ID MRE11_MOUSE Reviewed; 706 AA. AC Q61216; Q62430; DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 24-JAN-2024, entry version 188. DE RecName: Full=Double-strand break repair protein MRE11; DE EC=3.1.-.- {ECO:0000250|UniProtKB:P49959}; DE AltName: Full=Double-strand break repair protein MRE11A; DE Short=MmMRE11A; 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; Synonyms=Mre11a; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). RC STRAIN=CD-1; TISSUE=Testis; RA Oshiumi H., Shinohara A., Ogawa H.; RL Submitted (MAY-1996) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC STRAIN=C57BL/6J; TISSUE=Retina; 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 [3] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=17242355; DOI=10.1073/pnas.0609836104; RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; RT "Large-scale phosphorylation analysis of mouse liver."; RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). RN [4] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; SER-640; SER-648 AND RP SER-686, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [5] RP INTERACTION WITH CYREN. RX PubMed=30017584; DOI=10.1016/j.molcel.2018.06.018; RA Hung P.J., Johnson B., Chen B.R., Byrum A.K., Bredemeyer A.L., RA Yewdell W.T., Johnson T.E., Lee B.J., Deivasigamani S., Hindi I., RA Amatya P., Gross M.L., Paull T.T., Pisapia D.J., Chaudhuri J., RA Petrini J.J.H., Mosammaparast N., Amarasinghe G.K., Zha S., Tyler J.K., RA Sleckman B.P.; RT "MRI is a DNA damage response adaptor during classical non-homologous end RT joining."; RL Mol. Cell 71:332-342(2018). 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. The complex possesses single-strand CC endonuclease activity and double-strand-specific 3'-5' exonuclease CC activity, which are provided by MRE11. RAD50 may be required to bind CC DNA ends and hold them in close proximity. This could facilitate CC searches for short or long regions of sequence homology in the CC recombining DNA templates, and may also stimulate the activity of DNA CC ligases and/or restrict the nuclease activity of MRE11 to prevent CC nucleolytic degradation past a given point. The complex may also be CC required for DNA damage signaling via activation of the ATM kinase. In CC telomeres the MRN complex may modulate t-loop formation. CC {ECO:0000250|UniProtKB:P49959}. 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:0000250|UniProtKB:P49959}. CC -!- SUBUNIT: Component of the MRN complex composed of two heterodimers CC RAD50/MRE11 associated with a single NBN (By similarity). As part of CC the MRN complex, interacts with MCM9; the interaction recruits the CC complex to DNA repair sites (By similarity). Component of the BASC CC complex, at least composed of BRCA1, MSH2, MSH6, MLH1, ATM, BLM, RAD50, CC MRE11 and NBN (By similarity). Found in a complex with TERF2 (By CC similarity). Interacts with DCLRE1C/Artemis and DCLRE1B/Apollo (By CC similarity). Interacts with ATF2 (By similarity). Interacts with EXD2 CC (By similarity). Interacts with MRNIP (By similarity). Interacts with CC SAMHD1; leading to stimulate 3'-5' exonuclease activity (By CC similarity). Interacts (when ubiquitinated) with UBQLN4 (via its UBA CC domain) (By similarity). Interacts with CYREN (via XLF motif) CC (PubMed:30017584). {ECO:0000250|UniProtKB:P49959, CC ECO:0000269|PubMed:30017584}. CC -!- INTERACTION: CC Q61216; Q9R207: Nbn; NbExp=2; IntAct=EBI-2014813, EBI-2014862; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P49959}. CC Chromosome, telomere {ECO:0000250|UniProtKB:P49959}. Chromosome CC {ECO:0000250|UniProtKB:P49959}. Note=Localizes to discrete nuclear foci CC after treatment with genotoxic agents. {ECO:0000250|UniProtKB:P49959}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=A; CC IsoId=Q61216-1; Sequence=Displayed; CC Name=2; Synonyms=B; CC IsoId=Q61216-2; Sequence=VSP_003263; 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:0000250|UniProtKB:P49959}. CC -!- SIMILARITY: Belongs to the MRE11/RAD32 family. {ECO:0000305}. 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; U58987; AAB04955.1; -; mRNA. DR EMBL; U60318; AAB03664.1; -; mRNA. DR EMBL; BC065144; AAH65144.1; -; mRNA. DR CCDS; CCDS22827.1; -. [Q61216-1] DR CCDS; CCDS80958.1; -. [Q61216-2] DR RefSeq; NP_001297657.1; NM_001310728.1. [Q61216-2] DR RefSeq; NP_061206.1; NM_018736.3. [Q61216-1] DR RefSeq; XP_006510111.1; XM_006510048.2. DR RefSeq; XP_006510112.1; XM_006510049.2. DR AlphaFoldDB; Q61216; -. DR SMR; Q61216; -. DR BioGRID; 201486; 13. DR ComplexPortal; CPX-4703; MRN complex. DR DIP; DIP-46803N; -. DR IntAct; Q61216; 4. DR STRING; 10090.ENSMUSP00000034405; -. DR iPTMnet; Q61216; -. DR PhosphoSitePlus; Q61216; -. DR EPD; Q61216; -. DR jPOST; Q61216; -. DR MaxQB; Q61216; -. DR PaxDb; 10090-ENSMUSP00000034405; -. DR ProteomicsDB; 290057; -. [Q61216-1] DR ProteomicsDB; 290058; -. [Q61216-2] DR Pumba; Q61216; -. DR Antibodypedia; 706; 813 antibodies from 42 providers. DR DNASU; 17535; -. DR Ensembl; ENSMUST00000034405.11; ENSMUSP00000034405.5; ENSMUSG00000031928.16. [Q61216-1] DR Ensembl; ENSMUST00000115632.10; ENSMUSP00000111295.4; ENSMUSG00000031928.16. [Q61216-2] DR GeneID; 17535; -. DR KEGG; mmu:17535; -. DR UCSC; uc009ofc.1; mouse. [Q61216-1] DR UCSC; uc009ofd.1; mouse. [Q61216-2] DR AGR; MGI:1100512; -. DR CTD; 17535; -. DR MGI; MGI:1100512; Mre11a. DR VEuPathDB; HostDB:ENSMUSG00000031928; -. DR eggNOG; KOG2310; Eukaryota. DR GeneTree; ENSGT00390000017288; -. DR HOGENOM; CLU_009535_3_1_1; -. DR InParanoid; Q61216; -. DR OMA; NHLGYGE; -. DR OrthoDB; 169704at2759; -. DR PhylomeDB; Q61216; -. DR TreeFam; TF101105; -. DR Reactome; R-MMU-1834949; Cytosolic sensors of pathogen-associated DNA. DR Reactome; R-MMU-2559586; DNA Damage/Telomere Stress Induced Senescence. DR Reactome; R-MMU-5685938; HDR through Single Strand Annealing (SSA). DR Reactome; R-MMU-5685939; HDR through MMEJ (alt-NHEJ). DR Reactome; R-MMU-5685942; HDR through Homologous Recombination (HRR). DR Reactome; R-MMU-5693548; Sensing of DNA Double Strand Breaks. DR Reactome; R-MMU-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks. DR Reactome; R-MMU-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates. DR Reactome; R-MMU-5693571; Nonhomologous End-Joining (NHEJ). DR Reactome; R-MMU-5693579; Homologous DNA Pairing and Strand Exchange. DR Reactome; R-MMU-5693607; Processing of DNA double-strand break ends. DR Reactome; R-MMU-5693616; Presynaptic phase of homologous DNA pairing and strand exchange. DR Reactome; R-MMU-6804756; Regulation of TP53 Activity through Phosphorylation. DR Reactome; R-MMU-69473; G2/M DNA damage checkpoint. DR BioGRID-ORCS; 17535; 30 hits in 111 CRISPR screens. DR ChiTaRS; Mre11a; mouse. DR PRO; PR:Q61216; -. DR Proteomes; UP000000589; Chromosome 9. DR RNAct; Q61216; Protein. DR Bgee; ENSMUSG00000031928; Expressed in ectoderm and 235 other cell types or tissues. DR ExpressionAtlas; Q61216; baseline and differential. DR GO; GO:0070533; C:BRCA1-C complex; ISO:MGI. DR GO; GO:0000785; C:chromatin; ISO:MGI. DR GO; GO:0098687; C:chromosomal region; NAS:ComplexPortal. DR GO; GO:0000781; C:chromosome, telomeric region; ISO:MGI. DR GO; GO:0000794; C:condensed nuclear chromosome; ISO:MGI. DR GO; GO:0005737; C:cytoplasm; ISO:MGI. DR GO; GO:0030870; C:Mre11 complex; ISO:MGI. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI. DR GO; GO:0016605; C:PML body; IDA:BHF-UCL. DR GO; GO:0005657; C:replication fork; ISS:UniProtKB. DR GO; GO:0035861; C:site of double-strand break; ISS:UniProtKB. DR GO; GO:0008408; F:3'-5' exonuclease activity; ISO:MGI. DR GO; GO:0008296; F:3'-5'-DNA exonuclease activity; IEA:InterPro. DR GO; GO:0008409; F:5'-3' exonuclease activity; ISS:UniProtKB. DR GO; GO:0003677; F:DNA binding; IEA:Ensembl. DR GO; GO:0004520; F:DNA endonuclease activity; ISO:MGI. DR GO; GO:0003678; F:DNA helicase activity; IEA:Ensembl. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0030145; F:manganese ion binding; IEA:InterPro. DR GO; GO:0000014; F:single-stranded DNA endodeoxyribonuclease activity; ISO:MGI. DR GO; GO:0008283; P:cell population proliferation; IMP:MGI. DR GO; GO:0051276; P:chromosome organization; IMP:MGI. DR GO; GO:0006974; P:DNA damage response; ISS:UniProtKB. DR GO; GO:0000729; P:DNA double-strand break processing; NAS:ComplexPortal. DR GO; GO:0032508; P:DNA duplex unwinding; ISO:MGI. DR GO; GO:0110025; P:DNA strand resection involved in replication fork processing; ISS:UniProtKB. DR GO; GO:0006302; P:double-strand break repair; IMP:MGI. DR GO; GO:0000724; P:double-strand break repair via homologous recombination; ISS:UniProtKB. DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; ISO:MGI. DR GO; GO:0007129; P:homologous chromosome pairing at meiosis; IMP:MGI. DR GO; GO:0035825; P:homologous recombination; NAS: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; IMP:MGI. DR GO; GO:0044818; P:mitotic G2/M transition checkpoint; NAS:ComplexPortal. DR GO; GO:0031573; P:mitotic intra-S DNA damage checkpoint signaling; IMP:MGI. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI. DR GO; GO:0046597; P:negative regulation of viral entry into host cell; ISO:MGI. DR GO; GO:0031954; P:positive regulation of protein autophosphorylation; ISO:MGI. DR GO; GO:0032206; P:positive regulation of telomere maintenance; ISO:MGI. DR GO; GO:0007062; P:sister chromatid cohesion; ISO:MGI. DR GO; GO:0000723; P:telomere maintenance; IBA:GO_Central. DR GO; GO:0031860; P:telomeric 3' overhang formation; ISO:MGI. DR CDD; cd00840; MPP_Mre11_N; 1. DR Gene3D; 3.60.21.10; -; 1. DR Gene3D; 3.30.110.110; Mre11, capping domain; 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 NCBIfam; TIGR00583; mre11; 1. DR PANTHER; PTHR10139; DOUBLE-STRAND BREAK REPAIR PROTEIN MRE11; 1. DR PANTHER; PTHR10139:SF1; DOUBLE-STRAND BREAK REPAIR PROTEIN MRE11; 1. 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; Metallo-dependent phosphatases; 1. DR Genevisible; Q61216; MM. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Chromosome; DNA damage; DNA repair; KW Endonuclease; Exonuclease; 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:0000250|UniProtKB:P49959" FT CHAIN 2..706 FT /note="Double-strand break repair protein MRE11" FT /id="PRO_0000138674" FT REGION 505..706 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 505..528 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 529..563 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 584..638 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 658..681 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:0000250|UniProtKB:P49959" FT MOD_RES 2 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17242355, FT ECO:0007744|PubMed:21183079" FT MOD_RES 275 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P49959" FT MOD_RES 618 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P49959" FT MOD_RES 640 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 648 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 676 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P49959" FT MOD_RES 686 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 699 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P49959" FT CROSSLNK 255 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:P49959" FT VAR_SEQ 340..366 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.1" FT /id="VSP_003263" SQ SEQUENCE 706 AA; 80223 MW; 0F12F51902FC179A CRC64; MSPTDPLDDE DTFKILVATD IHLGFMEKDA VRGNDTFVTF DEILRLALEN EVDFILLGGD LFHENKPSRK TLHSCLELLR KYCMGDRPVQ FEVISDQSVN FGFSKFPWVN YQDGNLNISI PVFSIHGNHD DPTGADALCA LDVLSCAGFV NHFGRSMSVE KVDISPVLLQ KGSTKLALYG LGSIPDERLY RMFVNKKVTM LRPKEDENSW FNLFVIHQNR SKHGNTNFIP EQFLDDFIDL VIWGHEHECK IGPIKNEQQL FYVSQPGSSV VTSLSPGEAV KKHVGLLRIK GRKMNMQKLP LRTVRRFFIE DVVLANHPNL FNPDNPKVTQ AIQSFCLEKI EEMLDSAERE RLGNPQQPGK PLIRLRVDYS GGFEPFNVLR FSQKFVDRVA NPKDVIHFFR HREQKGKTGE EINFGMLITK PASEGATLRV EDLVKQYFQT AEKNVQLSLL TERGMGEAVQ EFVDKEEKDA IEELVKYQLE KTQRFLKERH IDALEDKIDE EVRRFRESRQ RNTNEEDDEV REAMSRARAL RSQSETSTSA FSAEDLSFDT SEQTANDSDD SLSAVPSRGR GRGRGRRGAR GQSSAPRGGS QRGRDTGLEI TTRGRSSKAT SSTSRNMSII DAFRSTRQQP SRNVAPKNYS ETIEVDDSDE DDIFPTNSRA DQRWSGTTSS KRMSQSQTAK GVDFESDEDD DDDPFMSSSC PRRNRR //