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Protein

DNA mismatch repair protein Msh2

Gene

Msh2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi669 – 6768ATPSequence Analysis

GO - Molecular functioni

  1. ADP binding Source: Ensembl
  2. ATPase activity Source: MGI
  3. ATP binding Source: UniProtKB-KW
  4. centromeric DNA binding Source: MGI
  5. damaged DNA binding Source: MGI
  6. dinucleotide repeat insertion binding Source: Ensembl
  7. DNA binding Source: UniProtKB
  8. DNA-dependent ATPase activity Source: GO_Central
  9. double-strand/single-strand DNA junction binding Source: GO_Central
  10. enzyme binding Source: MGI
  11. four-way junction DNA binding Source: GO_Central
  12. guanine/thymine mispair binding Source: MGI
  13. heteroduplex DNA loop binding Source: GO_Central
  14. magnesium ion binding Source: Ensembl
  15. mismatched DNA binding Source: MGI
  16. oxidized purine DNA binding Source: Ensembl
  17. protein C-terminus binding Source: MGI
  18. protein homodimerization activity Source: MGI
  19. protein kinase binding Source: MGI
  20. single base insertion or deletion binding Source: GO_Central
  21. single guanine insertion binding Source: Ensembl
  22. single-stranded DNA binding Source: Ensembl
  23. single thymine insertion binding Source: Ensembl
  24. Y-form DNA binding Source: GO_Central

GO - Biological processi

  1. B cell differentiation Source: MGI
  2. B cell mediated immunity Source: MGI
  3. cell cycle arrest Source: MGI
  4. cellular response to DNA damage stimulus Source: MGI
  5. determination of adult lifespan Source: MGI
  6. DNA repair Source: MGI
  7. double-strand break repair Source: MGI
  8. germ cell development Source: MGI
  9. intra-S DNA damage checkpoint Source: MGI
  10. intrinsic apoptotic signaling pathway in response to DNA damage Source: MGI
  11. intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: MGI
  12. in utero embryonic development Source: MGI
  13. isotype switching Source: MGI
  14. maintenance of DNA repeat elements Source: MGI
  15. male gonad development Source: MGI
  16. meiotic gene conversion Source: GO_Central
  17. meiotic mismatch repair Source: GO_Central
  18. mismatch repair Source: MGI
  19. negative regulation of DNA recombination Source: MGI
  20. negative regulation of neuron apoptotic process Source: MGI
  21. negative regulation of reciprocal meiotic recombination Source: GO_Central
  22. oxidative phosphorylation Source: MGI
  23. positive regulation of helicase activity Source: MGI
  24. postreplication repair Source: UniProtKB
  25. response to UV-B Source: MGI
  26. response to X-ray Source: MGI
  27. somatic hypermutation of immunoglobulin genes Source: MGI
  28. somatic recombination of immunoglobulin gene segments Source: MGI
  29. somatic recombination of immunoglobulin genes involved in immune response Source: MGI
Complete GO annotation...

Keywords - Biological processi

Cell cycle, DNA damage, DNA repair

Keywords - Ligandi

ATP-binding, DNA-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_320650. Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
REACT_331202. Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).

Names & Taxonomyi

Protein namesi
Recommended name:
DNA mismatch repair protein Msh2
Alternative name(s):
MutS protein homolog 2
Gene namesi
Name:Msh2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:101816. Msh2.

Subcellular locationi

  1. Nucleus Curated

GO - Cellular componenti

  1. membrane Source: MGI
  2. MutSalpha complex Source: MGI
  3. MutSbeta complex Source: MGI
  4. nuclear chromosome Source: GO_Central
  5. nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 935934DNA mismatch repair protein Msh2PRO_0000115184Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity
Modified residuei567 – 5671N6-acetyllysine1 Publication

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiP43247.
PaxDbiP43247.
PRIDEiP43247.

PTM databases

PhosphoSiteiP43247.

Expressioni

Gene expression databases

BgeeiP43247.
CleanExiMM_MSH2.
ExpressionAtlasiP43247. baseline and differential.
GenevestigatoriP43247.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

BioGridi201525. 4 interactions.
DIPiDIP-57027N.
IntActiP43247. 1 interaction.
STRINGi10090.ENSMUSP00000024967.

Structurei

3D structure databases

ProteinModelPortaliP43247.
SMRiP43247. Positions 1-930.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni601 – 67171Interaction with EXO1By similarityAdd
BLAST

Sequence similaritiesi

Belongs to the DNA mismatch repair MutS family.Curated

Phylogenomic databases

eggNOGiCOG0249.
HOGENOMiHOG000196498.
HOVERGENiHBG006399.
InParanoidiP43247.
KOiK08735.
OMAiTLQDCYR.
OrthoDBiEOG76DTRW.
PhylomeDBiP43247.
TreeFamiTF351780.

Family and domain databases

Gene3Di3.30.420.110. 1 hit.
3.40.50.300. 1 hit.
InterProiIPR011184. DNA_mismatch_repair_MutS.
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]
PfamiPF01624. 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]
PIRSFiPIRSF005813. MSH2. 1 hit.
SMARTiSM00534. MUTSac. 1 hit.
SM00533. MUTSd. 1 hit.
[Graphical view]
SUPFAMiSSF48334. SSF48334. 1 hit.
SSF52540. SSF52540. 1 hit.
SSF53150. SSF53150. 2 hits.
PROSITEiPS00486. DNA_MISMATCH_REPAIR_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P43247-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAVQPKETLQ LEGAAEAGFV RFFEGMPEKP STTVRLFDRG DFYTAHGEDA
60 70 80 90 100
LLAAREVFKT QGVIKYMGPA GSKTLQSVVL SKMNFESFVK DLLLVRQYRV
110 120 130 140 150
EVYKNKAGNK ASKENEWYLA FKASPGNLSQ FEDILFGNND MSASVGVMGI
160 170 180 190 200
KMAVVDGQRH VGVGYVDSTQ RKLGLCEFPE NDQFSNLEAL LIQIGPKECV
210 220 230 240 250
LPGGETTGDM GKLRQVIQRG GILITERKRA DFSTKDIYQD LNRLLKGKKG
260 270 280 290 300
EQINSAALPE MENQVAVSSL SAVIKFLELL SDDSNFGQFE LATFDFSQYM
310 320 330 340 350
KLDMAAVRAL NLFQGSVEDT TGSQSLAALL NKCKTAQGQR LVNQWIKQPL
360 370 380 390 400
MDRNRIEERL NLVEAFVEDS ELRQSLQEDL LRRFPDLNRL AKKFQRQAAN
410 420 430 440 450
LQDCYRLYQG INQLPSVIQA LEKYEGRHQA LLLAVFVTPL IDLRSDFSKF
460 470 480 490 500
QEMIETTLDM DQVENHEFLV KPSFDPNLSE LREVMDGLEK KMQSTLINAA
510 520 530 540 550
RGLGLDPGKQ IKLDSSAQFG YYFRVTCKEE KVLRNNKNFS TVDIQKNGVK
560 570 580 590 600
FTNSELSSLN EEYTKNKGEY EEAQDAIVKE IVNISSGYVE PMQTLNDVLA
610 620 630 640 650
HLDAIVSFAH VSNAAPVPYV RPVILEKGKG RIILKASRHA CVEVQDEVAF
660 670 680 690 700
IPNDVHFEKD KQMFHIITGP NMGGKSTYIR QTGVIVLMAQ IGCFVPCESA
710 720 730 740 750
EVSIVDCILA RVGAGDSQLK GVSTFMAEML ETASILRSAT KDSLIIIDEL
760 770 780 790 800
GRGTSTYDGF GLAWAISDYI ATKIGAFCMF ATHFHELTAL ANQIPTVNNL
810 820 830 840 850
HVTALTTEET LTMLYQVKKG VCDQSFGIHV AELANFPRHV IACAKQKALE
860 870 880 890 900
LEEFQNIGTS LGCDEAEPAA KRRCLEREQG EKIILEFLSK VKQVPFTAMS
910 920 930
EESISAKLKQ LKAEVVAKNN SFVNEIISRI KAPAP
Length:935
Mass (Da):104,151
Last modified:November 1, 1995 - v1
Checksum:i2111E9D5E3A8548A
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti733 – 7331A → S in AAA75027 (Ref. 2) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X81143 mRNA. Translation: CAA57049.1.
U21011 mRNA. Translation: AAA75027.1.
BC047117 mRNA. Translation: AAH47117.1.
CCDSiCCDS29019.1.
PIRiS53608.
RefSeqiNP_032654.1. NM_008628.2.
UniGeneiMm.4619.

Genome annotation databases

EnsembliENSMUST00000024967; ENSMUSP00000024967; ENSMUSG00000024151.
GeneIDi17685.
KEGGimmu:17685.
UCSCiuc008dva.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X81143 mRNA. Translation: CAA57049.1.
U21011 mRNA. Translation: AAA75027.1.
BC047117 mRNA. Translation: AAH47117.1.
CCDSiCCDS29019.1.
PIRiS53608.
RefSeqiNP_032654.1. NM_008628.2.
UniGeneiMm.4619.

3D structure databases

ProteinModelPortaliP43247.
SMRiP43247. Positions 1-930.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201525. 4 interactions.
DIPiDIP-57027N.
IntActiP43247. 1 interaction.
STRINGi10090.ENSMUSP00000024967.

PTM databases

PhosphoSiteiP43247.

Proteomic databases

MaxQBiP43247.
PaxDbiP43247.
PRIDEiP43247.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000024967; ENSMUSP00000024967; ENSMUSG00000024151.
GeneIDi17685.
KEGGimmu:17685.
UCSCiuc008dva.1. mouse.

Organism-specific databases

CTDi4436.
MGIiMGI:101816. Msh2.

Phylogenomic databases

eggNOGiCOG0249.
HOGENOMiHOG000196498.
HOVERGENiHBG006399.
InParanoidiP43247.
KOiK08735.
OMAiTLQDCYR.
OrthoDBiEOG76DTRW.
PhylomeDBiP43247.
TreeFamiTF351780.

Enzyme and pathway databases

ReactomeiREACT_320650. Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
REACT_331202. Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).

Miscellaneous databases

NextBioi292252.
PROiP43247.
SOURCEiSearch...

Gene expression databases

BgeeiP43247.
CleanExiMM_MSH2.
ExpressionAtlasiP43247. baseline and differential.
GenevestigatoriP43247.

Family and domain databases

Gene3Di3.30.420.110. 1 hit.
3.40.50.300. 1 hit.
InterProiIPR011184. DNA_mismatch_repair_MutS.
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]
PfamiPF01624. 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]
PIRSFiPIRSF005813. MSH2. 1 hit.
SMARTiSM00534. MUTSac. 1 hit.
SM00533. MUTSd. 1 hit.
[Graphical view]
SUPFAMiSSF48334. SSF48334. 1 hit.
SSF52540. SSF52540. 1 hit.
SSF53150. SSF53150. 2 hits.
PROSITEiPS00486. DNA_MISMATCH_REPAIR_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiMSH2_MOUSE
AccessioniPrimary (citable) accession number: P43247
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: April 1, 2015
This is version 126 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.