XRCC2_HUMAN
ID XRCC2_HUMAN Reviewed; 280 AA.
AC O43543; B2R925;
DT 03-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=DNA repair protein XRCC2;
DE AltName: Full=X-ray repair cross-complementing protein 2;
GN Name=XRCC2;
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 [GENOMIC DNA / MRNA].
RC TISSUE=Cervix carcinoma;
RX PubMed=9660962; DOI=10.1016/s1097-2765(00)80078-7;
RA Liu N., Lamerdin J.E., Tebbs R.S., Schild D., Tucker J.D., Shen M.R.,
RA Brookman K.W., Siciliano M.J., Walter C.A., Fan W., Narayana L.S.,
RA Zhou Z.-Q., Adamson A.W., Sorensen K.J., Chen D.J., Jones N.J.,
RA Thompson L.H.;
RT "XRCC2 and XRCC3, new human Rad51-family members, promote chromosome
RT stability and protect against DNA cross-links and other damages.";
RL Mol. Cell 1:783-793(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9126486; DOI=10.1006/geno.1997.4636;
RA Tambini C.E., George A.M., Rommens J.M., Tsui L.-C., Scherer S.W.,
RA Thacker J.;
RT "The XRCC2 DNA repair gene: identification of a positional candidate.";
RL Genomics 41:84-92(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC TISSUE=Cervix carcinoma;
RX PubMed=9628903; DOI=10.1093/nar/26.13.3084;
RA Cartwright R., Tambini C.E., Simpson P.J., Thacker J.;
RT "The XRCC2 DNA repair gene from human and mouse encodes a novel member of
RT the recA/RAD51 family.";
RL Nucleic Acids Res. 26:3084-3089(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-188 AND THR-221.
RG NIEHS SNPs program;
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [8]
RP FUNCTION, AND IDENTIFICATION IN THE BCDX2 COMPLEX WITH RAD51C; RAD51D AND
RP XRCC2.
RX PubMed=11751635; DOI=10.1101/gad.947001;
RA Masson J.Y., Tarsounas M.C., Stasiak A.Z., Stasiak A., Shah R.,
RA McIlwraith M.J., Benson F.E., West S.C.;
RT "Identification and purification of two distinct complexes containing the
RT five RAD51 paralogs.";
RL Genes Dev. 15:3296-3307(2001).
RN [9]
RP SUBUNIT.
RX PubMed=11744692; DOI=10.1074/jbc.m108306200;
RA Miller K.A., Yoshikawa D.M., McConnell I.R., Clark R., Schild D.,
RA Albala J.S.;
RT "RAD51C interacts with RAD51B and is central to a larger protein complex in
RT vivo exclusive of RAD51.";
RL J. Biol. Chem. 277:8406-8411(2002).
RN [10]
RP FUNCTION, AND SUBUNIT.
RX PubMed=11834724; DOI=10.1074/jbc.m105719200;
RA Kurumizaka H., Ikawa S., Nakada M., Enomoto R., Kagawa W., Kinebuchi T.,
RA Yamazoe M., Yokoyama S., Shibata T.;
RT "Homologous pairing and ring and filament structure formation activities of
RT the human Xrcc2*Rad51D complex.";
RL J. Biol. Chem. 277:14315-14320(2002).
RN [11]
RP IDENTIFICATION IN A COMPLEX WITH RAD51B; RAD51C AND RAD51D.
RX PubMed=11842112; DOI=10.1093/nar/30.4.1001;
RA Wiese C., Collins D.W., Albala J.S., Thompson L.H., Kronenberg A.,
RA Schild D.;
RT "Interactions involving the Rad51 paralogs Rad51C and XRCC3 in human
RT cells.";
RL Nucleic Acids Res. 30:1001-1008(2002).
RN [12]
RP IDENTIFICATION IN A COMPLEX WITH RAD51B; RAD51C AND RAD51D.
RX PubMed=11842113; DOI=10.1093/nar/30.4.1009;
RA Liu N., Schild D., Thelen M.P., Thompson L.H.;
RT "Involvement of Rad51C in two distinct protein complexes of Rad51 paralogs
RT in human cells.";
RL Nucleic Acids Res. 30:1009-1015(2002).
RN [13]
RP INTERACTION WITH RAD51D.
RX PubMed=14704354; DOI=10.1093/nar/gkg925;
RA Miller K.A., Sawicka D., Barsky D., Albala J.S.;
RT "Domain mapping of the Rad51 paralog protein complexes.";
RL Nucleic Acids Res. 32:169-178(2004).
RN [14]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21276791; DOI=10.1016/j.yexcr.2011.01.021;
RA Cappelli E., Townsend S., Griffin C., Thacker J.;
RT "Homologous recombination proteins are associated with centrosomes and are
RT required for mitotic stability.";
RL Exp. Cell Res. 317:1203-1213(2011).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10, AND IDENTIFICATION BY
RP MASS 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 [16]
RP FUNCTION OF THE BCDX2 COMPLEX.
RX PubMed=23149936; DOI=10.1128/mcb.00465-12;
RA Chun J., Buechelmaier E.S., Powell S.N.;
RT "Rad51 paralog complexes BCDX2 and CX3 act at different stages in the
RT BRCA1-BRCA2-dependent homologous recombination pathway.";
RL Mol. Cell. Biol. 33:387-395(2013).
RN [17]
RP ELECTRON MICROSCOPY OF THE BCDX2 COMPLEX, AND DNA-BINDING OF THE BCDX2
RP COMPLEX.
RX PubMed=20207730; DOI=10.1074/jbc.m109.074286;
RA Compton S.A., Ozgur S., Griffith J.D.;
RT "Ring-shaped Rad51 paralog protein complexes bind Holliday junctions and
RT replication forks as visualized by electron microscopy.";
RL J. Biol. Chem. 285:13349-13356(2010).
RN [18]
RP VARIANTS SER-16; ILE-61; TRP-91; VAL-95; CYS-231 AND VAL-270.
RX PubMed=22464251; DOI=10.1016/j.ajhg.2012.02.027;
RG Breast Cancer Family Registry;
RG Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer;
RA Park D.J., Lesueur F., Nguyen-Dumont T., Pertesi M., Odefrey F., Hammet F.,
RA Neuhausen S.L., John E.M., Andrulis I.L., Terry M.B., Daly M., Buys S.,
RA Le Calvez-Kelm F., Lonie A., Pope B.J., Tsimiklis H., Voegele C.,
RA Hilbers F.M., Hoogerbrugge N., Barroso A., Osorio A., Giles G.G.,
RA Devilee P., Benitez J., Hopper J.L., Tavtigian S.V., Goldgar D.E.,
RA Southey M.C.;
RT "Rare mutations in XRCC2 increase the risk of breast cancer.";
RL Am. J. Hum. Genet. 90:734-739(2012).
RN [19]
RP INVOLVEMENT IN FANCU.
RX PubMed=22232082; DOI=10.1136/jmedgenet-2011-100585;
RA Shamseldin H.E., Elfaki M., Alkuraya F.S.;
RT "Exome sequencing reveals a novel Fanconi group defined by XRCC2
RT mutation.";
RL J. Med. Genet. 49:184-186(2012).
RN [20]
RP VARIANTS ARG-47; GLN-75; VAL-95; ALA-118; TYR-120; PRO-133; GLN-164;
RP ALA-170; CYS-188; MET-194; LEU-199; GLY-207; VAL-220; SER-238; GLU-248;
RP CYS-258 AND VAL-270.
RX PubMed=23054243; DOI=10.1136/jmedgenet-2012-101191;
RA Hilbers F.S., Wijnen J.T., Hoogerbrugge N., Oosterwijk J.C., Collee M.J.,
RA Peterlongo P., Radice P., Manoukian S., Feroce I., Capra F., Couch F.J.,
RA Wang X., Guidugli L., Offit K., Shah S., Campbell I.G., Thompson E.R.,
RA James P.A., Trainer A.H., Gracia J., Benitez J., van Asperen C.J.,
RA Devilee P.;
RT "Rare variants in XRCC2 as breast cancer susceptibility alleles.";
RL J. Med. Genet. 49:618-620(2012).
RN [21]
RP VARIANTS SER-16; ARG-47; ILE-61; GLN-75; TRP-91; VAL-95; ALA-118; TYR-120;
RP PRO-133; GLN-164; ALA-170; CYS-188; HIS-188; MET-194; LEU-199; GLY-207;
RP VAL-220; CYS-231; SER-238; GLU-248; CYS-258 AND VAL-270, FUNCTION, AND
RP CHARACTERIZATION OF VARIANTS SER-16; ARG-47; ILE-61; GLN-75; TRP-91;
RP VAL-95; ALA-118; TYR-120; PRO-133; GLN-164; ALA-170; CYS-188; HIS-188;
RP MET-194; LEU-199; GLY-207; VAL-220; CYS-231; SER-238; GLU-248; CYS-258 AND
RP VAL-270.
RX PubMed=27233470; DOI=10.1002/humu.23019;
RA Hilbers F.S., Luijsterburg M.S., Wiegant W.W., Meijers C.M.,
RA Voelker-Albert M., Boonen R.A., van Asperen C.J., Devilee P.,
RA van Attikum H.;
RT "Functional analysis of missense variants in the putative breast cancer
RT susceptibility gene XRCC2.";
RL Hum. Mutat. 37:914-925(2016).
RN [22]
RP VARIANT SPGF50 PRO-14, AND INVOLVEMENT IN SPGF50.
RX PubMed=30042186; DOI=10.1136/jmedgenet-2017-105145;
RA Yang Y., Guo J., Dai L., Zhu Y., Hu H., Tan L., Chen W., Liang D., He J.,
RA Tu M., Wang K., Wu L.;
RT "XRCC2 mutation causes meiotic arrest, azoospermia and infertility.";
RL J. Med. Genet. 55:628-636(2018).
RN [23]
RP VARIANT POF17 PRO-14, AND INVOLVEMENT IN POF17.
RX PubMed=30489636; DOI=10.1111/cge.13475;
RA Zhang Y.X., Li H.Y., He W.B., Tu C., Du J., Li W., Lu G.X., Lin G.,
RA Yang Y., Tan Y.Q.;
RT "XRCC2 mutation causes premature ovarian insufficiency as well as non-
RT obstructive azoospermia in humans.";
RL Clin. Genet. 95:442-443(2019).
RN [24]
RP VARIANT 215-ARG--CYS-280 DEL.
RX PubMed=30237576; DOI=10.1038/s41436-018-0138-x;
RA Maddirevula S., Alzahrani F., Al-Owain M., Al Muhaizea M.A., Kayyali H.R.,
RA AlHashem A., Rahbeeni Z., Al-Otaibi M., Alzaidan H.I., Balobaid A.,
RA El Khashab H.Y., Bubshait D.K., Faden M., Yamani S.A., Dabbagh O.,
RA Al-Mureikhi M., Jasser A.A., Alsaif H.S., Alluhaydan I., Seidahmed M.Z.,
RA Alabbasi B.H., Almogarri I., Kurdi W., Akleh H., Qari A., Al Tala S.M.,
RA Alhomaidi S., Kentab A.Y., Salih M.A., Chedrawi A., Alameer S., Tabarki B.,
RA Shamseldin H.E., Patel N., Ibrahim N., Abdulwahab F., Samira M., Goljan E.,
RA Abouelhoda M., Meyer B.F., Hashem M., Shaheen R., AlShahwan S.,
RA Alfadhel M., Ben-Omran T., Al-Qattan M.M., Monies D., Alkuraya F.S.;
RT "Autozygome and high throughput confirmation of disease genes candidacy.";
RL Genet. Med. 21:736-742(2019).
CC -!- FUNCTION: Involved in the homologous recombination repair (HRR) pathway
CC of double-stranded DNA, thought to repair chromosomal fragmentation,
CC translocations and deletions. Part of the RAD51 paralog protein complex
CC BCDX2 which acts in the BRCA1-BRCA2-dependent HR pathway. Upon DNA
CC damage, BCDX2 acts downstream of BRCA2 recruitment and upstream of
CC RAD51 recruitment. BCDX2 binds predominantly to the intersection of the
CC four duplex arms of the Holliday junction and to junction of
CC replication forks. The BCDX2 complex was originally reported to bind
CC single-stranded DNA, single-stranded gaps in duplex DNA and
CC specifically to nicks in duplex DNA. {ECO:0000269|PubMed:11751635,
CC ECO:0000269|PubMed:11834724, ECO:0000269|PubMed:21276791,
CC ECO:0000269|PubMed:23149936, ECO:0000269|PubMed:27233470}.
CC -!- SUBUNIT: Interacts with RAD51D. Part of the BCDX2 complex consisting of
CC RAD51B, RAD51C, RAD51D and XRCC2; the complex has a ring-like structure
CC arranged into a flat disk around a central channel. In the absence of
CC DNA, the BCDX2 subcomplex XRCC2:RAD51D formed a multimeric ring
CC structure; in the presence of single-stranded DNA it formed a
CC filamentous structure with the ssDNA. {ECO:0000269|PubMed:11744692,
CC ECO:0000269|PubMed:11751635, ECO:0000269|PubMed:11834724,
CC ECO:0000269|PubMed:11842112, ECO:0000269|PubMed:11842113,
CC ECO:0000269|PubMed:14704354}.
CC -!- INTERACTION:
CC O43543; P50222: MEOX2; NbExp=3; IntAct=EBI-3918457, EBI-748397;
CC O43543; O43502: RAD51C; NbExp=3; IntAct=EBI-3918457, EBI-2267048;
CC O43543; O75771: RAD51D; NbExp=38; IntAct=EBI-3918457, EBI-1055693;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21276791}. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000269|PubMed:21276791}.
CC -!- DISEASE: Fanconi anemia, complementation group U (FANCU) [MIM:617247]:
CC A disorder affecting all bone marrow elements and resulting in anemia,
CC leukopenia and thrombopenia. It is associated with cardiac, renal and
CC limb malformations, dermal pigmentary changes, and a predisposition to
CC the development of malignancies. At the cellular level it is associated
CC with hypersensitivity to DNA-damaging agents, chromosomal instability
CC (increased chromosome breakage) and defective DNA repair.
CC {ECO:0000269|PubMed:22232082}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Spermatogenic failure 50 (SPGF50) [MIM:619145]: An autosomal
CC recessive infertility disorder characterized by azoospermia due to
CC meiotic arrest at the zygotene stage of prophase I.
CC {ECO:0000269|PubMed:30042186}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Premature ovarian failure 17 (POF17) [MIM:619146]: A form of
CC premature ovarian failure, an ovarian disorder defined as the cessation
CC of ovarian function under the age of 40 years. It is characterized by
CC oligomenorrhea or amenorrhea, in the presence of elevated levels of
CC serum gonadotropins and low estradiol. POF17 transmission pattern is
CC consistent with autosomal recessive inheritance.
CC {ECO:0000269|PubMed:30489636}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the RecA family. RAD51 subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/xrcc2/";
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DR EMBL; AF035587; AAC05369.1; -; mRNA.
DR EMBL; AC003109; AAC05802.1; -; Genomic_DNA.
DR EMBL; Y08837; CAA70065.1; -; mRNA.
DR EMBL; Y17033; CAA76597.1; -; Genomic_DNA.
DR EMBL; AF520762; AAM55241.1; -; Genomic_DNA.
DR EMBL; AK313607; BAG36372.1; -; mRNA.
DR EMBL; CH471173; EAW53968.1; -; Genomic_DNA.
DR EMBL; BC042137; AAH42137.1; -; mRNA.
DR CCDS; CCDS5933.1; -.
DR RefSeq; NP_005422.1; NM_005431.1.
DR AlphaFoldDB; O43543; -.
DR SMR; O43543; -.
DR BioGRID; 113350; 26.
DR CORUM; O43543; -.
DR DIP; DIP-24242N; -.
DR IntAct; O43543; 14.
DR MINT; O43543; -.
DR STRING; 9606.ENSP00000352271; -.
DR iPTMnet; O43543; -.
DR PhosphoSitePlus; O43543; -.
DR BioMuta; XRCC2; -.
DR EPD; O43543; -.
DR jPOST; O43543; -.
DR MassIVE; O43543; -.
DR MaxQB; O43543; -.
DR PaxDb; O43543; -.
DR PeptideAtlas; O43543; -.
DR PRIDE; O43543; -.
DR ProteomicsDB; 49042; -.
DR Antibodypedia; 18833; 378 antibodies from 36 providers.
DR DNASU; 7516; -.
DR Ensembl; ENST00000359321.2; ENSP00000352271.1; ENSG00000196584.3.
DR GeneID; 7516; -.
DR KEGG; hsa:7516; -.
DR MANE-Select; ENST00000359321.2; ENSP00000352271.1; NM_005431.2; NP_005422.1.
DR UCSC; uc003wld.4; human.
DR CTD; 7516; -.
DR DisGeNET; 7516; -.
DR GeneCards; XRCC2; -.
DR GeneReviews; XRCC2; -.
DR HGNC; HGNC:12829; XRCC2.
DR HPA; ENSG00000196584; Tissue enhanced (bone).
DR MalaCards; XRCC2; -.
DR MIM; 600375; gene.
DR MIM; 617247; phenotype.
DR MIM; 619145; phenotype.
DR MIM; 619146; phenotype.
DR neXtProt; NX_O43543; -.
DR OpenTargets; ENSG00000196584; -.
DR Orphanet; 84; Fanconi anemia.
DR Orphanet; 227535; Hereditary breast cancer.
DR Orphanet; 399805; Male infertility with azoospermia or oligozoospermia due to single gene mutation.
DR PharmGKB; PA37421; -.
DR VEuPathDB; HostDB:ENSG00000196584; -.
DR eggNOG; KOG2859; Eukaryota.
DR GeneTree; ENSGT00390000020445; -.
DR HOGENOM; CLU_059815_1_0_1; -.
DR InParanoid; O43543; -.
DR OMA; KHCLGRL; -.
DR OrthoDB; 1522846at2759; -.
DR PhylomeDB; O43543; -.
DR TreeFam; TF101202; -.
DR PathwayCommons; O43543; -.
DR Reactome; R-HSA-5685942; HDR through Homologous Recombination (HRR).
DR Reactome; R-HSA-5693554; Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA).
DR Reactome; R-HSA-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR Reactome; R-HSA-5693579; Homologous DNA Pairing and Strand Exchange.
DR Reactome; R-HSA-5693616; Presynaptic phase of homologous DNA pairing and strand exchange.
DR Reactome; R-HSA-9701192; Defective HDR through Homologous Recombination (HRR) due to BRCA1 loss-of-function.
DR Reactome; R-HSA-9704331; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function.
DR Reactome; R-HSA-9704646; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function.
DR Reactome; R-HSA-9709603; Impaired BRCA2 binding to PALB2.
DR SignaLink; O43543; -.
DR BioGRID-ORCS; 7516; 391 hits in 1090 CRISPR screens.
DR ChiTaRS; XRCC2; human.
DR GeneWiki; XRCC2; -.
DR GenomeRNAi; 7516; -.
DR Pharos; O43543; Tbio.
DR PRO; PR:O43543; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; O43543; protein.
DR Bgee; ENSG00000196584; Expressed in buccal mucosa cell and 206 other tissues.
DR ExpressionAtlas; O43543; baseline and differential.
DR Genevisible; O43543; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0033063; C:Rad51B-Rad51C-Rad51D-XRCC2 complex; IDA:UniProtKB.
DR GO; GO:0005657; C:replication fork; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR GO; GO:0140664; F:ATP-dependent DNA damage sensor activity; IEA:InterPro.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0007098; P:centrosome cycle; IMP:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IGI:BHF-UCL.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IMP:UniProtKB.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0051321; P:meiotic cell cycle; TAS:ProtInc.
DR GO; GO:0000278; P:mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0022008; P:neurogenesis; IEA:Ensembl.
DR GO; GO:0050769; P:positive regulation of neurogenesis; IEA:Ensembl.
DR GO; GO:2000269; P:regulation of fibroblast apoptotic process; IEA:Ensembl.
DR GO; GO:0010332; P:response to gamma radiation; IEA:Ensembl.
DR GO; GO:0010165; P:response to X-ray; IEA:Ensembl.
DR GO; GO:0001756; P:somitogenesis; IEA:Ensembl.
DR GO; GO:0042148; P:strand invasion; IDA:UniProtKB.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR013632; DNA_recomb/repair_Rad51_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR020588; RecA_ATP-bd.
DR InterPro; IPR030547; XRCC2.
DR PANTHER; PTHR46644; PTHR46644; 1.
DR Pfam; PF08423; Rad51; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50162; RECA_2; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Cytoskeleton; Disease variant; DNA damage; DNA recombination;
KW DNA repair; DNA-binding; Fanconi anemia; Nucleus; Phosphoprotein;
KW Premature ovarian failure; Reference proteome.
FT CHAIN 1..280
FT /note="DNA repair protein XRCC2"
FT /id="PRO_0000122948"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 14
FT /note="L -> P (in SPGF50 and POF17; due to a nucleotide
FT substitution that causes partial exon 2 skipping; patient
FT cells contain both normally spliced transcripts and
FT transcripts lacking exon 2; dbSNP:rs757140620)"
FT /evidence="ECO:0000269|PubMed:30042186,
FT ECO:0000269|PubMed:30489636"
FT /id="VAR_085247"
FT VARIANT 16
FT /note="A -> S (does not affect function in double-strand
FT break repair via homologous recombination as shown in
FT rescue assays of XRCC2-deficient cells; dbSNP:rs4987090)"
FT /evidence="ECO:0000269|PubMed:22464251,
FT ECO:0000269|PubMed:27233470"
FT /id="VAR_020403"
FT VARIANT 47
FT /note="H -> R (does not affect function in double-strand
FT break repair via homologous recombination as shown in
FT rescue assays of XRCC2-deficient cells; dbSNP:rs587780126)"
FT /evidence="ECO:0000269|PubMed:23054243,
FT ECO:0000269|PubMed:27233470"
FT /id="VAR_077167"
FT VARIANT 61
FT /note="L -> I (does not affect function in double-strand
FT break repair via homologous recombination as shown in
FT rescue assays of XRCC2-deficient cells; dbSNP:rs569810249)"
FT /evidence="ECO:0000269|PubMed:22464251,
FT ECO:0000269|PubMed:27233470"
FT /id="VAR_077168"
FT VARIANT 75
FT /note="E -> Q (does not affect function in double-strand
FT break repair via homologous recombination as shown in
FT rescue assays of XRCC2-deficient cells;
FT dbSNP:rs1327414828)"
FT /evidence="ECO:0000269|PubMed:23054243,
FT ECO:0000269|PubMed:27233470"
FT /id="VAR_077169"
FT VARIANT 91
FT /note="R -> W (rare variant; found in breast cancer;
FT unknown pathological significance; moderately decreased
FT function in double-strand break repair via homologous
FT recombination as shown in rescue assays of XRCC2-deficient
FT cells; dbSNP:rs730882043)"
FT /evidence="ECO:0000269|PubMed:22464251,
FT ECO:0000269|PubMed:27233470"
FT /id="VAR_077170"
FT VARIANT 95
FT /note="I -> V (does not affect function in double-strand
FT break repair via homologous recombination as shown in
FT rescue assays of XRCC2-deficient cells; dbSNP:rs140214637)"
FT /evidence="ECO:0000269|PubMed:22464251,
FT ECO:0000269|PubMed:23054243, ECO:0000269|PubMed:27233470"
FT /id="VAR_077171"
FT VARIANT 118
FT /note="V -> A (does not affect function in double-strand
FT break repair via homologous recombination as shown in
FT rescue assays of XRCC2-deficient cells; dbSNP:rs185815454)"
FT /evidence="ECO:0000269|PubMed:23054243,
FT ECO:0000269|PubMed:27233470"
FT /id="VAR_077172"
FT VARIANT 120
FT /note="C -> Y (rare variant; found in breast cancer;
FT unknown pathological significance; moderately decreased
FT function in double-strand break repair via homologous
FT recombination as shown in rescue assays of XRCC2-deficient
FT cells; dbSNP:rs1432878196)"
FT /evidence="ECO:0000269|PubMed:23054243,
FT ECO:0000269|PubMed:27233470"
FT /id="VAR_077173"
FT VARIANT 133
FT /note="L -> P (rare variant; found in breast cancer;
FT unknown pathological significance; moderately decreased
FT function in double-strand break repair via homologous
FT recombination as shown in rescue assays of XRCC2-deficient
FT cells; dbSNP:rs765276614)"
FT /evidence="ECO:0000269|PubMed:23054243,
FT ECO:0000269|PubMed:27233470"
FT /id="VAR_077174"
FT VARIANT 164
FT /note="E -> Q (does not affect function in double-strand
FT break repair via homologous recombination as shown in
FT rescue assays of XRCC2-deficient cells;
FT dbSNP:rs1215678098)"
FT /evidence="ECO:0000269|PubMed:23054243,
FT ECO:0000269|PubMed:27233470"
FT /id="VAR_077175"
FT VARIANT 170
FT /note="E -> A (does not affect function in double-strand
FT break repair via homologous recombination as shown in
FT rescue assays of XRCC2-deficient cells; dbSNP:rs778143946)"
FT /evidence="ECO:0000269|PubMed:23054243,
FT ECO:0000269|PubMed:27233470"
FT /id="VAR_077176"
FT VARIANT 188
FT /note="R -> C (does not affect function in double-strand
FT break repair via homologous recombination as shown in
FT rescue assays of XRCC2-deficient cells; dbSNP:rs139219364)"
FT /evidence="ECO:0000269|PubMed:23054243,
FT ECO:0000269|PubMed:27233470"
FT /id="VAR_077177"
FT VARIANT 188
FT /note="R -> H (does not affect function in double-strand
FT break repair via homologous recombination as shown in
FT rescue assays of XRCC2-deficient cells; dbSNP:rs3218536)"
FT /evidence="ECO:0000269|PubMed:27233470, ECO:0000269|Ref.4"
FT /id="VAR_020404"
FT VARIANT 194
FT /note="T -> M (does not affect function in double-strand
FT break repair via homologous recombination as shown in
FT rescue assays of XRCC2-deficient cells; dbSNP:rs775565256)"
FT /evidence="ECO:0000269|PubMed:23054243,
FT ECO:0000269|PubMed:27233470"
FT /id="VAR_077178"
FT VARIANT 199
FT /note="M -> L (likely benign variant; does not affect
FT function in double-strand break repair via homologous
FT recombination as shown in rescue assays of XRCC2-deficient
FT cells)"
FT /evidence="ECO:0000269|PubMed:23054243,
FT ECO:0000269|PubMed:27233470"
FT /id="VAR_077179"
FT VARIANT 207
FT /note="E -> G (does not affect function in double-strand
FT break repair via homologous recombination as shown in
FT rescue assays of XRCC2-deficient cells; dbSNP:rs61762969)"
FT /evidence="ECO:0000269|PubMed:23054243,
FT ECO:0000269|PubMed:27233470"
FT /id="VAR_077180"
FT VARIANT 215..280
FT /note="Missing (found in a patient with borderline
FT microcephaly, bilateral hypoplastic thumb, multiple cafe
FT late spots, strabismus and dysmorphic facial features;
FT unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:30237576"
FT /id="VAR_082157"
FT VARIANT 220
FT /note="D -> V (does not affect function in double-strand
FT break repair via homologous recombination as shown in
FT rescue assays of XRCC2-deficient cells; dbSNP:rs765021741)"
FT /evidence="ECO:0000269|PubMed:23054243,
FT ECO:0000269|PubMed:27233470"
FT /id="VAR_077181"
FT VARIANT 221
FT /note="I -> T (in dbSNP:rs3218537)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_029294"
FT VARIANT 231
FT /note="W -> C (does not affect function in double-strand
FT break repair via homologous recombination as shown in
FT rescue assays of XRCC2-deficient cells;
FT dbSNP:rs1267462913)"
FT /evidence="ECO:0000269|PubMed:22464251,
FT ECO:0000269|PubMed:27233470"
FT /id="VAR_077182"
FT VARIANT 238
FT /note="R -> S (does not affect function in double-strand
FT break repair via homologous recombination as shown in
FT rescue assays of XRCC2-deficient cells; dbSNP:rs534746330)"
FT /evidence="ECO:0000269|PubMed:23054243,
FT ECO:0000269|PubMed:27233470"
FT /id="VAR_077183"
FT VARIANT 248
FT /note="Q -> E (does not affect function in double-strand
FT break repair via homologous recombination as shown in
FT rescue assays of XRCC2-deficient cells; dbSNP:rs190900560)"
FT /evidence="ECO:0000269|PubMed:23054243,
FT ECO:0000269|PubMed:27233470"
FT /id="VAR_077184"
FT VARIANT 258
FT /note="R -> C (does not affect function in double-strand
FT break repair via homologous recombination as shown in
FT rescue assays of XRCC2-deficient cells; dbSNP:rs759300252)"
FT /evidence="ECO:0000269|PubMed:23054243,
FT ECO:0000269|PubMed:27233470"
FT /id="VAR_077185"
FT VARIANT 270
FT /note="F -> V (does not affect function in double-strand
FT break repair via homologous recombination as shown in
FT rescue assays of XRCC2-deficient cells; dbSNP:rs145085742)"
FT /evidence="ECO:0000269|PubMed:22464251,
FT ECO:0000269|PubMed:23054243, ECO:0000269|PubMed:27233470"
FT /id="VAR_077186"
SQ SEQUENCE 280 AA; 31956 MW; 5656277E74C06074 CRC64;
MCSAFHRAES GTELLARLEG RSSLKEIEPN LFADEDSPVH GDILEFHGPE GTGKTEMLYH
LTARCILPKS EGGLEVEVLF IDTDYHFDML RLVTILEHRL SQSSEEIIKY CLGRFFLVYC
SSSTHLLLTL YSLESMFCSH PSLCLLILDS LSAFYWIDRV NGGESVNLQE STLRKCSQCL
EKLVNDYRLV LFATTQTIMQ KASSSSEEPS HASRRLCDVD IDYRPYLCKA WQQLVKHRMF
FSKQDDSQSS NQFSLVSRCL KSNSLKKHFF IIGESGVEFC
