Q61216 · MRE11_MOUSE
- ProteinDouble-strand break repair protein MRE11
- GeneMre11
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids706 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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).
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).
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).
Cofactor
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.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 20 | Mn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 22 | Mn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 60 | Mn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 60 | Mn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 128 | Mn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Active site | 129 | Proton donor | ||||
Sequence: H | ||||||
Binding site | 217 | Mn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 245 | Mn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 247 | Mn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: H |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDouble-strand break repair protein MRE11
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ61216
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Localizes to DNA double-strand breaks (DSBs).
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Early embryonic lethality.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 129 | Knockin mice show early embryonic lethality and genomic instability. | ||||
Sequence: H → N | ||||||
Mutagenesis | 632-706 | Knockin mice show defects in ATM-dependent DNA repair. Female mice display subfertility due to defects in progression of meiotic prophase. | ||||
Sequence: Missing |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 48 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylserine | ||||
Sequence: S | ||||||
Modified residue | 2 | Phosphoserine | ||||
Sequence: S | ||||||
Chain | PRO_0000138674 | 2-706 | Double-strand break repair protein MRE11 | |||
Sequence: SPTDPLDDEDTFKILVATDIHLGFMEKDAVRGNDTFVTFDEILRLALENEVDFILLGGDLFHENKPSRKTLHSCLELLRKYCMGDRPVQFEVISDQSVNFGFSKFPWVNYQDGNLNISIPVFSIHGNHDDPTGADALCALDVLSCAGFVNHFGRSMSVEKVDISPVLLQKGSTKLALYGLGSIPDERLYRMFVNKKVTMLRPKEDENSWFNLFVIHQNRSKHGNTNFIPEQFLDDFIDLVIWGHEHECKIGPIKNEQQLFYVSQPGSSVVTSLSPGEAVKKHVGLLRIKGRKMNMQKLPLRTVRRFFIEDVVLANHPNLFNPDNPKVTQAIQSFCLEKIEEMLDSAERERLGNPQQPGKPLIRLRVDYSGGFEPFNVLRFSQKFVDRVANPKDVIHFFRHREQKGKTGEEINFGMLITKPASEGATLRVEDLVKQYFQTAEKNVQLSLLTERGMGEAVQEFVDKEEKDAIEELVKYQLEKTQRFLKERHIDALEDKIDEEVRRFRESRQRNTNEEDDEVREAMSRARALRSQSETSTSAFSAEDLSFDTSEQTANDSDDSLSAVPSRGRGRGRGRRGARGQSSAPRGGSQRGRDTGLEITTRGRSSKATSSTSRNMSIIDAFRSTRQQPSRNVAPKNYSETIEVDDSDEDDIFPTNSRADQRWSGTTSSKRMSQSQTAKGVDFESDEDDDDDPFMSSSCPRRNRR | ||||||
Cross-link | 255 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Modified residue | 275 | Phosphoserine | ||||
Sequence: S | ||||||
Cross-link | 282 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in UFM1) | ||||
Sequence: K | ||||||
Cross-link | 339 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Cross-link | 384 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) | ||||
Sequence: K | ||||||
Cross-link | 468 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) | ||||
Sequence: K | ||||||
Cross-link | 481 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Modified residue | 570 | Asymmetric dimethylarginine | ||||
Sequence: R | ||||||
Modified residue | 572 | Asymmetric dimethylarginine | ||||
Sequence: R | ||||||
Modified residue | 574 | Asymmetric dimethylarginine | ||||
Sequence: R | ||||||
Modified residue | 576 | Asymmetric dimethylarginine | ||||
Sequence: R | ||||||
Modified residue | 577 | Asymmetric dimethylarginine | ||||
Sequence: R | ||||||
Modified residue | 580 | Asymmetric dimethylarginine | ||||
Sequence: R | ||||||
Modified residue | 587 | Asymmetric dimethylarginine | ||||
Sequence: R | ||||||
Modified residue | 592 | Asymmetric dimethylarginine | ||||
Sequence: R | ||||||
Modified residue | 594 | Asymmetric dimethylarginine | ||||
Sequence: R | ||||||
Modified residue | 618 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 640 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 648 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 671 | N6-lactoyllysine | ||||
Sequence: K | ||||||
Modified residue | 674 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 676 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 686 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 699 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
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).
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).
Asymmetric dimethylation by PRMT1 promotes MRE11 exonuclease activity.
Lactylation at Lys-671 by CREBBP/CBP in response to DNA damage promotes DNA binding and MRE11 activity.
Acetylated on lysine residues by KAT2A /GCN5.
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.
SUMOylated by PIAS1, stabilizing MRE11 on chromatin during end resection. DeSUMOylated by SENP3 following removal from DNA double-strand breaks (DSBs).
Ufmylation at Lys-282 promotes MRE11 activity and is required for activation of the ATM and ATR kinases by the MRN complex.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
Component of the MRN complex composed of two heterodimers RAD50 and MRE11 associated with a single NBN (By similarity).
The MRN complexes dimerize on DNA to form joined MRN-MRN oligomers required for DNA double-strand break repair (By similarity).
As part of the MRN complex, interacts with MCM9; the interaction recruits the complex to DNA repair sites (By similarity).
Component of the BASC complex, at least composed of BRCA1, MSH2, MSH6, MLH1, ATM, BLM, RAD50, MRE11 and NBN (By similarity).
Found in a complex with TERF2 (By similarity).
Interacts with DCLRE1C/Artemis and DCLRE1B/Apollo (By similarity).
Interacts with ATF2 (By similarity).
Interacts with EXD2 (By similarity).
Interacts with MRNIP (By similarity).
Interacts with SAMHD1; leading to stimulate 3'-5' exonuclease activity (By similarity).
Interacts (when ubiquitinated) with UBQLN4 (via its UBA domain) (By similarity).
Interacts with CYREN (via XLF motif) (PubMed:30017584).
Interacts with GFI1; promoting methylation by PRMT1 (By similarity).
Interacts with DYNLL1; inhibiting the activity of MRE11 (By similarity).
Interacts with C1QBP and RAD50; interaction takes place in absence of DNA damage to form the MRC (MRE11-RAD50-C1QBP) complex that inhibits the activity of MRE11 (By similarity).
The MRN complexes dimerize on DNA to form joined MRN-MRN oligomers required for DNA double-strand break repair (By similarity).
As part of the MRN complex, interacts with MCM9; the interaction recruits the complex to DNA repair sites (By similarity).
Component of the BASC complex, at least composed of BRCA1, MSH2, MSH6, MLH1, ATM, BLM, RAD50, MRE11 and NBN (By similarity).
Found in a complex with TERF2 (By similarity).
Interacts with DCLRE1C/Artemis and DCLRE1B/Apollo (By similarity).
Interacts with ATF2 (By similarity).
Interacts with EXD2 (By similarity).
Interacts with MRNIP (By similarity).
Interacts with SAMHD1; leading to stimulate 3'-5' exonuclease activity (By similarity).
Interacts (when ubiquitinated) with UBQLN4 (via its UBA domain) (By similarity).
Interacts with CYREN (via XLF motif) (PubMed:30017584).
Interacts with GFI1; promoting methylation by PRMT1 (By similarity).
Interacts with DYNLL1; inhibiting the activity of MRE11 (By similarity).
Interacts with C1QBP and RAD50; interaction takes place in absence of DNA damage to form the MRC (MRE11-RAD50-C1QBP) complex that inhibits the activity of MRE11 (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q61216 | Nbn Q9R207 | 2 | EBI-2014813, EBI-2014862 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 87-117 | Interaction with NBN | ||||
Sequence: RPVQFEVISDQSVNFGFSKFPWVNYQDGNLN | ||||||
Compositional bias | 505-528 | Basic and acidic residues | ||||
Sequence: FRESRQRNTNEEDDEVREAMSRAR | ||||||
Region | 505-706 | Disordered | ||||
Sequence: FRESRQRNTNEEDDEVREAMSRARALRSQSETSTSAFSAEDLSFDTSEQTANDSDDSLSAVPSRGRGRGRGRRGARGQSSAPRGGSQRGRDTGLEITTRGRSSKATSSTSRNMSIIDAFRSTRQQPSRNVAPKNYSETIEVDDSDEDDIFPTNSRADQRWSGTTSSKRMSQSQTAKGVDFESDEDDDDDPFMSSSCPRRNRR | ||||||
Compositional bias | 529-563 | Polar residues | ||||
Sequence: ALRSQSETSTSAFSAEDLSFDTSEQTANDSDDSLS | ||||||
Motif | 570-594 | GAR | ||||
Sequence: RGRGRGRRGARGQSSAPRGGSQRGR | ||||||
Compositional bias | 584-638 | Polar residues | ||||
Sequence: SAPRGGSQRGRDTGLEITTRGRSSKATSSTSRNMSIIDAFRSTRQQPSRNVAPKN | ||||||
Compositional bias | 658-681 | Polar residues | ||||
Sequence: SRADQRWSGTTSSKRMSQSQTAKG |
Sequence similarities
Belongs to the MRE11/RAD32 family.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q61216-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- SynonymsA
- Length706
- Mass (Da)80,223
- Last updated1996-11-01 v1
- Checksum0F12F51902FC179A
Q61216-2
- Name2
- SynonymsB
- Differences from canonical
- 340-366: Missing
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
F6RX99 | F6RX99_MOUSE | Mre11a | 170 | ||
A0A1L1SQT7 | A0A1L1SQT7_MOUSE | Mre11a | 57 | ||
B2KF76 | B2KF76_MOUSE | Mre11a | 203 |
Features
Showing features for alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_003263 | 340-366 | in isoform 2 | |||
Sequence: Missing | ||||||
Compositional bias | 505-528 | Basic and acidic residues | ||||
Sequence: FRESRQRNTNEEDDEVREAMSRAR | ||||||
Compositional bias | 529-563 | Polar residues | ||||
Sequence: ALRSQSETSTSAFSAEDLSFDTSEQTANDSDDSLS | ||||||
Compositional bias | 584-638 | Polar residues | ||||
Sequence: SAPRGGSQRGRDTGLEITTRGRSSKATSSTSRNMSIIDAFRSTRQQPSRNVAPKN | ||||||
Compositional bias | 658-681 | Polar residues | ||||
Sequence: SRADQRWSGTTSSKRMSQSQTAKG |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U58987 EMBL· GenBank· DDBJ | AAB04955.1 EMBL· GenBank· DDBJ | mRNA | ||
U60318 EMBL· GenBank· DDBJ | AAB03664.1 EMBL· GenBank· DDBJ | mRNA | ||
BC065144 EMBL· GenBank· DDBJ | AAH65144.1 EMBL· GenBank· DDBJ | mRNA |