Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

DNA mismatch repair protein MSH2

Gene

MSH2

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
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 bind to DNA mismatches thereby initiating DNA repair. MSH2 seems to act as a scaffold for the other MutS homologs that provide substrate-binding and substrate specificity. When bound, heterodimers bend the DNA helix and shield approximately 20 base pairs. MutS alpha acts mainly to repair base-base and single insertion-deletion mismatches that occur during replication, but can also repair longer insertion-deletion loops (IDLs), although with decreasing efficiency as the size of the extrahelical loop increases. MutS beta acts mainly to repair IDLs from 2 to 13 nucleotides in size, but can also repair base-base and single insertion-deletion mismatches. After mismatch binding, MutS alpha or beta form a ternary complex with a MutL 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. Both subunits bind ATP, but with differing affinities, and their ATPase kinetics are also very different. MSH6 binds and hydrolyzes ATP rapidly, whereas MSH2 catalyzes ATP at a substantially slower rate. Binding to a mismatched base pair suppresses MSH6-catalyzed ATP hydrolysis, but not the activity of MSH2. ATP binding to both subunits is necessary to trigger a change in MutS alpha interaction with mismatched DNA, converting MutS alpha into a sliding clamp capable of hydrolysis-independent movement along DNA, and also facilitates formation of ternary complexes containing MutS and MutL proteins and the mismatch. MutS beta also has a role in regulation of heteroduplex formation during mitotic and meiotic recombination. MutS beta binds to DNA flap structures predicted to form during recombination, and is required for 3' non-homologous tail removal (NHTR). MutS beta-binding alters the DNA conformation of its substrate at the ds/ssDNA junction and may facilitate its recognition and/or cleavage by the downstream nucleotide excision repair (NER) RAD1-RAD10 endonuclease.19 Publications

Enzyme regulationi

Inhibited by Cd2+.2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi688 – 695ATPSequence analysis8

GO - Molecular functioni

  • ATPase activity Source: SGD
  • ATP binding Source: SGD
  • damaged DNA binding Source: GO_Central
  • double-strand/single-strand DNA junction binding Source: SGD
  • four-way junction DNA binding Source: SGD
  • mismatched DNA binding Source: InterPro

GO - Biological processi

  • chromatin silencing at silent mating-type cassette Source: SGD
  • DNA recombination Source: SGD
  • interstrand cross-link repair Source: SGD
  • maintenance of DNA repeat elements Source: GO_Central
  • meiotic gene conversion Source: SGD
  • meiotic mismatch repair Source: SGD
  • mismatch repair Source: SGD
  • mitotic recombination Source: SGD
  • negative regulation of reciprocal meiotic recombination Source: GO_Central
  • postreplication repair Source: GO_Central
  • reciprocal meiotic recombination Source: GO_Central
  • removal of nonhomologous ends Source: SGD
  • replication fork arrest Source: SGD
Complete GO annotation...

Keywords - Biological processi

DNA damage, DNA repair

Keywords - Ligandi

ATP-binding, DNA-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciYEAST:G3O-33490-MONOMER.
ReactomeiR-SCE-5358565. Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
R-SCE-5358606. 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
Ordered Locus Names:YOL090W
ORF Names:O0935
OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Taxonomic identifieri559292 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
Proteomesi
  • UP000002311 Componenti: Chromosome XV

Organism-specific databases

EuPathDBiFungiDB:YOL090W.
SGDiS000005450. MSH2.

Subcellular locationi

GO - Cellular componenti

  • MutSalpha complex Source: SGD
  • MutSbeta complex Source: SGD
  • nuclear chromosome Source: SGD
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi42Y → A: Moderately reduced activity in a mismatch repair assay. 1 Publication1
Mutagenesisi65K → A: Defective in a mismatch repair assay. 1 Publication1
Mutagenesisi317G → D: Partially defective in a mismatch repair assay. 2 Publications1
Mutagenesisi402L → F: Partially defective in a mismatch repair assay. 1 Publication1
Mutagenesisi430Q → K: Partially defective in a mismatch repair assay. 1 Publication1
Mutagenesisi518A → P: Defective in MMR, but not in NHTR. 1 Publication1
Mutagenesisi524D → Y: Partially defective in a mismatch repair assay. 1 Publication1
Mutagenesisi542R → P: Defective in a mismatch repair assay. 1 Publication1
Mutagenesisi561S → P: Causes strong defects in MutS alpha mismatch binding. Defective in MMR, but not in NHTR. 1 Publication1
Mutagenesisi564K → E: Causes strong defects in MutS alpha mismatch binding. Defective in MMR, but not in NHTR. 1 Publication1
Mutagenesisi566G → D: Defective in MMR, but not in NHTR. 1 Publication1
Mutagenesisi574L → S: Defective in MMR and in NHTR. 1 Publication1
Mutagenesisi584L → P: Defective in MMR and in NHTR. 1 Publication1
Mutagenesisi640P → L: Defective in a mismatch repair assay. 2 Publications1
Mutagenesisi656S → P: Causes defects in ATP-dependent dissociation of MutS alpha from mismatch DNA and in interactions between MutS alpha and MutL alpha. Defective in MMR, but not in NHTR. 1 Publication1
Mutagenesisi658H → Y: Fully functional in a mismatch repair assay. 1 Publication1
Mutagenesisi688G → A: Moderately reduced activity in a mismatch repair assay. 1 Publication1
Mutagenesisi693G → A or S: Has a dominant negative mutator effect. 2 Publications1
Mutagenesisi693G → D: Has no defect in mismatch DNA binding, but lacks ATP-induced conformational change. Defective in MMR and in NHTR. 2 Publications1
Mutagenesisi694K → A: Impairs ATP binding; reduces catalytic activity 1.6-fold for ATP hydrolysis. Has a dominant negative mutator effect. 3 Publications1
Mutagenesisi694K → R: Defective in MMR and in NHTR. 3 Publications1
Mutagenesisi695S → A: Has a dominant negative mutator effect. 1 Publication1
Mutagenesisi716C → F: Defective in a mismatch repair assay. 1 Publication1
Mutagenesisi730R → W: Disruptes MutS alpha ATPase activity, but does not affect ATP binding or interactions with MutL alpha. Defective in MMR, but not in NHTR. 1 Publication1
Mutagenesisi742S → F: Defective in MMR, but not in NHTR. 1 Publication1
Mutagenesisi742S → P: Defective in MMR and in NHTR. 1 Publication1
Mutagenesisi768E → A: Reduces catalytic activity 50-fold for ATP hydrolysis. 3 Publications1
Mutagenesisi773T → I: Defective in MMR and in NHTR. 1 Publication1
Mutagenesisi855G → D: Defective in MMR, but not in NHTR. 1 Publication1
Mutagenesisi859A → E: Defective in MMR, but not in NHTR. 1 Publication1
Mutagenesisi862V → D: Defective in MMR, but not in NHTR. 1 Publication1
Mutagenesisi863 – 868Missing : Defective in MMR and in NHTR. 1 Publication6

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001151911 – 964DNA mismatch repair protein MSH2Add BLAST964

Proteomic databases

MaxQBiP25847.
PRIDEiP25847.

PTM databases

iPTMnetiP25847.

Interactioni

Subunit structurei

Heterodimer consisting of MSH2-MSH6 (MutS alpha) or MSH2-MSH3 (MutS beta). Both heterodimers form a ternary complex with MutL alpha (MLH1-PMS1). MutS beta also forms a ternary complex with MutL beta (MLH1-MLH3), and possibly with a MLH1-MLH2 heterodimer. Both heterodimers interact with proliferating cell nuclear antigen (PCNA/POL30). This interaction is disrupted upon binding of the MutS heterodimers to mismatch DNA. Interacts with SAW1.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
EXO1P398753EBI-11352,EBI-6738
MSH3P253363EBI-11352,EBI-11362
MSH6Q038346EBI-11352,EBI-11383

Protein-protein interaction databases

BioGridi34312. 139 interactors.
DIPiDIP-2415N.
IntActiP25847. 35 interactors.
MINTiMINT-631153.

Structurei

3D structure databases

ProteinModelPortaliP25847.
SMRiP25847.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni851 – 964Interaction with MSH6Add BLAST114

Sequence similaritiesi

Belongs to the DNA mismatch repair MutS family.Curated

Phylogenomic databases

GeneTreeiENSGT00550000074867.
HOGENOMiHOG000196498.
InParanoidiP25847.
KOiK08735.
OMAiRRICERC.
OrthoDBiEOG092C0EWT.

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.
IPR032642. Msh2.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR11361:SF35. PTHR11361:SF35. 1 hit.
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.
PROSITEiPS00486. DNA_MISMATCH_REPAIR_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P25847-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSSTRPELKF SDVSEERNFY KKYTGLPKKP LKTIRLVDKG DYYTVIGSDA
60 70 80 90 100
IFVADSVYHT QSVLKNCQLD PVTAKNFHEP TKYVTVSLQV LATLLKLCLL
110 120 130 140 150
DLGYKVEIYD KGWKLIKSAS PGNIEQVNEL MNMNIDSSII IASLKVQWNS
160 170 180 190 200
QDGNCIIGVA FIDTTAYKVG MLDIVDNEVY SNLESFLIQL GVKECLVQDL
210 220 230 240 250
TSNSNSNAEM QKVINVIDRC GCVVTLLKNS EFSEKDVELD LTKLLGDDLA
260 270 280 290 300
LSLPQKYSKL SMGACNALIG YLQLLSEQDQ VGKYELVEHK LKEFMKLDAS
310 320 330 340 350
AIKALNLFPQ GPQNPFGSNN LAVSGFTSAG NSGKVTSLFQ LLNHCKTNAG
360 370 380 390 400
VRLLNEWLKQ PLTNIDEINK RHDLVDYLID QIELRQMLTS EYLPMIPDIR
410 420 430 440 450
RLTKKLNKRG NLEDVLKIYQ FSKRIPEIVQ VFTSFLEDDS PTEPVNELVR
460 470 480 490 500
SVWLAPLSHH VEPLSKFEEM VETTVDLDAY EENNEFMIKV EFNEELGKIR
510 520 530 540 550
SKLDTLRDEI HSIHLDSAED LGFDPDKKLK LENHHLHGWC MRLTRNDAKE
560 570 580 590 600
LRKHKKYIEL STVKAGIFFS TKQLKSIANE TNILQKEYDK QQSALVREII
610 620 630 640 650
NITLTYTPVF EKLSLVLAHL DVIASFAHTS SYAPIPYIRP KLHPMDSERR
660 670 680 690 700
THLISSRHPV LEMQDDISFI SNDVTLESGK GDFLIITGPN MGGKSTYIRQ
710 720 730 740 750
VGVISLMAQI GCFVPCEEAE IAIVDAILCR VGAGDSQLKG VSTFMVEILE
760 770 780 790 800
TASILKNASK NSLIIVDELG RGTSTYDGFG LAWAIAEHIA SKIGCFALFA
810 820 830 840 850
THFHELTELS EKLPNVKNMH VVAHIEKNLK EQKHDDEDIT LLYKVEPGIS
860 870 880 890 900
DQSFGIHVAE VVQFPEKIVK MAKRKANELD DLKTNNEDLK KAKLSLQEVN
910 920 930 940 950
EGNIRLKALL KEWIRKVKEE GLHDPSKITE EASQHKIQEL LRAIANEPEK
960
ENDNYLKYIK ALLL
Length:964
Mass (Da):108,884
Last modified:November 1, 1997 - v2
Checksum:i43FFD8A640138AE4
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti957 – 964KYIKALLL → EIYKSPCCYN in AAA34802 (PubMed:1459447).Curated8

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M84170 Genomic DNA. Translation: AAA34802.1.
X83121 Genomic DNA. Translation: CAA58189.1.
Z74832 Genomic DNA. Translation: CAA99102.1.
BK006948 Genomic DNA. Translation: DAA10694.1.
PIRiS57379.
RefSeqiNP_014551.1. NM_001183344.1.

Genome annotation databases

EnsemblFungiiYOL090W; YOL090W; YOL090W.
GeneIDi854063.
KEGGisce:YOL090W.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M84170 Genomic DNA. Translation: AAA34802.1.
X83121 Genomic DNA. Translation: CAA58189.1.
Z74832 Genomic DNA. Translation: CAA99102.1.
BK006948 Genomic DNA. Translation: DAA10694.1.
PIRiS57379.
RefSeqiNP_014551.1. NM_001183344.1.

3D structure databases

ProteinModelPortaliP25847.
SMRiP25847.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi34312. 139 interactors.
DIPiDIP-2415N.
IntActiP25847. 35 interactors.
MINTiMINT-631153.

PTM databases

iPTMnetiP25847.

Proteomic databases

MaxQBiP25847.
PRIDEiP25847.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblFungiiYOL090W; YOL090W; YOL090W.
GeneIDi854063.
KEGGisce:YOL090W.

Organism-specific databases

EuPathDBiFungiDB:YOL090W.
SGDiS000005450. MSH2.

Phylogenomic databases

GeneTreeiENSGT00550000074867.
HOGENOMiHOG000196498.
InParanoidiP25847.
KOiK08735.
OMAiRRICERC.
OrthoDBiEOG092C0EWT.

Enzyme and pathway databases

BioCyciYEAST:G3O-33490-MONOMER.
ReactomeiR-SCE-5358565. Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
R-SCE-5358606. Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).

Miscellaneous databases

PROiP25847.

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.
IPR032642. Msh2.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR11361:SF35. PTHR11361:SF35. 1 hit.
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.
PROSITEiPS00486. DNA_MISMATCH_REPAIR_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMSH2_YEAST
AccessioniPrimary (citable) accession number: P25847
Secondary accession number(s): D6W1X8, Q12423
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: November 1, 1997
Last modified: November 2, 2016
This is version 154 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Miscellaneous

Present with 1230 molecules/cell in log phase SD medium.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Yeast
    Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
  3. Yeast chromosome XV
    Yeast (Saccharomyces cerevisiae) chromosome XV: entries and gene names

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 one 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.