MRE11
entrez
4361
canonical
uniprot
P49959
canonical
ensembl
ENSG00000020922
resolver
ensp
ENSP00000325863
resolver
ensp
ENSP00000326094
resolver
ensp
ENSP00000376933
resolver
ensp
ENSP00000385614
resolver
ensp
ENSP00000526369
resolver
ensp
ENSP00000526370
resolver
ensp
ENSP00000526371
resolver
ensp
ENSP00000526372
resolver
ensp
ENSP00000526373
resolver
ensp
ENSP00000526374
resolver
ensp
ENSP00000606253
resolver
ensp
ENSP00000606255
resolver
ensp
ENSP00000614978
resolver
ensp
ENSP00000790771
resolver
enst
ENST00000393241
resolver
enst
ENST00000856311
resolver
enst
ENST00000856313
resolver
genesymbol
MRE11
resolver
genesymbol
MRE11A
resolver
genesymbol_syn
HNGS1
resolver
genesymbol_syn
MRE11A
resolver
hgnc
HGNC:7230
resolver
uniprot
B3KTC7
resolver
uniprot
F8W7U8
resolver
uniprot
O43475
resolver
uniprot
Q05D78
resolver
uniprot_entry
F8W7U8_HUMAN
resolver
uniprot_entry
MRE11_HUMAN
resolver
uniprot_entry
Q05D78_HUMAN
resolver
uniprot_sec
B3KTC7
resolver
uniprot_sec
O43475
resolver
activity_regulation
ACTIVITY REGULATION: Interaction with SAMHD1 stimulates the double-strand-specific 3'-5' exonuclease activity (PubMed:29670289). RBBP8/CtIP specifically promotes the endonuclease activity to clear protein-DNA adducts and generate clean double-strand break ends (PubMed:27814491, PubMed:27889449, PubMed:30787182). DYNLL1-binding inhibits the activity of MRE11 (PubMed:30464262, PubMed:37696958). MRE11 activity is inhibited by C1QBP: in absence of DNA damage, C1QBP interacts with unphosphorylated MRE11, preventing formation and activity of the MRN complex (PubMed:31353207). The mirin-derivative PFM39, specifically inhibits the 3'-5' exonuclease activity (PubMed:24316220). The N-alkylated mirin-derivatives PFM03 and PFM01 specifically inhibit the endonuclease activity (PubMed:24316220). {ECO:0000269|PubMed:24316220, ECO:0000269|PubMed:27814491, ECO:0000269|PubMed:27889449, ECO:0000269|PubMed:29670289, ECO:0000269|PubMed:30464262, ECO:0000269|PubMed:30787182, ECO:0000269|PubMed:31353207, ECO:0000269|PubMed:37696958}.
uniprot
proteins
amino_acid_sequence
MSTADALDDENTFKILVATDIHLGFMEKDAVRGNDTFVTLDEILRLAQENEVDFILLGGDLFHENKPSRKTLHTCLELLRKYCMGDRPVQFEILSDQSVNFGFSKFPWVNYQDGNLNISIPVFSIHGNHDDPTGADALCALDILSCAGFVNHFGRSMSVEKIDISPVLLQKGSTKIALYGLGSIPDERLYRMFVNKKVTMLRPKEDENSWFNLFVIHQNRSKHGSTNFIPEQFLDDFIDLVIWGHEHECKIAPTKNEQQLFYISQPGSSVVTSLSPGEAVKKHVGLLRIKGRKMNMHKIPLHTVRQFFMEDIVLANHPDIFNPDNPKVTQAIQSFCLEKIEEMLENAERERLGNSHQPEKPLVRLRVDYSGGFEPFSVLRFSQKFVDRVANPKDIIHFFRHREQKEKTGEEINFGKLITKPSEGTTLRVEDLVKQYFQTAEKNVQLSLLTERGMGEAVQEFVDKEEKDAIEELVKYQLEKTQRFLKERHIDALEDKIDEEVRRFRETRQKNTNEEDDEVREAMTRARALRSQSEESASAFSADDLMSIDLAEQMANDSDDSISAATNKGRGRGRGRRGGRGQNSASRGGSQRGRADTGLETSTRSRNSKTAVSASRNMSIIDAFKSTRQQPSRNVTTKNYSEVIEVDESDVEEDIFPTTSKTDQRWSSTSSSKIMSQSQVSKGVDFESSEDDDDDPFMNTSSLRRNRR
uniprot
proteins
disease_involvement
DISEASE: Ataxia-telangiectasia-like disorder 1 (ATLD1) [MIM:604391]: A rare disorder characterized by progressive cerebellar ataxia, dysarthria, abnormal eye movements, and absence of telangiectasia. ATLD patients show normal levels of total IgG, IgA and IgM, although there may be reduced levels of specific functional antibodies. At the cellular level, ATLD exhibits hypersensitivity to ionizing radiation and radioresistant DNA synthesis. {ECO:0000269|PubMed:10612394, ECO:0000269|PubMed:11371508, ECO:0000269|PubMed:15269180, ECO:0000269|PubMed:15574463, ECO:0000269|PubMed:19732584, ECO:0000269|PubMed:23080121, ECO:0000269|PubMed:24332946}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Note=Defects in MRE11 can be a cause of nephronophthisis-related ciliopathies (NPHP-RC), a group of recessive diseases that affect kidney, retina and brain. A homozygous truncating mutation MRE11 has been found in patients with cerebellar vermis hypoplasia, ataxia and dysarthria. {ECO:0000269|PubMed:22863007}.
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:11741547, PubMed:14657032, PubMed:22078559, PubMed:23080121, PubMed:24316220, PubMed:26240375, PubMed:27889449, PubMed:28867292, PubMed:29670289, PubMed:30464262, PubMed:30612738, PubMed:31353207, PubMed:37696958, PubMed:38128537, PubMed:9590181, PubMed:9651580, PubMed:9705271). 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:24316220, PubMed:28867292, PubMed:31353207, PubMed:38128537). 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:24316220, PubMed:27889449, PubMed:28867292, PubMed:36050397, PubMed:38128537). Within the MRN complex, MRE11 possesses both single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity (PubMed:11741547, PubMed:22078559, PubMed:24316220, PubMed:26240375, PubMed:27889449, PubMed:29670289, PubMed:31353207, PubMed:36563124, PubMed:9590181, PubMed:9651580, PubMed:9705271). After DSBs, MRE11 is loaded onto DSBs sites and cleaves DNA by cooperating with RBBP8/CtIP to initiate end resection (PubMed:27814491, PubMed:27889449, PubMed:30787182). MRE11 first endonucleolytically cleaves the 5' strand at DNA DSB ends to prevent non-homologous end joining (NHEJ) and licence HR (PubMed:24316220). 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 (PubMed:24316220, PubMed:28867292). RBBP8/CtIP specifically promotes the endonuclease activity of MRE11 to clear protein-DNA adducts and generate clean double-strand break ends (PubMed:27814491, PubMed:27889449, PubMed:30787182). MRE11 endonuclease activity is also enhanced by AGER/RAGE (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:14657032, PubMed:15064416, PubMed:15790808, PubMed:16622404). The MRN complex is also required for the processing of R-loops (PubMed:31537797). 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 (By similarity). In telomeres the MRN complex may modulate t-loop formation (PubMed:10888888). {ECO:0000250|UniProtKB:Q61216, ECO:0000269|PubMed:10888888, ECO:0000269|PubMed:11741547, ECO:0000269|PubMed:14657032, ECO:0000269|PubMed:15064416, ECO:0000269|PubMed:15790808, ECO:0000269|PubMed:16622404, ECO:0000269|PubMed:22078559, ECO:0000269|PubMed:23080121, ECO:0000269|PubMed:24316220, ECO:0000269|PubMed:26240375, ECO:0000269|PubMed:27814491, ECO:0000269|PubMed:27889449, ECO:0000269|PubMed:28867292, ECO:0000269|PubMed:29670289, ECO:0000269|PubMed:30464262, ECO:0000269|PubMed:30612738, ECO:0000269|PubMed:30787182, ECO:0000269|PubMed:31353207, ECO:0000269|PubMed:31537797, ECO:0000269|PubMed:36050397, ECO:0000269|PubMed:36563124, ECO:0000269|PubMed:37696958, ECO:0000269|PubMed:38128537, ECO:0000269|PubMed:9590181, ECO:0000269|PubMed:9651580, ECO:0000269|PubMed:9705271}.; FUNCTION: MRE11 contains two DNA-binding domains (DBDs), enabling it to bind both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). {ECO:0000305}.
uniprot
proteins
mass_dalton
80593
uniprot
proteins
mutagenesis
MUTAGEN 80; /note="R->A: Abolished interaction with NBN."; /evidence="ECO:0000269|PubMed:22078559"; MUTAGEN 87..117; /note="Missing: Abolished interaction with NBN."; /evidence="ECO:0000269|PubMed:22078559"; MUTAGEN 88; /note="P->W: Does not affect interaction with NBN."; /evidence="ECO:0000269|PubMed:22078559"; MUTAGEN 117; /note="N->L: Abolished interaction with NBN."; /evidence="ECO:0000269|PubMed:22078559"; MUTAGEN 121; /note="P->G: Abolished interaction with NBN."; /evidence="ECO:0000269|PubMed:22078559"; MUTAGEN 129..130; /note="HD->LV: Lacks the exonuclease activity."; /evidence="ECO:0000269|PubMed:27889449"; MUTAGEN 255; /note="K->R: In 4KR mutant; strongly decreased SUMOylation; when associated with R-384, R-416 and R-467."; /evidence="ECO:0000269|PubMed:36050397"; MUTAGEN 282; /note="K->R: Abolished ufmylation."; /evidence="ECO:0000269|PubMed:30783677"; MUTAGEN 339; /note="K->R: Abolished ubiquitination by RNF126; when associated with R-480."; /evidence="ECO:0000269|PubMed:36563124"; MUTAGEN 384; /note="K->R: In 4KR mutant; strongly decreased SUMOylation; when associated with R-255, R-416 and R-467."; /evidence="ECO:0000269|PubMed:36050397"; MUTAGEN 416; /note="K->R: In 4KR mutant; strongly decreased SUMOylation; when associated with R-255, R-384 and R-467."; /evidence="ECO:0000269|PubMed:36050397"; MUTAGEN 467; /note="K->R: In 4KR mutant; strongly decreased SUMOylation; when associated with R-255, R-384 and R-416."; /evidence="ECO:0000269|PubMed:36050397"; MUTAGEN 480; /note="K->R: Abolished ubiquitination by RNF126; when associated with R-339."; /evidence="ECO:0000269|PubMed:36563124"; MUTAGEN 531; /note="S->A: Does not affect phosphorylation by ATM; when associated with A-590."; /evidence="ECO:0000269|PubMed:26240375"; MUTAGEN 570..594; /note="RGRGRGRRGGRGQNSASRGGSQRGR->KGKGKGKKGGKGQNSASKGGSQKGK: Abolished methylation, leading to decreased exonuclease activity."; /evidence="ECO:0000269|PubMed:15741314"; MUTAGEN 572..576; /note="RGRGR->QGRGQ: Abolished interaction with C1QBP."; /evidence="ECO:0000269|PubMed:31353207"; MUTAGEN 590; /note="S->A: Does not affect phosphorylation by ATM; when associated with A-531."; /evidence="ECO:0000269|PubMed:26240375"; MUTAGEN 649; /note="S->A: Decreased phosphorylation; when associated with A-688."; /evidence="ECO:0000269|PubMed:28512243"; MUTAGEN 649; /note="S->D: Mimics phosphorylation; decreased ability to mediate DNA repair; when associated with D-688."; /evidence="ECO:0000269|PubMed:28512243"; MUTAGEN 673; /note="K->R: Abolished lactylation by CREBBP/CBP, leading to decreased DNA-binding."; /evidence="ECO:0000269|PubMed:38128537"; MUTAGEN 676..678; /note="SQS->AQA: Impaired phosphorylation by ATM, preventing interaction with C1QBP."; /evidence="ECO:0000269|PubMed:26240375, ECO:0000269|PubMed:31353207"; MUTAGEN 688; /note="S->A: Decreased phosphorylation; when associated with A-649."; /evidence="ECO:0000269|PubMed:28512243"; MUTAGEN 688; /note="S->D: Mimics phosphorylation; decreased ability to mediate DNA repair; when associated with D-649."; /evidence="ECO:0000269|PubMed:28512243
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by ATM at Ser-676 and Ser-678 in response to DNA damage, promoting MRE11 activity: phosphorylation activates MRE11 by preventing the interaction between MRE11 and the C1QBP inhibitor (PubMed:16601701, PubMed:26240375, PubMed:31353207). Phosphorylation at Ser-649 by PLK1 primes for phosphorylation at Ser-688 by CK2, inhibiting recruitment of the MRN complex to DNA damage sites (PubMed:28512243). {ECO:0000269|PubMed:16601701, ECO:0000269|PubMed:26240375, ECO:0000269|PubMed:28512243, ECO:0000269|PubMed:31353207}.; PTM: Asymmetric dimethylation by PRMT1 promotes MRE11 exonuclease activity. {ECO:0000269|PubMed:15741314, ECO:0000269|PubMed:29651020}.; PTM: Lactylation at Lys-673 by CREBBP/CBP in response to DNA damage promotes DNA binding and MRE11 activity. {ECO:0000269|PubMed:38128537}.; PTM: Acetylated on lysine residues by KAT2A /GCN5. {ECO:0000269|PubMed:38128537}.; PTM: Ubiquitinated following DNA damage (PubMed:30612738). Ubiquitination triggers interaction with UBQLN4, leading to MRE11 removal from chromatin and degradation by the proteasome (PubMed:30612738). Ubiquitinated at Lys-339 and Lys-480 by RNF126 via 'Lys-27'- and 'Lys-29'-linked polyubiquitin chains, promoting the exonuclease activity of MRE11 (PubMed:36563124). {ECO:0000269|PubMed:30612738, ECO:0000269|PubMed:36563124}.; PTM: SUMOylated by PIAS1, stabilizing MRE11 on chromatin during end resection (PubMed:36050397). DeSUMOylated by SENP3 following removal from DNA double-strand breaks (DSBs) (PubMed:36050397). {ECO:0000269|PubMed:36050397}.; PTM: Ufmylation at Lys-282 promotes MRE11 activity and is required for activation of the ATM and ATR kinases by the MRN complex. {ECO:0000269|PubMed:30783677}.; PTM: (Microbial infection) Following infection by adenovirus E4, ubiquitinated and degraded by a SCF-like E3 ubiquitin ligase complex containing viral proteins E1B-55K and E4-ORF6. {ECO:0000269|PubMed:12124628, ECO:0000269|PubMed:14657032}.
uniprot
proteins
protein_family
MRE11/RAD32 family
uniprot
proteins
pubmed
10612394
uniprot
proteins
pubmed
10783165
uniprot
proteins
pubmed
10839544
uniprot
proteins
pubmed
10888888
uniprot
proteins
pubmed
11196167
uniprot
proteins
pubmed
11371508
uniprot
proteins
pubmed
11741547
uniprot
proteins
pubmed
12124628
uniprot
proteins
pubmed
14657032
uniprot
proteins
pubmed
14684699
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15064416
uniprot
proteins
pubmed
15269180
uniprot
proteins
pubmed
15456891
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15574463
uniprot
proteins
pubmed
15723659
uniprot
proteins
pubmed
15741314
uniprot
proteins
pubmed
15790808
uniprot
proteins
pubmed
15916964
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
16601701
uniprot
proteins
pubmed
16622404
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
18469862
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19732584
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20943970
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22078559
uniprot
proteins
pubmed
22223895
uniprot
proteins
pubmed
22863007
uniprot
proteins
pubmed
23080121
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24316220
uniprot
proteins
pubmed
24332946
uniprot
proteins
pubmed
26215093
uniprot
proteins
pubmed
26240375
uniprot
proteins
pubmed
26807646
uniprot
proteins
pubmed
27568553
uniprot
proteins
pubmed
27814491
uniprot
proteins
pubmed
27889449
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
28512243
uniprot
proteins
pubmed
28834754
uniprot
proteins
pubmed
28867292
uniprot
proteins
pubmed
29651020
uniprot
proteins
pubmed
29670289
uniprot
proteins
pubmed
30464262
uniprot
proteins
pubmed
30612738
uniprot
proteins
pubmed
30783677
uniprot
proteins
pubmed
30787182
uniprot
proteins
pubmed
31353207
uniprot
proteins
pubmed
31537797
uniprot
proteins
pubmed
33918759
uniprot
proteins
pubmed
36050397
uniprot
proteins
pubmed
36563124
uniprot
proteins
pubmed
36577401
uniprot
proteins
pubmed
37696958
uniprot
proteins
pubmed
38128537
uniprot
proteins
pubmed
8530104
uniprot
proteins
pubmed
9590181
uniprot
proteins
pubmed
9651580
uniprot
proteins
pubmed
9705271
uniprot
proteins
sequence_length
708
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10783165, ECO:0000269|PubMed:26215093}. Chromosome {ECO:0000269|PubMed:15916964, ECO:0000269|PubMed:26215093, ECO:0000269|PubMed:26240375, ECO:0000269|PubMed:28512243, ECO:0000269|PubMed:30612738}. Chromosome, telomere {ECO:0000269|PubMed:10888888, ECO:0000269|PubMed:36050397}. Note=Localizes to DNA double-strand breaks (DSBs). {ECO:0000269|PubMed:15916964, ECO:0000269|PubMed:26240375, ECO:0000269|PubMed:28512243, ECO:0000269|PubMed:30612738, ECO:0000269|PubMed:36050397}.
uniprot
proteins