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Protein

Double-strand break repair protein MRE11A

Gene

MRE11A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 MRE11A. 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 MRE11A to prevent nucleolytic degradation past a given point (PubMed:9651580, PubMed:9590181, PubMed:9705271, PubMed:11741547). 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).5 Publications

Cofactori

Mn2+By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei129 – 1291Proton donorBy similarity

GO - Molecular functioni

  • 3'-5' exonuclease activity Source: CACAO
  • double-stranded DNA binding Source: ProtInc
  • endodeoxyribonuclease activity Source: CACAO
  • manganese ion binding Source: InterPro
  • nuclease activity Source: BHF-UCL
  • protein C-terminus binding Source: UniProtKB
  • single-stranded DNA endodeoxyribonuclease activity Source: CACAO

GO - Biological processi

  • cell proliferation Source: Ensembl
  • cellular response to DNA damage stimulus Source: MGI
  • DNA duplex unwinding Source: BHF-UCL
  • DNA recombination Source: ProtInc
  • DNA repair Source: Reactome
  • double-strand break repair Source: Reactome
  • double-strand break repair via homologous recombination Source: Reactome
  • double-strand break repair via nonhomologous end joining Source: CACAO
  • double-strand break repair via synthesis-dependent strand annealing Source: Reactome
  • heart development Source: Ensembl
  • innate immune response Source: Reactome
  • intra-S DNA damage checkpoint Source: GO_Central
  • mitotic G2 DNA damage checkpoint Source: Ensembl
  • negative regulation of apoptotic process Source: BHF-UCL
  • negative regulation of DNA endoreduplication Source: BHF-UCL
  • negative regulation of viral entry into host cell Source: Ensembl
  • nucleic acid phosphodiester bond hydrolysis Source: GOC
  • positive regulation of kinase activity Source: BHF-UCL
  • positive regulation of protein autophosphorylation Source: BHF-UCL
  • positive regulation of telomere maintenance Source: BHF-UCL
  • positive regulation of type I interferon production Source: Reactome
  • reciprocal meiotic recombination Source: ProtInc
  • regulation of mitotic recombination Source: ProtInc
  • sister chromatid cohesion Source: BHF-UCL
  • synapsis Source: Ensembl
  • telomere maintenance via telomerase Source: ProtInc
  • telomeric 3' overhang formation Source: BHF-UCL
  • viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Endonuclease, Exonuclease, Hydrolase, Nuclease

Keywords - Biological processi

DNA damage, DNA repair, Host-virus interaction, Meiosis

Keywords - Ligandi

Manganese

Enzyme and pathway databases

ReactomeiR-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-69473. G2/M DNA damage checkpoint.
R-HSA-912446. Meiotic recombination.

Names & Taxonomyi

Protein namesi
Recommended name:
Double-strand break repair protein MRE11A
Alternative name(s):
Meiotic recombination 11 homolog 1
Short name:
MRE11 homolog 1
Meiotic recombination 11 homolog A
Short name:
MRE11 homolog A
Gene namesi
Name:MRE11A
Synonyms:HNGS1, MRE11
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:7230. MRE11A.

Subcellular locationi

  • Nucleus 1 Publication
  • Chromosometelomere 1 Publication

  • Note: Localizes to discrete nuclear foci after treatment with genotoxic agents.1 Publication

GO - Cellular componenti

  • condensed nuclear chromosome Source: Ensembl
  • cytosol Source: Reactome
  • Mre11 complex Source: BHF-UCL
  • nuclear chromatin Source: Ensembl
  • nuclear chromosome, telomeric region Source: BHF-UCL
  • nucleoplasm Source: HPA
  • nucleus Source: ProtInc
  • perinuclear region of cytoplasm Source: Ensembl
  • PML body Source: BHF-UCL
  • site of double-strand break Source: UniProtKB
Complete GO annotation...

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.
See also OMIM:604391
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti117 – 1171N → S in ATLD1. 1 Publication
VAR_008513

Defects in MRE11A 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 MRE11A has been found in patients with cerebellar vermis hypoplasia, ataxia and dysarthria.

Keywords - Diseasei

Ciliopathy, Disease mutation

Organism-specific databases

MalaCardsiMRE11A.
MIMi604391. phenotype.
Orphaneti251347. Ataxia-telangiectasia-like disorder.
145. Hereditary breast and ovarian cancer syndrome.
PharmGKBiPA30934.

Chemistry

ChEMBLiCHEMBL3308929.

Polymorphism and mutation databases

BioMutaiMRE11A.
DMDMi17380137.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedCombined sources
Chaini2 – 708707Double-strand break repair protein MRE11APRO_0000138672Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineCombined sources
Modified residuei2 – 21PhosphoserineBy similarity
Modified residuei641 – 6411PhosphoserineBy similarity
Modified residuei649 – 6491PhosphoserineCombined sources
Modified residuei688 – 6881PhosphoserineCombined sources
Modified residuei689 – 6891PhosphoserineCombined sources
Modified residuei701 – 7011PhosphoserineCombined sources

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP49959.
MaxQBiP49959.
PaxDbiP49959.
PRIDEiP49959.

PTM databases

iPTMnetiP49959.
PhosphoSiteiP49959.

Miscellaneous databases

PMAP-CutDBP49959.

Expressioni

Gene expression databases

BgeeiP49959.
CleanExiHS_MRE11A.
ExpressionAtlasiP49959. baseline and differential.
GenevisibleiP49959. HS.

Organism-specific databases

HPAiCAB004081.
HPA002691.

Interactioni

Subunit structurei

Component of the MRN complex composed of two heterodimers RAD50/MRE11A associated with a single NBN (PubMed:9651580, PubMed:9590181, PubMed:9705271, PubMed:10839544). Component of the BASC complex, at least composed of BRCA1, MSH2, MSH6, MLH1, ATM, BLM, RAD50, MRE11A and NBN (PubMed:10783165). Found in a complex with TERF2 (PubMed:10888888). Interacts with DCLRE1C/Artemis and DCLRE1B/Apollo (PubMed:15456891, PubMed:15723659). Interacts with ATF2 (PubMed:15916964). Interacts with EXD2 (PubMed:26807646).7 Publications
(Microbial infection) Interacts with herpes simplex virus 1 protein UL12 (PubMed:20943970).1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
FANCD2Q9BXW96EBI-396513,EBI-359343
H2AFXP161046EBI-396513,EBI-494830
HTTP428585EBI-396513,EBI-466029
NBNO609343EBI-396513,EBI-494844
RAD17O759432EBI-396513,EBI-968231

GO - Molecular functioni

  • protein C-terminus binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110501. 106 interactions.
DIPiDIP-33238N.
IntActiP49959. 30 interactions.
MINTiMINT-131851.
STRINGi9606.ENSP00000325863.

Structurei

Secondary structure

1
708
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi9 – 113Combined sources
Beta strandi12 – 187Combined sources
Turni24 – 263Combined sources
Turni30 – 345Combined sources
Helixi35 – 4915Combined sources
Beta strandi53 – 575Combined sources
Beta strandi62 – 665Combined sources
Helixi69 – 8315Combined sources
Beta strandi122 – 1243Combined sources
Beta strandi128 – 1303Combined sources
Turni134 – 1374Combined sources
Helixi140 – 1478Combined sources
Beta strandi149 – 1524Combined sources
Beta strandi162 – 1643Combined sources
Beta strandi167 – 1715Combined sources
Beta strandi174 – 1818Combined sources
Helixi186 – 1949Combined sources
Beta strandi198 – 2003Combined sources
Helixi207 – 2093Combined sources
Beta strandi210 – 2167Combined sources
Beta strandi223 – 2286Combined sources
Helixi231 – 2333Combined sources
Beta strandi240 – 2434Combined sources
Beta strandi250 – 2556Combined sources
Turni257 – 2593Combined sources
Beta strandi262 – 2654Combined sources
Helixi276 – 2794Combined sources
Beta strandi283 – 2908Combined sources
Beta strandi293 – 3008Combined sources
Beta strandi302 – 3043Combined sources
Beta strandi307 – 3137Combined sources
Helixi314 – 3163Combined sources
Turni318 – 3203Combined sources
Helixi328 – 35023Combined sources
Turni351 – 3533Combined sources
Beta strandi355 – 3573Combined sources
Beta strandi362 – 3687Combined sources
Turni370 – 3723Combined sources
Helixi379 – 3857Combined sources
Turni386 – 3883Combined sources
Beta strandi392 – 3998Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3T1IX-ray3.00A/B/C/D1-411[»]
ProteinModelPortaliP49959.
SMRiP49959. Positions 8-400.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the MRE11/RAD32 family.Curated

Phylogenomic databases

eggNOGiKOG2310. Eukaryota.
COG0420. LUCA.
GeneTreeiENSGT00390000017288.
HOGENOMiHOG000216581.
HOVERGENiHBG052508.
InParanoidiP49959.
KOiK10865.
OMAiRMFVNKQ.
OrthoDBiEOG7VB2F1.
PhylomeDBiP49959.
TreeFamiTF101105.

Family and domain databases

Gene3Di3.60.21.10. 2 hits.
InterProiIPR004843. Calcineurin-like_PHP_apaH.
IPR029052. Metallo-depent_PP-like.
IPR003701. Mre11.
IPR007281. Mre11_DNA-bd.
[Graphical view]
PANTHERiPTHR10139:SF1. PTHR10139:SF1. 1 hit.
PfamiPF00149. Metallophos. 1 hit.
PF04152. Mre11_DNA_bind. 1 hit.
[Graphical view]
PIRSFiPIRSF000882. DSB_repair_MRE11. 1 hit.
SMARTiSM01347. Mre11_DNA_bind. 1 hit.
[Graphical view]
SUPFAMiSSF56300. SSF56300. 2 hits.
TIGRFAMsiTIGR00583. 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. AlignAdd to basket

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

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

Show »
Length:680
Mass (Da):77,642
Checksum:iB36BA7EC8CE79BEE
GO
Isoform 3 (identifier: P49959-3) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:711
Mass (Da):81,070
Checksum:i10AE0AC05AFB9351
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti31 – 311V → A in AAC78721 (PubMed:8530104).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti104 – 1041S → C in cancer. 1 Publication
VAR_011625
Natural varianti117 – 1171N → S in ATLD1. 1 Publication
VAR_008513
Natural varianti157 – 1571M → V.
Corresponds to variant rs147771140 [ dbSNP | Ensembl ].
VAR_011626
Natural varianti237 – 2371F → C in a breast cancer sample; somatic mutation. 1 Publication
VAR_036416
Natural varianti302 – 3021H → Y in a breast cancer sample; somatic mutation. 1 Publication
VAR_036417
Natural varianti305 – 3051R → W in ovarian cancer. 1 Publication
VAR_025528
Natural varianti468 – 4681D → G.1 Publication
Corresponds to variant rs1805367 [ dbSNP | Ensembl ].
VAR_019288
Natural varianti503 – 5031R → H in cancer. 1 Publication
VAR_011627
Natural varianti572 – 5721R → Q in cancer. 1 Publication
Corresponds to variant rs200085146 [ dbSNP | Ensembl ].
VAR_011628
Natural varianti698 – 6981M → V.1 Publication
Corresponds to variant rs1805362 [ dbSNP | Ensembl ].
VAR_019289

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 77MSTADAL → MNRNISHQKG in isoform 3. 1 PublicationVSP_057350
Alternative sequencei595 – 62228Missing in isoform 2. 1 PublicationVSP_003262Add
BLAST

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
, AF303379, AF303380, AF303381, AF303382, AF303383, AF303384, AF303385, AF303386, AF303387, AF303388, AF303389, AF303390, AF303391, AF303392, AF303393, 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.
CCDSiCCDS8298.1. [P49959-2]
CCDS8299.1. [P49959-1]
RefSeqiNP_005581.2. NM_005590.3. [P49959-2]
NP_005582.1. NM_005591.3. [P49959-1]
XP_011541139.1. XM_011542837.1. [P49959-1]
UniGeneiHs.192649.

Genome annotation databases

EnsembliENST00000323929; ENSP00000325863; ENSG00000020922. [P49959-1]
ENST00000323977; ENSP00000326094; ENSG00000020922. [P49959-2]
ENST00000407439; ENSP00000385614; ENSG00000020922. [P49959-3]
GeneIDi4361.
KEGGihsa:4361.
UCSCiuc001peu.4. human. [P49959-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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
, AF303379, AF303380, AF303381, AF303382, AF303383, AF303384, AF303385, AF303386, AF303387, AF303388, AF303389, AF303390, AF303391, AF303392, AF303393, 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.
CCDSiCCDS8298.1. [P49959-2]
CCDS8299.1. [P49959-1]
RefSeqiNP_005581.2. NM_005590.3. [P49959-2]
NP_005582.1. NM_005591.3. [P49959-1]
XP_011541139.1. XM_011542837.1. [P49959-1]
UniGeneiHs.192649.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3T1IX-ray3.00A/B/C/D1-411[»]
ProteinModelPortaliP49959.
SMRiP49959. Positions 8-400.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110501. 106 interactions.
DIPiDIP-33238N.
IntActiP49959. 30 interactions.
MINTiMINT-131851.
STRINGi9606.ENSP00000325863.

Chemistry

ChEMBLiCHEMBL3308929.

PTM databases

iPTMnetiP49959.
PhosphoSiteiP49959.

Polymorphism and mutation databases

BioMutaiMRE11A.
DMDMi17380137.

Proteomic databases

EPDiP49959.
MaxQBiP49959.
PaxDbiP49959.
PRIDEiP49959.

Protocols and materials databases

DNASUi4361.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000323929; ENSP00000325863; ENSG00000020922. [P49959-1]
ENST00000323977; ENSP00000326094; ENSG00000020922. [P49959-2]
ENST00000407439; ENSP00000385614; ENSG00000020922. [P49959-3]
GeneIDi4361.
KEGGihsa:4361.
UCSCiuc001peu.4. human. [P49959-1]

Organism-specific databases

CTDi4361.
GeneCardsiMRE11A.
HGNCiHGNC:7230. MRE11A.
HPAiCAB004081.
HPA002691.
MalaCardsiMRE11A.
MIMi600814. gene.
604391. phenotype.
neXtProtiNX_P49959.
Orphaneti251347. Ataxia-telangiectasia-like disorder.
145. Hereditary breast and ovarian cancer syndrome.
PharmGKBiPA30934.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2310. Eukaryota.
COG0420. LUCA.
GeneTreeiENSGT00390000017288.
HOGENOMiHOG000216581.
HOVERGENiHBG052508.
InParanoidiP49959.
KOiK10865.
OMAiRMFVNKQ.
OrthoDBiEOG7VB2F1.
PhylomeDBiP49959.
TreeFamiTF101105.

Enzyme and pathway databases

ReactomeiR-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-69473. G2/M DNA damage checkpoint.
R-HSA-912446. Meiotic recombination.

Miscellaneous databases

ChiTaRSiMRE11A. human.
GeneWikiiMRE11A.
GenomeRNAii4361.
NextBioi17163.
PMAP-CutDBP49959.
PROiP49959.
SOURCEiSearch...

Gene expression databases

BgeeiP49959.
CleanExiHS_MRE11A.
ExpressionAtlasiP49959. baseline and differential.
GenevisibleiP49959. HS.

Family and domain databases

Gene3Di3.60.21.10. 2 hits.
InterProiIPR004843. Calcineurin-like_PHP_apaH.
IPR029052. Metallo-depent_PP-like.
IPR003701. Mre11.
IPR007281. Mre11_DNA-bd.
[Graphical view]
PANTHERiPTHR10139:SF1. PTHR10139:SF1. 1 hit.
PfamiPF00149. Metallophos. 1 hit.
PF04152. Mre11_DNA_bind. 1 hit.
[Graphical view]
PIRSFiPIRSF000882. DSB_repair_MRE11. 1 hit.
SMARTiSM01347. Mre11_DNA_bind. 1 hit.
[Graphical view]
SUPFAMiSSF56300. SSF56300. 2 hits.
TIGRFAMsiTIGR00583. mre11. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Isolation and characterization of the human MRE11 homologue."
    Petrini J.H.J., Walsh M.E., Dimare C., Chen X.-N., Korenberg J.R., Weaver D.T.
    Genomics 29:80-86(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
  2. Petrini J.H.J., Walsh M.E., Dimare C., Chen X.-N., Korenberg J.R., Weaver D.T.
    Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: SEQUENCE REVISION TO C-TERMINUS.
  3. "Molecular cloning and functional characterization of hNGS1, a yeast and human MRE11 homolog."
    Chamankhah M., Wei Y., Xiao W.
    Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  4. "The 3' to 5' exonuclease activity of Mre 11 facilitates repair of DNA double-strand breaks."
    Paull T.T., Gellert M.
    Mol. Cell 1:969-979(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH RAD50.
  5. "hMRE11: genomic structure and a null mutation identified in a transcript protected from nonsense-mediated mRNA decay."
    Pitts S.A., Kullar H.S., Stankovic T., Stewart G.S., Last J.I.K., Bedenham T., Armstrong S.J., Piane M., Chessa L., Taylor A.M.R., Byrd P.J.
    Hum. Mol. Genet. 10:1155-1162(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
  6. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
    Tissue: Tongue.
  7. NIEHS SNPs program
    Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLY-468 AND VAL-698.
  8. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  9. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Brain.
  10. "The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response."
    Carney J.P., Maser R.S., Olivares H., Davis E.M., Le Beau M., Yates J.R. III, Hays L., Morgan W.F., Petrini J.H.J.
    Cell 93:477-486(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN DSB REPAIR, IDENTIFICATION IN THE MRN COMPLEX WITH RAD50 AND NBN.
  11. "Nuclease activities in a complex of human recombination and DNA repair factors Rad50, Mre11, and p95."
    Trujillo K.M., Yuan S.-S.F., Lee E.Y.-H.P., Sung P.
    J. Biol. Chem. 273:21447-21450(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN DSB REPAIR, IDENTIFICATION IN THE MRN COMPLEX WITH RAD50 AND NBN.
  12. "BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures."
    Wang Y., Cortez D., Yazdi P., Neff N., Elledge S.J., Qin J.
    Genes Dev. 14:927-939(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, IDENTIFICATION IN THE BASC COMPLEX WITH BRCA1; MSH2; MSH6; MLH1; ATM; BLM; RAD50 AND NBN.
  13. "Functional link between ataxia-telangiectasia and Nijmegen breakage syndrome gene products."
    Zhao S., Weng Y.-C., Yuan S.-S.F., Lin Y.-T., Hsu H.-C., Lin S.-C., Gerbino E., Song M.-H., Zdzienicka M.Z., Gatti R.A., Shay J.W., Ziv Y., Shiloh Y., Lee E.Y.-H.P.
    Nature 405:473-477(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION IN THE MRN COMPLEX WITH RAD50 AND NBN.
  14. "Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres."
    Zhu X.-D., Kuester B., Mann M., Petrini J.H.J., de Lange T.
    Nat. Genet. 25:347-352(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN TELOMERES, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE A COMPLEX WITH TERF2, SUBCELLULAR LOCATION.
  15. "Human Rad50/Mre11 is a flexible complex that can tether DNA ends."
    de Jager M., van Noort J., van Gent D.C., Dekker C., Kanaar R., Wyman C.
    Mol. Cell 8:1129-1135(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  16. "Artemis is a phosphorylation target of ATM and ATR and is involved in the G2/M DNA damage checkpoint response."
    Zhang X., Succi J., Feng Z., Prithivirajsingh S., Story M.D., Legerski R.J.
    Mol. Cell. Biol. 24:9207-9220(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH DCLRE1C.
  17. "Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex."
    Lee J.-H., Paull T.T.
    Science 304:93-96(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN ATM ACTIVATION.
  18. "Ataxia-telangiectasia-mutated dependent phosphorylation of Artemis in response to DNA damage."
    Chen L., Morio T., Minegishi Y., Nakada S., Nagasawa M., Komatsu K., Chessa L., Villa A., Lecis D., Delia D., Mizutani S.
    Cancer Sci. 96:134-141(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH DCLRE1C.
  19. "ATM-dependent phosphorylation of ATF2 is required for the DNA damage response."
    Bhoumik A., Takahashi S., Breitweiser W., Shiloh Y., Jones N., Ronai Z.
    Mol. Cell 18:577-587(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ATF2, SUBCELLULAR LOCATION.
  20. "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
    Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
    Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  21. "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
    Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
    Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  22. "Snm1B/Apollo mediates replication fork collapse and S Phase checkpoint activation in response to DNA interstrand cross-links."
    Bae J.B., Mukhopadhyay S.S., Liu L., Zhang N., Tan J., Akhter S., Liu X., Shen X., Li L., Legerski R.J.
    Oncogene 27:5045-5056(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH DCLRE1B.
  23. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-649; SER-688; SER-689 AND SER-701, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  24. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
    Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
    Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS], IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  25. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-649; SER-688 AND SER-689, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  26. "Physical interaction between the herpes simplex virus type 1 exonuclease, UL12, and the DNA double-strand break-sensing MRN complex."
    Balasubramanian N., Bai P., Buchek G., Korza G., Weller S.K.
    J. Virol. 84:12504-12514(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HERPES SIMPLEX VIRUS 1 UL12.
  27. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
    Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
    Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-688 AND SER-689, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  28. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  29. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
    Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
    Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-688 AND SER-689, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  30. "Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signaling."
    Chaki M., Airik R., Ghosh A.K., Giles R.H., Chen R., Slaats G.G., Wang H., Hurd T.W., Zhou W., Cluckey A., Gee H.Y., Ramaswami G., Hong C.J., Hamilton B.A., Cervenka I., Ganji R.S., Bryja V., Arts H.H.
    , van Reeuwijk J., Oud M.M., Letteboer S.J., Roepman R., Husson H., Ibraghimov-Beskrovnaya O., Yasunaga T., Walz G., Eley L., Sayer J.A., Schermer B., Liebau M.C., Benzing T., Le Corre S., Drummond I., Janssen S., Allen S.J., Natarajan S., O'Toole J.F., Attanasio M., Saunier S., Antignac C., Koenekoop R.K., Ren H., Lopez I., Nayir A., Stoetzel C., Dollfus H., Massoudi R., Gleeson J.G., Andreoli S.P., Doherty D.G., Lindstrad A., Golzio C., Katsanis N., Pape L., Abboud E.B., Al-Rajhi A.A., Lewis R.A., Omran H., Lee E.Y., Wang S., Sekiguchi J.M., Saunders R., Johnson C.A., Garner E., Vanselow K., Andersen J.S., Shlomai J., Nurnberg G., Nurnberg P., Levy S., Smogorzewska A., Otto E.A., Hildebrandt F.
    Cell 150:533-548(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN NPHP-RC.
  31. "Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
    Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
    Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS], IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  32. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-649; SER-688 AND SER-689, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  33. Cited for: FUNCTION, INTERACTION WITH EXD2.
  34. "The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder."
    Stewart G.S., Maser R.S., Stankovic T., Bressan D.A., Kaplan M.I., Jaspers N.G.J., Raams A., Byrd P.J., Petrini J.H.J., Taylor A.M.R.
    Cell 99:577-587(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT ATLD1 SER-117.
  35. "Alterations of the double-strand break repair gene MRE11 in cancer."
    Fukuda T., Sumiyoshi T., Takahashi M., Kataoka T., Asahara T., Inui H., Watatani M., Yasutomi M., Kamada N., Miyagawa K.
    Cancer Res. 61:23-26(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS CANCER CYS-104; HIS-503 AND GLN-572.
  36. "Mutation screening of Mre11 complex genes: indication of RAD50 involvement in breast and ovarian cancer susceptibility."
    Heikkinen K., Karppinen S.-M., Soini Y., Maekinen M., Winqvist R.
    J. Med. Genet. 40:E131-E131(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT OVARIAN CANCER TRP-305.
  37. Cited for: VARIANTS [LARGE SCALE ANALYSIS] CYS-237 AND TYR-302.

Entry informationi

Entry nameiMRE11_HUMAN
AccessioniPrimary (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: May 11, 2016
This is version 176 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

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.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.