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UniProtKB - P49959 (MRE11_HUMAN)

Entry version 219 (02 Dec 2020)
Sequence version 3 (26 Sep 2001)
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Protein

Double-strand break repair protein MRE11

Gene

MRE11

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<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

Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis (PubMed:9651580, PubMed:9590181, PubMed:9705271, PubMed:11741547, PubMed:29670289). The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11 (PubMed:9651580, PubMed:9590181, PubMed:9705271, PubMed:11741547, PubMed:29670289). RAD50 may be required to bind DNA ends and hold them in close proximity (PubMed:9651580, PubMed:9590181, PubMed:9705271, PubMed:11741547, PubMed:29670289). 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, PubMed:30612738). 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).7 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.

<p>This subsection of the 'Function' section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Mn2+By similarity

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Interaction with SAMHD1 stimulates the double-strand-specific 3'-5' exonuclease activity.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei129Proton donorBy similarity1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionEndonuclease, Exonuclease, Hydrolase, Nuclease
Biological processDNA damage, DNA repair, Host-virus interaction, Meiosis
LigandManganese

Enzyme and pathway databases

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		P49959

Reactome - a knowledgebase of biological pathways and processes

More...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

SIGNOR Signaling Network Open Resource

More...SIGNORi		P49959

<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

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>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
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:MRE11Imported
Synonyms:HNGS1, MRE11A
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 11

Organism-specific databases

Eukaryotic Pathogen and Host Database Resources

More...EuPathDBi		HostDB:ENSG00000020922.12

Human Gene Nomenclature Database

More...HGNCi		HGNC:7230, MRE11

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		600814, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_P49959

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Chromosome, Nucleus, Telomere

<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

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_008513117N → S in ATLD1. 1 PublicationCorresponds to variant dbSNP:rs137852760EnsemblClinVar.1
Defects in MRE11 can be a cause of nephronophthisis-related ciliopathies (NPHP-RC), a group of recessive diseases that affect kidney, retina and brain. A homozygous truncating mutation MRE11 has been found in patients with cerebellar vermis hypoplasia, ataxia and dysarthria.1 Publication

Keywords - Diseasei

Ciliopathy, Disease mutation

Organism-specific databases

DisGeNET

More...DisGeNETi		4361

MalaCards human disease database

More...MalaCardsi		MRE11
MIMi604391, phenotype

Open Targets

More...OpenTargetsi		ENSG00000020922

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		251347, Ataxia-telangiectasia-like disorder
145, Hereditary breast and ovarian cancer syndrome
240760, Nijmegen breakage syndrome-like disorder

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA30934

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		P49959, Tbio

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL3308929

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		MRE11

Domain mapping of disease mutations (DMDM)

More...DMDMi		17380137

<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

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section indicates that the initiator methionine is cleaved from the mature protein.<p><a href='/help/init_met' target='_top'>More...</a></p>Initiator methionineiRemovedCombined sources
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001386722 – 708Double-strand break repair protein MRE11Add BLAST707

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei2N-acetylserineCombined sources1
Modified residuei2PhosphoserineBy similarity1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki255Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei275PhosphoserineCombined sources1
Cross-linki416Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei619PhosphoserineCombined sources1
Cross-linki625Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei641PhosphoserineBy similarity1
Modified residuei649PhosphoserineCombined sources1
Modified residuei678PhosphoserineCombined sources1
Modified residuei688PhosphoserineCombined sources1
Modified residuei689PhosphoserineCombined sources1
Modified residuei701PhosphoserineCombined sources1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Ubiquitinated following DNA damage. Ubiquitination triggers interaction with UBQLN4, leading to MRE11 removal from chromatin and degradation by the proteasome.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

More...EPDi		P49959

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		P49959

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		P49959

MaxQB - The MaxQuant DataBase

More...MaxQBi		P49959

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		P49959

PeptideAtlas

More...PeptideAtlasi		P49959

PRoteomics IDEntifications database

More...PRIDEi		P49959

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		3675
56186 [P49959-1]
56187 [P49959-2]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		P49959

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		P49959

SwissPalm database of S-palmitoylation events

More...SwissPalmi		P49959

<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

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000020922, Expressed in calcaneal tendon and 223 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		P49959, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		P49959, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000020922, Low tissue specificity

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>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).

Interacts (when ubiquitinated) with UBQLN4 (via its UBA domain) (PubMed:30612738).

16 Publications

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

1 Publication

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		110501, 172 interactors

ComplexPortal: manually curated resource of macromolecular complexes

More...ComplexPortali		CPX-4442, MRN complex

CORUM comprehensive resource of mammalian protein complexes

More...CORUMi		P49959

Database of interacting proteins

More...DIPi		DIP-33238N

Protein interaction database and analysis system

More...IntActi		P49959, 51 interactors

Molecular INTeraction database

More...MINTi		P49959

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000325863

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		P49959

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		P49959, protein

<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

1708
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		P49959

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

<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

Belongs to the MRE11/RAD32 family.Curated

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG2310, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00390000017288

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_009535_3_1_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		P49959

Identification of Orthologs from Complete Genome Data

More...OMAi		QWMRPET

Database for complete collections of gene phylogenies

More...PhylomeDBi		P49959

TreeFam database of animal gene trees

More...TreeFami		TF101105

Family and domain databases

Conserved Domains Database

More...CDDi		cd00840, MPP_Mre11_N, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		3.30.110.110, 1 hit
3.60.21.10, 1 hit

Integrated resource of protein families, domains and functional sites

More...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
IPR041796, Mre11_N

Pfam protein domain database

More...Pfami		View protein in Pfam
PF00149, Metallophos, 1 hit
PF04152, Mre11_DNA_bind, 1 hit

PIRSF; a whole-protein classification database

More...PIRSFi		PIRSF000882, DSB_repair_MRE11, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM01347, Mre11_DNA_bind, 1 hit

TIGRFAMs; a protein family database

More...TIGRFAMsi		TIGR00583, mre11, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform. This section is only present in reviewed entries, i.e. in UniProtKB/Swiss-Prot.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

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

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

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali 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
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> 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

Show »
Length:711
Mass (Da):81,070
Checksum:i10AE0AC05AFB9351
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8W7U8F8W7U8_HUMAN
Double-strand break repair protein
MRE11
707Annotation score:

Annotation score:3 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
F5GXT0F5GXT0_HUMAN
Double-strand break repair protein ...
MRE11
221Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
F5H256F5H256_HUMAN
Double-strand break repair protein ...
MRE11
127Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
F5H742F5H742_HUMAN
Double-strand break repair protein ...
MRE11
111Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti31V → A in AAC78721 (PubMed:8530104).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_011625104S → C in cancer. 1 PublicationCorresponds to variant dbSNP:rs748434421EnsemblClinVar.1
Natural variantiVAR_008513117N → S in ATLD1. 1 PublicationCorresponds to variant dbSNP:rs137852760EnsemblClinVar.1
Natural variantiVAR_011626157M → V. Corresponds to variant dbSNP:rs147771140EnsemblClinVar.1
Natural variantiVAR_036416237F → C in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_036417302H → Y in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_025528305R → W in ovarian cancer. 1 PublicationCorresponds to variant dbSNP:rs372000848EnsemblClinVar.1
Natural variantiVAR_019288468D → G1 PublicationCorresponds to variant dbSNP:rs1805367Ensembl.1
Natural variantiVAR_011627503R → H in cancer. 1 PublicationCorresponds to variant dbSNP:rs774057024EnsemblClinVar.1
Natural variantiVAR_011628572R → Q in cancer. 1 PublicationCorresponds to variant dbSNP:rs200085146EnsemblClinVar.1
Natural variantiVAR_019289698M → V1 PublicationCorresponds to variant dbSNP:rs1805362EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0573501 – 7MSTADAL → MNRNISHQKG in isoform 3. 1 Publication7
Alternative sequenceiVSP_003262595 – 622Missing in isoform 2. 1 PublicationAdd BLAST28

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...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]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000323929; ENSP00000325863; ENSG00000020922 [P49959-1]
ENST00000323977; ENSP00000326094; ENSG00000020922 [P49959-2]
ENST00000407439; ENSP00000385614; ENSG00000020922 [P49959-3]

Database of genes from NCBI RefSeq genomes

More...GeneIDi		4361

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:4361

UCSC genome browser

More...UCSCi		uc001peu.4, human [P49959-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross%5Freferences%5Fsection">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

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
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_011542837.2 [P49959-1]
XP_016873261.1, XM_017017772.1 [P49959-1]

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 entryMethodResolution (Å)ChainPositionsPDBsum
3T1IX-ray3.00A/B/C/D1-411[»]
SMRiP49959
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi110501, 172 interactors
ComplexPortaliCPX-4442, MRN complex
CORUMiP49959
DIPiDIP-33238N
IntActiP49959, 51 interactors
MINTiP49959
STRINGi9606.ENSP00000325863

Chemistry databases

BindingDBiP49959
ChEMBLiCHEMBL3308929

PTM databases

iPTMnetiP49959
PhosphoSitePlusiP49959
SwissPalmiP49959

Polymorphism and mutation databases

BioMutaiMRE11
DMDMi17380137

Proteomic databases

EPDiP49959
jPOSTiP49959
MassIVEiP49959
MaxQBiP49959
PaxDbiP49959
PeptideAtlasiP49959
PRIDEiP49959
ProteomicsDBi3675
56186 [P49959-1]
56187 [P49959-2]

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...Antibodypediai		706, 673 antibodies

The CPTC Antibody Portal

More...CPTCi		P49959, 1 antibody

The DNASU plasmid repository

More...DNASUi		4361

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

Comparative Toxicogenomics Database

More...CTDi		4361
DisGeNETi4361
EuPathDBiHostDB:ENSG00000020922.12

GeneCards: human genes, protein and diseases

More...GeneCardsi		MRE11
HGNCiHGNC:7230, MRE11
HPAiENSG00000020922, Low tissue specificity
MalaCardsiMRE11
MIMi600814, gene
604391, phenotype
neXtProtiNX_P49959
OpenTargetsiENSG00000020922
Orphaneti251347, Ataxia-telangiectasia-like disorder
145, Hereditary breast and ovarian cancer syndrome
240760, Nijmegen breakage syndrome-like disorder
PharmGKBiPA30934

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG2310, Eukaryota
GeneTreeiENSGT00390000017288
HOGENOMiCLU_009535_3_1_1
InParanoidiP49959
OMAiQWMRPET
PhylomeDBiP49959
TreeFamiTF101105

Enzyme and pathway databases

PathwayCommonsiP49959
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-6804756, Regulation of TP53 Activity through Phosphorylation
R-HSA-69473, G2/M DNA damage checkpoint
R-HSA-912446, Meiotic recombination
SIGNORiP49959

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		4361, 305 hits in 852 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		MRE11A, human

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		MRE11A

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		4361
PharosiP49959, Tbio

Protein Ontology

More...PROi		PR:P49959
RNActiP49959, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000020922, Expressed in calcaneal tendon and 223 other tissues
ExpressionAtlasiP49959, baseline and differential
GenevisibleiP49959, HS

Family and domain databases

CDDicd00840, MPP_Mre11_N, 1 hit
Gene3Di3.30.110.110, 1 hit
3.60.21.10, 1 hit
InterProiView protein in InterPro
IPR004843, Calcineurin-like_PHP_ApaH
IPR029052, Metallo-depent_PP-like
IPR003701, Mre11
IPR007281, Mre11_DNA-bd
IPR038487, Mre11_DNA-bd_sf
IPR041796, Mre11_N
PfamiView protein in Pfam
PF00149, Metallophos, 1 hit
PF04152, Mre11_DNA_bind, 1 hit
PIRSFiPIRSF000882, DSB_repair_MRE11, 1 hit
SMARTiView protein in SMART
SM01347, Mre11_DNA_bind, 1 hit
TIGRFAMsiTIGR00583, mre11, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...ProtoNeti		Search...

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<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 subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiMRE11_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P49959
Secondary accession number(s): B3KTC7, O43475
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: September 26, 2001
Last modified: December 2, 2020
This is version 219 of the entry and version 3 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

<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

Keywords - Technical termi

3D-structure, Reference proteome

Documents

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