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 11-NOV-2015, entry version 170. DE RecName: 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=MRE11A; Synonyms=HNGS1, MRE11; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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 RT and human MRE11 homolog."; RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). 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., RA Byrd P.J.; RT "hMRE11: genomic structure and a null mutation identified in a RT transcript 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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., RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S., RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., RA 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] 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 RT the G2/M DNA damage checkpoint response."; RL Mol. Cell. Biol. 24:9207-9220(2004). RN [11] 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 [12] 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., RA Ronai Z.; RT "ATM-dependent phosphorylation of ATF2 is required for the DNA damage RT response."; RL Mol. Cell 18:577-587(2005). RN [13] 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., RA Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in RT signaling networks."; RL Cell 127:635-648(2006). RN [14] 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 RT the kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [15] 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., RA Liu X., Shen X., Li L., Legerski R.J.; RT "Snm1B/Apollo mediates replication fork collapse and S Phase RT checkpoint activation in response to DNA interstrand cross-links."; RL Oncogene 27:5045-5056(2008). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-649; SER-688; SER-689 RP AND SER-701, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-649; SER-688 AND RP SER-689, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 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 RT exonuclease, UL12, and the DNA double-strand break-sensing MRN RT complex."; RL J. Virol. 84:12504-12514(2010). RN [20] 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., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [21] 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., RA Buerckstuemmer T., 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 [22] 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., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [23] 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., RA Wang H., Hurd T.W., Zhou W., Cluckey A., Gee H.Y., Ramaswami G., RA Hong C.J., Hamilton B.A., Cervenka I., Ganji R.S., Bryja V., RA Arts H.H., van Reeuwijk J., Oud M.M., Letteboer S.J., Roepman R., RA Husson H., Ibraghimov-Beskrovnaya O., Yasunaga T., Walz G., Eley L., RA Sayer J.A., Schermer B., Liebau M.C., Benzing T., Le Corre S., RA Drummond I., Janssen S., Allen S.J., Natarajan S., O'Toole J.F., RA Attanasio M., Saunier S., Antignac C., Koenekoop R.K., Ren H., RA Lopez I., Nayir A., Stoetzel C., Dollfus H., Massoudi R., RA Gleeson J.G., Andreoli S.P., Doherty D.G., Lindstrad A., Golzio C., RA Katsanis N., Pape L., Abboud E.B., Al-Rajhi A.A., Lewis R.A., RA 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 [24] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.M111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., RA Meinnel T., 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 [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-649; SER-688 AND RP SER-689, 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [26] 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 RT individuals with an ataxia-telangiectasia-like disorder."; RL Cell 99:577-587(1999). RN [27] RP VARIANTS CANCER CYS-104; HIS-503 AND GLN-572. RX PubMed=11196167; RA Fukuda T., Sumiyoshi T., Takahashi M., Kataoka T., Asahara T., RA Inui H., 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 [28] 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 RT involvement in breast and ovarian cancer susceptibility."; RL J. Med. Genet. 40:E131-E131(2003). RN [29] 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., RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C., RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., RA Vogelstein B., Kinzler K.W., Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal RT cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Component of the MRN complex, which plays a central role CC in double-strand break (DSB) repair, DNA recombination, CC maintenance of telomere integrity and meiosis. The complex CC possesses single-strand endonuclease activity and double-strand- CC specific 3'-5' exonuclease activity, which are provided by MRE11A. CC RAD50 may be required to bind DNA ends and hold them in close CC proximity. This could facilitate searches for short or long CC regions of sequence homology in the recombining DNA templates, and CC may also stimulate the activity of DNA ligases and/or restrict the CC nuclease activity of MRE11A to prevent nucleolytic degradation CC past a given point. The complex may also be required for DNA CC damage signaling via activation of the ATM kinase. In telomeres CC the MRN complex may modulate t-loop formation. CC -!- COFACTOR: CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250}; CC -!- SUBUNIT: Component of the MRN complex composed of two heterodimers CC RAD50/MRE11A associated with a single NBN. Component of the BASC CC complex, at least composed of BRCA1, MSH2, MSH6, MLH1, ATM, BLM, CC RAD50, MRE11A and NBN (By similarity). Interacts with CC DCLRE1C/Artemis and DCLRE1B/Apollo. Interacts with ATF2. Interacts CC with herpes simplex virus 1 protein UL12 (PubMed:20943970). CC {ECO:0000250, ECO:0000269|PubMed:15456891, CC ECO:0000269|PubMed:15723659, ECO:0000269|PubMed:15916964, CC ECO:0000269|PubMed:18469862, ECO:0000269|PubMed:20943970}. CC -!- INTERACTION: CC Q9BXW9:FANCD2; NbExp=6; IntAct=EBI-396513, EBI-359343; CC P16104:H2AFX; NbExp=6; IntAct=EBI-396513, EBI-494830; CC P42858:HTT; NbExp=5; IntAct=EBI-396513, EBI-466029; CC O60934:NBN; NbExp=2; IntAct=EBI-396513, EBI-494844; CC O75943:RAD17; NbExp=2; IntAct=EBI-396513, EBI-968231; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Note=Localizes to CC discrete nuclear foci after treatment with genotoxic agents. CC {ECO:0000250}. 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 Note=No experimental confirmation available.; CC -!- DISEASE: Ataxia-telangiectasia-like disorder 1 (ATLD1) CC [MIM:604391]: A rare disorder characterized by progressive CC cerebellar ataxia, dysarthria, abnormal eye movements, and absence CC of telangiectasia. ATLD patients show normal levels of total IgG, CC IgA and IgM, although there may be reduced levels of specific CC functional antibodies. At the cellular level, ATLD exhibits CC hypersensitivity to ionizing radiation and radioresistant DNA CC synthesis. {ECO:0000269|PubMed:10612394}. Note=The disease is CC caused by mutations affecting the gene represented in this entry. CC -!- DISEASE: Note=Defects in MRE11A can be a cause of CC nephronophthisis-related ciliopathies (NPHP-RC), a group of CC recessive diseases that affect kidney, retina and brain. A CC homozygous truncating mutation MRE11A has been found in patients CC with cerebellar vermis hypoplasia, ataxia and dysarthria. CC -!- MISCELLANEOUS: In case of infection by adenovirus E4, the MRN CC complex is inactivated and degraded by viral oncoproteins, thereby CC preventing 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 CC and 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 --------------------------------------------------------------------------- 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; 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_011542837.1. [P49959-1] DR UniGene; Hs.192649; -. DR PDB; 3T1I; X-ray; 3.00 A; A/B/C/D=1-411. DR PDBsum; 3T1I; -. DR ProteinModelPortal; P49959; -. DR SMR; P49959; 8-400. DR BioGrid; 110501; 84. DR DIP; DIP-33238N; -. DR IntAct; P49959; 22. DR MINT; MINT-131851; -. DR STRING; 9606.ENSP00000325863; -. DR PhosphoSite; P49959; -. DR BioMuta; MRE11A; -. DR DMDM; 17380137; -. DR MaxQB; P49959; -. DR PaxDb; P49959; -. DR PRIDE; P49959; -. DR DNASU; 4361; -. DR Ensembl; ENST00000323929; ENSP00000325863; ENSG00000020922. [P49959-1] DR Ensembl; ENST00000323977; ENSP00000326094; ENSG00000020922. [P49959-2] DR Ensembl; ENST00000407439; ENSP00000385614; ENSG00000020922. [P49959-3] DR GeneID; 4361; -. DR KEGG; hsa:4361; -. DR UCSC; uc001peu.2; human. [P49959-1] DR UCSC; uc001pev.2; human. [P49959-2] DR UCSC; uc009ywj.2; human. DR CTD; 4361; -. DR GeneCards; MRE11A; -. DR HGNC; HGNC:7230; MRE11A. DR HPA; CAB004081; -. DR HPA; HPA002691; -. DR MIM; 600814; gene. DR MIM; 604391; phenotype. DR neXtProt; NX_P49959; -. DR Orphanet; 251347; Ataxia-telangiectasia-like disorder. DR Orphanet; 145; Hereditary breast and ovarian cancer syndrome. DR PharmGKB; PA30934; -. DR eggNOG; KOG2310; Eukaryota. DR eggNOG; COG0420; LUCA. DR GeneTree; ENSGT00390000017288; -. DR HOGENOM; HOG000216581; -. DR HOVERGEN; HBG052508; -. DR InParanoid; P49959; -. DR KO; K10865; -. DR OMA; RMFVNKQ; -. DR OrthoDB; EOG7VB2F1; -. DR PhylomeDB; P49959; -. DR TreeFam; TF101105; -. 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-69473; G2/M DNA damage checkpoint. DR Reactome; R-HSA-75177; Assembly of the RAD50-MRE11-NBS1 complex at DNA double-strand breaks. DR Reactome; R-HSA-912446; Meiotic recombination. DR ChiTaRS; MRE11A; human. DR GeneWiki; MRE11A; -. DR GenomeRNAi; 4361; -. DR NextBio; 17163; -. DR PMAP-CutDB; P49959; -. DR PRO; PR:P49959; -. DR Proteomes; UP000005640; Chromosome 11. DR Bgee; P49959; -. DR CleanEx; HS_MRE11A; -. DR ExpressionAtlas; P49959; baseline and differential. DR Genevisible; P49959; HS. DR GO; GO:0000785; C:chromatin; IBA:GO_Central. DR GO; GO:0000794; C:condensed nuclear chromosome; IEA:Ensembl. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0030870; C:Mre11 complex; NAS:BHF-UCL. DR GO; GO:0000790; C:nuclear chromatin; IEA:Ensembl. DR GO; GO:0000784; C:nuclear chromosome, telomeric region; IDA:BHF-UCL. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; TAS:ProtInc. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl. 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:0003690; F:double-stranded DNA binding; TAS:ProtInc. DR GO; GO:0004520; F:endodeoxyribonuclease activity; IDA:CACAO. 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:0006284; P:base-excision repair; IBA:GO_Central. DR GO; GO:0008283; P:cell proliferation; IEA:Ensembl. DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:MGI. 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:Reactome. DR GO; GO:0006302; P:double-strand break repair; TAS:Reactome. DR GO; GO:0000724; P:double-strand break repair via homologous recombination; TAS:Reactome. DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IDA:CACAO. DR GO; GO:0007507; P:heart development; IEA:Ensembl. DR GO; GO:0045087; P:innate immune response; TAS:Reactome. DR GO; GO:0031573; P:intra-S DNA damage checkpoint; IBA:GO_Central. DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint; IEA:Ensembl. DR GO; GO:0032876; P:negative regulation of DNA endoreduplication; IMP:BHF-UCL. DR GO; GO:0046597; P:negative regulation of viral entry into host cell; IEA:Ensembl. DR GO; GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; IDA:GOC. 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:0032481; P:positive regulation of type I interferon production; TAS:Reactome. 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:0007129; P:synapsis; IEA:Ensembl. DR GO; GO:0007004; P:telomere maintenance via telomerase; TAS:ProtInc. DR GO; GO:0016032; P:viral process; IEA:UniProtKB-KW. DR Gene3D; 3.60.21.10; -; 2. DR InterPro; IPR004843; Calcineurin-like_PHP_apaH. DR InterPro; IPR003701; DNA_repair_Mre11. DR InterPro; IPR029052; Metallo-depent_PP-like. DR InterPro; IPR007281; Mre11_DNA-bd. DR PANTHER; PTHR10139; PTHR10139; 1. DR Pfam; PF00149; Metallophos; 1. DR Pfam; PF04152; Mre11_DNA_bind; 1. DR PIRSF; PIRSF000882; DSB_repair_MRE11; 1. DR SUPFAM; SSF56300; SSF56300; 2. DR TIGRFAMs; TIGR00583; mre11; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Ciliopathy; KW Complete proteome; Disease mutation; DNA damage; DNA repair; KW Endonuclease; Exonuclease; Host-virus interaction; Hydrolase; KW Manganese; Meiosis; Nuclease; Nucleus; Phosphoprotein; Polymorphism; KW Reference proteome. FT INIT_MET 1 1 Removed. {ECO:0000244|PubMed:19413330, FT ECO:0000244|PubMed:22223895}. FT CHAIN 2 708 Double-strand break repair protein FT MRE11A. FT /FTId=PRO_0000138672. FT ACT_SITE 129 129 Proton donor. {ECO:0000250}. FT MOD_RES 2 2 N-acetylserine. FT {ECO:0000244|PubMed:19413330, FT ECO:0000244|PubMed:22223895}. FT MOD_RES 2 2 Phosphoserine. FT {ECO:0000250|UniProtKB:Q61216}. FT MOD_RES 641 641 Phosphoserine. FT {ECO:0000250|UniProtKB:Q61216}. FT MOD_RES 649 649 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 688 688 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 689 689 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 701 701 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT VAR_SEQ 1 7 MSTADAL -> MNRNISHQKG (in isoform 3). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_057350. FT VAR_SEQ 595 622 Missing (in isoform 2). FT {ECO:0000303|PubMed:8530104}. FT /FTId=VSP_003262. FT VARIANT 104 104 S -> C (in cancer). FT {ECO:0000269|PubMed:11196167}. FT /FTId=VAR_011625. FT VARIANT 117 117 N -> S (in ATLD1). FT {ECO:0000269|PubMed:10612394}. FT /FTId=VAR_008513. FT VARIANT 157 157 M -> V (in dbSNP:rs147771140). FT /FTId=VAR_011626. FT VARIANT 237 237 F -> C (in a breast cancer sample; FT somatic mutation). FT {ECO:0000269|PubMed:16959974}. FT /FTId=VAR_036416. FT VARIANT 302 302 H -> Y (in a breast cancer sample; FT somatic mutation). FT {ECO:0000269|PubMed:16959974}. FT /FTId=VAR_036417. FT VARIANT 305 305 R -> W (in ovarian cancer). FT {ECO:0000269|PubMed:14684699}. FT /FTId=VAR_025528. FT VARIANT 468 468 D -> G (in dbSNP:rs1805367). FT {ECO:0000269|Ref.7}. FT /FTId=VAR_019288. FT VARIANT 503 503 R -> H (in cancer). FT {ECO:0000269|PubMed:11196167}. FT /FTId=VAR_011627. FT VARIANT 572 572 R -> Q (in cancer; dbSNP:rs200085146). FT {ECO:0000269|PubMed:11196167}. FT /FTId=VAR_011628. FT VARIANT 698 698 M -> V (in dbSNP:rs1805362). FT {ECO:0000269|Ref.7}. FT /FTId=VAR_019289. FT CONFLICT 31 31 V -> A (in Ref. 1; AAC78721). FT {ECO:0000305}. FT HELIX 9 11 {ECO:0000244|PDB:3T1I}. FT STRAND 12 18 {ECO:0000244|PDB:3T1I}. FT TURN 24 26 {ECO:0000244|PDB:3T1I}. FT TURN 30 34 {ECO:0000244|PDB:3T1I}. FT HELIX 35 49 {ECO:0000244|PDB:3T1I}. FT STRAND 53 57 {ECO:0000244|PDB:3T1I}. FT STRAND 62 66 {ECO:0000244|PDB:3T1I}. FT HELIX 69 83 {ECO:0000244|PDB:3T1I}. FT STRAND 122 124 {ECO:0000244|PDB:3T1I}. FT STRAND 128 130 {ECO:0000244|PDB:3T1I}. FT TURN 134 137 {ECO:0000244|PDB:3T1I}. FT HELIX 140 147 {ECO:0000244|PDB:3T1I}. FT STRAND 149 152 {ECO:0000244|PDB:3T1I}. FT STRAND 162 164 {ECO:0000244|PDB:3T1I}. FT STRAND 167 171 {ECO:0000244|PDB:3T1I}. FT STRAND 174 181 {ECO:0000244|PDB:3T1I}. FT HELIX 186 194 {ECO:0000244|PDB:3T1I}. FT STRAND 198 200 {ECO:0000244|PDB:3T1I}. FT HELIX 207 209 {ECO:0000244|PDB:3T1I}. FT STRAND 210 216 {ECO:0000244|PDB:3T1I}. FT STRAND 223 228 {ECO:0000244|PDB:3T1I}. FT HELIX 231 233 {ECO:0000244|PDB:3T1I}. FT STRAND 240 243 {ECO:0000244|PDB:3T1I}. FT STRAND 250 255 {ECO:0000244|PDB:3T1I}. FT TURN 257 259 {ECO:0000244|PDB:3T1I}. FT STRAND 262 265 {ECO:0000244|PDB:3T1I}. FT HELIX 276 279 {ECO:0000244|PDB:3T1I}. FT STRAND 283 290 {ECO:0000244|PDB:3T1I}. FT STRAND 293 300 {ECO:0000244|PDB:3T1I}. FT STRAND 302 304 {ECO:0000244|PDB:3T1I}. FT STRAND 307 313 {ECO:0000244|PDB:3T1I}. FT HELIX 314 316 {ECO:0000244|PDB:3T1I}. FT TURN 318 320 {ECO:0000244|PDB:3T1I}. FT HELIX 328 350 {ECO:0000244|PDB:3T1I}. FT TURN 351 353 {ECO:0000244|PDB:3T1I}. FT STRAND 355 357 {ECO:0000244|PDB:3T1I}. FT STRAND 362 368 {ECO:0000244|PDB:3T1I}. FT TURN 370 372 {ECO:0000244|PDB:3T1I}. FT HELIX 379 385 {ECO:0000244|PDB:3T1I}. FT TURN 386 388 {ECO:0000244|PDB:3T1I}. FT STRAND 392 399 {ECO:0000244|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 //