Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P43247 (MSH2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 116. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
DNA mismatch repair protein Msh2
Alternative name(s):
MutS protein homolog 2
Gene names
Name:Msh2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length935 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. In melanocytes may modulate both UV-B-induced cell cycle regulation and apoptosis By similarity.

Subunit structure

Heterodimer consisting of MSH2-MSH6 (MutS alpha) or MSH2-MSH3 (MutS beta). Both heterodimer form a ternary complex with MutL alpha (MLH1-PMS1). Interacts with EXO1. Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Interacts with ATR. Interacts with SLX4/BTBD12; this interaction is direct and links MutS beta to SLX4, a subunit of different structure-specific endonucleases By similarity. Interacts with SMARCAD1 By similarity.

Subcellular location

Nucleus Probable.

Sequence similarities

Belongs to the DNA mismatch repair MutS family.

Ontologies

Keywords
   Biological processCell cycle
DNA damage
DNA repair
   Cellular componentNucleus
   LigandATP-binding
DNA-binding
Nucleotide-binding
   PTMAcetylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processATP catabolic process

Inferred from mutant phenotype PubMed 14568978. Source: GOC

B cell differentiation

Inferred from mutant phenotype PubMed 9697843. Source: MGI

B cell mediated immunity

Inferred from mutant phenotype PubMed 9697843PubMed 9927509. Source: MGI

DNA repair

Inferred from mutant phenotype PubMed 12687013. Source: MGI

cell cycle arrest

Inferred from mutant phenotype PubMed 12687013. Source: MGI

cellular response to DNA damage stimulus

Inferred from mutant phenotype PubMed 10097137PubMed 10720738PubMed 11429706PubMed 14744764. Source: MGI

determination of adult lifespan

Inferred from mutant phenotype PubMed 10545954. Source: MGI

double-strand break repair

Inferred from mutant phenotype PubMed 17912366. Source: MGI

germ cell development

Inferred from mutant phenotype PubMed 17912366. Source: MGI

in utero embryonic development

Inferred from genetic interaction PubMed 9288110. Source: MGI

intra-S DNA damage checkpoint

Inferred from genetic interaction PubMed 15533840. Source: MGI

intrinsic apoptotic signaling pathway in response to DNA damage

Inferred from mutant phenotype PubMed 10097137PubMed 14744764. Source: MGI

intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator

Inferred from genetic interaction PubMed 10097137. Source: MGI

isotype switching

Inferred from mutant phenotype PubMed 10430621PubMed 12743174. Source: MGI

maintenance of DNA repeat elements

Inferred from Biological aspect of Ancestor. Source: RefGenome

male gonad development

Inferred from mutant phenotype PubMed 17912366. Source: MGI

meiotic gene conversion

Inferred from Biological aspect of Ancestor. Source: RefGenome

meiotic mismatch repair

Inferred from Biological aspect of Ancestor. Source: RefGenome

mismatch repair

Inferred from direct assay PubMed 9157971PubMed 9244348. Source: MGI

negative regulation of DNA recombination

Inferred from mutant phenotype PubMed 10545954PubMed 7628020. Source: MGI

negative regulation of neuron apoptotic process

Inferred from mutant phenotype PubMed 16805809. Source: MGI

negative regulation of reciprocal meiotic recombination

Inferred from Biological aspect of Ancestor. Source: RefGenome

oxidative phosphorylation

Inferred from mutant phenotype PubMed 16805809. Source: MGI

positive regulation of helicase activity

Inferred from electronic annotation. Source: Ensembl

postreplication repair

Inferred from sequence or structural similarity. Source: UniProtKB

response to UV-B

Inferred from mutant phenotype PubMed 15166087. Source: MGI

response to X-ray

Inferred from mutant phenotype PubMed 12687013. Source: MGI

somatic hypermutation of immunoglobulin genes

Inferred from mutant phenotype PubMed 14568978PubMed 9607916PubMed 9697842PubMed 9697843. Source: MGI

somatic recombination of immunoglobulin gene segments

Inferred from mutant phenotype PubMed 11828012PubMed 14563316PubMed 14568978PubMed 15955838. Source: MGI

somatic recombination of immunoglobulin genes involved in immune response

Inferred from genetic interaction PubMed 12743174. Source: MGI

   Cellular_componentMutSalpha complex

Inferred from direct assay PubMed 16713580. Source: MGI

MutSbeta complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

nuclear chromosome

Inferred from Biological aspect of Ancestor. Source: RefGenome

nucleus

Inferred from direct assay PubMed 14744764PubMed 9443401. Source: MGI

   Molecular_functionADP binding

Inferred from electronic annotation. Source: Ensembl

ATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

ATPase activity

Inferred from mutant phenotype PubMed 14568978. Source: MGI

DNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

DNA-dependent ATPase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Y-form DNA binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

centromeric DNA binding

Inferred from direct assay PubMed 16260499. Source: MGI

damaged DNA binding

Inferred from mutant phenotype PubMed 10545954PubMed 7628020. Source: MGI

dinucleotide repeat insertion binding

Inferred from electronic annotation. Source: Ensembl

double-strand/single-strand DNA junction binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

four-way junction DNA binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

guanine/thymine mispair binding

Inferred from sequence orthology PubMed 16713580. Source: MGI

loop DNA binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

magnesium ion binding

Inferred from electronic annotation. Source: Ensembl

mismatched DNA binding

Inferred from mutant phenotype PubMed 14744764PubMed 7550317. Source: MGI

oxidized purine DNA binding

Inferred from electronic annotation. Source: Ensembl

single base insertion or deletion binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

single guanine insertion binding

Inferred from electronic annotation. Source: Ensembl

single thymine insertion binding

Inferred from electronic annotation. Source: Ensembl

single-stranded DNA binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 935934DNA mismatch repair protein Msh2
PRO_0000115184

Regions

Nucleotide binding669 – 6768ATP Potential
Region601 – 67171Interaction with EXO1 By similarity

Amino acid modifications

Modified residue21N-acetylalanine By similarity
Modified residue5671N6-acetyllysine Ref.4

Experimental info

Sequence conflict7331A → S in AAA75027. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P43247 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: 2111E9D5E3A8548A

FASTA935104,151
        10         20         30         40         50         60 
MAVQPKETLQ LEGAAEAGFV RFFEGMPEKP STTVRLFDRG DFYTAHGEDA LLAAREVFKT 

        70         80         90        100        110        120 
QGVIKYMGPA GSKTLQSVVL SKMNFESFVK DLLLVRQYRV EVYKNKAGNK ASKENEWYLA 

       130        140        150        160        170        180 
FKASPGNLSQ FEDILFGNND MSASVGVMGI KMAVVDGQRH VGVGYVDSTQ RKLGLCEFPE 

       190        200        210        220        230        240 
NDQFSNLEAL LIQIGPKECV LPGGETTGDM GKLRQVIQRG GILITERKRA DFSTKDIYQD 

       250        260        270        280        290        300 
LNRLLKGKKG EQINSAALPE MENQVAVSSL SAVIKFLELL SDDSNFGQFE LATFDFSQYM 

       310        320        330        340        350        360 
KLDMAAVRAL NLFQGSVEDT TGSQSLAALL NKCKTAQGQR LVNQWIKQPL MDRNRIEERL 

       370        380        390        400        410        420 
NLVEAFVEDS ELRQSLQEDL LRRFPDLNRL AKKFQRQAAN LQDCYRLYQG INQLPSVIQA 

       430        440        450        460        470        480 
LEKYEGRHQA LLLAVFVTPL IDLRSDFSKF QEMIETTLDM DQVENHEFLV KPSFDPNLSE 

       490        500        510        520        530        540 
LREVMDGLEK KMQSTLINAA RGLGLDPGKQ IKLDSSAQFG YYFRVTCKEE KVLRNNKNFS 

       550        560        570        580        590        600 
TVDIQKNGVK FTNSELSSLN EEYTKNKGEY EEAQDAIVKE IVNISSGYVE PMQTLNDVLA 

       610        620        630        640        650        660 
HLDAIVSFAH VSNAAPVPYV RPVILEKGKG RIILKASRHA CVEVQDEVAF IPNDVHFEKD 

       670        680        690        700        710        720 
KQMFHIITGP NMGGKSTYIR QTGVIVLMAQ IGCFVPCESA EVSIVDCILA RVGAGDSQLK 

       730        740        750        760        770        780 
GVSTFMAEML ETASILRSAT KDSLIIIDEL GRGTSTYDGF GLAWAISDYI ATKIGAFCMF 

       790        800        810        820        830        840 
ATHFHELTAL ANQIPTVNNL HVTALTTEET LTMLYQVKKG VCDQSFGIHV AELANFPRHV 

       850        860        870        880        890        900 
IACAKQKALE LEEFQNIGTS LGCDEAEPAA KRRCLEREQG EKIILEFLSK VKQVPFTAMS 

       910        920        930 
EESISAKLKQ LKAEVVAKNN SFVNEIISRI KAPAP 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and expression of the Xenopus and mouse Msh2 DNA mismatch repair genes."
Varlet I., Pallard C., Radman M., Moreau J., de Wind N.
Nucleic Acids Res. 22:5723-5728(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: BALB/c.
[2]"Mouse MutS homolog 2 (mMSH2) c-DNA sequence from -56."
Lipford J.R., Kane M.F., Kolodner R.D.
Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"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].
Strain: FVB/N.
Tissue: Mammary gland.
[4]"SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-567, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X81143 mRNA. Translation: CAA57049.1.
U21011 mRNA. Translation: AAA75027.1.
BC047117 mRNA. Translation: AAH47117.1.
PIRS53608.
RefSeqNP_032654.1. NM_008628.2.
UniGeneMm.4619.

3D structure databases

ProteinModelPortalP43247.
SMRP43247. Positions 1-930.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201525. 3 interactions.
DIPDIP-57027N.
IntActP43247. 1 interaction.
STRING10090.ENSMUSP00000024967.

PTM databases

PhosphoSiteP43247.

Proteomic databases

PaxDbP43247.
PRIDEP43247.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000024967; ENSMUSP00000024967; ENSMUSG00000024151.
GeneID17685.
KEGGmmu:17685.
UCSCuc008dva.1. mouse.

Organism-specific databases

CTD4436.
MGIMGI:101816. Msh2.

Phylogenomic databases

eggNOGCOG0249.
HOGENOMHOG000196498.
HOVERGENHBG006399.
InParanoidP43247.
KOK08735.
OMAVGAGDCQ.
OrthoDBEOG76DTRW.
PhylomeDBP43247.
TreeFamTF351780.

Gene expression databases

ArrayExpressP43247.
BgeeP43247.
CleanExMM_MSH2.
GenevestigatorP43247.

Family and domain databases

Gene3D3.30.420.110. 1 hit.
3.40.50.300. 1 hit.
InterProIPR011184. DNA_mismatch_repair_MSH2.
IPR007695. DNA_mismatch_repair_MutS-lik_N.
IPR000432. DNA_mismatch_repair_MutS_C.
IPR007861. DNA_mismatch_repair_MutS_clamp.
IPR007696. DNA_mismatch_repair_MutS_core.
IPR007860. DNA_mmatch_repair_MutS_con_dom.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamPF01624. MutS_I. 1 hit.
PF05188. MutS_II. 1 hit.
PF05192. MutS_III. 1 hit.
PF05190. MutS_IV. 1 hit.
PF00488. MutS_V. 1 hit.
[Graphical view]
PIRSFPIRSF005813. MSH2. 1 hit.
SMARTSM00534. MUTSac. 1 hit.
SM00533. MUTSd. 1 hit.
[Graphical view]
SUPFAMSSF48334. SSF48334. 1 hit.
SSF52540. SSF52540. 1 hit.
SSF53150. SSF53150. 2 hits.
PROSITEPS00486. DNA_MISMATCH_REPAIR_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio292252.
PROP43247.
SOURCESearch...

Entry information

Entry nameMSH2_MOUSE
AccessionPrimary (citable) accession number: P43247
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: April 16, 2014
This is version 116 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot