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Protein

DNA mismatch repair protein MSH6

Gene

MSH6

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. MSH6 provides substrate-binding and substrate specificity to the complex. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs. 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. After mismatch binding, 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 by the MutS alpha complex is crucial for MMR. 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. May also be involved in resolution of recombination intermediates.19 Publications

Miscellaneous

Present with 5330 molecules/cell in log phase SD medium.1 Publication

Enzyme regulationi

Inhibited by Cd2+.2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi228 – 299Add BLAST72
Nucleotide bindingi982 – 989ATPSequence analysis8

GO - Molecular functioni

  • ATPase activity Source: SGD
  • ATP binding Source: SGD
  • damaged DNA binding Source: GO_Central
  • DNA-dependent ATPase activity Source: GO_Central
  • double-strand/single-strand DNA junction binding Source: GO_Central
  • four-way junction DNA binding Source: SGD
  • heteroduplex DNA loop binding Source: GO_Central
  • Y-form DNA binding Source: GO_Central

GO - Biological processi

  • interstrand cross-link repair Source: SGD
  • maintenance of DNA repeat elements Source: GO_Central
  • meiotic mismatch repair Source: SGD
  • mismatch repair Source: SGD
  • replication fork arrest Source: SGD

Keywordsi

Molecular functionDNA-binding
Biological processDNA damage, DNA repair
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciYEAST:G3O-29700-MONOMER
ReactomeiR-SCE-5358565 Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)

Names & Taxonomyi

Protein namesi
Recommended name:
DNA mismatch repair protein MSH6
Alternative name(s):
MutS protein homolog 6
Postmeiotic segregation protein 3
Gene namesi
Name:MSH6
Synonyms:PMS3
Ordered Locus Names:YDR097C
ORF Names:YD8557.04C
OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Taxonomic identifieri559292 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
Proteomesi
  • UP000002311 Componenti: Chromosome IV

Organism-specific databases

EuPathDBiFungiDB:YDR097C
SGDiS000002504 MSH6

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cell wall Cytoskeleton Vacuole Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi26 – 27KQ → AA: Partially functional in a mismatch repair assay; when associated with 33-AA-34. 1 Publication2
Mutagenesisi33 – 34FF → AA: Abolishes interaction with PCNA (POL30), but only causes a moderate mismatch repair defect. Partially functional in a mismatch repair assay; when associated with 26-AA-27. 2 Publications2
Mutagenesisi301L → V: Fully functional in a mismatch repair assay. 1 Publication1
Mutagenesisi313P → A: Fully functional in a mismatch repair assay. 1 Publication1
Mutagenesisi337F → A: Shows defects in both homoduplex and mispair DNA binding and is only partially functional in a mismatch repair assay. 3 Publications1
Mutagenesisi337F → H, I or Y: Partially functional in a mismatch repair assay. 3 Publications1
Mutagenesisi337F → K: Completely abolishes mismatch repair. 3 Publications1
Mutagenesisi337F → S in MSH6-6; partially functional in a mismatch repair assay. 3 Publications1
Mutagenesisi339E → A: Defective in repairing 8-oxo-G-A mismatches. 2 Publications1
Mutagenesisi340 – 343LYEK → CFAE in MSH6-340; shows defects in mispair DNA binding, but not in homoduplex DNA binding. 1 Publication4
Mutagenesisi368G → A: Moderately reduced activity in a mismatch repair assay. 1 Publication1
Mutagenesisi370P → A: Partially functional in a mismatch repair assay. 1 Publication1
Mutagenesisi393Q → A: Moderately reduced activity in a mismatch repair assay. 1 Publication1
Mutagenesisi393Q → R in MSH6-5; partially functional in a mismatch repair assay. 1 Publication1
Mutagenesisi412R → A: Completely abolishes mismatch repair. 1 Publication1
Mutagenesisi412R → G in MSH6-7; partially functional in a mismatch repair assay. 1 Publication1
Mutagenesisi421G → D in PMS3-1; completely abolishes mismatch repair. 1 Publication1
Mutagenesisi477G → R: Partially functional in a mismatch repair assay. 1 Publication1
Mutagenesisi848K → A: Fully functional in a mismatch repair assay. 1 Publication1
Mutagenesisi852R → A: Moderately reduced activity in a mismatch repair assay. 1 Publication1
Mutagenesisi987G → D: Has no defect in mismatch DNA binding, but lacks ATP-induced conformational change. 1 Publication1
Mutagenesisi988K → A: Impairs ATP binding; reduces catalytic activity 13-fold for ATP hydrolysis. 2 Publications1
Mutagenesisi1036S → P in MSH6-4; defective for ATP-induced sliding clamp formation and assembly of ternary complexes with MutL alpha. 2 Publications1
Mutagenesisi1062E → A: Reduces catalytic activity 13-fold for ATP hydrolysis. 3 Publications1
Mutagenesisi1067G → D in MSH6-3; defective for ATP-induced sliding clamp formation and assembly of ternary complexes with MutL alpha. 2 Publications1
Mutagenesisi1096H → A in MSH6-9; shows normal mispair binding and dissociation, but fails to show complete mispair activation of the ATPase. 1 Publication1
Mutagenesisi1142G → D in MSH6-2; defective for ATP-induced sliding clamp formation, but assembles ternary complexes with MutL alpha. 2 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001152131 – 1242DNA mismatch repair protein MSH6Add BLAST1242

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei102PhosphoserineCombined sources1
Modified residuei145PhosphoserineCombined sources1
Modified residuei150PhosphoserineCombined sources1
Modified residuei201PhosphoserineCombined sources1
Modified residuei451PhosphothreonineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ03834
PaxDbiQ03834
PRIDEiQ03834

PTM databases

iPTMnetiQ03834

Interactioni

Subunit structurei

Heterodimer consisting of MSH2-MSH6 (MutS alpha). Forms a ternary complex with MutL alpha (MLH1-PMS1). MutS alpha interacts with proliferating cell nuclear antigen (PCNA/POL30). This interaction is disrupted upon binding of MutS alpha to mismatch DNA.5 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi32152, 109 interactors
ComplexPortaliCPX-1037 DNA mismatch repair MutSalpha complex
DIPiDIP-2423N
ELMiQ03834
IntActiQ03834, 47 interactors
MINTiQ03834
STRINGi4932.YDR097C

Structurei

3D structure databases

ProteinModelPortaliQ03834
SMRiQ03834
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni305 – 421Mispair-binding domainAdd BLAST117

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi27 – 34PIP box8

Domaini

The PIP box serves as a PCNA(POL30)-recognition and -binding motif.

Sequence similaritiesi

Belongs to the DNA mismatch repair MutS family.Curated

Phylogenomic databases

GeneTreeiENSGT00550000075024
HOGENOMiHOG000189303
InParanoidiQ03834
KOiK08737
OMAiELRHPCM
OrthoDBiEOG092C0EWT

Family and domain databases

Gene3Di3.30.420.110, 1 hit
3.40.1170.10, 1 hit
InterProiView protein in InterPro
IPR015536 DNA_mismatch_repair_MSH6_C
IPR007695 DNA_mismatch_repair_MutS-lik_N
IPR017261 DNA_mismatch_repair_MutS/MSH
IPR000432 DNA_mismatch_repair_MutS_C
IPR007861 DNA_mismatch_repair_MutS_clamp
IPR007696 DNA_mismatch_repair_MutS_core
IPR016151 DNA_mismatch_repair_MutS_N
IPR036187 DNA_mismatch_repair_MutS_sf
IPR007860 DNA_mmatch_repair_MutS_con_dom
IPR036678 MutS_con_dom_sf
IPR027417 P-loop_NTPase
PANTHERiPTHR11361:SF31 PTHR11361:SF31, 1 hit
PfamiView protein in Pfam
PF01624 MutS_I, 1 hit
PF05188 MutS_II, 1 hit
PF05192 MutS_III, 1 hit
PF05190 MutS_IV, 1 hit
PF00488 MutS_V, 1 hit
PIRSFiPIRSF037677 DNA_mis_repair_Msh6, 1 hit
SMARTiView protein in SMART
SM00534 MUTSac, 1 hit
SM00533 MUTSd, 1 hit
SUPFAMiSSF48334 SSF48334, 1 hit
SSF52540 SSF52540, 1 hit
SSF53150 SSF53150, 1 hit
SSF55271 SSF55271, 1 hit
PROSITEiView protein in PROSITE
PS00486 DNA_MISMATCH_REPAIR_2, 1 hit

Sequencei

Sequence statusi: Complete.

Q03834-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAPATPKTSK TAHFENGSTS SQKKMKQSSL LSFFSKQVPS GTPSKKVQKP
60 70 80 90 100
TPATLENTAT DKITKNPQGG KTGKLFVDVD EDNDLTIAEE TVSTVRSDIM
110 120 130 140 150
HSQEPQSDTM LNSNTTEPKS TTTDEDLSSS QSRRNHKRRV NYAESDDDDS
160 170 180 190 200
DTTFTAKRKK GKVVDSESDE DEYLPDKNDG DEDDDIADDK EDIKGELAED
210 220 230 240 250
SGDDDDLISL AETTSKKKFS YNTSHSSSPF TRNISRDNSK KKSRPNQAPS
260 270 280 290 300
RSYNPSHSQP SATSKSSKFN KQNEERYQWL VDERDAQRRP KSDPEYDPRT
310 320 330 340 350
LYIPSSAWNK FTPFEKQYWE IKSKMWDCIV FFKKGKFFEL YEKDALLANA
360 370 380 390 400
LFDLKIAGGG RANMQLAGIP EMSFEYWAAQ FIQMGYKVAK VDQRESMLAK
410 420 430 440 450
EMREGSKGIV KRELQCILTS GTLTDGDMLH SDLATFCLAI REEPGNFYNE
460 470 480 490 500
TQLDSSTIVQ KLNTKIFGAA FIDTATGELQ MLEFEDDSEC TKLDTLMSQV
510 520 530 540 550
RPMEVVMERN NLSTLANKIV KFNSAPNAIF NEVKAGEEFY DCDKTYAEII
560 570 580 590 600
SSEYFSTEED WPEVLKSYYD TGKKVGFSAF GGLLYYLKWL KLDKNLISMK
610 620 630 640 650
NIKEYDFVKS QHSMVLDGIT LQNLEIFSNS FDGSDKGTLF KLFNRAITPM
660 670 680 690 700
GKRMMKKWLM HPLLRKNDIE SRLDSVDSLL QDITLREQLE ITFSKLPDLE
710 720 730 740 750
RMLARIHSRT IKVKDFEKVI TAFETIIELQ DSLKNNDLKG DVSKYISSFP
760 770 780 790 800
EGLVEAVKSW TNAFERQKAI NENIIVPQRG FDIEFDKSMD RIQELEDELM
810 820 830 840 850
EILMTYRKQF KCSNIQYKDS GKEIYTIEIP ISATKNVPSN WVQMAANKTY
860 870 880 890 900
KRYYSDEVRA LARSMAEAKE IHKTLEEDLK NRLCQKFDAH YNTIWMPTIQ
910 920 930 940 950
AISNIDCLLA ITRTSEYLGA PSCRPTIVDE VDSKTNTQLN GFLKFKSLRH
960 970 980 990 1000
PCFNLGATTA KDFIPNDIEL GKEQPRLGLL TGANAAGKST ILRMACIAVI
1010 1020 1030 1040 1050
MAQMGCYVPC ESAVLTPIDR IMTRLGANDN IMQGKSTFFV ELAETKKILD
1060 1070 1080 1090 1100
MATNRSLLVV DELGRGGSSS DGFAIAESVL HHVATHIQSL GFFATHYGTL
1110 1120 1130 1140 1150
ASSFKHHPQV RPLKMSILVD EATRNVTFLY KMLEGQSEGS FGMHVASMCG
1160 1170 1180 1190 1200
ISKEIIDNAQ IAADNLEHTS RLVKERDLAA NNLNGEVVSV PGGLQSDFVR
1210 1220 1230 1240
IAYGDGLKNT KLGSGEGVLN YDWNIKRNVL KSLFSIIDDL QS
Length:1,242
Mass (Da):140,080
Last modified:November 1, 1996 - v1
Checksum:i11A6883AADCFA222
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z47746 Genomic DNA Translation: CAA87671.1
BK006938 Genomic DNA Translation: DAA11942.1
PIRiS51246
RefSeqiNP_010382.3, NM_001180405.3

Genome annotation databases

EnsemblFungiiYDR097C; YDR097C; YDR097C
GeneIDi851671
KEGGisce:YDR097C

Similar proteinsi

Entry informationi

Entry nameiMSH6_YEAST
AccessioniPrimary (citable) accession number: Q03834
Secondary accession number(s): D6VS82
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 1, 1996
Last modified: July 18, 2018
This is version 167 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

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 IV
    Yeast (Saccharomyces cerevisiae) chromosome IV: entries and gene names

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