Mre11
entrez
17535
canonical
uniprot
Q61216
canonical
ensembl
ENSMUSG00000031928
resolver
ensp
ENSMUSP00000034405
resolver
ensp
ENSMUSP00000111295
resolver
genesymbol
Mre11
resolver
genesymbol
Mre11a
resolver
genesymbol_syn
Mre11a
resolver
uniprot
Q3TU24
resolver
uniprot
Q3URU4
resolver
uniprot
Q62430
resolver
uniprot
Q8BRV3
resolver
uniprot_entry
MRE11_MOUSE
resolver
uniprot_entry
Q3TU24_MOUSE
resolver
uniprot_entry
Q3URU4_MOUSE
resolver
uniprot_entry
Q8BRV3_MOUSE
resolver
uniprot_sec
Q62430
resolver
activity_regulation
ACTIVITY REGULATION: Interaction with SAMHD1 stimulates the double-strand-specific 3'-5' exonuclease activity. RBBP8/CtIP specifically promotes the endonuclease activity to clear protein-DNA adducts and generate clean double-strand break ends. DYNLL1-binding inhibits the activity of MRE11. MRE11 activity is inhibited by C1QBP: in absence of DNA damage, C1QBP interacts with unphosphorylated MRE11, preventing formation and activity of the MRN complex. {ECO:0000250|UniProtKB:P49959}.
uniprot
proteins
amino_acid_sequence
MSPTDPLDDEDTFKILVATDIHLGFMEKDAVRGNDTFVTFDEILRLALENEVDFILLGGDLFHENKPSRKTLHSCLELLRKYCMGDRPVQFEVISDQSVNFGFSKFPWVNYQDGNLNISIPVFSIHGNHDDPTGADALCALDVLSCAGFVNHFGRSMSVEKVDISPVLLQKGSTKLALYGLGSIPDERLYRMFVNKKVTMLRPKEDENSWFNLFVIHQNRSKHGNTNFIPEQFLDDFIDLVIWGHEHECKIGPIKNEQQLFYVSQPGSSVVTSLSPGEAVKKHVGLLRIKGRKMNMQKLPLRTVRRFFIEDVVLANHPNLFNPDNPKVTQAIQSFCLEKIEEMLDSAERERLGNPQQPGKPLIRLRVDYSGGFEPFNVLRFSQKFVDRVANPKDVIHFFRHREQKGKTGEEINFGMLITKPASEGATLRVEDLVKQYFQTAEKNVQLSLLTERGMGEAVQEFVDKEEKDAIEELVKYQLEKTQRFLKERHIDALEDKIDEEVRRFRESRQRNTNEEDDEVREAMSRARALRSQSETSTSAFSAEDLSFDTSEQTANDSDDSLSAVPSRGRGRGRGRRGARGQSSAPRGGSQRGRDTGLEITTRGRSSKATSSTSRNMSIIDAFRSTRQQPSRNVAPKNYSETIEVDDSDEDDIFPTNSRADQRWSGTTSSKRMSQSQTAKGVDFESDEDDDDDPFMSSSCPRRNRR
uniprot
proteins
ec_number
3.1.-.-
uniprot
proteins
function
FUNCTION: Core component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis (PubMed:14690604, PubMed:17291760, PubMed:18854157). The MRN complex is involved in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), an error-free mechanism which primarily occurs during S and G2 phases (PubMed:18854157). The complex (1) mediates the end resection of damaged DNA, which generates proper single-stranded DNA, a key initial steps in HR, and is (2) required for the recruitment of other repair factors and efficient activation of ATM and ATR upon DNA damage (PubMed:14690604, PubMed:18854157). Within the MRN complex, MRE11 possesses both single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity (PubMed:18854157). After DSBs, MRE11 is loaded onto DSBs sites and cleaves DNA by cooperating with RBBP8/CtIP to initiate end resection (By similarity). MRE11 first endonucleolytically cleaves the 5' strand at DNA DSB ends to prevent non-homologous end joining (NHEJ) and licence HR (By similarity). It then generates a single-stranded DNA gap via 3' to 5' exonucleolytic degradation to create entry sites for EXO1- and DNA2-mediated 5' to 3' long-range resection, which is required for single-strand invasion and recombination (By similarity). RBBP8/CtIP specifically promotes the endonuclease activity of MRE11 to clear protein-DNA adducts and generate clean double-strand break ends (By similarity). MRE11 endonuclease activity is also enhanced by AGER/RAGE (PubMed:28977635). The MRN complex is also required for DNA damage signaling via activation of the ATM and ATR kinases: the nuclease activity of MRE11 is not required to activate ATM and ATR (PubMed:18854157). The MRN complex is also required for the processing of R-loops (By similarity). The MRN complex is involved in the activation of the cGAS-STING pathway induced by DNA damage during tumorigenesis: the MRN complex acts by displacing CGAS from nucleosome sequestration, thereby activating it (PubMed:38200309). In telomeres the MRN complex may modulate t-loop formation (By similarity). {ECO:0000250|UniProtKB:P49959, ECO:0000269|PubMed:14690604, ECO:0000269|PubMed:17291760, ECO:0000269|PubMed:18854157, ECO:0000269|PubMed:28977635, ECO:0000269|PubMed:38200309}.
uniprot
proteins
mass_dalton
80223
uniprot
proteins
mutagenesis
MUTAGEN 129; /note="H->N: Knockin mice show early embryonic lethality and genomic instability."; /evidence="ECO:0000269|PubMed:18854157"; MUTAGEN 632..706; /note="Missing: Knockin mice show defects in ATM-dependent DNA repair. Female mice display subfertility due to defects in progression of meiotic prophase."; /evidence="ECO:0000269|PubMed:14690604
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by ATM at Ser-674 and Ser-676 in response to DNA damage, promoting MRE11 activity: phosphorylation activates MRE11 by preventing the interaction between MRE11 and the C1QBP inhibitor (By similarity). Phosphorylation at Ser-648 by PLK1 primes for phosphorylation at Ser-686 by CK2, inhibiting recruitment of the MRN complex to DNA damage sites (By similarity). {ECO:0000250|UniProtKB:P49959}.; PTM: Asymmetric dimethylation by PRMT1 promotes MRE11 exonuclease activity. {ECO:0000250|UniProtKB:P49959}.; PTM: Lactylation at Lys-671 by CREBBP/CBP in response to DNA damage promotes DNA binding and MRE11 activity. {ECO:0000250|UniProtKB:P49959}.; PTM: Acetylated on lysine residues by KAT2A /GCN5. {ECO:0000250|UniProtKB:P49959}.; PTM: Ubiquitinated following DNA damage. Ubiquitination triggers interaction with UBQLN4, leading to MRE11 removal from chromatin and degradation by the proteasome. Ubiquitinated at Lys-339 and Lys-481 by RNF126 via 'Lys-27'- and 'Lys-29'-linked polyubiquitin chains, promoting the exonuclease activity of MRE11. {ECO:0000250|UniProtKB:P49959}.; PTM: SUMOylated by PIAS1, stabilizing MRE11 on chromatin during end resection. DeSUMOylated by SENP3 following removal from DNA double-strand breaks (DSBs). {ECO:0000250|UniProtKB:P49959}.; PTM: Ufmylation at Lys-282 promotes MRE11 activity and is required for activation of the ATM and ATR kinases by the MRN complex. {ECO:0000250|UniProtKB:P49959}.
uniprot
proteins
protein_family
MRE11/RAD32 family
uniprot
proteins
pubmed
14690604
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17242355
uniprot
proteins
pubmed
17291760
uniprot
proteins
pubmed
18854157
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
28977635
uniprot
proteins
pubmed
30017584
uniprot
proteins
pubmed
38200309
uniprot
proteins
pubmed
9224597
uniprot
proteins
sequence_length
706
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P49959}. Chromosome {ECO:0000250|UniProtKB:P49959}. Chromosome, telomere {ECO:0000250|UniProtKB:P49959}. Note=Localizes to DNA double-strand breaks (DSBs). {ECO:0000250|UniProtKB:P49959}.
uniprot
proteins