Reviewed,
UniProtKB/Swiss-Prot P49959 (MRE11_HUMAN)
Last modified
June 16, 2009.
Version 100.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Double-strand break repair protein MRE11A Alternative name(s): MRE11 meiotic recombination 11 homolog A MRE11 homolog 1 | ||||
| Gene names |
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| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 708 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| 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 structure | 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. |
| Subcellular location | Nucleus By similarity. Note: Localizes to discrete nuclear foci after treatment with genotoxic agents By similarity. |
| Post-translational modification | Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 |
| Involvement in 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. Ref.17 Defects in MRE11A may be a cause of breast cancer. |
| 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. |
| Sequence similarities | Belongs to the MRE11/RAD32 family. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| CCNE1 | P24864 | 1 | EBI-396513,EBI-519526 | |
| H2AFX | P16104 | 1 | EBI-396513,EBI-494830 | |
| NBN | O60934 | 1 | EBI-396513,EBI-494844 |
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: P49959-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: P49959-2) The sequence of this isoform differs from the canonical sequence as follows: 595-622: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 708 | 708 | Double-strand break repair protein MRE11A | PRO_0000138672 | |||||
Sites | |||||||||
| Active site | 129 | 1 | Proton donor By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 74 | 1 | Phosphothreonine Ref.10 | ||||||
| Modified residue | 649 | 1 | Phosphoserine Ref.15 | ||||||
| Modified residue | 678 | 1 | Phosphoserine Ref.13 | ||||||
| Modified residue | 688 | 1 | Phosphoserine Ref.10 Ref.11 Ref.12 Ref.14 Ref.15 | ||||||
| Modified residue | 689 | 1 | Phosphoserine Ref.10 Ref.12 Ref.14 Ref.15 | ||||||
Natural variations | |||||||||
| Alternative sequence | 595 – 622 | 28 | Missing in isoform 2. | VSP_003262 | |||||
| Natural variant | 104 | 1 | S → C in cancer. Ref.18 | VAR_011625 | |||||
| Natural variant | 117 | 1 | N → S in ATLD. Ref.17 | VAR_008513 | |||||
| Natural variant | 157 | 1 | M → V | VAR_011626 | |||||
| Natural variant | 237 | 1 | F → C in a breast cancer sample; somatic mutation. Ref.20 | VAR_036416 | |||||
| Natural variant | 302 | 1 | H → Y in a breast cancer sample; somatic mutation. Ref.20 | VAR_036417 | |||||
| Natural variant | 305 | 1 | R → W in ovarian cancer. Ref.19 | VAR_025528 | |||||
| Natural variant | 468 | 1 | D → G: dbSNP rs1805367. Ref.6 | VAR_019288 | |||||
| Natural variant | 503 | 1 | R → H in cancer. Ref.18 | VAR_011627 | |||||
| Natural variant | 572 | 1 | R → Q in cancer. Ref.18 | VAR_011628 | |||||
| Natural variant | 698 | 1 | M → V: dbSNP rs1805362. Ref.6 | VAR_019289 | |||||
Experimental info | |||||||||
| Sequence conflict | 31 | 1 | V → A in AAC78721. Ref.1 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [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: 8530104] [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: 9651580] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). |
| [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: 11371508] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). |
| [6] | NIEHS SNPs program Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLY-468 AND VAL-698. |
| [7] | "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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain. |
| [8] | "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: 15456891] [Abstract] Cited for: INTERACTION WITH DCLRE1C. |
| [9] | "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: 15723659] [Abstract] Cited for: INTERACTION WITH DCLRE1C. |
| [10] | "Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-74; SER-688 AND SER-689, MASS SPECTROMETRY. Tissue: Epithelium. |
| [11] | "Global phosphoproteome of HT-29 human colon adenocarcinoma cells." Kim J.-E., Tannenbaum S.R., White F.M. J. Proteome Res. 4:1339-1346(2005) [PubMed: 16083285] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-688, MASS SPECTROMETRY. |
| [12] | "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: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-688 AND SER-689, MASS SPECTROMETRY. Tissue: Epithelium. |
| [13] | "ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-678, MASS SPECTROMETRY. |
| [14] | "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: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-688 AND SER-689, MASS SPECTROMETRY. |
| [15] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-649; SER-688 AND SER-689, MASS SPECTROMETRY. |
| [16] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [17] | "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: 10612394] [Abstract] Cited for: VARIANT ATLD SER-117. |
| [18] | "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: 11196167] [Abstract] Cited for: VARIANTS CANCER CYS-104; HIS-503 AND GLN-572. |
| [19] | "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: 14684699] [Abstract] Cited for: VARIANT OVARIAN CANCER TRP-305. |
| [20] | "The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. Velculescu V.E.Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] CYS-237 AND TYR-302. |
| + | Additional computationally mapped references. |
Web resources
Cross-references
Sequence databases | |
|---|---|
| U37359 mRNA. Translation: AAC78721.1. AF022778 mRNA. Translation: AAD10197.1. AF073362 mRNA. Translation: AAC36249.1. AF303395 AF303394 Genomic DNA. Translation: AAK18790.1. AY584241 Genomic DNA. Translation: AAS79320.1. BC063458 mRNA. Translation: AAH63458.1. | |
| IPI | IPI00029159. IPI00218853. |
| RefSeq | NP_005582.1. |
| UniGene | Hs.192649 |
3D structure databases | |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | P49959. 5 interactions. |
PTM databases | |
| PhosphoSite | P49959. |
Proteomic databases | |
| PRIDE | P49959. |
Genome annotation databases | |
| Ensembl | ENSG00000020922. Homo sapiens. [Contig view] |
| GeneID | 4361. |
Organism-specific databases | |
| GeneCards | GC11M093790. |
| H-InvDB | HIX0010030. |
| HGNC | HGNC:7230. MRE11A. |
| HPA | CAB004081. HPA002691. |
| MIM | 600814. gene. 604391. phenotype. |
| PharmGKB | PA30934. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOGENOM | P49959. |
| HOVERGEN | P49959. |
| OMA | P49959. GEAVKKH. |
Enzyme and pathway databases | |
| Pathway_Interaction_DB | bard1pathway. BARD1 signaling events. telomerasepathway. Regulation of Telomerase. |
| Reactome | REACT_216. DNA Repair. |
Gene expression databases | |
| ArrayExpress | P49959. |
| Bgee | P49959. |
| CleanEx | HS_MRE11A. |
| GermOnline | ENSG00000020922. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR003701. DNA_repair. IPR004843. M-pesterase. IPR007281. Mre11_DNA_bd. [Graphical view] |
| PANTHER | PTHR10139. DNA_repair. 1 hit. |
| Pfam | PF00149. Metallophos. 1 hit. PF04152. Mre11_DNA_bind. 1 hit. [Graphical view] |
| PIRSF | PIRSF000882. DSB_repair_MRE11. 1 hit. |
| TIGRFAMs | TIGR00583. mre11. 1 hit. |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 17163. |
| PMAP-CutDB | P49959. |
| SOURCE | Search... |
Entry information
| Entry name | MRE11_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P49959 Secondary accession number(s): O43475 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 11 Human chromosome 11: entries, gene names and cross-references to MIM |
| 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 |
| SIMILARITY comments Index of protein domains and families |

Clusters with


