYAGSTD ENTDSEEHQE PPDLPVPELP
DFFQGKHFFL YGEFPGDERR KLIRYVTAFN GELEDYMSDR VQFVITAQEW DPSFEEALMD
NPSLAFVRPR WIYSCNEKQK LLPHQLYGVV PQA
