MRE11_HUMAN
ID MRE11_HUMAN Reviewed; 708 AA.
AC P49959; B3KTC7; O43475;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 26-SEP-2001, sequence version 3.
DT 03-AUG-2022, entry version 226.
DE RecName: Full=Double-strand break repair protein MRE11;
DE EC=3.1.-.- {ECO:0000269|PubMed:29670289};
DE AltName: Full=Double-strand break repair protein MRE11A;
DE AltName: Full=Meiotic recombination 11 homolog 1;
DE Short=MRE11 homolog 1;
DE AltName: Full=Meiotic recombination 11 homolog A;
DE Short=MRE11 homolog A;
GN Name=MRE11 {ECO:0000312|HGNC:HGNC:7230}; Synonyms=HNGS1, MRE11A;
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] (ISOFORM 2).
RX PubMed=8530104; DOI=10.1006/geno.1995.1217;
RA Petrini J.H.J., Walsh M.E., Dimare C., Chen X.-N., Korenberg J.R.,
RA Weaver D.T.;
RT "Isolation and characterization of the human MRE11 homologue.";
RL Genomics 29:80-86(1995).
RN [2]
RP SEQUENCE REVISION TO C-TERMINUS.
RA Petrini J.H.J., Walsh M.E., Dimare C., Chen X.-N., Korenberg J.R.,
RA Weaver D.T.;
RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Chamankhah M., Wei Y., Xiao W.;
RT "Molecular cloning and functional characterization of hNGS1, a yeast and
RT human MRE11 homolog.";
RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND INTERACTION WITH
RP RAD50.
RX PubMed=9651580; DOI=10.1016/s1097-2765(00)80097-0;
RA Paull T.T., Gellert M.;
RT "The 3' to 5' exonuclease activity of Mre 11 facilitates repair of DNA
RT double-strand breaks.";
RL Mol. Cell 1:969-979(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=11371508; DOI=10.1093/hmg/10.11.1155;
RA Pitts S.A., Kullar H.S., Stankovic T., Stewart G.S., Last J.I.K.,
RA Bedenham T., Armstrong S.J., Piane M., Chessa L., Taylor A.M.R., Byrd P.J.;
RT "hMRE11: genomic structure and a null mutation identified in a transcript
RT protected from nonsense-mediated mRNA decay.";
RL Hum. Mol. Genet. 10:1155-1162(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Tongue;
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 [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLY-468 AND VAL-698.
RG NIEHS SNPs program;
RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [10]
RP FUNCTION IN DSB REPAIR, AND IDENTIFICATION IN THE MRN COMPLEX WITH RAD50
RP AND NBN.
RX PubMed=9590181; DOI=10.1016/s0092-8674(00)81175-7;
RA Carney J.P., Maser R.S., Olivares H., Davis E.M., Le Beau M.,
RA Yates J.R. III, Hays L., Morgan W.F., Petrini J.H.J.;
RT "The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage
RT of double-strand break repair to the cellular DNA damage response.";
RL Cell 93:477-486(1998).
RN [11]
RP FUNCTION IN DSB REPAIR, AND IDENTIFICATION IN THE MRN COMPLEX WITH RAD50
RP AND NBN.
RX PubMed=9705271; DOI=10.1074/jbc.273.34.21447;
RA Trujillo K.M., Yuan S.-S.F., Lee E.Y.-H.P., Sung P.;
RT "Nuclease activities in a complex of human recombination and DNA repair
RT factors Rad50, Mre11, and p95.";
RL J. Biol. Chem. 273:21447-21450(1998).
RN [12]
RP SUBCELLULAR LOCATION, AND IDENTIFICATION IN THE BASC COMPLEX WITH BRCA1;
RP MSH2; MSH6; MLH1; ATM; BLM; RAD50 AND NBN.
RX PubMed=10783165;
RA Wang Y., Cortez D., Yazdi P., Neff N., Elledge S.J., Qin J.;
RT "BASC, a super complex of BRCA1-associated proteins involved in the
RT recognition and repair of aberrant DNA structures.";
RL Genes Dev. 14:927-939(2000).
RN [13]
RP IDENTIFICATION IN THE MRN COMPLEX WITH RAD50 AND NBN.
RX PubMed=10839544; DOI=10.1038/35013083;
RA Zhao S., Weng Y.-C., Yuan S.-S.F., Lin Y.-T., Hsu H.-C., Lin S.-C.,
RA Gerbino E., Song M.-H., Zdzienicka M.Z., Gatti R.A., Shay J.W., Ziv Y.,
RA Shiloh Y., Lee E.Y.-H.P.;
RT "Functional link between ataxia-telangiectasia and Nijmegen breakage
RT syndrome gene products.";
RL Nature 405:473-477(2000).
RN [14]
RP FUNCTION IN TELOMERES, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION
RP IN THE A COMPLEX WITH TERF2, AND SUBCELLULAR LOCATION.
RX PubMed=10888888; DOI=10.1038/77139;
RA Zhu X.-D., Kuester B., Mann M., Petrini J.H.J., de Lange T.;
RT "Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human
RT telomeres.";
RL Nat. Genet. 25:347-352(2000).
RN [15]
RP FUNCTION.
RX PubMed=11741547; DOI=10.1016/s1097-2765(01)00381-1;
RA de Jager M., van Noort J., van Gent D.C., Dekker C., Kanaar R., Wyman C.;
RT "Human Rad50/Mre11 is a flexible complex that can tether DNA ends.";
RL Mol. Cell 8:1129-1135(2001).
RN [16]
RP INTERACTION WITH DCLRE1C.
RX PubMed=15456891; DOI=10.1128/mcb.24.20.9207-9220.2004;
RA Zhang X., Succi J., Feng Z., Prithivirajsingh S., Story M.D.,
RA Legerski R.J.;
RT "Artemis is a phosphorylation target of ATM and ATR and is involved in the
RT G2/M DNA damage checkpoint response.";
RL Mol. Cell. Biol. 24:9207-9220(2004).
RN [17]
RP FUNCTION IN ATM ACTIVATION.
RX PubMed=15064416; DOI=10.1126/science.1091496;
RA Lee J.-H., Paull T.T.;
RT "Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1
RT complex.";
RL Science 304:93-96(2004).
RN [18]
RP INTERACTION WITH DCLRE1C.
RX PubMed=15723659; DOI=10.1111/j.1349-7006.2005.00019.x;
RA Chen L., Morio T., Minegishi Y., Nakada S., Nagasawa M., Komatsu K.,
RA Chessa L., Villa A., Lecis D., Delia D., Mizutani S.;
RT "Ataxia-telangiectasia-mutated dependent phosphorylation of Artemis in
RT response to DNA damage.";
RL Cancer Sci. 96:134-141(2005).
RN [19]
RP INTERACTION WITH ATF2, AND SUBCELLULAR LOCATION.
RX PubMed=15916964; DOI=10.1016/j.molcel.2005.04.015;
RA Bhoumik A., Takahashi S., Breitweiser W., Shiloh Y., Jones N., Ronai Z.;
RT "ATM-dependent phosphorylation of ATF2 is required for the DNA damage
RT response.";
RL Mol. Cell 18:577-587(2005).
RN [20]
RP IDENTIFICATION BY 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 [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [22]
RP INTERACTION WITH DCLRE1B.
RX PubMed=18469862; DOI=10.1038/onc.2008.139;
RA Bae J.B., Mukhopadhyay S.S., Liu L., Zhang N., Tan J., Akhter S., Liu X.,
RA Shen X., Li L., Legerski R.J.;
RT "Snm1B/Apollo mediates replication fork collapse and S Phase checkpoint
RT activation in response to DNA interstrand cross-links.";
RL Oncogene 27:5045-5056(2008).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-649; SER-688; SER-689 AND
RP SER-701, AND IDENTIFICATION BY MASS 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 [24]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-649; SER-688 AND SER-689, AND
RP IDENTIFICATION BY MASS 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 [26]
RP INTERACTION WITH HERPES SIMPLEX VIRUS 1 UL12.
RX PubMed=20943970; DOI=10.1128/jvi.01506-10;
RA Balasubramanian N., Bai P., Buchek G., Korza G., Weller S.K.;
RT "Physical interaction between the herpes simplex virus type 1 exonuclease,
RT UL12, and the DNA double-strand break-sensing MRN complex.";
RL J. Virol. 84:12504-12514(2010).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-688 AND SER-689, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [28]
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).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-688 AND SER-689, 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 [30]
RP INVOLVEMENT IN NPHP-RC.
RX PubMed=22863007; DOI=10.1016/j.cell.2012.06.028;
RA Chaki M., Airik R., Ghosh A.K., Giles R.H., Chen R., Slaats G.G., Wang H.,
RA Hurd T.W., Zhou W., Cluckey A., Gee H.Y., Ramaswami G., Hong C.J.,
RA Hamilton B.A., Cervenka I., Ganji R.S., Bryja V., Arts H.H.,
RA van Reeuwijk J., Oud M.M., Letteboer S.J., Roepman R., Husson H.,
RA Ibraghimov-Beskrovnaya O., Yasunaga T., Walz G., Eley L., Sayer J.A.,
RA Schermer B., Liebau M.C., Benzing T., Le Corre S., Drummond I., Janssen S.,
RA Allen S.J., Natarajan S., O'Toole J.F., Attanasio M., Saunier S.,
RA Antignac C., Koenekoop R.K., Ren H., Lopez I., Nayir A., Stoetzel C.,
RA Dollfus H., Massoudi R., Gleeson J.G., Andreoli S.P., Doherty D.G.,
RA Lindstrad A., Golzio C., Katsanis N., Pape L., Abboud E.B., Al-Rajhi A.A.,
RA Lewis R.A., Omran H., Lee E.Y., Wang S., Sekiguchi J.M., Saunders R.,
RA Johnson C.A., Garner E., Vanselow K., Andersen J.S., Shlomai J.,
RA Nurnberg G., Nurnberg P., Levy S., Smogorzewska A., Otto E.A.,
RA Hildebrandt F.;
RT "Exome capture reveals ZNF423 and CEP164 mutations, linking renal
RT ciliopathies to DNA damage response signaling.";
RL Cell 150:533-548(2012).
RN [31]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [32]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-275; SER-619; SER-678;
RP SER-688 AND SER-689, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=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 [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-649; SER-688 AND SER-689, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [34]
RP IDENTIFICATION IN THE MRN COMPLEX, INTERACTION WITH MCM9, AND SUBCELLULAR
RP LOCATION.
RX PubMed=26215093; DOI=10.1038/ncomms8744;
RA Lee K.Y., Im J.S., Shibata E., Park J., Handa N., Kowalczykowski S.C.,
RA Dutta A.;
RT "MCM8-9 complex promotes resection of double-strand break ends by MRE11-
RT RAD50-NBS1 complex.";
RL Nat. Commun. 6:7744-7744(2015).
RN [35]
RP INTERACTION WITH MRNIP.
RX PubMed=27568553; DOI=10.1016/j.celrep.2016.07.087;
RA Staples C.J., Barone G., Myers K.N., Ganesh A., Gibbs-Seymour I.,
RA Patil A.A., Beveridge R.D., Daye C., Beniston R., Maslen S., Ahel I.,
RA Skehel J.M., Collis S.J.;
RT "MRNIP/C5orf45 interacts with the MRN complex and contributes to the DNA
RT damage response.";
RL Cell Rep. 16:2565-2575(2016).
RN [36]
RP FUNCTION, AND INTERACTION WITH EXD2.
RX PubMed=26807646; DOI=10.1038/ncb3303;
RA Broderick R., Nieminuszczy J., Baddock H.T., Deshpande R.A., Gileadi O.,
RA Paull T.T., McHugh P.J., Niedzwiedz W.;
RT "EXD2 promotes homologous recombination by facilitating DNA end
RT resection.";
RL Nat. Cell Biol. 18:271-280(2016).
RN [37]
RP INTERACTION WITH SAMHD1.
RX PubMed=28834754; DOI=10.1016/j.celrep.2017.08.008;
RA Daddacha W., Koyen A.E., Bastien A.J., Head P.E., Dhere V.R., Nabeta G.N.,
RA Connolly E.C., Werner E., Madden M.Z., Daly M.B., Minten E.V., Whelan D.R.,
RA Schlafstein A.J., Zhang H., Anand R., Doronio C., Withers A.E., Shepard C.,
RA Sundaram R.K., Deng X., Dynan W.S., Wang Y., Bindra R.S., Cejka P.,
RA Rothenberg E., Doetsch P.W., Kim B., Yu D.S.;
RT "SAMHD1 promotes DNA end resection to facilitate DNA repair by homologous
RT recombination.";
RL Cell Rep. 20:1921-1935(2017).
RN [38]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-255; LYS-416 AND LYS-625, AND
RP IDENTIFICATION BY MASS 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 [39]
RP FUNCTION, ACTIVITY REGULATION, AND INTERACTION WITH SAMHD1.
RX PubMed=29670289; DOI=10.1038/s41586-018-0050-1;
RA Coquel F., Silva M.J., Techer H., Zadorozhny K., Sharma S.,
RA Nieminuszczy J., Mettling C., Dardillac E., Barthe A., Schmitz A.L.,
RA Promonet A., Cribier A., Sarrazin A., Niedzwiedz W., Lopez B., Costanzo V.,
RA Krejci L., Chabes A., Benkirane M., Lin Y.L., Pasero P.;
RT "SAMHD1 acts at stalled replication forks to prevent interferon
RT induction.";
RL Nature 557:57-61(2018).
RN [40]
RP FUNCTION, UBIQUITINATION, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP UBQLN4.
RX PubMed=30612738; DOI=10.1016/j.cell.2018.11.024;
RA Jachimowicz R.D., Beleggia F., Isensee J., Velpula B.B., Goergens J.,
RA Bustos M.A., Doll M.A., Shenoy A., Checa-Rodriguez C., Wiederstein J.L.,
RA Baranes-Bachar K., Bartenhagen C., Hertwig F., Teper N., Nishi T.,
RA Schmitt A., Distelmaier F., Luedecke H.J., Albrecht B., Krueger M.,
RA Schumacher B., Geiger T., Hoon D.S.B., Huertas P., Fischer M., Hucho T.,
RA Peifer M., Ziv Y., Reinhardt H.C., Wieczorek D., Shiloh Y.;
RT "UBQLN4 represses homologous recombination and is overexpressed in
RT aggressive tumors.";
RL Cell 0:0-0(2019).
RN [41]
RP VARIANT ATLD1 SER-117.
RX PubMed=10612394; DOI=10.1016/s0092-8674(00)81547-0;
RA Stewart G.S., Maser R.S., Stankovic T., Bressan D.A., Kaplan M.I.,
RA Jaspers N.G.J., Raams A., Byrd P.J., Petrini J.H.J., Taylor A.M.R.;
RT "The DNA double-strand break repair gene hMRE11 is mutated in individuals
RT with an ataxia-telangiectasia-like disorder.";
RL Cell 99:577-587(1999).
RN [42]
RP VARIANTS CANCER CYS-104; HIS-503 AND GLN-572.
RX PubMed=11196167;
RA Fukuda T., Sumiyoshi T., Takahashi M., Kataoka T., Asahara T., Inui H.,
RA Watatani M., Yasutomi M., Kamada N., Miyagawa K.;
RT "Alterations of the double-strand break repair gene MRE11 in cancer.";
RL Cancer Res. 61:23-26(2001).
RN [43]
RP VARIANT OVARIAN CANCER TRP-305.
RX PubMed=14684699; DOI=10.1136/jmg.40.12.e131;
RA Heikkinen K., Karppinen S.-M., Soini Y., Maekinen M., Winqvist R.;
RT "Mutation screening of Mre11 complex genes: indication of RAD50 involvement
RT in breast and ovarian cancer susceptibility.";
RL J. Med. Genet. 40:E131-E131(2003).
RN [44]
RP VARIANTS [LARGE SCALE ANALYSIS] CYS-237 AND TYR-302.
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).
CC -!- FUNCTION: Component of the MRN complex, which plays a central role in
CC double-strand break (DSB) repair, DNA recombination, maintenance of
CC telomere integrity and meiosis (PubMed:9651580, PubMed:9590181,
CC PubMed:9705271, PubMed:11741547, PubMed:29670289). The complex
CC possesses single-strand endonuclease activity and double-strand-
CC specific 3'-5' exonuclease activity, which are provided by MRE11
CC (PubMed:9651580, PubMed:9590181, PubMed:9705271, PubMed:11741547,
CC PubMed:29670289). RAD50 may be required to bind DNA ends and hold them
CC in close proximity (PubMed:9651580, PubMed:9590181, PubMed:9705271,
CC PubMed:11741547, PubMed:29670289). This could facilitate searches for
CC short or long regions of sequence homology in the recombining DNA
CC templates, and may also stimulate the activity of DNA ligases and/or
CC restrict the nuclease activity of MRE11 to prevent nucleolytic
CC degradation past a given point (PubMed:9651580, PubMed:9590181,
CC PubMed:9705271, PubMed:11741547, PubMed:29670289, PubMed:30612738). The
CC complex may also be required for DNA damage signaling via activation of
CC the ATM kinase (PubMed:15064416). In telomeres the MRN complex may
CC modulate t-loop formation (PubMed:10888888).
CC {ECO:0000269|PubMed:10888888, ECO:0000269|PubMed:11741547,
CC ECO:0000269|PubMed:15064416, ECO:0000269|PubMed:29670289,
CC ECO:0000269|PubMed:30612738, ECO:0000269|PubMed:9590181,
CC ECO:0000269|PubMed:9705271}.
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Interaction with SAMHD1 stimulates the double-
CC strand-specific 3'-5' exonuclease activity.
CC {ECO:0000269|PubMed:29670289}.
CC -!- SUBUNIT: Component of the MRN complex composed of two heterodimers
CC RAD50/MRE11 associated with a single NBN (PubMed:9651580,
CC PubMed:9590181, PubMed:9705271, PubMed:10839544, PubMed:26215093). As
CC part of the MRN complex, interacts with MCM9; the interaction recruits
CC the complex to DNA repair sites (PubMed:26215093). Component of the
CC BASC complex, at least composed of BRCA1, MSH2, MSH6, MLH1, ATM, BLM,
CC RAD50, MRE11 and NBN (PubMed:10783165). Found in a complex with TERF2
CC (PubMed:10888888). Interacts with DCLRE1C/Artemis and DCLRE1B/Apollo
CC (PubMed:15456891, PubMed:15723659, PubMed:18469862). Interacts with
CC ATF2 (PubMed:15916964). Interacts with EXD2 (PubMed:26807646).
CC Interacts with MRNIP (PubMed:27568553). Interacts with SAMHD1; leading
CC to stimulate 3'-5' exonuclease activity (PubMed:28834754,
CC PubMed:29670289). Interacts (when ubiquitinated) with UBQLN4 (via its
CC UBA domain) (PubMed:30612738). Interacts with CYREN (via XLF motif) (By
CC similarity). {ECO:0000250|UniProtKB:Q61216,
CC ECO:0000269|PubMed:10783165, ECO:0000269|PubMed:10839544,
CC ECO:0000269|PubMed:10888888, ECO:0000269|PubMed:15456891,
CC ECO:0000269|PubMed:15723659, ECO:0000269|PubMed:15916964,
CC ECO:0000269|PubMed:18469862, ECO:0000269|PubMed:26215093,
CC ECO:0000269|PubMed:26807646, ECO:0000269|PubMed:27568553,
CC ECO:0000269|PubMed:28834754, ECO:0000269|PubMed:29670289,
CC ECO:0000269|PubMed:30612738, ECO:0000269|PubMed:9590181,
CC ECO:0000269|PubMed:9651580, ECO:0000269|PubMed:9705271}.
CC -!- SUBUNIT: (Microbial infection) Interacts with herpes simplex virus 1
CC protein UL12 (PubMed:20943970). {ECO:0000269|PubMed:20943970}.
CC -!- INTERACTION:
CC P49959; Q9BXW9: FANCD2; NbExp=6; IntAct=EBI-396513, EBI-359343;
CC P49959; P16104: H2AX; NbExp=7; IntAct=EBI-396513, EBI-494830;
CC P49959; P42858: HTT; NbExp=5; IntAct=EBI-396513, EBI-466029;
CC P49959; P49959: MRE11; NbExp=3; IntAct=EBI-396513, EBI-396513;
CC P49959; O60934: NBN; NbExp=5; IntAct=EBI-396513, EBI-494844;
CC P49959; O75943: RAD17; NbExp=2; IntAct=EBI-396513, EBI-968231;
CC P49959; Q99708: RBBP8; NbExp=3; IntAct=EBI-396513, EBI-745715;
CC P49959; P03243-1; Xeno; NbExp=2; IntAct=EBI-396513, EBI-1927377;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10783165,
CC ECO:0000269|PubMed:26215093}. Chromosome, telomere
CC {ECO:0000269|PubMed:10888888}. Chromosome {ECO:0000269|PubMed:26215093,
CC ECO:0000269|PubMed:30612738}. Note=Localizes to discrete nuclear foci
CC after treatment with genotoxic agents. {ECO:0000269|PubMed:10783165,
CC ECO:0000269|PubMed:26215093, ECO:0000269|PubMed:30612738}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P49959-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P49959-2; Sequence=VSP_003262;
CC Name=3;
CC IsoId=P49959-3; Sequence=VSP_057350;
CC -!- PTM: Ubiquitinated following DNA damage. Ubiquitination triggers
CC interaction with UBQLN4, leading to MRE11 removal from chromatin and
CC degradation by the proteasome. {ECO:0000269|PubMed:30612738}.
CC -!- DISEASE: Ataxia-telangiectasia-like disorder 1 (ATLD1) [MIM:604391]: A
CC rare disorder characterized by progressive cerebellar ataxia,
CC dysarthria, abnormal eye movements, and absence of telangiectasia. ATLD
CC patients show normal levels of total IgG, IgA and IgM, although there
CC may be reduced levels of specific functional antibodies. At the
CC cellular level, ATLD exhibits hypersensitivity to ionizing radiation
CC and radioresistant DNA synthesis. {ECO:0000269|PubMed:10612394}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Note=Defects in MRE11 can be a cause of nephronophthisis-
CC related ciliopathies (NPHP-RC), a group of recessive diseases that
CC affect kidney, retina and brain. A homozygous truncating mutation MRE11
CC has been found in patients with cerebellar vermis hypoplasia, ataxia
CC and dysarthria. {ECO:0000269|PubMed:22863007}.
CC -!- MISCELLANEOUS: In case of infection by adenovirus E4, the MRN complex
CC is inactivated and degraded by viral oncoproteins, thereby preventing
CC concatenation of viral genomes in infected cells.
CC -!- SIMILARITY: Belongs to the MRE11/RAD32 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MRE11ID247.html";
CC -!- WEB RESOURCE: Name=MRE11base; Note=MRE11A mutation db;
CC URL="http://structure.bmc.lu.se/idbase/MRE11Abase/";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/mre11a/";
CC ---------------------------------------------------------------------------
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DR EMBL; U37359; AAC78721.1; -; mRNA.
DR EMBL; AF022778; AAD10197.1; -; mRNA.
DR EMBL; AF073362; AAC36249.1; -; mRNA.
DR EMBL; AF303395; AAK18790.1; -; Genomic_DNA.
DR EMBL; AF303379; AAK18790.1; JOINED; Genomic_DNA.
DR EMBL; AF303380; AAK18790.1; JOINED; Genomic_DNA.
DR EMBL; AF303381; AAK18790.1; JOINED; Genomic_DNA.
DR EMBL; AF303382; AAK18790.1; JOINED; Genomic_DNA.
DR EMBL; AF303383; AAK18790.1; JOINED; Genomic_DNA.
DR EMBL; AF303384; AAK18790.1; JOINED; Genomic_DNA.
DR EMBL; AF303385; AAK18790.1; JOINED; Genomic_DNA.
DR EMBL; AF303386; AAK18790.1; JOINED; Genomic_DNA.
DR EMBL; AF303387; AAK18790.1; JOINED; Genomic_DNA.
DR EMBL; AF303388; AAK18790.1; JOINED; Genomic_DNA.
DR EMBL; AF303389; AAK18790.1; JOINED; Genomic_DNA.
DR EMBL; AF303390; AAK18790.1; JOINED; Genomic_DNA.
DR EMBL; AF303391; AAK18790.1; JOINED; Genomic_DNA.
DR EMBL; AF303392; AAK18790.1; JOINED; Genomic_DNA.
DR EMBL; AF303393; AAK18790.1; JOINED; Genomic_DNA.
DR EMBL; AF303394; AAK18790.1; JOINED; Genomic_DNA.
DR EMBL; AK095388; BAG53039.1; -; mRNA.
DR EMBL; AY584241; AAS79320.1; -; Genomic_DNA.
DR EMBL; AP000765; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000786; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF455448; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC063458; AAH63458.1; -; mRNA.
DR CCDS; CCDS8298.1; -. [P49959-2]
DR CCDS; CCDS8299.1; -. [P49959-1]
DR RefSeq; NP_005581.2; NM_005590.3. [P49959-2]
DR RefSeq; NP_005582.1; NM_005591.3. [P49959-1]
DR RefSeq; XP_011541139.1; XM_011542837.2. [P49959-1]
DR RefSeq; XP_016873261.1; XM_017017772.1. [P49959-1]
DR PDB; 3T1I; X-ray; 3.00 A; A/B/C/D=1-411.
DR PDBsum; 3T1I; -.
DR AlphaFoldDB; P49959; -.
DR SMR; P49959; -.
DR BioGRID; 110501; 215.
DR ComplexPortal; CPX-4442; MRN complex.
DR CORUM; P49959; -.
DR DIP; DIP-33238N; -.
DR IntAct; P49959; 58.
DR MINT; P49959; -.
DR STRING; 9606.ENSP00000325863; -.
DR BindingDB; P49959; -.
DR ChEMBL; CHEMBL3308929; -.
DR GlyGen; P49959; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P49959; -.
DR PhosphoSitePlus; P49959; -.
DR SwissPalm; P49959; -.
DR BioMuta; MRE11; -.
DR DMDM; 17380137; -.
DR EPD; P49959; -.
DR jPOST; P49959; -.
DR MassIVE; P49959; -.
DR MaxQB; P49959; -.
DR PaxDb; P49959; -.
DR PeptideAtlas; P49959; -.
DR PRIDE; P49959; -.
DR ProteomicsDB; 3675; -.
DR ProteomicsDB; 56186; -. [P49959-1]
DR ProteomicsDB; 56187; -. [P49959-2]
DR Antibodypedia; 706; 713 antibodies from 42 providers.
DR CPTC; P49959; 2 antibodies.
DR DNASU; 4361; -.
DR Ensembl; ENST00000323929.8; ENSP00000325863.4; ENSG00000020922.13. [P49959-1]
DR Ensembl; ENST00000323977.7; ENSP00000326094.3; ENSG00000020922.13. [P49959-2]
DR Ensembl; ENST00000407439.7; ENSP00000385614.3; ENSG00000020922.13. [P49959-3]
DR GeneID; 4361; -.
DR KEGG; hsa:4361; -.
DR MANE-Select; ENST00000323929.8; ENSP00000325863.4; NM_005591.4; NP_005582.1.
DR UCSC; uc001peu.4; human. [P49959-1]
DR CTD; 4361; -.
DR DisGeNET; 4361; -.
DR GeneCards; MRE11; -.
DR HGNC; HGNC:7230; MRE11.
DR HPA; ENSG00000020922; Low tissue specificity.
DR MalaCards; MRE11; -.
DR MIM; 600814; gene.
DR MIM; 604391; phenotype.
DR neXtProt; NX_P49959; -.
DR OpenTargets; ENSG00000020922; -.
DR Orphanet; 251347; Ataxia-telangiectasia-like disorder.
DR Orphanet; 145; Hereditary breast and ovarian cancer syndrome.
DR Orphanet; 240760; Nijmegen breakage syndrome-like disorder.
DR PharmGKB; PA30934; -.
DR VEuPathDB; HostDB:ENSG00000020922; -.
DR eggNOG; KOG2310; Eukaryota.
DR GeneTree; ENSGT00390000017288; -.
DR HOGENOM; CLU_009535_3_1_1; -.
DR InParanoid; P49959; -.
DR OMA; QWMRPET; -.
DR PhylomeDB; P49959; -.
DR TreeFam; TF101105; -.
DR PathwayCommons; P49959; -.
DR Reactome; R-HSA-1834949; Cytosolic sensors of pathogen-associated DNA.
DR Reactome; R-HSA-2559586; DNA Damage/Telomere Stress Induced Senescence.
DR Reactome; R-HSA-3270619; IRF3-mediated induction of type I IFN.
DR Reactome; R-HSA-5685938; HDR through Single Strand Annealing (SSA).
DR Reactome; R-HSA-5685939; HDR through MMEJ (alt-NHEJ).
DR Reactome; R-HSA-5685942; HDR through Homologous Recombination (HRR).
DR Reactome; R-HSA-5693548; Sensing of DNA Double Strand Breaks.
DR Reactome; R-HSA-5693554; Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA).
DR Reactome; R-HSA-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-HSA-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR Reactome; R-HSA-5693571; Nonhomologous End-Joining (NHEJ).
DR Reactome; R-HSA-5693579; Homologous DNA Pairing and Strand Exchange.
DR Reactome; R-HSA-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-HSA-5693616; Presynaptic phase of homologous DNA pairing and strand exchange.
DR Reactome; R-HSA-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-HSA-69473; G2/M DNA damage checkpoint.
DR Reactome; R-HSA-912446; Meiotic recombination.
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-9709570; Impaired BRCA2 binding to RAD51.
DR Reactome; R-HSA-9709603; Impaired BRCA2 binding to PALB2.
DR SignaLink; P49959; -.
DR SIGNOR; P49959; -.
DR BioGRID-ORCS; 4361; 330 hits in 1084 CRISPR screens.
DR ChiTaRS; MRE11A; human.
DR GeneWiki; MRE11A; -.
DR GenomeRNAi; 4361; -.
DR Pharos; P49959; Tbio.
DR PRO; PR:P49959; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P49959; protein.
DR Bgee; ENSG00000020922; Expressed in calcaneal tendon and 175 other tissues.
DR ExpressionAtlas; P49959; baseline and differential.
DR Genevisible; P49959; HS.
DR GO; GO:0070533; C:BRCA1-C complex; IPI:ComplexPortal.
DR GO; GO:0098687; C:chromosomal region; IC:ComplexPortal.
DR GO; GO:0000781; C:chromosome, telomeric region; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030870; C:Mre11 complex; IDA:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0016605; C:PML body; IDA:BHF-UCL.
DR GO; GO:0005657; C:replication fork; IDA:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB.
DR GO; GO:0008408; F:3'-5' exonuclease activity; IDA:CACAO.
DR GO; GO:0008296; F:3'-5'-exodeoxyribonuclease activity; IEA:InterPro.
DR GO; GO:0008409; F:5'-3' exonuclease activity; IDA:UniProtKB.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0003690; F:double-stranded DNA binding; TAS:ProtInc.
DR GO; GO:0004520; F:endodeoxyribonuclease activity; IDA:CACAO.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0030145; F:manganese ion binding; IEA:InterPro.
DR GO; GO:0004518; F:nuclease activity; TAS:BHF-UCL.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0000014; F:single-stranded DNA endodeoxyribonuclease activity; IDA:CACAO.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0000729; P:DNA double-strand break processing; TAS:Reactome.
DR GO; GO:0032508; P:DNA duplex unwinding; IMP:BHF-UCL.
DR GO; GO:0006310; P:DNA recombination; TAS:ProtInc.
DR GO; GO:0006281; P:DNA repair; TAS:ProtInc.
DR GO; GO:0110025; P:DNA strand resection involved in replication fork processing; IDA:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; TAS:ProtInc.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IDA:UniProtKB.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IDA:CACAO.
DR GO; GO:0007129; P:homologous chromosome pairing at meiosis; IEA:Ensembl.
DR GO; GO:0035825; P:homologous recombination; IC:ComplexPortal.
DR GO; GO:0042138; P:meiotic DNA double-strand break formation; IBA:GO_Central.
DR GO; GO:0097552; P:mitochondrial double-strand break repair via homologous recombination; IBA:GO_Central.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; IBA:GO_Central.
DR GO; GO:0044818; P:mitotic G2/M transition checkpoint; IC:ComplexPortal.
DR GO; GO:0031573; P:mitotic intra-S DNA damage checkpoint signaling; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:BHF-UCL.
DR GO; GO:0033674; P:positive regulation of kinase activity; IDA:BHF-UCL.
DR GO; GO:0031954; P:positive regulation of protein autophosphorylation; IDA:BHF-UCL.
DR GO; GO:0032206; P:positive regulation of telomere maintenance; IMP:BHF-UCL.
DR GO; GO:0007131; P:reciprocal meiotic recombination; TAS:ProtInc.
DR GO; GO:0000019; P:regulation of mitotic recombination; TAS:ProtInc.
DR GO; GO:0007062; P:sister chromatid cohesion; IMP:BHF-UCL.
DR GO; GO:0000723; P:telomere maintenance; IBA:GO_Central.
DR GO; GO:0007004; P:telomere maintenance via telomerase; TAS:ProtInc.
DR GO; GO:0031860; P:telomeric 3' overhang formation; IMP:BHF-UCL.
DR CDD; cd00840; MPP_Mre11_N; 1.
DR Gene3D; 3.30.110.110; -; 1.
DR Gene3D; 3.60.21.10; -; 1.
DR InterPro; IPR004843; Calcineurin-like_PHP_ApaH.
DR InterPro; IPR029052; Metallo-depent_PP-like.
DR InterPro; IPR003701; Mre11.
DR InterPro; IPR038487; Mre11_capping_dom.
DR InterPro; IPR007281; Mre11_DNA-bd.
DR InterPro; IPR041796; Mre11_N.
DR Pfam; PF00149; Metallophos; 1.
DR Pfam; PF04152; Mre11_DNA_bind; 1.
DR PIRSF; PIRSF000882; DSB_repair_MRE11; 1.
DR SMART; SM01347; Mre11_DNA_bind; 1.
DR SUPFAM; SSF56300; SSF56300; 1.
DR TIGRFAMs; TIGR00583; mre11; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Chromosome; Ciliopathy;
KW Disease variant; DNA damage; DNA repair; Endonuclease; Exonuclease;
KW Host-virus interaction; Hydrolase; Isopeptide bond; Manganese; Meiosis;
KW Nuclease; Nucleus; Phosphoprotein; Reference proteome; Telomere;
KW Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895"
FT CHAIN 2..708
FT /note="Double-strand break repair protein MRE11"
FT /id="PRO_0000138672"
FT REGION 507..540
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 556..614
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 651..708
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 507..528
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 583..614
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 660..684
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 129
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61216"
FT MOD_RES 275
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 619
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 641
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61216"
FT MOD_RES 649
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:24275569"
FT MOD_RES 678
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 688
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 ECO:0007744|PubMed:24275569"
FT MOD_RES 689
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 ECO:0007744|PubMed:24275569"
FT MOD_RES 701
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT CROSSLNK 255
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 416
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 625
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..7
FT /note="MSTADAL -> MNRNISHQKG (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057350"
FT VAR_SEQ 595..622
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8530104"
FT /id="VSP_003262"
FT VARIANT 104
FT /note="S -> C (in cancer; dbSNP:rs748434421)"
FT /evidence="ECO:0000269|PubMed:11196167"
FT /id="VAR_011625"
FT VARIANT 117
FT /note="N -> S (in ATLD1; dbSNP:rs137852760)"
FT /evidence="ECO:0000269|PubMed:10612394"
FT /id="VAR_008513"
FT VARIANT 157
FT /note="M -> V (in dbSNP:rs147771140)"
FT /id="VAR_011626"
FT VARIANT 237
FT /note="F -> C (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036416"
FT VARIANT 302
FT /note="H -> Y (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036417"
FT VARIANT 305
FT /note="R -> W (in ovarian cancer; dbSNP:rs372000848)"
FT /evidence="ECO:0000269|PubMed:14684699"
FT /id="VAR_025528"
FT VARIANT 468
FT /note="D -> G (in dbSNP:rs1805367)"
FT /evidence="ECO:0000269|Ref.7"
FT /id="VAR_019288"
FT VARIANT 503
FT /note="R -> H (in cancer; dbSNP:rs774057024)"
FT /evidence="ECO:0000269|PubMed:11196167"
FT /id="VAR_011627"
FT VARIANT 572
FT /note="R -> Q (in cancer; dbSNP:rs200085146)"
FT /evidence="ECO:0000269|PubMed:11196167"
FT /id="VAR_011628"
FT VARIANT 698
FT /note="M -> V (in dbSNP:rs1805362)"
FT /evidence="ECO:0000269|Ref.7"
FT /id="VAR_019289"
FT CONFLICT 31
FT /note="V -> A (in Ref. 1; AAC78721)"
FT /evidence="ECO:0000305"
FT HELIX 9..11
FT /evidence="ECO:0007829|PDB:3T1I"
FT STRAND 12..18
FT /evidence="ECO:0007829|PDB:3T1I"
FT TURN 24..26
FT /evidence="ECO:0007829|PDB:3T1I"
FT TURN 30..34
FT /evidence="ECO:0007829|PDB:3T1I"
FT HELIX 35..49
FT /evidence="ECO:0007829|PDB:3T1I"
FT STRAND 53..57
FT /evidence="ECO:0007829|PDB:3T1I"
FT STRAND 62..66
FT /evidence="ECO:0007829|PDB:3T1I"
FT HELIX 69..83
FT /evidence="ECO:0007829|PDB:3T1I"
FT STRAND 122..124
FT /evidence="ECO:0007829|PDB:3T1I"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:3T1I"
FT TURN 134..137
FT /evidence="ECO:0007829|PDB:3T1I"
FT HELIX 140..147
FT /evidence="ECO:0007829|PDB:3T1I"
FT STRAND 149..152
FT /evidence="ECO:0007829|PDB:3T1I"
FT STRAND 162..164
FT /evidence="ECO:0007829|PDB:3T1I"
FT STRAND 167..171
FT /evidence="ECO:0007829|PDB:3T1I"
FT STRAND 174..181
FT /evidence="ECO:0007829|PDB:3T1I"
FT HELIX 186..194
FT /evidence="ECO:0007829|PDB:3T1I"
FT STRAND 198..200
FT /evidence="ECO:0007829|PDB:3T1I"
FT HELIX 207..209
FT /evidence="ECO:0007829|PDB:3T1I"
FT STRAND 210..216
FT /evidence="ECO:0007829|PDB:3T1I"
FT STRAND 223..228
FT /evidence="ECO:0007829|PDB:3T1I"
FT HELIX 231..233
FT /evidence="ECO:0007829|PDB:3T1I"
FT STRAND 240..243
FT /evidence="ECO:0007829|PDB:3T1I"
FT STRAND 250..255
FT /evidence="ECO:0007829|PDB:3T1I"
FT TURN 257..259
FT /evidence="ECO:0007829|PDB:3T1I"
FT STRAND 262..265
FT /evidence="ECO:0007829|PDB:3T1I"
FT HELIX 276..279
FT /evidence="ECO:0007829|PDB:3T1I"
FT STRAND 283..290
FT /evidence="ECO:0007829|PDB:3T1I"
FT STRAND 293..300
FT /evidence="ECO:0007829|PDB:3T1I"
FT STRAND 302..304
FT /evidence="ECO:0007829|PDB:3T1I"
FT STRAND 307..313
FT /evidence="ECO:0007829|PDB:3T1I"
FT HELIX 314..316
FT /evidence="ECO:0007829|PDB:3T1I"
FT TURN 318..320
FT /evidence="ECO:0007829|PDB:3T1I"
FT HELIX 328..350
FT /evidence="ECO:0007829|PDB:3T1I"
FT TURN 351..353
FT /evidence="ECO:0007829|PDB:3T1I"
FT STRAND 355..357
FT /evidence="ECO:0007829|PDB:3T1I"
FT STRAND 362..368
FT /evidence="ECO:0007829|PDB:3T1I"
FT TURN 370..372
FT /evidence="ECO:0007829|PDB:3T1I"
FT HELIX 379..385
FT /evidence="ECO:0007829|PDB:3T1I"
FT TURN 386..388
FT /evidence="ECO:0007829|PDB:3T1I"
FT STRAND 392..399
FT /evidence="ECO:0007829|PDB:3T1I"
SQ SEQUENCE 708 AA; 80593 MW; D94ABFBDDF6106AD CRC64;
MSTADALDDE NTFKILVATD IHLGFMEKDA VRGNDTFVTL DEILRLAQEN EVDFILLGGD
LFHENKPSRK TLHTCLELLR KYCMGDRPVQ FEILSDQSVN FGFSKFPWVN YQDGNLNISI
PVFSIHGNHD DPTGADALCA LDILSCAGFV NHFGRSMSVE KIDISPVLLQ KGSTKIALYG
LGSIPDERLY RMFVNKKVTM LRPKEDENSW FNLFVIHQNR SKHGSTNFIP EQFLDDFIDL
VIWGHEHECK IAPTKNEQQL FYISQPGSSV VTSLSPGEAV KKHVGLLRIK GRKMNMHKIP
LHTVRQFFME DIVLANHPDI FNPDNPKVTQ AIQSFCLEKI EEMLENAERE RLGNSHQPEK
PLVRLRVDYS GGFEPFSVLR FSQKFVDRVA NPKDIIHFFR HREQKEKTGE EINFGKLITK
PSEGTTLRVE DLVKQYFQTA EKNVQLSLLT ERGMGEAVQE FVDKEEKDAI EELVKYQLEK
TQRFLKERHI DALEDKIDEE VRRFRETRQK NTNEEDDEVR EAMTRARALR SQSEESASAF
SADDLMSIDL AEQMANDSDD SISAATNKGR GRGRGRRGGR GQNSASRGGS QRGRADTGLE
TSTRSRNSKT AVSASRNMSI IDAFKSTRQQ PSRNVTTKNY SEVIEVDESD VEEDIFPTTS
KTDQRWSSTS SSKIMSQSQV SKGVDFESSE DDDDDPFMNT SSLRRNRR
