MRE11

Functionⁱ

Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis. The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11. RAD50 may be required to bind DNA ends and hold them in close proximity. This could facilitate searches for short or long regions of sequence homology in the recombining DNA templates, and may also stimulate the activity of DNA ligases and/or restrict the nuclease activity of MRE11 to prevent nucleolytic degradation past a given point (PubMed:9651580, PubMed:9590181, PubMed:9705271, PubMed:11741547, PubMed:29670289). The complex may also be required for DNA damage signaling via activation of the ATM kinase (PubMed:15064416). In telomeres the MRN complex may modulate t-loop formation (PubMed:10888888).6 Publications

Miscellaneous

In case of infection by adenovirus E4, the MRN complex is inactivated and degraded by viral oncoproteins, thereby preventing concatenation of viral genomes in infected cells.

Cofactorⁱ

Mn²⁺By similarity

Activity regulationⁱ

Sites

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Active siteⁱ	129	Proton donorBy similarity		1

GO - Molecular functionⁱ

3'-5' exonuclease activity
Source: CACAO
Inferred from direct assayⁱ
- 9651580
- 9705271
5'-3' exonuclease activity
Source: UniProtKB
Inferred from direct assayⁱ
- 29670289
cadherin binding
Source: BHF-UCL
Inferred from high throughput direct assayⁱ
- 25468996
double-stranded DNA binding
Source: ProtInc
Traceable author statementⁱ
- 10802669
double-stranded telomeric DNA binding
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
endodeoxyribonuclease activity
Source: CACAO
Inferred from direct assayⁱ
- 9705271
endonuclease activity
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
identical protein binding
Source: IntAct
Inferred from physical interactionⁱ
- 22078559
manganese ion binding
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
nuclease activity
Source: BHF-UCL
Traceable author statementⁱ
- 15790808
protein C-terminus binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 9590181
single-stranded DNA endodeoxyribonuclease activity
Source: CACAO
Inferred from direct assayⁱ
- 9705271
single-stranded telomeric DNA binding
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

base-excision repair
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
cell proliferation Source: Ensembl
cellular response to DNA damage stimulus
Source: UniProtKB
Inferred from direct assayⁱ
- 29670289
DNA double-strand break processing Source: Reactome
DNA duplex unwinding
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 15790808
DNA recombination
Source: ProtInc
Traceable author statementⁱ
- 9705271
DNA repair
Source: ProtInc
Traceable author statementⁱ
- 9705271
- 9931460
DNA replication Source: Reactome
DNA strand resection involved in replication fork processing
Source: UniProtKB
Inferred from direct assayⁱ
- 29670289
double-strand break repair
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
double-strand break repair via homologous recombination
Source: UniProtKB
Inferred from direct assayⁱ
- 29670289
double-strand break repair via nonhomologous end joining
Source: CACAO
Inferred from direct assayⁱ
- 9651580
intra-S DNA damage checkpoint
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
meiotic DNA double-strand break formation
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
mitochondrial double-strand break repair via homologous recombination
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
mitotic G2 DNA damage checkpoint
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
negative regulation of apoptotic process
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 16374507
negative regulation of DNA endoreduplication
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 15917200
positive regulation of kinase activity
Source: BHF-UCL
Inferred from direct assayⁱ
- 15790808
positive regulation of protein autophosphorylation
Source: BHF-UCL
Inferred from direct assayⁱ
- 15790808
positive regulation of telomere maintenance
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 16374507
positive regulation of type I interferon production Source: Reactome
reciprocal meiotic recombination
Source: ProtInc
Traceable author statementⁱ
- 8530104
- 9931460
regulation of mitotic recombination
Source: ProtInc
Traceable author statementⁱ
- 8530104
sister chromatid cohesion
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 15917200
synapsis Source: Ensembl
telomere maintenance
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
telomere maintenance via telomerase
Source: ProtInc
Traceable author statementⁱ
- 9705271
- 9931460
telomeric 3' overhang formation
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 16374507
viral process Source: UniProtKB-KW

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Endonuclease, Exonuclease, Hydrolase, Nuclease
Biological process	DNA damage, DNA repair, Host-virus interaction, Meiosis
Ligand	Manganese

Enzyme and pathway databases

Reactomeⁱ	R-HSA-1834949 Cytosolic sensors of pathogen-associated DNA R-HSA-2559586 DNA Damage/Telomere Stress Induced Senescence R-HSA-3270619 IRF3-mediated induction of type I IFN R-HSA-5685938 HDR through Single Strand Annealing (SSA) R-HSA-5685939 HDR through MMEJ (alt-NHEJ) R-HSA-5685942 HDR through Homologous Recombination (HRR) R-HSA-5693548 Sensing of DNA Double Strand Breaks R-HSA-5693554 Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks R-HSA-5693568 Resolution of D-loop Structures through Holliday Junction Intermediates R-HSA-5693571 Nonhomologous End-Joining (NHEJ) R-HSA-5693579 Homologous DNA Pairing and Strand Exchange R-HSA-5693607 Processing of DNA double-strand break ends R-HSA-5693616 Presynaptic phase of homologous DNA pairing and strand exchange R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation R-HSA-69473 G2/M DNA damage checkpoint R-HSA-912446 Meiotic recombination
SIGNORⁱ	P49959

Reactomeⁱ

R-HSA-1834949 Cytosolic sensors of pathogen-associated DNA
R-HSA-2559586 DNA Damage/Telomere Stress Induced Senescence
R-HSA-3270619 IRF3-mediated induction of type I IFN
R-HSA-5685938 HDR through Single Strand Annealing (SSA)
R-HSA-5685939 HDR through MMEJ (alt-NHEJ)
R-HSA-5685942 HDR through Homologous Recombination (HRR)
R-HSA-5693548 Sensing of DNA Double Strand Breaks
R-HSA-5693554 Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)
R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-5693568 Resolution of D-loop Structures through Holliday Junction Intermediates
R-HSA-5693571 Nonhomologous End-Joining (NHEJ)
R-HSA-5693579 Homologous DNA Pairing and Strand Exchange
R-HSA-5693607 Processing of DNA double-strand break ends
R-HSA-5693616 Presynaptic phase of homologous DNA pairing and strand exchange
R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation
R-HSA-69473 G2/M DNA damage checkpoint
R-HSA-912446 Meiotic recombination

SIGNORⁱ

P49959

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Double-strand break repair protein MRE11 (EC:3.1.-.-1 Publication) Alternative name(s): Double-strand break repair protein MRE11A Meiotic recombination 11 homolog 1 Short name: MRE11 homolog 1 Meiotic recombination 11 homolog A Short name: MRE11 homolog A
Gene namesⁱ	Name:MRE11Imported Synonyms:HNGS1, MRE11A
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 11

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000020922.12
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:7230 MRE11
MIMⁱ	600814 gene
neXtProtⁱ	NX_P49959

Keywords - Cellular componentⁱ

Chromosome, Nucleus, Telomere

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Ataxia-telangiectasia-like disorder 1 (ATLD1)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA 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.

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_008513	117	N → S in ATLD1. 1 PublicationCorresponds to variant dbSNP:rs137852760EnsemblClinVar.		1

Keywords - Diseaseⁱ

Ciliopathy, Disease mutation

Organism-specific databases

DisGeNET More...DisGeNETⁱ	4361
MalaCards human disease database More...MalaCardsⁱ	MRE11
MIMⁱ	604391 phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000020922
Orphanetⁱ	251347 Ataxia-telangiectasia-like disorder 145 Hereditary breast and ovarian cancer syndrome 240760 Nijmegen breakage syndrome-like disorder
PharmGKBⁱ	PA30934

Chemistry databases

ChEMBLⁱ	CHEMBL3308929

ChEMBLⁱ

CHEMBL3308929

Polymorphism and mutation databases

BioMutaⁱ	MRE11A
DMDMⁱ	17380137

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Initiator methionineⁱ		RemovedCombined sources
ChainⁱPRO_0000138672	2 – 708	Double-strand break repair protein MRE11Add BLAST		707

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	2	N-acetylserineCombined sources	1
Modified residueⁱ	2	PhosphoserineBy similarity	1
Cross-linkⁱ	255	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residueⁱ	275	PhosphoserineCombined sources	1
Cross-linkⁱ	416	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residueⁱ	619	PhosphoserineCombined sources	1
Cross-linkⁱ	625	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residueⁱ	641	PhosphoserineBy similarity	1
Modified residueⁱ	649	PhosphoserineCombined sources	1
Modified residueⁱ	678	PhosphoserineCombined sources	1
Modified residueⁱ	688	PhosphoserineCombined sources	1
Modified residueⁱ	689	PhosphoserineCombined sources	1
Modified residueⁱ	701	PhosphoserineCombined sources	1

Keywords - PTMⁱ

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDⁱ	P49959
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	P49959
PaxDbⁱ	P49959
PeptideAtlas More...PeptideAtlasⁱ	P49959
PRIDEⁱ	P49959
ProteomicsDBⁱ	56186 56187 [P49959-2]

PTM databases

iPTMnetⁱ	P49959
PhosphoSitePlusⁱ	P49959

Miscellaneous databases

PMAP-CutDBⁱ	P49959

PMAP-CutDBⁱ

P49959

Expressionⁱ

Gene expression databases

Bgeeⁱ	ENSG00000020922 Expressed in 208 organ(s), highest expression level in kidney
CleanExⁱ	HS_MRE11A
ExpressionAtlasⁱ	P49959 baseline and differential
Genevisibleⁱ	P49959 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	CAB004081 HPA002691

HPAⁱ

CAB004081
HPA002691

Interactionⁱ

Subunit structureⁱ

Component of the MRN complex composed of two heterodimers RAD50/MRE11 associated with a single NBN (PubMed:9651580, PubMed:9590181, PubMed:9705271, PubMed:10839544, PubMed:26215093). As part of the MRN complex, interacts with MCM9; the interaction recruits the complex to DNA repair sites (PubMed:26215093). Component of the BASC complex, at least composed of BRCA1, MSH2, MSH6, MLH1, ATM, BLM, RAD50, MRE11 and NBN (PubMed:10783165). Found in a complex with TERF2 (PubMed:10888888). Interacts with DCLRE1C/Artemis and DCLRE1B/Apollo (PubMed:15456891, PubMed:15723659, PubMed:18469862). Interacts with ATF2 (PubMed:15916964). Interacts with EXD2 (PubMed:26807646). Interacts with MRNIP (PubMed:27568553). Interacts with SAMHD1; leading to stimulate 3'-5' exonuclease activity (PubMed:28834754, PubMed:29670289).15 Publications

(Microbial infection) Interacts with herpes simplex virus 1 protein UL12 (PubMed:20943970).1 Publication

Binary interactionsⁱ

With	Entry	#Exp.	IntAct	Notes
itself		3	EBI-396513,EBI-396513
	P03243-1	2	EBI-396513,EBI-1927377	From a different organism.
FANCD2	Q9BXW9	6	EBI-396513,EBI-359343
H2AFX	P16104	7	EBI-396513,EBI-494830
HTT	P42858	5	EBI-396513,EBI-466029
NBN	O60934	4	EBI-396513,EBI-494844
RAD17	O75943	2	EBI-396513,EBI-968231
RBBP8	Q99708	3	EBI-396513,EBI-745715

GO - Molecular functionⁱ

cadherin binding
Source: BHF-UCL
Inferred from high throughput direct assayⁱ
- 25468996
identical protein binding
Source: IntAct
Inferred from physical interactionⁱ
- 22078559
protein C-terminus binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 9590181

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	110501, 128 interactors
CORUMⁱ	P49959
Database of interacting proteins More...DIPⁱ	DIP-33238N
IntActⁱ	P49959, 40 interactors
Molecular INTeraction database More...MINTⁱ	P49959
STRINGⁱ	9606.ENSP00000325863

Chemistry databases

BindingDBⁱ

P49959

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Helixⁱ	9 – 11	Combined sources	3
Beta strandⁱ	12 – 18	Combined sources	7
Turnⁱ	24 – 26	Combined sources	3
Turnⁱ	30 – 34	Combined sources	5
Helixⁱ	35 – 49	Combined sources	15
Beta strandⁱ	53 – 57	Combined sources	5
Beta strandⁱ	62 – 66	Combined sources	5
Helixⁱ	69 – 83	Combined sources	15
Beta strandⁱ	122 – 124	Combined sources	3
Beta strandⁱ	128 – 130	Combined sources	3
Turnⁱ	134 – 137	Combined sources	4
Helixⁱ	140 – 147	Combined sources	8
Beta strandⁱ	149 – 152	Combined sources	4
Beta strandⁱ	162 – 164	Combined sources	3
Beta strandⁱ	167 – 171	Combined sources	5
Beta strandⁱ	174 – 181	Combined sources	8
Helixⁱ	186 – 194	Combined sources	9
Beta strandⁱ	198 – 200	Combined sources	3
Helixⁱ	207 – 209	Combined sources	3
Beta strandⁱ	210 – 216	Combined sources	7
Beta strandⁱ	223 – 228	Combined sources	6
Helixⁱ	231 – 233	Combined sources	3
Beta strandⁱ	240 – 243	Combined sources	4
Beta strandⁱ	250 – 255	Combined sources	6
Turnⁱ	257 – 259	Combined sources	3
Beta strandⁱ	262 – 265	Combined sources	4
Helixⁱ	276 – 279	Combined sources	4
Beta strandⁱ	283 – 290	Combined sources	8
Beta strandⁱ	293 – 300	Combined sources	8
Beta strandⁱ	302 – 304	Combined sources	3
Beta strandⁱ	307 – 313	Combined sources	7
Helixⁱ	314 – 316	Combined sources	3
Turnⁱ	318 – 320	Combined sources	3
Helixⁱ	328 – 350	Combined sources	23
Turnⁱ	351 – 353	Combined sources	3
Beta strandⁱ	355 – 357	Combined sources	3
Beta strandⁱ	362 – 368	Combined sources	7
Turnⁱ	370 – 372	Combined sources	3
Helixⁱ	379 – 385	Combined sources	7
Turnⁱ	386 – 388	Combined sources	3
Beta strandⁱ	392 – 399	Combined sources	8

Show more details

3D structure databases

ProteinModelPortalⁱ	P49959
SMRⁱ	P49959
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Sequence similaritiesⁱ

Belongs to the MRE11/RAD32 family.Curated

Phylogenomic databases

eggNOGⁱ	KOG2310 Eukaryota COG0420 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00390000017288
HOGENOMⁱ	HOG000216581
HOVERGENⁱ	HBG052508
InParanoidⁱ	P49959
KEGG Orthology (KO) More...KOⁱ	K10865
OMAⁱ	RMFVNKQ
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G06P4
PhylomeDBⁱ	P49959
TreeFamⁱ	TF101105

Family and domain databases

Gene3Dⁱ	3.30.110.110, 1 hit 3.60.21.10, 1 hit
InterProⁱ	View protein in InterPro IPR004843 Calcineurin-like_PHP_ApaH IPR029052 Metallo-depent_PP-like IPR003701 Mre11 IPR007281 Mre11_DNA-bd IPR038487 Mre11_DNA-bd_sf
PANTHERⁱ	PTHR10139 PTHR10139, 1 hit
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00149 Metallophos, 1 hit PF04152 Mre11_DNA_bind, 1 hit
PIRSFⁱ	PIRSF000882 DSB_repair_MRE11, 1 hit
SMARTⁱ	View protein in SMART SM01347 Mre11_DNA_bind, 1 hit
TIGRFAMsⁱ	TIGR00583 mre11, 1 hit

Sequences (3+)ⁱ

Sequence statusⁱ: Complete.

Sequence processingⁱ: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsⁱ produced by alternative splicing. Align Add to basket

This entry has 3 described isoforms and 4 potential isoforms that are computationally mapped.Show all Align All

Isoform 1 (identifier: P49959-1) [UniParc]FASTA Add to basket

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.

« Hide

        10         20         30         40         50
MSTADALDDE NTFKILVATD IHLGFMEKDA VRGNDTFVTL DEILRLAQEN 
        60         70         80         90        100
EVDFILLGGD LFHENKPSRK TLHTCLELLR KYCMGDRPVQ FEILSDQSVN 
       110        120        130        140        150
FGFSKFPWVN YQDGNLNISI PVFSIHGNHD DPTGADALCA LDILSCAGFV 
       160        170        180        190        200
NHFGRSMSVE KIDISPVLLQ KGSTKIALYG LGSIPDERLY RMFVNKKVTM 
       210        220        230        240        250
LRPKEDENSW FNLFVIHQNR SKHGSTNFIP EQFLDDFIDL VIWGHEHECK 
       260        270        280        290        300
IAPTKNEQQL FYISQPGSSV VTSLSPGEAV KKHVGLLRIK GRKMNMHKIP 
       310        320        330        340        350
LHTVRQFFME DIVLANHPDI FNPDNPKVTQ AIQSFCLEKI EEMLENAERE 
       360        370        380        390        400
RLGNSHQPEK PLVRLRVDYS GGFEPFSVLR FSQKFVDRVA NPKDIIHFFR 
       410        420        430        440        450
HREQKEKTGE EINFGKLITK PSEGTTLRVE DLVKQYFQTA EKNVQLSLLT 
       460        470        480        490        500
ERGMGEAVQE FVDKEEKDAI EELVKYQLEK TQRFLKERHI DALEDKIDEE 
       510        520        530        540        550
VRRFRETRQK NTNEEDDEVR EAMTRARALR SQSEESASAF SADDLMSIDL 
       560        570        580        590        600
AEQMANDSDD SISAATNKGR GRGRGRRGGR GQNSASRGGS QRGRADTGLE 
       610        620        630        640        650
TSTRSRNSKT AVSASRNMSI IDAFKSTRQQ PSRNVTTKNY SEVIEVDESD 
       660        670        680        690        700
VEEDIFPTTS KTDQRWSSTS SSKIMSQSQV SKGVDFESSE DDDDDPFMNT 

SSLRRNRR

Length:708

Mass (Da):80,593

Last modified:September 26, 2001 - v3

Checksum:ⁱD94ABFBDDF6106AD

GO

Isoform 2 (identifier: P49959-2) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
595-622: Missing.

« Hide

        10         20         30         40         50
MSTADALDDE NTFKILVATD IHLGFMEKDA VRGNDTFVTL DEILRLAQEN 
        60         70         80         90        100
EVDFILLGGD LFHENKPSRK TLHTCLELLR KYCMGDRPVQ FEILSDQSVN 
       110        120        130        140        150
FGFSKFPWVN YQDGNLNISI PVFSIHGNHD DPTGADALCA LDILSCAGFV 
       160        170        180        190        200
NHFGRSMSVE KIDISPVLLQ KGSTKIALYG LGSIPDERLY RMFVNKKVTM 
       210        220        230        240        250
LRPKEDENSW FNLFVIHQNR SKHGSTNFIP EQFLDDFIDL VIWGHEHECK 
       260        270        280        290        300
IAPTKNEQQL FYISQPGSSV VTSLSPGEAV KKHVGLLRIK GRKMNMHKIP 
       310        320        330        340        350
LHTVRQFFME DIVLANHPDI FNPDNPKVTQ AIQSFCLEKI EEMLENAERE 
       360        370        380        390        400
RLGNSHQPEK PLVRLRVDYS GGFEPFSVLR FSQKFVDRVA NPKDIIHFFR 
       410        420        430        440        450
HREQKEKTGE EINFGKLITK PSEGTTLRVE DLVKQYFQTA EKNVQLSLLT 
       460        470        480        490        500
ERGMGEAVQE FVDKEEKDAI EELVKYQLEK TQRFLKERHI DALEDKIDEE 
       510        520        530        540        550
VRRFRETRQK NTNEEDDEVR EAMTRARALR SQSEESASAF SADDLMSIDL 
       560        570        580        590        600
AEQMANDSDD SISAATNKGR GRGRGRRGGR GQNSASRGGS QRGRAFKSTR 
       610        620        630        640        650
QQPSRNVTTK NYSEVIEVDE SDVEEDIFPT TSKTDQRWSS TSSSKIMSQS 
       660        670        680
QVSKGVDFES SEDDDDDPFM NTSSLRRNRR

Show »

Length:680

Mass (Da):77,642

Checksum:ⁱB36BA7EC8CE79BEE

GO

Isoform 3 (identifier: P49959-3) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
1-7: MSTADAL → MNRNISHQKG

« Hide

        10         20         30         40         50
MNRNISHQKG DDENTFKILV ATDIHLGFME KDAVRGNDTF VTLDEILRLA 
        60         70         80         90        100
QENEVDFILL GGDLFHENKP SRKTLHTCLE LLRKYCMGDR PVQFEILSDQ 
       110        120        130        140        150
SVNFGFSKFP WVNYQDGNLN ISIPVFSIHG NHDDPTGADA LCALDILSCA 
       160        170        180        190        200
GFVNHFGRSM SVEKIDISPV LLQKGSTKIA LYGLGSIPDE RLYRMFVNKK 
       210        220        230        240        250
VTMLRPKEDE NSWFNLFVIH QNRSKHGSTN FIPEQFLDDF IDLVIWGHEH 
       260        270        280        290        300
ECKIAPTKNE QQLFYISQPG SSVVTSLSPG EAVKKHVGLL RIKGRKMNMH 
       310        320        330        340        350
KIPLHTVRQF FMEDIVLANH PDIFNPDNPK VTQAIQSFCL EKIEEMLENA 
       360        370        380        390        400
ERERLGNSHQ PEKPLVRLRV DYSGGFEPFS VLRFSQKFVD RVANPKDIIH 
       410        420        430        440        450
FFRHREQKEK TGEEINFGKL ITKPSEGTTL RVEDLVKQYF QTAEKNVQLS 
       460        470        480        490        500
LLTERGMGEA VQEFVDKEEK DAIEELVKYQ LEKTQRFLKE RHIDALEDKI 
       510        520        530        540        550
DEEVRRFRET RQKNTNEEDD EVREAMTRAR ALRSQSEESA SAFSADDLMS 
       560        570        580        590        600
IDLAEQMAND SDDSISAATN KGRGRGRGRR GGRGQNSASR GGSQRGRADT 
       610        620        630        640        650
GLETSTRSRN SKTAVSASRN MSIIDAFKST RQQPSRNVTT KNYSEVIEVD 
       660        670        680        690        700
ESDVEEDIFP TTSKTDQRWS STSSSKIMSQ SQVSKGVDFE SSEDDDDDPF 
       710 
MNTSSLRRNR R

Note: No experimental confirmation available.

Show »

Length:711

Mass (Da):81,070

Checksum:ⁱ10AE0AC05AFB9351

GO

Computationally mapped potential isoform sequencesⁱ

There are 4 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

Entry	Entry name	Protein names	Gene names	Length	Annotation

F8W7U8	F8W7U8_HUMAN	Double-strand break repair protein Double-strand break repair protein	MRE11	707	Annotation score:
F5GXT0	F5GXT0_HUMAN	Double-strand break repair protein ... Double-strand break repair protein MRE11	MRE11	221	Annotation score:
F5H742	F5H742_HUMAN	Double-strand break repair protein ... Double-strand break repair protein MRE11	MRE11	111	Annotation score:
F5H256	F5H256_HUMAN	Double-strand break repair protein ... Double-strand break repair protein MRE11	MRE11	127	Annotation score:

Experimental Info

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Sequence conflictⁱ	31	V → A in AAC78721 (PubMed:8530104).Curated		1

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_011625	104	S → C in cancer. 1 PublicationCorresponds to variant dbSNP:rs748434421EnsemblClinVar.	1
Natural variantⁱVAR_008513	117	N → S in ATLD1. 1 PublicationCorresponds to variant dbSNP:rs137852760EnsemblClinVar.	1
Natural variantⁱVAR_011626	157	M → V. Corresponds to variant dbSNP:rs147771140EnsemblClinVar.	1
Natural variantⁱVAR_036416	237	F → C in a breast cancer sample; somatic mutation. 1 Publication	1
Natural variantⁱVAR_036417	302	H → Y in a breast cancer sample; somatic mutation. 1 Publication	1
Natural variantⁱVAR_025528	305	R → W in ovarian cancer. 1 PublicationCorresponds to variant dbSNP:rs372000848EnsemblClinVar.	1
Natural variantⁱVAR_019288	468	D → G1 PublicationCorresponds to variant dbSNP:rs1805367Ensembl.	1
Natural variantⁱVAR_011627	503	R → H in cancer. 1 PublicationCorresponds to variant dbSNP:rs774057024EnsemblClinVar.	1
Natural variantⁱVAR_011628	572	R → Q in cancer. 1 PublicationCorresponds to variant dbSNP:rs200085146EnsemblClinVar.	1
Natural variantⁱVAR_019289	698	M → V1 PublicationCorresponds to variant dbSNP:rs1805362EnsemblClinVar.	1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Alternative sequenceⁱVSP_057350	1 – 7	MSTADAL → MNRNISHQKG in isoform 3. 1 Publication		7
Alternative sequenceⁱVSP_003262	595 – 622	Missing in isoform 2. 1 PublicationAdd BLAST		28

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	U37359 mRNA Translation: AAC78721.1 AF022778 mRNA Translation: AAD10197.1 AF073362 mRNA Translation: AAC36249.1 AF303395 AF303394 Genomic DNA Translation: AAK18790.1 AK095388 mRNA Translation: BAG53039.1 AY584241 Genomic DNA Translation: AAS79320.1 AP000765 Genomic DNA No translation available. AP000786 Genomic DNA No translation available. KF455448 Genomic DNA No translation available. BC063458 mRNA Translation: AAH63458.1
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS8298.1 [P49959-2] CCDS8299.1 [P49959-1]
NCBI Reference Sequences More...RefSeqⁱ	NP_005581.2, NM_005590.3 [P49959-2] NP_005582.1, NM_005591.3 [P49959-1] XP_011541139.1, XM_011542837.2 [P49959-1] XP_016873261.1, XM_017017772.1 [P49959-1]
UniGeneⁱ	Hs.192649

Genome annotation databases

Ensemblⁱ	ENST00000323929; ENSP00000325863; ENSG00000020922 [P49959-1] ENST00000323977; ENSP00000326094; ENSG00000020922 [P49959-2] ENST00000407439; ENSP00000385614; ENSG00000020922 [P49959-3]
GeneIDⁱ	4361
KEGGⁱ	hsa:4361
UCSC genome browser More...UCSCⁱ	uc001peu.4 human [P49959-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing, Polymorphism

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
P49959	Double-strand break repair protein		HUMAN		708	UniRef100_P49959
MRE11 isoform 9 (Fragment)		PONAB		111
Double-strand break repair protein MRE11 (Fragment)		HUMAN		111
Double-strand break repair protein MRE11 (Fragment)		HUMAN		127
MRE11 isoform 8 (Fragment)		PONAB		127
+1

Protein	Similar proteins		Species	Score	Length	Source
P49959	Double-strand break repair protein MRE11		MACFA		707	UniRef90_P49959
Double-strand break repair protein		HUMAN		708
MRE11 isoform 9 (Fragment)		PONAB		111
Double-strand break repair protein		AILME		712
Double-strand break repair protein		OTOGA		712
+140
P49959-2	Double-strand break repair protein		CALJA		681	UniRef90_P49959-2
Double-strand break repair protein		SAIBB		681
Double-strand break repair protein		PROCO		681
Double-strand break repair protein		Cebus capucinus imitator		681
Double-strand break repair protein		ODORO		681
+22
P49959-3	Double-strand break repair protein		PANTR		762	UniRef90_P49959-3
Meiotic recombination 11 (Fragment)		Muntiacus vaginalis		35
Double-strand break repair protein		wild yak		714
Double-strand break repair protein		SAIBB		709
Double-strand break repair protein		CALJA		709
+41

Protein	Similar proteins		Species	Score	Length	Source
P49959	Double-strand break repair protein MRE11		MACFA		707	UniRef50_P49959
Double-strand break repair protein MRE11		CHICK		700
Double-strand break repair protein MRE11		XENLA		711
Double-strand break repair protein MRE11		RAT		706
Double-strand break repair protein MRE11		MOUSE		706
+570

Cross-referencesⁱ

Web resourcesⁱ

Atlas of Genetics and Cytogenetics in Oncology and Haematology

MRE11base

MRE11A mutation db

NIEHS-SNPs

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	U37359 mRNA Translation: AAC78721.1 AF022778 mRNA Translation: AAD10197.1 AF073362 mRNA Translation: AAC36249.1 AF303395 AF303394 Genomic DNA Translation: AAK18790.1 AK095388 mRNA Translation: BAG53039.1 AY584241 Genomic DNA Translation: AAS79320.1 AP000765 Genomic DNA No translation available. AP000786 Genomic DNA No translation available. KF455448 Genomic DNA No translation available. BC063458 mRNA Translation: AAH63458.1
CCDSⁱ	CCDS8298.1 [P49959-2] CCDS8299.1 [P49959-1]
RefSeqⁱ	NP_005581.2, NM_005590.3 [P49959-2] NP_005582.1, NM_005591.3 [P49959-1] XP_011541139.1, XM_011542837.2 [P49959-1] XP_016873261.1, XM_017017772.1 [P49959-1]
UniGeneⁱ	Hs.192649

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	3T1I	X-ray	3.00	A/B/C/D	1-411	[»]
ProteinModelPortalⁱ	P49959
SMRⁱ	P49959
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	110501, 128 interactors
CORUMⁱ	P49959
DIPⁱ	DIP-33238N
IntActⁱ	P49959, 40 interactors
MINTⁱ	P49959
STRINGⁱ	9606.ENSP00000325863

Chemistry databases

BindingDBⁱ	P49959
ChEMBLⁱ	CHEMBL3308929

PTM databases

iPTMnetⁱ	P49959
PhosphoSitePlusⁱ	P49959

Polymorphism and mutation databases

BioMutaⁱ	MRE11A
DMDMⁱ	17380137

Proteomic databases

EPDⁱ	P49959
MaxQBⁱ	P49959
PaxDbⁱ	P49959
PeptideAtlasⁱ	P49959
PRIDEⁱ	P49959
ProteomicsDBⁱ	56186 56187 [P49959-2]

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	4361
Structural Biology Knowledgebase	Search...

Genome annotation databases

Ensemblⁱ	ENST00000323929; ENSP00000325863; ENSG00000020922 [P49959-1] ENST00000323977; ENSP00000326094; ENSG00000020922 [P49959-2] ENST00000407439; ENSP00000385614; ENSG00000020922 [P49959-3]
GeneIDⁱ	4361
KEGGⁱ	hsa:4361
UCSCⁱ	uc001peu.4 human [P49959-1]

Organism-specific databases

CTDⁱ	4361
DisGeNETⁱ	4361
EuPathDBⁱ	HostDB:ENSG00000020922.12
GeneCardsⁱ	MRE11
HGNCⁱ	HGNC:7230 MRE11
HPAⁱ	CAB004081 HPA002691
MalaCardsⁱ	MRE11
MIMⁱ	600814 gene 604391 phenotype
neXtProtⁱ	NX_P49959
OpenTargetsⁱ	ENSG00000020922
Orphanetⁱ	251347 Ataxia-telangiectasia-like disorder 145 Hereditary breast and ovarian cancer syndrome 240760 Nijmegen breakage syndrome-like disorder
PharmGKBⁱ	PA30934
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG2310 Eukaryota COG0420 LUCA
GeneTreeⁱ	ENSGT00390000017288
HOGENOMⁱ	HOG000216581
HOVERGENⁱ	HBG052508
InParanoidⁱ	P49959
KOⁱ	K10865
OMAⁱ	RMFVNKQ
OrthoDBⁱ	EOG091G06P4
PhylomeDBⁱ	P49959
TreeFamⁱ	TF101105

Enzyme and pathway databases

Reactomeⁱ	R-HSA-1834949 Cytosolic sensors of pathogen-associated DNA R-HSA-2559586 DNA Damage/Telomere Stress Induced Senescence R-HSA-3270619 IRF3-mediated induction of type I IFN R-HSA-5685938 HDR through Single Strand Annealing (SSA) R-HSA-5685939 HDR through MMEJ (alt-NHEJ) R-HSA-5685942 HDR through Homologous Recombination (HRR) R-HSA-5693548 Sensing of DNA Double Strand Breaks R-HSA-5693554 Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks R-HSA-5693568 Resolution of D-loop Structures through Holliday Junction Intermediates R-HSA-5693571 Nonhomologous End-Joining (NHEJ) R-HSA-5693579 Homologous DNA Pairing and Strand Exchange R-HSA-5693607 Processing of DNA double-strand break ends R-HSA-5693616 Presynaptic phase of homologous DNA pairing and strand exchange R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation R-HSA-69473 G2/M DNA damage checkpoint R-HSA-912446 Meiotic recombination
SIGNORⁱ	P49959

Reactomeⁱ

R-HSA-1834949 Cytosolic sensors of pathogen-associated DNA
R-HSA-2559586 DNA Damage/Telomere Stress Induced Senescence
R-HSA-3270619 IRF3-mediated induction of type I IFN
R-HSA-5685938 HDR through Single Strand Annealing (SSA)
R-HSA-5685939 HDR through MMEJ (alt-NHEJ)
R-HSA-5685942 HDR through Homologous Recombination (HRR)
R-HSA-5693548 Sensing of DNA Double Strand Breaks
R-HSA-5693554 Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)
R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-5693568 Resolution of D-loop Structures through Holliday Junction Intermediates
R-HSA-5693571 Nonhomologous End-Joining (NHEJ)
R-HSA-5693579 Homologous DNA Pairing and Strand Exchange
R-HSA-5693607 Processing of DNA double-strand break ends
R-HSA-5693616 Presynaptic phase of homologous DNA pairing and strand exchange
R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation
R-HSA-69473 G2/M DNA damage checkpoint
R-HSA-912446 Meiotic recombination

SIGNORⁱ

P49959

Miscellaneous databases

ChiTaRSⁱ	MRE11A human
GeneWikiⁱ	MRE11A
GenomeRNAiⁱ	4361
PMAP-CutDBⁱ	P49959
Protein Ontology More...PROⁱ	PR:P49959
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000020922 Expressed in 208 organ(s), highest expression level in kidney
CleanExⁱ	HS_MRE11A
ExpressionAtlasⁱ	P49959 baseline and differential
Genevisibleⁱ	P49959 HS

Family and domain databases

Gene3Dⁱ	3.30.110.110, 1 hit 3.60.21.10, 1 hit
InterProⁱ	View protein in InterPro IPR004843 Calcineurin-like_PHP_ApaH IPR029052 Metallo-depent_PP-like IPR003701 Mre11 IPR007281 Mre11_DNA-bd IPR038487 Mre11_DNA-bd_sf
PANTHERⁱ	PTHR10139 PTHR10139, 1 hit
Pfamⁱ	View protein in Pfam PF00149 Metallophos, 1 hit PF04152 Mre11_DNA_bind, 1 hit
PIRSFⁱ	PIRSF000882 DSB_repair_MRE11, 1 hit
SMARTⁱ	View protein in SMART SM01347 Mre11_DNA_bind, 1 hit
TIGRFAMsⁱ	TIGR00583 mre11, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	MRE11_HUMAN
Accessionⁱ	P49959Primary (citable) accession number: P49959 Secondary accession number(s): B3KTC7, O43475
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
	Last sequence update:	September 26, 2001
	Last modified:	November 7, 2018
	This is version 202 of the entry and version 3 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Complete proteome, Reference proteome

Documents

SIMILARITY comments
Index of protein domains and families
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
PDB cross-references
Index of Protein Data Bank (PDB) cross-references
Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM

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UniProtKB - P49959 (MRE11_HUMAN)

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Double-strand break repair protein MRE11

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

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Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Keywords - Diseasei

Organism-specific databases

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Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

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Keywords - PTMi

Proteomic databases

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<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

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GO - Molecular functioni

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Chemistry databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

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Natural variant

Alternative sequence

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Keywords - Coding sequence diversityi

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<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

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Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Web resourcesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ