MRE11_MOUSE
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 03-AUG-2022, entry version 180.
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, Pancreas,
RC 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}.
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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. [Q61216-1]
DR RefSeq; XP_006510112.1; XM_006510049.2. [Q61216-2]
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; Q61216; -.
DR PRIDE; Q61216; -.
DR ProteomicsDB; 290057; -. [Q61216-1]
DR ProteomicsDB; 290058; -. [Q61216-2]
DR Antibodypedia; 706; 713 antibodies from 42 providers.
DR DNASU; 17535; -.
DR Ensembl; ENSMUST00000034405; ENSMUSP00000034405; ENSMUSG00000031928. [Q61216-1]
DR Ensembl; ENSMUST00000115632; ENSMUSP00000111295; ENSMUSG00000031928. [Q61216-2]
DR GeneID; 17535; -.
DR KEGG; mmu:17535; -.
DR UCSC; uc009ofc.1; mouse. [Q61216-1]
DR UCSC; uc009ofd.1; mouse. [Q61216-2]
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; QWMRPET; -.
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 107 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 231 other tissues.
DR ExpressionAtlas; Q61216; baseline and differential.
DR Genevisible; Q61216; MM.
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; IC: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'-exodeoxyribonuclease activity; IEA:InterPro.
DR GO; GO:0008409; F:5'-3' exonuclease activity; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; ISO:MGI.
DR GO; GO:0003678; F:DNA helicase activity; ISO:MGI.
DR GO; GO:0004520; F:endodeoxyribonuclease activity; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0030145; F:manganese ion binding; IEA:InterPro.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
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:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0051276; P:chromosome organization; IMP:MGI.
DR GO; GO:0000729; P:DNA double-strand break processing; IC: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; 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; IMP:MGI.
DR GO; GO:0044818; P:mitotic G2/M transition checkpoint; IC: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:0033674; P:positive regulation of kinase activity; 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; 3.30.110.110; -; 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 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
