ID:MRE11_HUMAN DESCRIPTION: RecName: Full=Double-strand break repair protein MRE11A; AltName: Full=Meiotic recombination 11 homolog 1; Short=MRE11 homolog 1; AltName: Full=Meiotic recombination 11 homolog A; Short=MRE11 homolog A; FUNCTION: 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. The complex may also be required for DNA damage signaling via activation of the ATM kinase. In telomeres the MRN complex may modulate t-loop formation. COFACTOR: Manganese (By similarity). SUBUNIT: Component of the MRN complex composed of two heterodimers RAD50/MRE11A associated with a single NBN. Component of the BASC complex, at least composed of BRCA1, MSH2, MSH6, MLH1, ATM, BLM, RAD50, MRE11A and NBN (By similarity). Interacts with DCLRE1C/Artemis and DCLRE1B/Apollo. INTERACTION: O60934:NBN; NbExp=2; IntAct=EBI-396513, EBI-494844; SUBCELLULAR LOCATION: Nucleus (By similarity). Note=Localizes to discrete nuclear foci after treatment with genotoxic agents (By similarity). PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. DISEASE: Defects in MRE11A are a cause of ataxia telangiectasia- like disorder (ATLD) [MIM:604391]. ATLD is a disease with the same clinical feature than ataxia-telangiectasia but with a somewhat milder clinical course. DISEASE: Note=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. 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. SIMILARITY: Belongs to the MRE11/RAD32 family. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/MRE11ID247.html"; WEB RESOURCE: Name=MRE11base; Note=MRE11A mutation db; URL="http://bioinf.uta.fi/MRE11Abase/"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/mre11a/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P49959
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000019 regulation of mitotic recombination GO:0000724 double-strand break repair via homologous recombination GO:0000729 DNA double-strand break processing GO:0006260 DNA replication GO:0006281 DNA repair GO:0006302 double-strand break repair GO:0006303 double-strand break repair via nonhomologous end joining GO:0006310 DNA recombination GO:0006974 cellular response to DNA damage stimulus GO:0007004 telomere maintenance via telomerase GO:0007062 sister chromatid cohesion GO:0007095 mitotic G2 DNA damage checkpoint GO:0007129 synapsis GO:0007131 reciprocal meiotic recombination GO:0008283 cell proliferation GO:0016032 viral process GO:0031573 intra-S DNA damage checkpoint GO:0031860 telomeric 3' overhang formation GO:0031954 positive regulation of protein autophosphorylation GO:0032206 positive regulation of telomere maintenance GO:0032481 positive regulation of type I interferon production GO:0032508 DNA duplex unwinding GO:0032876 negative regulation of DNA endoreduplication GO:0033674 positive regulation of kinase activity GO:0043066 negative regulation of apoptotic process GO:0051276 chromosome organization GO:0051321 meiotic cell cycle GO:0090305 nucleic acid phosphodiester bond hydrolysis
JD238021 - Sequence 219045 from Patent EP1572962. JD238022 - Sequence 219046 from Patent EP1572962. JD135678 - Sequence 116702 from Patent EP1572962. JD135676 - Sequence 116700 from Patent EP1572962. JD135679 - Sequence 116703 from Patent EP1572962. JD079062 - Sequence 60086 from Patent EP1572962. JD217447 - Sequence 198471 from Patent EP1572962. JD211386 - Sequence 192410 from Patent EP1572962. JD194629 - Sequence 175653 from Patent EP1572962. JD537266 - Sequence 518290 from Patent EP1572962. JD194628 - Sequence 175652 from Patent EP1572962. JD179261 - Sequence 160285 from Patent EP1572962. JD481173 - Sequence 462197 from Patent EP1572962. JD413481 - Sequence 394505 from Patent EP1572962. JD198175 - Sequence 179199 from Patent EP1572962. JD212781 - Sequence 193805 from Patent EP1572962. JD222898 - Sequence 203922 from Patent EP1572962. JD249986 - Sequence 231010 from Patent EP1572962. JD249987 - Sequence 231011 from Patent EP1572962. JD148386 - Sequence 129410 from Patent EP1572962. JD463902 - Sequence 444926 from Patent EP1572962. JD478655 - Sequence 459679 from Patent EP1572962. JD543376 - Sequence 524400 from Patent EP1572962. JD249985 - Sequence 231009 from Patent EP1572962. JD140149 - Sequence 121173 from Patent EP1572962. JD144686 - Sequence 125710 from Patent EP1572962. JD368274 - Sequence 349298 from Patent EP1572962. JD543375 - Sequence 524399 from Patent EP1572962. JD478654 - Sequence 459678 from Patent EP1572962. JD543374 - Sequence 524398 from Patent EP1572962. JD222935 - Sequence 203959 from Patent EP1572962. JD497842 - Sequence 478866 from Patent EP1572962. JD303095 - Sequence 284119 from Patent EP1572962. JD049814 - Sequence 30838 from Patent EP1572962. JD503358 - Sequence 484382 from Patent EP1572962. JD304093 - Sequence 285117 from Patent EP1572962. JD446222 - Sequence 427246 from Patent EP1572962. JD159760 - Sequence 140784 from Patent EP1572962. JD239580 - Sequence 220604 from Patent EP1572962. JD436324 - Sequence 417348 from Patent EP1572962. JD147886 - Sequence 128910 from Patent EP1572962. JD237403 - Sequence 218427 from Patent EP1572962. JD454354 - Sequence 435378 from Patent EP1572962. JD479788 - Sequence 460812 from Patent EP1572962. JD499377 - Sequence 480401 from Patent EP1572962. JD507033 - Sequence 488057 from Patent EP1572962. JD528683 - Sequence 509707 from Patent EP1572962. JD473369 - Sequence 454393 from Patent EP1572962. JD305256 - Sequence 286280 from Patent EP1572962. JD504137 - Sequence 485161 from Patent EP1572962. AK095388 - Homo sapiens cDNA FLJ38069 fis, clone CTONG2015434, highly similar to DOUBLE-STRAND BREAK REPAIR PROTEIN MRE11A. BC063458 - Homo sapiens MRE11 meiotic recombination 11 homolog A (S. cerevisiae), mRNA (cDNA clone MGC:74523 IMAGE:5181691), complete cds. U37359 - Homo sapiens MRE11 homologue hMre11 mRNA, complete cds. AF022778 - Homo sapiens DNA recombination and repair protein (MRE11B) mRNA, complete cds. JD237511 - Sequence 218535 from Patent EP1572962. AF073362 - Homo sapiens endo/exonuclease Mre11 (MRE11A) mRNA, complete cds. AB528047 - Synthetic construct DNA, clone: pF1KB9980, Homo sapiens MRE11A gene for MRE11 meiotic recombination 11 homolog A, without stop codon, in Flexi system. AK308318 - Homo sapiens cDNA, FLJ98266. BC017823 - Homo sapiens MRE11 meiotic recombination 11 homolog A (S. cerevisiae), mRNA (cDNA clone IMAGE:4687479), partial cds. BC005241 - Homo sapiens MRE11 meiotic recombination 11 homolog A (S. cerevisiae), mRNA (cDNA clone IMAGE:3997666), complete cds. BT006730 - Homo sapiens MRE11 meiotic recombination 11 homolog A (S. cerevisiae) mRNA, complete cds. JF432288 - Synthetic construct Homo sapiens clone IMAGE:100073465 MRE11 meiotic recombination 11 homolog A (S. cerevisiae) (MRE11A) gene, encodes complete protein. KJ904507 - Synthetic construct Homo sapiens clone ccsbBroadEn_13901 MRE11A gene, encodes complete protein. KU178199 - Homo sapiens MRE11 meiotic recombination 11-like protein A isoform 1 (MRE11A) mRNA, partial cds. KU178200 - Homo sapiens MRE11 meiotic recombination 11-like protein A isoform 2 (MRE11A) mRNA, complete cds, alternatively spliced. JD135425 - Sequence 116449 from Patent EP1572962. JD266642 - Sequence 247666 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_atrbrcaPathway - Role of BRCA1, BRCA2 and ATR in Cancer Susceptibility h_atmPathway - ATM Signaling Pathway
Reactome (by CSHL, EBI, and GO)
Protein P49959 (Reactome details) participates in the following event(s):
R-HSA-75172 Formation of RAD50:MRE11 complex R-HSA-3204303 MRE11 binds cytosolic DNA R-HSA-75174 Association of RAD50:MRE11A complex with NBN (NBS1) via MRE11A interaction R-HSA-3785768 MRN complex binds DNA double strand breaks R-HSA-5682020 MRN complex binds shortened telomeres R-HSA-5687675 LIG3 ligates remaining SSBs in MMEJ R-HSA-5686410 BLM mediates dissolution of double Holliday junction R-HSA-5686657 ERCC1:XPF cleaves flaps generated by SSA R-HSA-5693589 D-loop dissociation and strand annealing R-HSA-5693599 Association of Ku heterodimer with ends of DNA double-strand break R-HSA-5687465 MRN complex binds RBBP8 R-HSA-5693612 MRN complex bound to DNA ends recruits ATM R-HSA-5682018 MRN complex bound to shortened telomeres recruits ATM R-HSA-5685838 CX3 complex binds D-loop structures R-HSA-5693620 D-loop formation mediated by PALB2, BRCA2 and RAD51 R-HSA-5682044 KAT5 acetylates ATM at DNA DSBs R-HSA-5693540 MRN activates ATM R-HSA-5693598 ATM phosphorylates NBN R-HSA-5687464 MRN and RBBP8 resect DNA DSBs in MMEJ R-HSA-6792712 KAT5 acetylates ATM at shortened telomeres R-HSA-5682026 MRN bound to shortened telomeres activates ATM R-HSA-5687484 PARP1 or PARP2, FEN1 and POLQ are recruited to MMEJ site R-HSA-5687673 MRN recruits LIG3:XRCC1 to MMEJ sites R-HSA-5687664 FEN1 cleaves displaced ssDNA flaps during MMEJ R-HSA-5684081 MRN complex binds CDK2 and RBBP8 R-HSA-5693602 ATM recognizes H2AFX-Nucleosomes R-HSA-5684071 RNF4 ubiquitinates MDC1 R-HSA-5693593 D-loop extension by DNA polymerases R-HSA-5693584 Cleavage of Holliday junctions by GEN1 or SLX1A:SLX4:MUS81:EME1,(MUS81:EME2) R-HSA-5686440 MUS81:EME1,EME2 cleaves D-loop R-HSA-5687640 POLQ extends annealed 3'-ssDNA overhangs in MMEJ R-HSA-5687653 PARP1,PARP2 dimers bound to MMEJ sites autoPARylate R-HSA-5693583 MDC1 associates with gamma-H2AFX at nuclear foci R-HSA-5683967 EYA1-4 dephosphorylates tyrosine Y142 of H2AFX R-HSA-5683986 APBB1 and MAPK8 bind diphosphorylated H2AFX R-HSA-5693549 ATM phosphorylates histone H2AFX on S139 at DNA DSBs R-HSA-5684096 CDK2 phosphorylates RBBP8 R-HSA-5684140 ATM phosphorylates RBBP8 R-HSA-5693608 Initial resection of double-strand break ends R-HSA-5684108 BRCA1 binds phosphorylated RBBP8 R-HSA-5693542 Association of RPA complexes with ssDNA at resected DNA DSBs R-HSA-5685994 Long-range resection of DNA DSBs by EXO1 or DNA2 R-HSA-5685341 BCDX2 complex stabilizes RAD51 filament R-HSA-5693561 RAD51 binds BRCA2 at resected DNA DSBs R-HSA-5685985 EXO1 or DNA2 in complex with BLM or WRN binds initially resected DNA DSBs along with BRIP1 recruitment R-HSA-5682967 WHSC1 binds DNA DSBs R-HSA-5693536 ATM phosphorylates MDC1 R-HSA-5683964 ATM phosphorylates EYA1-4 R-HSA-5684875 Binding of ATR:ATRIP to RPA at resected DNA DSBs R-HSA-5682983 ATM phosphorylates WHSC1 R-HSA-5682965 WHSC1 dimethylates histone H4 on lysine K21 at DSBs R-HSA-5682992 KDM4A,B bind H4K20Me2 R-HSA-5685011 ATR activation at DNA DSBs R-HSA-5684887 Activation of CHEK1 at resected DNA DSBs R-HSA-5684882 CHEK1 is recruited to resected DNA DSBs R-HSA-5693580 Association of RAD52 with the RPA complex at resected DNA DSBs R-HSA-5685156 ATR phosphorylates RPA2 R-HSA-5682588 RNF8 binds phosphorylated MDC1 at DNA DSBs R-HSA-5693566 TP53BP1 associates with H4K20Me2 at DNA DSBs R-HSA-5683077 RNF8 and RNF168 ubiquitinate KDM4A,B R-HSA-5693564 Association of RAD51 with RAD52:DNA double-strand break ends R-HSA-5682586 HERC2 and PIAS4 are recruited to DNA DSBs R-HSA-5682629 HERC2 facilitates UBE2N:UBE2V2 binding to RNF8 R-HSA-5682607 PIAS4 SUMOylates HERC2 with SUMO1 at DNA DSBs R-HSA-5682863 RNF168 binds DNA DSBs R-HSA-5682858 RNF8 and RNF168 ubiquitinate H2AFX R-HSA-5683384 UIMC1 and FAM175A bind DNA DSBs R-HSA-5683405 PPP5C dephosphorylates TP53BP1 R-HSA-5683425 ATM phosphorylates TP53BP1 at DNA DSBs R-HSA-6799332 ATR phosphorylates TP53 R-HSA-5686642 RAD52 promotes single strand annealing at resected DNA DSBs R-HSA-5682598 ATM phosphorylates HERC2 R-HSA-5693551 Phosphorylation of BRCA1-A complex at multiple sites by ATM R-HSA-5683385 Formation of BRCA1-A complex at DNA DSBs R-HSA-5683735 CHEK2 is recruited to DNA DSBs R-HSA-5683801 CHEK2 phosphorylates BRCA1 R-HSA-69891 Phosphorylation and activation of CHEK2 by ATM R-HSA-5684052 PIAS4 SUMOylates MDC1 R-HSA-5686685 RIF1 and PAX1IP bind TP53BP1 at DNA DSBs R-HSA-5686900 TP53BP1 recruits DCLRE1C to ATM R-HSA-5686704 Activated ATM phosphorylates DCLRE1C R-HSA-5693548 Sensing of DNA Double Strand Breaks R-HSA-1834949 Cytosolic sensors of pathogen-associated DNA R-HSA-2559586 DNA Damage/Telomere Stress Induced Senescence R-HSA-5685939 HDR through MMEJ (alt-NHEJ) R-HSA-5693568 Resolution of D-loop Structures through Holliday Junction Intermediates R-HSA-5685938 HDR through Single Strand Annealing (SSA) R-HSA-5693554 Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) R-HSA-5693571 Nonhomologous End-Joining (NHEJ) R-HSA-5693606 DNA Double Strand Break Response R-HSA-168249 Innate Immune System R-HSA-2559583 Cellular Senescence R-HSA-5693538 Homology Directed Repair R-HSA-5693579 Homologous DNA Pairing and Strand Exchange R-HSA-5693537 Resolution of D-Loop Structures R-HSA-5693567 HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA) R-HSA-5693532 DNA Double-Strand Break Repair R-HSA-168256 Immune System R-HSA-912446 Meiotic recombination R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks R-HSA-2262752 Cellular responses to stress R-HSA-5693607 Processing of DNA double-strand break ends R-HSA-5685942 HDR through Homologous Recombination (HRR) R-HSA-73894 DNA Repair R-HSA-1500620 Meiosis R-HSA-8953897 Cellular responses to external stimuli R-HSA-5693616 Presynaptic phase of homologous DNA pairing and strand exchange R-HSA-1474165 Reproduction R-HSA-1640170 Cell Cycle R-HSA-69473 G2/M DNA damage checkpoint R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation R-HSA-69481 G2/M Checkpoints R-HSA-5633007 Regulation of TP53 Activity R-HSA-69620 Cell Cycle Checkpoints R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-212436 Generic Transcription Pathway R-HSA-73857 RNA Polymerase II Transcription R-HSA-74160 Gene expression (Transcription)
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
